Abstract:Objective To compare the efficacy of pan-retinal,sectoral,and ischemic area-targeted laser photocoagu-lation in the treatment of proliferative diabetic retinopathy(PDR).Methods A prospective cohort study was conducted,en-rolling 88 PDR patients admitted to the Department of Ophthalmology,Bengbu Third People's Hospital from November 2021 to April 2025.According to the laser photocoagulation treatment area,patients were divided into the pan-retinal photocoagula-tion(PRP)group(n=28),the sectoral group(n=30),and the ischemic area-targeted group(n=30).Best corrected visual acuity(BCVA)was measured using the international standard visual acuity chart;central macular thickness(CMT)and foveal avascular zone(FAZ)area were measured by optical coherence tomography(OCT),and retinal nerve fiber layer(RNFL)thick-ness in the inferior,nasal,superior,and temporal quadrants around the optic disc was also measured.All measurements were taken preoperatively and 1 month postoperatively.The incidence of postoperative complications was recorded and compared among the groups.Results At 1 month postoperatively,BCVA(LogMAR)improved significantly in all three groups com-pared to preoperative levels(t=10.552,10.232,and 8.822,respectively;all P＜0.05).A significant difference in BCVA(Log-MAR)was observed among the three groups(F=11.825,P＜0.05).Pairwise comparisons revealed that the sectoral group achieved the lowest LogMAR values(indicating the best visual acuity),followed by the PRP group,while the ischemic area-targeted group showed the highest values(all P＜0.05).Postoperative CMT decreased in all three groups compared to preopera-tive levels(t=12.745,15.551,8.972,all P＜0.05),with a statistically significant difference in CMT among the three groups(F=26.019,P＜0.001).Pairwise comparisons showed the order of reduction was:sectoral group＜PRP group＜ischemic area-tar-geted group(all P＜0.05).In contrast,no significant differences were found in FAZ area before and after laser treatment in any group(all P＞0.05).After surgery,RNFL thickness in the inferior,nasal,superior,and temporal quadrants decreased in all three groups compared to preoperative levels,with the order of reduction being:sectoral group＜PRP group＜ischemic area-targe-ted group(allP＜0.05).The complication rates in the sectoral group(3.33％)and ischemic area-targeted group(6.67％)were significantly lower than that in the PRP group(28.57％)(x2=9.850,P=0.007).Conclusion Sectoral retinal laser photocoag-ulation is more conducive to improving visual acuity,reducing central macular thickness and retinal nerve fiber layer thickness in all quadrants in PDR patients,and is associated with a lower risk of complications,demonstrating safety and reliability.

Abstract:Objective To study the expression of transmembrane p24 trafficking protein 2(TMED2)and sialic acid-binding immunoglobulin-type lectins 15(Siglec15)in cutaneous malignant melanoma(CMM)and their clinicopathological features,immune cell infiltration,and prognostic significance.Methods A total of 109 patients with CMM admitted to the Department of Dermatology,the Fifth Medical Center of Chinese PLA General Hospital from April 2019 to April 2022 were selected as the research subjects.The protein and mRNA expressions of TMED2 and Siglecl5 in CMM tissues were detected by immunohistochemical staining and quantitative real-time PCR(qPCR).R language was used to analyze the relationship be-tween TMED2,Siglec15 expression and immune cell infiltration in the TCGA database.Kaplan-Meier survival analysis and Cox multivariate regression analysis were used to evaluate the effect of TMED2 and Siglec15 protein expression on the prog-nosis of CMM patients.Results The positive rates of TMED2 and Siglec15 in cancer tissues were 67.89％(74/109)and 64.22％(70/109),respectively,which were significantly higher than those in adjacent tissues[7.34％(8/109)and 9.17％(10/109)](x2/P=85.151/＜0.001,71.087/＜0.001).The mRNA expression levels of TMED2 and Siglecl5 in CMM cancer tissues were 2.52±0.54 and 3.03±0.46,respectively,which were significantly higher than those in adjacent tissues(0.93±0.25 and 1.05±0.28)(t/P=27.896/＜0.001,38.387/＜0.001).Analysis of TCGA database showed that TMED2 expression in CMM tissues was positively correlated with Treg cells,macrophages,and neutrophils(r/P=0.310/＜0.001,0.254/＜0.001,0.226/＜0.001),and negatively correlated with CD56+NK cells,CD8+T cells,and NK cells(r/P=-0.407/＜0.001,-0.344/＜0.001,-0.298/＜0.001).Siglec15 expression was positively correlated with Treg cells,macrophages,and follicular helper T cells(TFH)(r/P=0.433/＜0.001,0.488/＜0.001,0.416/＜0.001).The positive rates of TMED2 and Siglec15 in CMM tissues were significantly higher in patients with clinical stage ⅢA-B and lymph node metastasis(x2/P=11.957/0.001,10.366/0.001;12.789/＜0.001,17.217/＜0.001).The 3-year overall survival rate of the TMED2-positive group was 68.92％(51/74),which was significantly lower than that of the negative group(85.71％,30/35)(Log-rank x2=3.320,P＜0.001).The 3-year overall survival rate of the Siglec15-positive group was 67.14％(47/70),which was significantly lower than that of the negative group(87.18％,34/39)(Log-rank x2=5.580,P＜0.001).Clinical stage ⅢA-B,lymph node metastasis,TMED2 positivity,and Siglec15 positivity were inde-pendent risk factors affecting the prognosis of CMM patients[HR(95％CI)=1.665(1.145-2.421),1.383(1.101-1.736),1.508(1.192-1.908),1.391(1.139-1.699)].Conclusion The elevated expression of TMED2 and Siglec15 in CMM is associated with tumor immune infiltration and adverse clinicopathological features,and they represent novel biomarkers for evaluating the prognosis of CMM.

Abstract:Gastrointestinal tumors are one of the leading causes of cancer-related deaths worldwide.Their initiation and progression are driven by the complex interactions of multiple factors including genetics,the environment and microbial ecology,posing a severe threat to human health.Current clinical treatments are plagued by marked interindividual variability in efficacy,along with a high risk of drug resistance and recurrence,making it an urgent priority to explore novel pathogenic mechanisms and therapeutic targets.With the development of technologies such as metagenomic sequencing,the traditional no-tion that the blood of healthy individuals and tumor patients is"sterile"has been overturned,and the role of circulating micro-organisms(CM)in gastrointestinal tumors has attracted widespread attention.CMs participate in the tumorigenesis and pro-gression of gastrointestinal tumors by regulating inflammation,immunity,and angiogenesis in the tumor microenvironment,of-fering a new perspective for clinical diagnosis and treatment.However,relevant research is still limited by technical drawbacks in detection,incomplete elucidation of specific mechanisms,and the lack of large-sample validation in clinical translation.Go-ing forward,it is necessary to optimize detection technologies,further decipher the molecular mechanisms underlying CM-me-diated regulation of gastrointestinal tumors,and conduct large-scale clinical studies to validate the diagnostic value of microbial biomarkers and the efficacy of targeted interventions,thereby providing new strategies for the precise prevention and treatment of gastrointestinal tumors.

Abstract:Objective This study aims to explore the effects of aerobic exercise intervention combined with probiot-ics on metabolic indicators and cardiopulmonary function in obese patients with type 2 diabetes mellitus and metabolic syn-drome(T2DM-MS).Methods From August 2022 to August 2024,163 T2DM-MS patients who visited the Department of General Practice at First Hospital of Shanxi Medical University were assigned into a test group(aerobic exercise intervention combined with probiotics)and a control group(probiotics alone)using a random number table method,with 80 patients in each group.The changes in clinical parameters,blood glucose indicators,metabolic indicators,lung function,and heart function were compared between the two groups.Results After treatment,waist circumference and blood pressure decreased in both groups,with the test group showing significantly lower values than the control group(t/P=2.260/0.025,2.613/0.010,2.279/0.024,2.195/0.030).There was no significant change in BMI in the control group before and after treatment(P＞0.05),while BMI in the test group decreased and was significantly lower than that in the control group(t/P=1.988/0.049).FPG,HbA1c,and 2hPG decreased in both groups after treatment,with significantly lower levels in the test group compared to the control group(t/P=5.128/＜0.001,4.727/＜0.001,3.499/0.001).After treatment,TC,TG,and LDL-C in the test group decreased and were significantly lower than those in the control group(t/P=2.235/0.027,3.292/＜0.001,4.997/＜0.001),while HDL-C lev-els increased and were significantly higher than those in the control group(t/P=2.412/0.017).After treatment,forced vital ca-pacity(FVC),forced expiratory volume in one second(FEV1),and maximum voluntary ventilation(MVV)in the test group increased and were significantly higher than those in the control group.No statistically significant differences were observed in these pulmonary function indicators in the control group before and after intervention.After treatment,left ventricular ejection fraction(LVEF)in the test group increased(and was significantly higher than that in the control group),while left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)decreased(and were significantly lower than those in the control group).Compared with before intervention,no statistically significant differences were observed in various cardiac function indicators in the control group.Conclusion Aerobic exercise intervention combined with probiotics can significantly improve glucose and lipid metabolism indicators and cardiopulmonary function in patients with T2DM-MS,providing new insights for comprehensive intervention of this disease.

Abstract:Sepsis is multi-organ dysfunction due to a dysregulated response to infection.Due to the high morbidity,high mortality and high treatment costs,and the lack of effective treatment methods,the global medical burden has become in-creasingly serious in recent years,so it is imperative to explore the mechanism of the occurrence and development of sepsis and find new therapeutic drugs that may improve or prevent the occurrence and development of sepsis.Studies have found that itaconic acid,as a naturally occurring metabolite in immune cells,plays an important role in regulating inflammation and im-mune metabolism,and may be a very promising drug for the prevention and treatment of sepsis.This article reviews the re-search progress on the mechanism of action and efficacy of itaconic acid in the treatment of sepsis and the protection of multi-organ function,in order to provide more ideas and help for the research and treatment of sepsis.

Abstract:Objective To analyze the relationship between serum levels of CBP/p300 interacting transactivator 2(CITED2),brain and muscle Arnt-like 1(BMAL1),and NOP2/Sun RNA methyltransferase 3(NSUN3)and the condition of patients with sepsis complicated by acute kidney injury(AKI),and their impact on prognosis.Methods A total of 123 pa-tients with sepsis complicated by AKI admitted to the Department of Critical Care Medicine at Tangdu Hospital,Air Force Medical University,between February 2023 and March 2025 were selected as the sepsis-AKI group.According to AKI staging criteria,cases were classified into stage Ⅰ(45 cases),stage Ⅱ(40 cases),and stage Ⅲ(38 cases).Patients were divided into a survival subgroup(81 cases)and a mortality subgroup(42 cases)based on 28-day survival status.Additionally,115 patients with uncomplicated sepsis admitted during the same period were selected as the sepsis group,and 123 healthy volunteers con-stituted the healthy control group.ELISA was used to detect serum CITED2 levels.Quantitative real-time PCR(qRT-PCR)was used to detect the relative expression levels of serum BMAL1 mRNA and NSUN3 mRNA.Pearson correlation analysis was used to examine relationships between variables.Multivariate Cox proportional hazards analysis was performed to identify factors associated with poor prognosis.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predic-tive value of these biomarkers for poor prognosis in patients with sepsis complicated by AKI.Results Serum CITED2 and NSUN3 mRNA levels progressively increased across the healthy control,sepsis,and sepsis-AKI groups,while serum BMAL1 mRNA levels progressively decreased(F=544.535,728.950,478.098;all P＜0.001).Serum CITED2 and NSUN3 mRNA levels progressively increased across stages Ⅰ,Ⅱ,and Ⅲ,while serum BMAL1 mRNA levels progressively decreased(F=33.532,22.012,72.544;all P＜0.001).The mortality subgroup exhibited significantly higher serum CITED2 and NSUN3 mRNA levels,higher APACHE Ⅱ scores,higher SOFA scores,and higher serum creatinine levels compared to the survival subgroup,while serum BMAL1 mRNA levels were significantly lower(t/x2=7.514,7.639,7.732,9.627,6.264,all P＜0.001).Serum CITED2 was positively correlated with APACHE Ⅱ and SOFA scores(r=0.512,0.508,both P＜0.001);serum NSUN3 mRNA was positively correlated with APACHE Ⅱ and SOFA scores(r=0.506,0.513,both P＜0.001);and serum BMAL1 mRNA was negatively correlated with APACHE Ⅱ and SOFA scores(r=-0.527,-0.519,both P＜0.001).Elevated CITED2,NSUN3 mRNA,APACHE Ⅱ score,and SOFA score were independent risk factors for poor prognosis[HR(95％CI)=2.078(1.353-3.192),2.343(1.458-3.765),2.436(1.763-3.366),2.651(1.777-3.954)],while elevated BMAL1 mRNA was an inde-pendent protective factor[HR(95％CI)=0.314(0.172-0.572)].The AUC values for predicting poor prognosis in sepsis-asso-ciated AKI patients using serum CITED2,BMAL1 mRNA,NSUN3 mRNA individually and in combination were 0.794,0.814,0.810,and 0.916,respectively.The combined assessment demonstrated superior predictive value compared to individual markers(Z=2.780,2.084,2.435;P=0.005,0.037,0.015).Conclusion Patients with sepsis-associated AKI exhibit elevated serum levels of CITED2 and NSUN3 alongside decreased BMAL1 levels.These three markers correlate with disease severity and poor prognosis,potentially serving as biomarkers for predicting 28-day mortality in patients with sepsis-associated AKI.

Abstract:Objective To investigate the predictive value of serum macrophage colony-stimulating factor(M-CSF)and intercellular adhesion molecule-1(ICAM-1)levels for postoperative adhesive intestinal obstruction in children.Methods A total of 152 pediatric patients with intestinal adhesions after abdominal surgery who were admitted to the Department of General Surgery of the First Hospital of Hebei Medical University from January 2023 to June 2024 were enrolled.Based on imaging findings from upright abdominal radiographs,abdominal ultrasonography,and computed tomography(CT),patients were divided into an intestinal obstruction subgroup(n=50)and a non-obstruction subgroup(n=102).In addition,50 age-and sex-matched healthy children who underwent physical examinations during the same period were included as the healthy con-trol group.Fasting venous blood samples were collected from all participants,and serum levels of M-CSF and ICAM-1 were measured using enzyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was performed to evaluate the re-lationships between serum M-CSF and ICAM-1 levels and inflammatory indicators,including white blood cell(WBC)count,C-reactive protein(CRP),and procalcitonin(PCT).Multivariate logistic regression analysis was used to identify independent risk factors for postoperative adhesive intestinal obstruction.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of serum M-CSF and ICAM-1 levels.Results Serum M-CSF and ICAM-1 levels were significantly higher in the adhesive intestinal obstruction group than in the healthy control group(M-CSF:t=11.152,P＜0.001;ICAM-1:t=8.701,P＜0.001).The incidence of intestinal obstruction among the 152 patients with adhesions was 32.89％(50/152).The intestinal obstruction subgroup showed significantly higher WBC,CRP,and PCT levels compared with the non-ob-struction subgroup(WBC:t=13.816,P＜0.00l;CRP:t=34.123,P＜0.001;PCT:t=19.216,P＜0.001).Pearson correlation anal-ysis indicated that serum M-CSF levels were positively correlated with WBC(r=0.683,P=0.013),CRP(r=0.701,P=0.008),and PCT(r=0.782,P=0.027),while serum ICAM-1 levels were positively correlated with WBC(r=0.659,P=0.024),CRP(r=0.712,P=0.011),and PCT(r=0.747,P=0.003).Multivariate logistic regression analysis revealed that elevated WBC,CRP,and PCT levels were independent risk factors for postoperative adhesive intestinal obstruction[WBC:OR=1.317,95％CI(1.233-3.989);CRP:OR=2.429,95％CI(1.506-4.038);PCT:OR=1.103,95％CI(0.738-2.899)].The area under the ROC curve(AUC)for M-CSF,ICAM-1,and their combined detection in predicting adhesive intestinal obstruction was 0.694,0.752,and 0.820,respectively.The AUC of the combined detection was higher than that of either marker alone.Conclusion Serum M-CSF and ICAM-1 levels are elevated in children with postoperative adhesive intestinal obstruction and are associated with disease severity.Combined detection of these two biomarkers provides a higher predictive value for the occurrence of postop-erative adhesive intestinal obstruction than individual testing.

Abstract:We present three cases of autoimmune glial fibrillary acidic protein astrocytopathy(GFAP-A)with detailed clinical information and review the relevant literature.

Abstract:Objective To evaluate the clinical utility of metagenomic next-generation sequencing(mNGS)for etio-logic diagnosis in severe pneumonia and to compare its performance with conventional microbiological testing and serological assays.Methods We retrospectively included 127 patients with severe pneumonia admitted to the intensive care unit of the Department of Pulmonary and Critical Care Medicine Ⅱ,The Second Hospital of Hebei Medical University from February 2021 to October 2022;all underwent mNGS testing.Bronchoalveolar lavage fluid(BALF)was collected via flexible bronchos-copy.Samples underwent mNGS,conventional microbiology(smear,culture,and acid-fast staining),and serological testing(IgM panel for nine respiratory pathogens and PCR-based nucleic acid detection).Pathogen positivity rates and inter-method agreement were compared to assess the accuracy and timeliness of mNGS testing.Results The overall positivity rate of mNGS testing was 89.76％,significantly higher than that of conventional microbiology(63.78％)and serology testing(51.18％)(all P＜0.05).For bacterial detection,the mNGS positivity rate(71.65％)exceeded those of conventional microbiolo-gy(55.12％,P=0.006)and serology testing(10.24％,P＜0.001).For fungal detection,mNGS likewise outperformed conven-tional microbiology(62.99％vs.21.26％)and serology testing(11.81％),with all pairwise differences achieving statistical significance(all P＜0.001).In contrast,serology testing was superior to mNGS for detecting atypical pathogens(9.45％vs.2.36％,P=0.017).Agreement between mNGS and either conventional microbiology or serology testing was poor(Kappa＜0.4).For mixed infections,mNGS yielded a significantly higher positivity rate(65.35％)than conventional microbiology(11.81％)and serology testing(17.32％),with all pairwise differences achieving statistical significance(all P＜0.001).Conclu-sion mNGS demonstrates a high positivity rate and offers broad,rapid detection advantages for etiologic diagnosis in severe pneumonia,with particularly strong performance for bacterial and fungal pathogens and for identifying mixed infections.

Abstract:Objective To investigate the correlation and clinical value of miR-34a and PSPC1 expression in cancer-ous tissues with clinicopathological features of oral squamous cell carcinoma(OSCC).Methods A total of 101 OSCC pa-tients(OSCC group)and 68 patients with benign oral diseases(control group)treated at Union Hospital,Tongji Medical Col-lege,Huazhong University of Science and Technology from January 2020 to January 2023 were selected as the study subjects.The expression of miR-34a and PSPC1 was detected.Spearman rank correlation or Pearson correlation analysis was used to analyze their correlation with clinicopathological features.Receiver operating characteristic(ROC)curves and DeLong's meth-od were used to analyze sensitivity,specificity,and AUC.Cox regression analysis was used to identify adverse prognostic risk factors.Kaplan-Meier curves were used for survival analysis.Results MiR-34a expression in OSCC tissue was lower than that in adjacent normal tissue and the control group,while PSPC1 expression was higher than that in adjacent normal tissue and the control group(F/P=401.394/＜0.001,215.425/＜0.001).Patients with tTMB ≥20 mut/Mb,ctDNA positive,CTC posi-tive,moderately or poorly differentiated tumors,and TNM stage Ⅲ-Ⅳ showed lower miR-34a expression than patients with tTMB＜20 mut/Mb,ctDNA negative,CTC negative,well-differentiated tumors,and TNM stage Ⅰ-Ⅱ(t/P=2.919/0.004,3.881/＜0.001,5.937/＜0.001,4.223/＜0.001,8.371/＜0.001).PSPC1 expression was higher in patients with tTMB ≥20 mut/Mb,ctDNA positive,CTC positive,moderately or poorly differentiated tumors,and TNM stage Ⅲ-Ⅳ(t/P=4.226/＜0.001,5.177/＜0.001,6.923/＜0.001,5.024/＜0.001,6.127/＜0.001).In the OSCC group,miR-34a expression was negatively correlated with tTMB,ctDNA,CTCs,pathological grade,and TNM stage(rs/P=-0.659/0.021,-0.617/0.035,-0.645/0.018,-0.629/0.007,-0.627/0.029).PSPC1 expression was positively correlated with tTMB,ctDNA,CTCs,pathological grade,and TNM stage(rs/P=0.605/0.011,0.633/0.003,0.645/0.031,0.619/0.029,0.644/0.025).The combination of miR-34a and PSPC1 was significantly more effective than either marker alone in predicting poor prognosis in patients with oral squamous cell carcinoma(Z/P=7.012/＜0.05,6.848/＜0.05).MiR-34a ≤ 0.79,PSPC1 ≥0.86,tTMB ≥20 mut/Mb,ctDNA positive,CTC pos-itive,moderately to poorly differentiated pathological grade,and TNM stage Ⅲ-Ⅳ were risk factors for poor prognosis of oral squamous cell carcinoma[HR(95％CI)=4.162(1.322-7.002),3.357(1.276-5.438),2.517(1.089-3.945),2.447(1.013-3.882),2.748(1.127-4.370),1.844(1.056-2.632),2.106(1.101-3.112)].OSCC patients with miR-34a ≤0.79 and PSPC1 ≥0.86 had a significantly lower median survival than those with miR-34a＞0.79 or PSPC1＜0.86(Log Rank x2=9.421,P＜0.001).Con-clusion The expression of miR-34a and PSPC1 in cancerous tissue is significantly associated with disease severity,poor prognosis,and overall survival in OSCC.Combined detection of both markers has greater clinical value in OSCC.

Abstract:Objective To explore the relationship between promoter methylation of ATP-binding cassette transporter G1(ABCG1)gene and the onset of diabetic kidney disease(DKD).Methods A retrospective analysis was conducted on the test results of 60 blood samples collected from the Affiliated Hospital of Inner Mongolia Medical University between Decem-ber 2023 and December 2024.The samples were divided into three groups:20 patients with DKD(DKD group),20 patients with type 2 diabetes mellitus(DM group),and 20 healthy individuals(healthy control group).Clinical data and biochemical in-dicators of each group were collected.The methylation level of the ABCG1 gene promoter in serum was detected using the bi-sulfite sequencing method.Differences in the aforementioned indicators among the three groups were compared.Logistic re-gression analysis and receiver operating characteristic(ROC)curve analysis were applied to explore the correlation between the methylation level of the ABCG1 gene promoter and the occurrence of DKD in patients with type 2 diabetes mellitus.Re-sults Compared with the healthy control group,the levels of HbA1c and FPG were increased,and HDL was decreased in both the DM group and the DKD group(F/P=65.357/＜0.001,33.140/＜0.001,11.634/＜0.001).In the DKD group,LDL,SCr,and BUN were increased,and eGFR was decreased(t/P=3.125/0.003,3.186/0.003,3.317/0.002,-4.348/＜0.001).Compared with the DM group,SCr and BUN were increased,and eGFR was decreased in the DKD group(t/P=3.047/0.004,2.534/0.016,3.353/0.002).There were no statistically significant differences in TC,TG,LDL,HDL,HbA1c,and FPG between the DM group and the DKD group(all P＞0.05).The methylation levels of the ABCG1 gene promoter region in the three groups de-creased progressively,and the difference was statistically significant(x2=7.381,P＜0.05).Compared with the healthy control group,ABCG1 promoter methylation in the DKD group was significantly decreased(x2=6.160,P＜0.05),while there was no statistically significant difference in ABCG1 methylation in the DM group(x2=1.938,P＞0.05).In addition,when comparing the DM group with the DKD group,there was no statistically significant difference in ABCG1 promoter methylation(x2=2.297,P＞0.05).Elevated LDL and decreased eGFR were independent risk factors for the development of DKD in patients with type 2 diabetes,while increased methylation level of the ABCG1 gene promoter was a protective factor[OR(95％CI)=10.738(1.139-101.238),0.818(0.694-0.964),0.001(0.000-0.195)].The AUCs for predicting the occurrence of DKD in patients with type 2 diabetes using LDL,eGFR,ABCG1 gene promoter methylation,and their combination were 0.712,0.835,0.650,and 0.951,respectively.The combination of the three was superior to each individual predictor(differences were compared using the DeLong method)(Z/P=3.353/0.001,1.949/0.041,5.401/＜0.001).Conclusion Demethylation of the ABCG1 gene promoter may be involved in the pathogenesis of DKD,and detection of the methylation level of the ABCG1 gene promoter may be helpful for the diagnosis of DKD.

Abstract:Objective To investigate the relationship between serum pyruvate kinase M2(PKM2)and serpin family A member 3(SERPINA3)levels and white matter degeneration and cognitive impairment in patients with lacunar cerebral in-farction.Methods A total of 193 patients with lacunar cerebral infarction admitted to the Department of Neurology,the Third Hospital of Heilongjiang Province from May 2020 to May 2025 were selected as the lacunar cerebral infarction group.Ac-cording to the Fazekas score,patients were divided into a subgroup without leukoaraiosis(89 cases)and a subgroup with leu-koaraiosis(104 cases).According to the Montreal Cognitive Assessment(MoCA)score,patients were divided into a normal cognition subgroup(95 cases)and a cognitive impairment subgroup(98 cases).In addition,193 healthy subjects from the same period were randomly selected as the healthy control group.Serum PKM2 and SERPINA3 levels were detected by enzyme-linked immunosorbent assay.Spearman rank correlation analysis was used to analyze the correlation between serum PKM2,SERPINA3 levels and the degree of white matter degeneration and cognitive impairment.Multivariate logistic regression anal-ysis was used to identify factors influencing cognitive impairment in patients with lacunar cerebral infarction.Receiver operat-ing characteristic(ROC)curve analysis was used to evaluate the diagnostic value of serum PKM2 and SERPINA3 levels for cognitive impairment in patients with lacunar cerebral infarction.Results Serum PKM2 and SERPINA3 levels were signifi-cantly higher in the lacunar infarction group than in the healthy control group(t/P=15.776/＜0.001,23.092/＜0.001).With in-creasing severity of white matter degeneration,serum PKM2 and SERPINA3 levels progressively increased across mild,mod-erate,and severe white matter degeneration subgroups(F/P=22.141/＜0.001,52.482/＜0.001).Serum PKM2 and SERPINA3 levels were positively correlated with the degree of white matter degeneration(rs/P=0.621/＜0.001,0.597/＜0.001).Serum PKM2 and SERPINA3 levels were significantly higher in the cognitive impairment subgroup than in the normal cognition sub-group(t/P=10.812/＜0.001,8.986/＜0.001).Serum PKM2 and SERPINA3 levels were positively correlated with the degree of cognitive impairment(rs/P=0.708/＜0.001,0.692/＜0.001).Age,elevated homocysteine(Hcy),white matter degeneration,ele-vated PKM2,and elevated SERPINA3 were independent risk factors for cognitive impairment in patients with lacunar infarc-tion[OR(95％CI)=1.432(1.193-1.718),2.863(1.517-5.403),2.241(1.406-3.573),1.865(1.334-2.607),2.071(1.367-3.138)].The AUCs for PKM2,SERPINA3,and their combination in diagnosing cognitive impairment were 0.802,0.825,and 0.907,respectively.The combined diagnostic value was significantly greater than that of either marker alone(Z/P=2.804/0.001,2.290/0.004).Conclusion Serum PKM2 and SERPINA3 expression is upregulated in patients with lacunar cerebral infarction and is associated with white matter degeneration and cognitive impairment.Early combined detection of these mark-ers may assist in the clinical diagnosis of cognitive impairment.

Abstract:Objective To investigate the expression and clinical significance of serum calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)and phospholipase D2(PLD2)in patients with severe acute pancreatitis(SAP)complicated by sepsis.Methods A total of 105 patients with SAP complicated by sepsis admitted to the Intensive Care Unit,First Affiliated Hospital of Xinjiang Medical University,from January 2021 to January 2025 were prospectively enrolled as the sepsis group.According to disease severity,they were divided into the general sepsis subgroup(n=45)and the septic shock subgroup(n=60).Based on 90-day outcomes,patients were further divided into the death subgroup(n=41)and survival subgroup(n=64).Another 105 SAP patients without sepsis,matched 1∶1 during the same period,were included as the non-sepsis group.Serum CaMKⅡ and PLD2 levels were measured by enzyme-linked immunosorbent assay.The relationship between serum CaMK Ⅱand PLD2 levels and disease severity in SAP patients with sepsis was analyzed using point-biserial correlation analysis.Multi-variate logistic regression analysis was used to analyze the influencing factors of prognosis and death in patients with SAP complicated with sepsis.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive efficacy of serum CaMK Ⅱ and PLD2 levels on the prognosis and death of patients with SAP complicated with sepsis.Results Serum CaMKⅡ and PLD2 levels were significantly higher in the sepsis group than in the non-sepsis group(t/P=10.109/＜0.001 and 9.100/＜0.001,respectively).Patients in the septic shock subgroup had higher serum CaMKⅡ and PLD2 levels than those in the general sepsis subgroup(t/P=5.458/＜0.001 and 5.503/＜0.001,respectively).Point-biserial correlation analysis revealed that serum CaMKⅡ and PLD2 levels were positively correlated with disease severity in SAP patients with sepsis(r/P=0.574/＜0.001 and 0.563/＜0.001,respectively).The death subgroup had higher proportions of septic shock,sequential organ failure as-sessment(SOFA)scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores,and serum CaMK Ⅱ and PLD2 levels than the survival subgroup(t/P=3.622/＜0.001,3.355/0.001,12.005/＜0.001,6.036/＜0.001,and 5.419/＜0.001,re-spectively).Multivariate logistic regression identified septic shock,higher SOFA and APACHE Ⅱ scores,and elevated CaMKⅡ and PLD2 levels as independent risk factors for mortality in SAP patients with sepsis[OR(95％CI)=4.708(1.076-20.599),1.436(1.097-1.880),1.237(1.088-1.405),1.037(1.016-1.059),and 1.046(1.016-1.077),respectively].The areas under the ROC curves(AUCs)for serum CaMK Ⅱ,PLD2,and their combination in predicting mortality were 0.795,0.782,and 0.907,respectively.The combined detection showed significantly higher predictive performance than either marker alone(Z/P=2.990/0.003 and 3.141/0.002).Conclusion Elevated serum CaMKⅡ and PLD2 levels are closely associated with dis-ease progression in SAP patients complicated by sepsis.The combined measurement of serum CaMK Ⅱ and PLD2 provides high predictive value for mortality in these patients.

Abstract:Chimeric Antigen Receptor Natural Killer(CAR-NK)cells as a new strategy for immunotherapy of prostate cancer.This article reviews the construction of CAR-NK cells with prostate-specific Membrane Antigen(PSMA)and Prostate Stem Cell Antigen(PSCA)as key targets.Significant anti-tumor effects achieved in preclinical studies.At the same time,strategies such as optimizing the CAR structure,combining immune checkpoint inhibitors,and molecular targeted drugs were explored to enhance efficacy and safety.Despite the challenges in clinical translation,CAR-NK cell therapy is expected to offer a new treatment option for patients with prostate cancer.This article provides a comprehensive review of the research progress of CAR-NK cell technology in the treatment of prostate cancer.

Abstract:Alzheimer's disease(AD)is a neurodegenerative disorder characterised primarily by progressive cognitive impairment and memory loss,with existing single-target drug treatments showing limited efficacy.Fufang Congrong Yizhi cap-sule exerts its pharmacological mechanisms through multi-component,multi-target interventions in AD pathological processes,including inhibition of β-amyloid deposition and tau protein phosphorylation,anti-neuroinflammation,antioxidative stress,and neuroprotection.This article aims to provide a reference for in-depth research and rational clinical application of Fufang Congrong Yizhi capsule,and to clarify the need for future large-scale,long-term randomised controlled trials to verify its long-term efficacy and safety,offering new approaches for AD treatment.

Abstract:Objective To investigate the expression levels of death-associated protein 3(DAP3)and programmed cell death molecule 10(PDCD10)in hepatocellular carcinoma(HCC)tissues,analyze their correlation with invasion and me-tastasis indicators,and evaluate their predictive value for the prognosis of HCC patients.Methods A total of 148 HCC tissue specimens surgically resected from the Department of Oncology,Yibin First People's Hospital from February 2020 to February 2022 were selected.Immunohistochemistry was performed to detect the protein expression levels of DAP3 and PDCD10.Quantitative real-time PCR was used to detect the mRNA expression of DAP3,PDCD10,and invasion and metasta-sis-related genes Snail,N-cadherin(N-cad),and E-cadherin(E-cad).The Kaplan-Meier method and Cox proportional hazards regression model were used to identify independent factors affecting the prognosis of HCC patients.Results The positive rate of DAP3 in cancer tissues[70.27％(104/148)vs.6.76％(10/148)]was significantly higher than that in adjacent tissues;the positive rate of PDCD10 in cancer tissues[74.32％(110/148)vs.5.41％(8/148)]was also significantly higher than that in adjacent tissues(x2=126.058,146.619,both P＜0.001).The mRNA expression levels of DAP3,PDCD10,Snail,and N-cad were significantly increased in HCC cancer tissues,while E-cad mRNA expression was significantly decreased(t=52.620,48.361,55.643,39.695,28.074,all P＜0.001).The mRNA expression of DAP3 and PDCD10 in HCC tissues was positively correlated with Snail and N-cad mRNA(r=0.668,0.710;0.654,0.698,all P＜0.001),and negatively correlated with E-cad mRNA expression(r=-0.654,-0.725,all P＜0.001).The protein expression of DAP3 and PDCD10 in HCC tissues from pa-tients with CNLC stage Ⅱ-Ⅲ was significantly higher than that in patients with CNLC stage Ⅰ(x2=13.954/＜0.001,4.913/0.027).The 3-year overall survival rate of the DAP3-positive group was 34.62％(36/104),which was significantly lower than that of the DAP3-negative group(84.09％,37/44)(Log-rank x2=18.270,P＜0.001).The 3-year overall survival rate of the PDCD 10-positive group was 37.27％(41/110),which was significantly lower than that of the PDCD10-negative group(84.21％,32/38)(Log-rank x2=11.000,P=0.001).CNLC stage Ⅱ-Ⅲ,DAP3 positivity,and PDCD10 positivity were inde-pendent risk factors affecting the prognosis of HCC patients[HR(95％CI)=1.603(1.167-2.202),1.840(1.319-2.568),1.775(1.275-2.473)].Conclusion The elevated expression of DAP3 and PDCD10 in HCC is closely associated with tumor inva-sion and metastasis,and these proteins may serve as potential biomarkers for evaluating the prognosis of HCC patients.

Abstract:This article reports the clinical data of 3 patients with IgG4 hyper-secretory Castleman disease and reviews the relevant literature.

Abstract:Objective To analyze the expression of serum thioredoxin-1(Trx1)and programmed cell death factor 4(PDCD4)in sepsis patients and their relationship with 28-day survival.Methods The clinical data of 146 patients with sepsis admitted to the Department of Intensive Care Medicine of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2018 to December 2021(study group)and 146 volunteers who underwent physical examina-tions in the hospital at a 1∶1 ratio during the same period(healthy control group)were retrospectively collected.Patients in the study group were divided into the simple sepsis subgroup(112 cases)and the septic shock subgroup(34 cases)according to disease severity,and into the survival subgroup(106 cases)and the death subgroup(40 cases)according to 28-day survival status.Enzyme-linked immunosorbent assay was used to detect serum levels of Trxl and PDCD4 in all subjects.Point-biserial correlation analysis was used to investigate the correlation between serum Trx1,PDCD4 levels and the severity of sepsis.Cox regression analysis and receiver operating characteristic(ROC)curve analysis were used to evaluate the relationship and pre-dictive value between serum Trx1 and PDCD4 levels and 28-day survival in sepsis patients.Results Compared with the healthy control group,serum PDCD4 levels were significantly increased and serum Trx1 levels were significantly decreased in the study group(t/P=43.407/＜0.001,8.867/＜0.001).Compared with the simple sepsis subgroup,the septic shock subgroup showed significantly increased serum PDCD4 levels and decreased serum Trx1 levels(t/P=3.320/＜0.001,5.106/＜0.001).Point-biserial correlation analysis showed that serum Trx1 levels were negatively correlated with disease severity,while serum PDCD4 levels were positively correlated with disease severity(r/P=-0.441/＜0.001,0.303/＜0.001).High APACHE Ⅱ score,high CRP level,and high serum PDCD4 level at admission were independent risk factors for 28-day survival in sepsis patients,while high serum Trx1 level was an independent protective factor[HR(95％CI)=1.106(1.033-1.184),1.014(1.004-1.023),1.078(1.029-1.128),0.770(0.653-0.907)].The AUCs for serum Trx1,PDCD4,and their combination in predicting 28-day survival in sepsis patients were 0.814,0.807,and 0.886,respectively.The combined predictive value was significantly better than that of either marker alone(Z/P=1.670/0.047,1.787/0.035).Conclusion Serum Trxl levels are decreased and PDCD4 levels are increased in sepsis patients.The expression levels of both markers are correlated with disease severity and 28-day survival.Combined detection of Trx1 and PDCD4 provides improved predictive value for 28-day survival in sepsis patients.

Abstract:Objective To investigate the characteristics of serum neutrophil extracellular traps(NETs)in patients with septic shock and their predictive value for the risk of developing multiple organ dysfunction syndrome(MODS).Meth-ods This prospective observational study included 212 patients with septic shock treated at our hospital between May 2023 and May 2025.The patients were divided into a MODS group and a non-MODS group based on whether MODS occurred during hospitalization.Basic clinical characteristics,septic shock features,treatment details,and serum NETs markers at admis-sion were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify inde-pendent factors associated with MODS in septic shock patients.The predictive efficacy of individual and combined NETs markers for MODS in septic shock patients was evaluated using receiver operating characteristic(ROC)curves and the area under the curve(AUC).Results The MODS group had higher age,proportion of diabetes comorbidity,proportion of mixed infections,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)scores at the first diagnosis of septic shock after admission,Sequential Organ Failure Assessment(SOFA)scores,and serum levels of circulating free DNA(cfDNA),citrulli-nated histone H3(CitH3),myeloperoxidase(MPO),and neutrophil elastase(NE)compared to the non-MODS group(t/x2/P=2.342/0.020,4.707/0.030,4.222/＜0.001,5.131/＜0.001,3.630/＜0.001,3.512/0.001,3.728/＜0.001,3.210/0.002).Diabetes comor-bidity,mixed infections,higher APACHE Ⅱ scores,higher SOFA scores,and elevated serum levels of cfDNA,CitH3,MPO,and NE were identified as risk factors for MODS in septic shock patients[OR(95％CI)=2.187(1.007-4.750),2.123(1.031-4.373),1.178(1.055-1.315),1.615(1.226-2.127),1.010(1.001-1.020),1.035(1.014-1.056),1.045(1.022-1.067),1.012(1.004-1.035)].The AUCs for serum cfDNA,CitH3,MPO,NE,and their combination in predicting MODS risk in septic shock patients were 0.628,0.642,0.610,0.600,and 0.806,respectively.The combined prediction of the four NETs markers demonstrated the highest efficacy(Z=4.056,3.816,4.720,4.814,all P＜0.001).Conclusion Serum levels of NETs markers,including cfDNA,CitH3,MPO,and NE,are significantly elevated in septic shock patients who develop MODS and are inde-pendent risk factors for MODS.The combined detection of NETs markers provides a new approach for the early clinical pre-diction of MODS risk in septic shock patients.

Abstract:Objective To investigate the expression of prolyl hydroxylase 2(EGLN1)and solute carrier family 27 member 6(SLC27A6)in nasopharyngeal carcinoma(NPC)tissues,their correlation with stemness genes,and their prognostic significance.Methods A total of 132 NPC patients diagnosed and treated in the Department of Otolaryngology at Affiliated Hospital of Guizhou Medical University from March 2018 to March 2020 were selected as the research subjects.Quantitative real-time PCR(qPCR)was used to detect the mRNA expression levels of EGLN1,SLC27A6,and stemness-related genes[oc-tamer-binding transcription factor 4(OCT4),sex-determining region Y box protein 2(SOX2),and NANOG]in NPC tissues,and Pearson correlation analysis was performed to assess their relationships.Immunohistochemistry was used to detect the pro-tein expression of EGLN1 and SLC27A6 in NPC tissues.Kaplan-Meier survival analysis and Cox regression were used to identify risk factors affecting the prognosis of NPC patients.Results The mRNA expression levels of EGLN1,SLC27A6,OCT4,SOX2,and NANOG in NPC tissues were significantly higher than those in adjacent normal tissues(t/P=46.841/＜0.001,44.102/＜0.001,46.396/＜0.001,52.522/＜0.001,45.576/＜0.001).The mRNA expression of EGLN1 and SLC27A6 in NPC tissues was positively correlated with OCT4,SOX2,and NANOG(r=0.708,0.692,0.669;0.641,0.721,0.784,all P＜0.001).The positive rates of EGLN1 and SLC27A6 protein expression in NPC tissues were 62.12％(82/132)and 60.61％(80/132),respectively,which were significantly higher than those in adjacent tissues[9.09％(12/132)and 6.06％(8/132)](x2=80.951,88.364,both P＜0.001).The positive rates of EGLN1 and SLC27A6 in cancer tissues were significantly higher in NPC patients with TNM stage Ⅲ-Ⅳ than in those with stage Ⅰ-Ⅱ,and also higher in patients with lymph node metastasis than in those without lymph node metastasis(x2/P=31.034/＜0.001,14.314/＜0.001,5.811/0.016,10.725/0.001).The 5-year survival rates of patients in the EGLN1-positive and EGLN1-negative groups were 56.10％(46/82)and 88.00％(44/50),respectively,with a statistically significant difference(Log-rank x2=14.530,P=0.004).The 5-year survival rates of patients in the SLC27A6-positive and SLC27A6-negative groups were 55.00％(44/80)and 88.46％(46/52),respectively,with a statistically significant difference(Log-rank x2=15.860,P＜0.001).TNM stage Ⅲ-Ⅳ,lymph node metastasis,EGLN1 positivity,and SLC27A6 positivity were independent risk factors affecting the prognosis of NPC patients[OR(95％CI)=1.602(1.166-2.200),1.540(1.242-1.911),1.379(1.124-1.690),1.302(1.075-1.578)].Conclusion The expression of EGLN1 and SLC27A6 is upregulated in NPC and positively correlated with the expression of stemness-related genes,suggesting their po-tential as novel tumor markers for prognostic evaluation of NPC.