Abstract:Objective To analyze the clinical features and risk factors of infections in patients with primary glomerulonephritis(PGN)receiving immunosuppressive therapy.Methods A total of 296 PGN patients received immunosuppressive therapy.The clinical features,immunosuppressive regimens and corticosteroids dosage were compared between infected and non-infected group.The risk factors of infections were analyzed by Logistic regression model.Results Infections occurred in 95 of 296 PGN cases(32.1%),including 21 severe infections(14.5%).The highest incidence of infections(45.8%)was within 3 months of immunosuppressive therapy,mainly respiratory tract infection.Compared with non-infection group,serum albumin(ALB)was decreased,while urinary albumin/creatinine ratio(UACR)and neutrophil/lymphocyte ratio(NLR)increased in infection group(P<0.05).Multivariate logistic regression analysis showed that NLR and ALB were independent risk and protective factors for infections(OR=1.251,P=0.005;OR=0.936,P=0.001),respectively.Conclusion PGN patients have a high incidence of infections within 3 months of immunosuppressive therapy,especially respiratory tract infection.High NLR and low ALB are the risk factors for infections in PGN patients receiving immunosuppressive therapy.

Abstract:Objective To develop murine models of lung cancer induced by chronic inflammation and carcinogens,and investigate the key role of chemokine receptor 3(CXCR3)in the progression of lung cancer induced by chronic inflammation.Methods Thirty-four female A/J mice were randomly divided into two groups:a control group(n=17,treated with intratracheal instillation of normal saline),and a treatment group(n=17,treated with intratracheal instillation of 0.5 μg/g lipopolysaccharide(LPS)),both treatments were lasted for 6 weeks.Three mice were randomly selected from each group to evaluate the effects of pneumonia modeling.During the lung cancer treatment phase,the control group was randomly divided into a blank control(NC)group(n=7)and a 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone(NNK)group(n=7).Similarly,the treatment group was randomly divided into an LPS group(n=7)and an LPS-NNK group(n=7).The NC and LPS groups were intraperitoneally injected with normal saline,whereas the NNK and LPS-NNK groups were injected with NNK(3 mg per mouse)for lung cancer modeling.The dosing was administered every two weeks for a total period of four weeks.After the tumor-bearing period,mice underwent lung tissue sampling.Surface pulmonary tumor nodules were counted,pathological changes were evaluated by HE staining,and the expression levels of interleukin 1β(IL-1β)and the cellular transforming proto-oncogene(KRAS)in lung tissue were measured via q RT-PCR.Differentially expressed genes were identified through transcriptome sequencing and differential analysis.Flow cytometry was used to evaluate the effect of the differentially expressed gene CXCR3 on the cell cycle.Western blot was performed to compare the protein expression levels of cyclin D1(CCND1),cyclin-dependent kinase inhibitor 1(P21),X-Ray Repair Cross Complementing 5(XRCC5),and phosphorylated H2A.X Variant Histone(γH2AX)following gene silencing.Results Compared to the NC and LPS groups,the lung cancer incidence in the NNK and LPS-NNK groups reached 100%.The average number of tumor cancer nodules in the LPS-NNK group was significantly higher than that in the NNK group(P<0.000 1).In comparison to the NC group,the differences in IL-1β and KRAS expression levels among the LPS,NNK,and LPS-NNK groups were statistically significant(P<0.01).The candidate gene CXCR3 was identified through transcriptome sequencing,differential analysis,and other methods.After CXCR3 knockdown,the proportion of cells significantly decreased in the G1 phase,and notably increased in the S phase(P<0.05).Protein analysis revealed a downregulation in the expression of CCND1 and XRCC5,alongside an upregulation in the expression of P21 and γH2AX(P<0.05).Conclusion CXCR3 is potentially a pivotal regulatory factor in the malignant transformation of lung cancer induced by chronic inflammation.

Abstract:Chronic respiratory diseases(CRDs),primarily bronchial asthma and chronic obstructive pulmonary disease(COPD),are characterized by chronic airway inflammation and remodeling.Their high morbidity and mortality rates present major challenges to global health.Interleukin-13(IL-13),a central mediator of the type 2 immunity,activate the JAK-STAT6 signaling pathway via the IL-4Rα/IL-13Rα1 receptor complex,or regulate in tumors and fibrotic diseases through IL-13Rα2.In the pathogenesis of asthma and COPD,IL-13 promotes pathological changes-including mucus hypersecretion,goblet cell hyperplasia,airway smooth muscle abnormalities,and epithelial barrier disruption via the JAK-STAT6 pathway.This review examines current states and future prospects of therapeutic strategies targeting IL-13,such as monoclonal antibodies and cell therapies,aiming to provide knowledge for targeted therapy.

Abstract:Endometrial repair involves the proliferation of endometrial cells,re-epithelialization,and vascular remodeling.This physiological process is precise and complex,modulated by multifactorial determinants,and closely related to endometrial receptivity and embryo implantation.The incidence of infertility due to endometrial damage is increasing annually,and patients with severe endometrial damage are significantly troubled.Consequently,elucidating the molecular mechanisms related to endometrial repair is of utmost importance.However,research on the signaling pathways associated with endometrial repair is currently limited,and many molecular mechanisms remain unexplained.Accumulating evidence implicates that endometrial repair is closely associated with the MAPK,PI3K/AKT,TGF-β,Wnt/β-catenin,and Notch signaling pathways.This review summarizes the research progress of these signaling pathways in the context of endometrial repair.

Abstract:Objective To investigate the efficacy and safety of a quadruple antiemetic regimen(fosaprepitant combined with palonosetron,dexamethasone,and olanzapine)versus triple therapy for chemotherapy-induced nausea and vomiting(CINV)in nasopharyngeal carcinoma(NPC)patients.Methods A retrospective analysis was conducted on 124 NPC patients receiving chemotherapy at the Affiliated Hospital of Guangdong Medical University from September 2022 to September 2024.Patients were divided into a control group(n=61,triple regimen)and an observation group(n=63,quadruple regimen).The primary outcome was the effective control rate of CINV.Secondary outcomes included the incidence of acute and delayed CINV,body weight changes,and adverse events.Results The observation group demonstrated a significantly higher effective control rate of CINV and lower incidence of both acute and delayed CINV compared to the control group(P<0.05).No significant differences were observed in body weight changes or adverse events between the two groups(P>0.05).Conclusion The quadruple antiemetic regimen significantly improves the effective control rate of CINV in NPC patients undergoing chemotherapy,particularly for delayed symptoms,without increasing adverse events.It is recommended as the standard antiemetic protocol for NPC chemotherapy.

Abstract:The airway epithelial barrier,serving as a critical defense system of the respiratory tract,maintains respiratory system homeostasis through its complex cellular composition and multifunctional properties.Disruption of the epithelial barrier integrity may contribute to the initiation and progression of various airway diseases.Conventional two-dimensional cell culture models are insufficient in accurately replicating the pathophysiological processes of these diseases,thereby limiting the in-depth exploration of disease mechanisms and the development of effective therapeutic strategies.Airway organoid technology has successfully mimicked the function of the airway epithelial barrier by establishing a complex multicellular system encompassing ciliated cells,goblet cells,and basal cells.In recent years,this innovative approach has been extensively utilized to model chronic airway diseases,elucidate infection mechanisms,and assess environmental toxicity.Focusing on the structural types of in vitro airway epithelial cultures and the cellular sources for organoid generation,this review summarizes the technical advancements of airway organoids,evaluates their potential applications in airway disease research,and explores future developmental directions to enhance understanding of disease mechanisms and accelerate clinical translation.

Abstract:Efferocytosis,the highly coordinated process by which phagocytes clear apoptotic cells,is essential for maintaining pulmonary homeostasis and regulating immune responses under both physiological and pathological conditions.This process relies on the precise integration of"find-me,""eat-me,"and"don't eat-me"signals that enable phagocytes,including macrophages and dendritic cells,to identify and engulf apoptotic cells,thereby preventing secondary necrosis and excessive inflammation.Efferocytosis not only removes harmful cellular debris but also promotes the release of anti-inflammatory cytokines and drives immunometabolic reprogramming,collectively facilitating inflammation resolution and tissue repair.Impaired efferocytosis leads to the accumulation of apoptotic cells and the release of damage-associated molecular patterns,contributing to the pathogenesis of multiple lung diseases,including chronic obstructive pulmonary disease,asthma,acute respiratory distress syndrome,and idiopathic pulmonary fibrosis.In this review,we summarize the process and the mechanisms of efferocytosis,discuss the roles of efferocytosis in the pathogenesis of lung diseases,and highlight recent advances in efferocytosis-centered therapies,providing new strategies for treating lung diseases by modulating efferocytosis.

Abstract:Objective To generate a wzc-knockout strain of the hypervirulent Klebsiella Pneumoniae(hvKP)KPN234 and investigate the effect of wzc gene deletion on the bacterial capsule and virulence.Methods A sgRNA targeting the wzc gene was designed,and the CRISPR/Cas9 gene knockout vector was constructed and electroporated into KPN234.After dual antibiotic screening using apramycin and kanamycin and plasmid curing,the wzc gene knockout strain was obtained.PCR and whole-genome sequencing were used to confirm the gene knockout and the absence of off-target effects,and Western blot was utilized to verify the absence of Wzc protein expression in the knockout strain.The growth curve of the wzc gene knockout strain was plotted to assess the effect of gene knockout on bacterial growth.The effects of gene knockout on capsular polysaccharides synthesis were evaluated using string test,viscosity semi-quantitative test,and capsular polysaccharide quantitative test.The virulence of the modified bacteria was subsequently evaluated by Galleria mellonella larva infection test.Results After the gene knockout procedure,the hvKP KPN234 lost the wzc gene with no mutations detected at other sites,confirming the successful gene knockout.The generated wzc gene knockout strain exhibited significantly reduced mucous property of the colony and its capacity to synthesize capsular polysaccharides(P<0.001).Moreover,and the virulence of the wzc-deficient strain was significantly decreased in the Galleria mellonella larval infection test(P<0.001).Conclusion The successful construction of wzc gene knockout hvKP strain establishes a foundation for further research on the mechanism of the wzc gene in hvKP.

Abstract:Chronic post-surgical pain is a significant issue that affects patients'recovery after surgery.As a long-acting local anesthetic,ropivacaine is widely used in postoperative pain management due to its effective analgesic properties and low toxicity,and it has shown potential in preventing chronic post-surgical pain.Innovations in drug delivery systems have extended the duration of ropivacaine's analgesic effects.Looking ahead,with the advancement of personalized medicine and multimodal analgesia,ropivacaine holds great potential for future applications in managing chronic post-surgical pain.This paper reviews the research progress on ropivacaine in the management of chronic postoperative pain,provides a literature review and summary of pharmacological properties(low toxicity and long-lasting effect),its clinical application value in various surgical types,as well as future development directions.

Abstract:The application and advancement of nanomaterials have addressed numerous challenges in daily life and industrial practices,with their implementation significantly optimizing outcomes.As a global health threat,cancer is characterized by its high incidence,mortality rates,and severe complications.For malignancies of varying types and anatomical locations,personalized engineering of iron-based nanomaterials loaded with specific anticancer drugs enables targeted therapeutic delivery.This strategy not only maximizes medication safety and efficacy for cancer patients but also reduces required dosages,thereby lowering biotoxicity and alleviating adverse reactions.Moreover,through adjustments in surface modification methods,material selection,structural configurations,metal combinations,and drug payloads,iron-based nanomaterials can be tailored to develop diverse therapeutic modalities and protocols.This article therefore presents the advantages of iron-based nanomaterials in tumor treatment,focusing on their capabilities for targeted drug delivery,low-dose precision therapy,and structural-functional versatility,while briefly elaborating on the underlying mechanisms.The discussion aims to provide valuable references for advancing personalized precision medicine utilizing iron-based nanomaterials.

Abstract:As biotechnology advances,antibody drugs are crucial in treating diseases.However,wild-type antibodies can't meet the clinical needs for various disease therapies.IgG antibodies,which are prevalent in serum,have a unique Y-shaped structure that enables antigen binding and mediates biological activity,with the Fc(Fragment crystallizable)region playing a key role.Therefore,Fc region engineering has become a vital focus in antibody drug design and development.This article focuses on the Fc region of IgG antibodies and elaborates on its key mechanisms of action in antibody drugs,including the impact of its interactions with Fcγ receptors and Fc neonatal receptor on immune effects and half-life.It details various strategies for Fc region modification,such as amino acid mutations and glycosylation modifications,and discusses the enhancing or reducing effects of these strategies on antibody effector functions and the changes in antibody half-life respectively.By comparing the biological activity functions of different modification types and citing research achievements of Fc modification in antibody drug development,this review looks forward to the possibilities of further exploring Fc region modification in the future and provides inspiration for the research and development of antibody drugs.

Abstract:The transcription factor specificity protein 1(Sp1)is a core member of the Sp protein family.Its activity is regulated by non-coding RNAs and various molecules.Sp1 binds to the promoters of downstream genes to modulate transcription,thereby influencing the development and progression of multiple diseases.This review summarizes the regulatory mechanisms of Sp1 in respiratory diseases,including asthma,chronic obstructive pulmonary disease,pulmonary fibrosis and lung cancer.Sp1 contributes to the pathogenesis of asthma by regulating airway inflammation,remodeling,inflammatory cell function and epithelial cell status.Sp1 affects the progression of chronic obstructive pulmonary disease by regulating pathological processes such as lung epithelial cell senescence,airway inflammatory responses and mucus secretion.Furthermore,Sp1 modulates the occurrence,proliferation,invasion and metastasis of lung tumors by binding to the promoters of lung cancer-related genes.

Abstract:Objective To measure interleukin-24(IL-24)levels in pleural effusions from patients with tuberculosis and lung adenocarcinoma and to evaluate its diagnostic value in differentiating between tuberculous pleural effusion(TPE)and lung adenocarcinoma-associated malignant pleural effusion(LA-MPE).Methods A total of 102 patients with confirmed pleural effusions were enrolled,including 48 TPE and 54 cases of LA-MPE cases.IL-24 concentrations in pleural fluid were measured by enzyme-linked immunosorbent assay(ELISA).Spearman's rank correlation coefficient was used to analyze the correlation between pleural fluid IL-24 levels and clinical parameters.A multivariable diagnostic model was constructed using univariate logistic regression.Results The median concentration of pleural fluid IL-24 in patients with TPE and LA-MPE was 1 031.19 ng/L(464.58 to 2 270.30)and 4 344.68 ng/L(1 733.93 to 10 915.25),respectively,with a significant higher IL-24 levels in LA-MPE compared to TPE(P<0.01).Pleural fluid IL-24 demonstrated utility as a biomarker for distinguishing TPE from LA-MPE,with a cut-off value of 3 316 ng/L,yielding an under the curve(AUC)of 0.835,a specificity of 95.8%,and a sensitivity of 61.1%.Furthermore,guided by univariate logistic regression analysis,we developed a multivariable diagnostic model incorporating CYFRA21-1,CEA,and IL-24.The resulting model,IL-24+CYFRA21-1+CEA,demonstrated the enhanced diagnostic performance.Correlation analysis revealed that in the LA-MPE group,pleural fluid IL-24 positively correlated with pleural fluid adenosine deaminase(ADA)and blood neutrophil count,but negatively correlated with pleural fluid glucose levels.In the TPE group,pleural fluid IL-24 was positively correlated with pleural fluid lactate dehydrogenase(LDH),serum LDH,and blood monocyte count.Conclusion Pleural fluid IL-24 serves as a novel biomarker for differentiating TPE from LA-MPE.The combination of IL-24,CYFRA21-1,and CEA significantly enhances diagnostic accuracy,demonstrating strong potential for clinical differential diagnosis.

Abstract:As a key organ of the urinary system,the kidney is involved in various diseases,including renal tumors,kidney stones,acute kidney injury,chronic kidney disease,and nephritis,all of which seriously threaten human health.Globally,the incidence of kidney diseases is continuously rising,posing significant challenges to the medical system.Pyrroloquinoline quinone(PQQ)is a novel redox enzyme cofactor that has attracted considerable attention due to its prominent activities in antioxidation,anti-inflammation,and mitochondrial protection.In recent years,its role in kidney diseases has gradually become a research focus.This article first elaborates on the biological functions of PQQ,then explores its mechanisms of action and safety characteristics,and finally reviews the research progress of PQQ in acute kidney injury,chronic kidney disease,diabetic kidney disease,renal calcium oxalate stones,and other kidney diseases,and prospects its application potential as a therapeutic target for kidney diseases.

Abstract:Objective To investigate the value of quantitative histogram parameters derived from contrast-enhanced computed tomography(CT)in differentiating benign from malignant thyroid nodules.Methods A retrospective analysis was conducted on a cohort of 86 patients with thyroid nodules confirmed by surgical pathology,comprising 44 malignant cases and 42 benign cases.All patients underwent dual-phase contrast-enhanced CT scans.Regions of interest(ROIs)were delineated on non-contrast,arterial-phase,and venous-phase CT images.First-order statistical parameters of CT histogram(CTH)features within the ROIs were extracted using the medical imaging analysis software(MaZda),including mean,variance,skewness,kurtosis,and percentiles(Perc.01%,Perc.10%,Perc.50%,Perc.90%,Perc.99%).Logistic regression and receiver operating characteristic(ROC)curve analysis were employed to evaluate the diagnostic efficacy of individual and combined CTH parameters in distinguishing between benign and malignant thyroid nodules.Results Eight parameters showed statistically significant differences between the two groups:variance,skewness,kurtosis,Perc.50%,Perc.90%,and Perc.99%in the arterial phase,as well as skewness and Perc.50%in the venous phase.Among these parameters,Perc.90%and Perc.99%in the arterial phase demonstrated comparable and the highest diagnostic performance.Arterial-phase kurtosis,Perc.50%,Perc.90%,and venous-phase Perc.50%were identified as independent predictors for differentiating between benign and malignant thyroid nodules.The combination of these four parameters yielded the highest diagnostic efficacy(AUC=0.714).Conclusion The quantitative parameters derived from contrast-enhanced CT histograms may serve as auxiliary references for differentiating between benign and malignant thyroid nodules.

Abstract:Objective To investigate the effect of CD4+T cell depletion on blood-brain barrier(BBB)integrity in a mouse model of anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis.Methods Twenty-four 8-week-old female C57BL/6J mice were randomly divided into 4 groups(n=6 per group).The groups were as follows:the normal group(subcutaneously injected with phosphate-buffered saline on the back),the anti-NMDAR encephalitis model group(abbreviated as the model group,subcutaneously injected with GluN1356-385 polypeptide on the back),the anti-NMDAR encephalitis model intervention group(abbreviated as the model intervention group,in which anti-NMDAR encephalitis model mice were intraperitoneally injected with anti-CD4 monoclonal antibodies),and the anti-NMDAR encephalitis model control group(abbreviated as the model control group,in which anti-NMDAR encephalitis model mice were intraperitoneally injected with isotype control antibodies).Cell-based immunofluorescence was used to detect anti-GluN1 subunit antibodies in the serum of model mice to verify the successful establishment of the model.Western blot was employed to detect the expression changes of tight junction proteins zonula occludens-1(ZO-1),Claudin-5,matrix metalloproteinase 9(MMP-9),and the M1 polarization marker protein CD68 of microglia in the brain tissue.Immunofluorescence was used to detect the morphological changes of microglia.The open-field test and the novel object recognition test were used to detect the behavioral changes in mice.Results Compared with the normal mice,the serum anti-GluN1 subunit antibody was positive in the model mice,indicating successful establishment of anti-NMDAR encephalitis model mice.Compared with the normal group,the expression of tight junction proteins ZO-1 and Claudin-5 in the brain tissue of the model group was significantly decreased.In the hippocampus,the number of microglial branches was significantly increased and the branch length was significantly shortened,and the expression of CD68,a marker protein for M1 polarization of microglia,was significantly upregulated(P<0.001 or 0.05).Compared with the model control group,after depleting CD4+T cells in the model intervention group,the motor and anxiety levels of mice were not affected(P>0.05),while the novel object recognition ability was significantly improved(P<0.05).The expression of tight junction proteins ZO-1 and Claudin-5 in the brain tissue was significantly increased(P<0.05),the number of microglial branches was significantly decreased and the branch length was significantly increased(P<0.001),and the expression of CD68,a marker protein for M1 polarization of microglia,was significantly decreased(P<0.01).Conclusion In a mouse model of anti-NMDAR encephalitis,CD4+T cell depletion helps restore BBB tight junction integrity,improves cognitive function,and shifts microglial polarization from the pro-inflammatory M1 phenotype toward anti-inflammatory M2 phenotype.

Abstract:Liver cancer is a common malignant tumor,and surgical resection remains the primary treatment for early-stage liver cancer.Central-type hepatocellular carcinoma,located near vital hepatic blood vessels and bile ducts,poses significant challenges for surgical resection due to its unique and complex anatomical position.However,with the advancement of laparoscopic technology and the continuous refinement of the concept of anatomical liver resection(ALR),resection of central-type hepatocellular carcinoma has become more precise and minimally invasive.Laparoscopic anatomical resection has evolved into a mainstream surgical approach.This article presents a comprehensive review of the surgical approaches for central liver cancer,including the operative techniques such as hepatic portal occlusion,control of central venous pressure,determination of resection margins,and auxiliary technologies like three-dimensional visualization,indocyanine green fluorescence imaging,and intraoperative ultrasound in the context of anatomical resection of central liver cancer.

Abstract:Objective To study the roles of the Aha1 gene in the regulation of the cell proliferation and apoptosis in cervical cancer HeLa cells.Methods Aha1 expression in cervical cancer and paracancerous non-tumor tissues was investigated via bioinformatics analysis and immunohistochemical assay,along with its correlation with prognosis.Aha1 siRNA,or the Aha1 expression vector was transfected into the HeLa cells to silence or overexpress Aha1.And then,the proliferation of HeLa cells was examined using CCK8 assays and colony formation assays.HeLa cell apoptosis was detected by flow cytometry with PI and Annexin-V stain.Protein levels were examined by western blotting assay.Results Bioinformatics and immunohistochemical analyses confirmed that Aha1 was significantly overexpressed in cervical cancer tissues compared to normal tissues,with predominant cytoplasmic localization(P<0.05 and P<0.01,respectively).Although Aha1 knockdown failed to affect HeLa cell proliferation and apoptosis(P>0.05),its overexpression significantly suppressed cell proliferation and promoted apoptosis(P<0.05).Conclusion Aha1 gene overexpression in HeLa cells significantly inhibits cell proliferation and induces apoptosis.

Abstract:Radiology imaging technologies,including X-ray imaging,CT,PET,and SPECT,play an indispensable role in clinical diagnostics and biomedical research.As the core detection medium of imaging devices,the performance of inorganic scintillator materials directly determines the spatial,time and energy resolution of imaging systems.This article systematically reviews the advancements in the application of inorganic scintillators within medical imaging,covering both traditional oxide materials(e.g.,CdWO4,BGO,YAP:Ce,LSO:Ce,GOS)and emerging metal halide materials(e.g.,Cs3Cu2I5,Rb2AgBr3).Improving scintillation performance through methods such as doping modification,defect regulation,and the optimization of crystal growth processes is a pivotal direction in the current development of scintillator materials.

Abstract:Objective To investigate the value of three drainage methods after laparoscopic common bile duct exploration(LCBDE)in elderly patients with common bile duct stones.Methods Retrospective analysis of clinical data of 156 elderly patients with common bile duct stones treated with LCBDE.According to the postoperative drainage method,patients were divided into groups A(T-tube drainage),B(nasobiliary drainage with primary duct closure),and C(single-pigtail biliary stent placement with primary closure).The perioperative indicators,inflammatory indicators,quality of life,and complications of the three groups were compared.Results Compared with Group C,both Group A and Group B exhibited significantly longer bile duct operation time,surgical time,ambulation time,postoperative exhaust time,and hospitalization time(P<0.01).When compared with Group B,Group A had significantly shorter surgical time and common bile duct operation time,but longer time to postoperative exhaust,time to ambulation,and hospitalization(P<0.05 or 0.01).The concentrations of CRP,PCT,white blood cells,IL-6,and TNF-α at 3 days after surgery were lowest in group C,followed by group B,and highest in group A(P<0.05 or 0.01).At 14 days after surgery,the physiological function score,mental state score,daily living ability score,symptomatology score,and social activity score of Group B and Group C were all higher than those of Group A(P<0.01).Conclusion In elderly patients undergoing LCBDE for common bile duct stones,single pig tail biliary stent placement with primary suturing is associated with improved perioperative indicators,reduced postoperative inflammatory reactions and better quality of life compared with T-tube or nasobiliary drainage.