Abstract:Objective To explore the clinical efficacy of porcine fibrin glue in the wound surface after endoscopic sub-mucosal dissection(ESD)for larger gastric lesions(maximum diameter of the lesion≥2 cm and<5 cm).Methods Ninety cases of ESD due to benign submucosal lesions of the stomach and early gastric cancer were selected and divided into the study group and control group,with 45 cases in each group.In the study group,we sprayed fibrin glue on the surgical wound before the endoscopic withdrawal operation was completed,while in the control group,we did not perform this oper-ation.The incidence of postoperative complications,length of hospital stay,hospitalization expenses and wound healing rate one month after surgery were compared between the two groups.Results No perforation occurred in either group af-ter the operation.There were 3 cases of postoperative fever in both the study group and the control group,and they recov-ered well after anti-infection and symptomatic treatment.In the study group,there was 1 case(2.22%)of postoperative bleeding,and in the control group,there were 5 cases(11.11%)of postoperative bleeding.All the bleeding was success-fully stopped by gastroscopy surgery.The incidence of postoperative bleeding in the study group was lower than that in the control group(P<0.05).Gastroscopy was reexamined one month after the operation.The wound healing rates of the study group and the control group were 93.33%(42/45)and 77.78%(35/45),respectively.The wound healing rate of the study group was higher than that of the control group(P<0.05).There were no statistically significant differences in the length of hospitalization or hospitalization cost between the two groups(both P>0.05).Conclusion For larger gastric le-sions,spraying fibrin glue on the wound surface after ESD can effectively reduce the incidence of postoperative bleeding,improve the wound healing rate,and will not significantly increase the length of hospital stay and cost.

Abstract:Objective To understand the current status of physician trust among patients with papillary thyroid mi-crocarcinoma(PTMC)who were converted from follow-up to surgical treatment,and to analyze its influencing factors.Methods A total of 140 patients with PTMC who were converted from follow-up to surgical treatment were selected for the study.These patients were diagnosed with PTMC before hospitalization,and met the disease progression criteria during monitoring and underwent surgical treatment.The postoperative pathology confirmed papillary thyroid carcinoma.The Wake Forest Physician Trust Scale(WF-PTS)was used to evaluate the patients'trust in their physicians.Questionnaires were used to collect patients'general sociodemographic data,treatment-related information,the degree of fear of disease progression[Chinese version of the Fear of Progression Questionnaire-Short Form(FoP-Q-SF)],and the situation of treat-ment decision-making conflicts[Chinese version of the Decision Conflict Scale(DCS)].Multiple linear regression analy-sis was conducted to analyze the influencing factors of the level of trust in physicians.Results The WF-PTS score of this group of patients was(29.36±5.16)points,which was at a medium level.The results of univariate analysis showed that previous hospitalization experience,preoperative follow-up time,presence or absence of lymph node metastasis,surgical method,and postoperative complications were factors influencing the level of trust in physicians(all P<0.05).The level of trust in physicians of PTMC patients who were converted from follow-up to surgery was negatively correlated with the de-gree of fear of disease progression and the level of treatment decision conflict(r=-0.718 and-0.710,respectively;all P<0.05).Taking the WF-PTS score as the dependent variable and previous hospitalization experience,preoperative follow-up time,presence or absence of lymph node metastasis,surgical method,postoperative complications,FoP-Q-SF score,and DCS score as independent variables,multiple linear regression analysis was conducted using the stepwise method.The results showed that FoP-Q-SF score,DCS score,presence or absence of lymph node metastasis,and postoperative complications were independent influencing factors of the level of trust in physicians of PTMC patients who were converted from follow-up to surgery(all P<0.05).Conclusions The physician trust level of PTMC patients converted from follow-up to surgical treatment needs further improvement.The FoP-Q-SF score,DCS score,presence or absence of lymph node metastasis,and whether there are postoperative complications are independent influencing factors of physician trust in PTMC patients converted from follow-up to surgical treatment.

Abstract:Objective To analyze the application value of thyroid biopsy combined with BRAF V600E gene detec-tion in the diagnosis of papillary thyroid carcinoma(PTC).Methods A retrospective study was conducted on 293 pa-tients with thyroid nodules who underwent thyroid surgery.Preoperative thyroid biopsy and BRAF V600E gene testing were performed,and intraoperative pathological results were used as the gold standard.A paired four grid table was used to eval-uate the diagnostic efficacy of thyroid biopsy,BRAF V600E gene testing,and their combination for PTC.Logistic regres-sion was used to construct a diagnostic PTC model combining biopsy and BRAF V600E gene testing.Results Among 293 patients in the intraoperative pathological diagnosis,there were 283 cases of PTC and 10 cases of non-PTC.Among 283 pathologically diagnosed PTC patients,241 cases were diagnosed with PTC and 42 cases were diagnosed with non-PTC through thyroid biopsy,with a positive rate of 85.61%;the BRAF V600E gene test results showed 280 cases of PTC and 3 cases of non-PTC,with a positive rate of 98.94%in biopsy.Compared with thyroid biopsy,BRAF V600E gene detection in diagnosis of PTC had a higher positive rate(P<0.05).The accuracy,sensitivity,and specificity of thyroid biopsy in di-agnosing PTC were 85.7%,85.2%,and 100%,respectively;the accuracy,sensitivity,and specificity of BRAF V600E gene testing for diagnosing PTC were 99.0%,98.9%,and 100%,respectively;the accuracy,sensitivity,and specificity of the combined detection and diagnosis of PTC were 100%,100%,and 100%,respectively.The diagnostic model of PTC using biopsy combined with BRAF V600E was Logit(P/1-P)=-0.147+1.165×biopsy smear results+1.431×BRAF V600E gene detection results.The total score of the LogP type combined model of biopsy smear and BRAF V600E gene de-tection in diagnosing PTC was 181 points.Conclusion The combination of thyroid biopsy and BRAF V600E gene test-ing has high diagnostic value in PTC.

Abstract:Non-diabetic chronic kidney disease(CKD)shares similar risks of end-stage renal disease(ESRD)and a higher incidence of cardiovascular complications with diabetic kidney disease,yet current standard clinical regimens show suboptimal therapeutic effects.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)exert renoprotective effects in non-diabetic CKD through both direct and indirect mechanisms,involving metabolic regulation,anti-inflammatory responses,and anti-fibrotic processes.Clinical studies indicate that GLP-1 RAs reduce proteinuria levels and maintain renal function stability in patients with non-diabetic CKD,and the therapeutic effects are particularly significant in patients with obesity-or hypertension-related non-diabetic CKD.Future research should further explore the combination strategies of GLP-1 RAs with existing sodium-glucose cotransporter-2(SGLT2)inhibitors,and investigate biomarker-based personalized applica-tion schemes to improve the prognosis of patients with non-diabetic CKD.

Abstract:Objective To explore whether ellagic acid(EA)affects mitophagy in endothelial cells under high glu-cose environment by regulating the PTEN-induced kinase 1(PINK1)/Parkin signaling pathway.Methods EA-hy926 cells(human umbilical vein endothelial cells)in the logarithmic growth phase were randomly divided into the control group,model group,and EA group,with 3 replicate wells in each group.The model group and EA group were cultured in DMEM medium containing 50 mmol/L glucose for 24 h to establish the high glucose-induced endothelial cell injury mod-els.The EA group was further cultured for 24 h after adding 40 nmol/L EA working solution,while the control group re-ceived no treatment.At 24 h of culture,CCK-8 assay was used to detect cell proliferation activity,tube formation assay was performed to observe cell tube formation ability,transmission electron microscopy was used to observe mitochondrial structure,Western blotting was applied to detect PINK1 and Parkin proteins,and molecular docking analysis was used to evaluate the binding between EA and PINK1.Results Compared with the control group,the model group showed lower cell survival rate and shorter total lumen length(both P<0.05).Compared with the model group,the EA group had higher cell survival rate and longer total lumen length(both P<0.05).Compared with the control group,the model group exhibit-ed mitochondrial swelling,cristae loss,and vacuolization.In contrast,most mitochondria in the EA group showed re-paired damaged cristae,alleviated vacuolization,and a near-normal morphological structure.The relative expression lev-els of PINK1 and Parkin proteins in the model group were significantly lower than those in the control group(both P<0.05),while those in the EA group were significantly higher than those in the model group(both P<0.05).The binding energy between EA and PINK1 was-11.5 kcal/mol,and EA formed 6 hydrogen bonds with amino acid residues of PINK1 protein.Conclusion EA may promote mitophagy in EA-hy926 cells under high glucose environment by up-regulating the PINK1/Parkin signaling pathway,thereby improving cell proliferation activity and tube formation ability.

Abstract:Endoplasmic reticulum stress(ERS)is a cellular response to the accumulation of misfolded or improperly folded proteins.In recent years,the role and mechanisms of ERS in the pathogenesis and progression of osteoarthritis(OA)have garnered significant research attention.ERS can promote the development and progression of OA by inducing chondrocyte apoptosis,chondrocyte autophagy,extracellular matrix degradation,and chondrocyte-mediated inflammatory responses.Clinically,pharmacological modulation of ERS-related signaling pathways has been explored as a therapeutic strategy for OA.In-depth research on the specific mechanism of ERS in the development and progression of OA may pro-vide new ideas for the prevention and treatment of OA.

Abstract:Osteoporosis is a bone metabolic disease characterized by decreased bone mass,destruction of bone micro-structure,increased bone fragility,and increased susceptibility to fractures.Its occurrence is closely related to various fac-tors such as aging,changes in hormone levels,nutritional deficiencies,and drug effects.Dioscin(Dio)is a natural active component widely distributed in the roots,stems,leaves and other parts of medicinal plants of the Dioscoreaceae family such as yam and pangolin.It has anti-inflammatory,liver-protecting,antioxidant and anti-tumor effects.Dio regulates bone metabolism-related signaling pathways such as the Hedgehog signaling pathway,P53 apoptosis-stimulating protein 2 antibody/nuclear factor κB signaling pathway,osteoproteinin/nuclear factor κB receptor activator ligand/nuclear factor κB receptor activator signaling pathway,and phosphatidylinositol-3 kinase/protein kinase B/mitogen-activated protein kinase signaling pathway.It affects the expression of key bone metabolism-related factors,promotes the proliferation,differentia-tion and bone formation of osteoblasts,and simultaneously inhibits the generation and bone resorption activity of osteo-clasts,exerting the preventive and therapeutic effects of OP.A thorough understanding of the mechanism of Dio in the pre-vention and treatment of OP can provide new ideas for subsequent research on the prevention and control of OP.

Abstract:Gastrointestinal tumors represent one of the most common malignant tumors worldwide,with their develop-ment,progression,and pesticide tolerance closely associated with alterations in the tumor microenvironment.Currently,conventional cell and animal models are unable to accurately capture the complexity and heterogeneity of tumors.Three-di-mensional(3D)bioprinting technology,an emerging biomanufacturing technology,holds significant potential for investi-gating tumorigenesis mechanisms.There are four main types of 3D bioprinting technology:inkjet bioprinting,extrusion bioprinting,laser-assisted bioprinting,and photo-curing bioprinting.This technology enables the construction of models for gastric cancer,colorectal cancer,and colorectal cancer liver metastasis through various approaches.It is widely ap-plied in simulating the tumor microenvironment,drug screening,personalized treatment,and studies on tumor metastasis mechanisms.

Abstract:Objective To observe the regulatory effect of the extract of Lindera aggregata on the nuclear factor-κB(NF-κB)pathway in lung tissues of mice with acute lung injury(ALI),and to explore its underlying mechanism.Meth-ods Thirty-two C57BL/6J mice were randomly divided into four groups:the normal group,the model group,the Lindera aggregata extract group,and the dexamethasone group,with 8 mice in each group.The model group,Lindera aggregata ex-tract group,and dexamethasone group were intratracheally instilled with 5 mg/kg LPS to establish the ALI models,while the normal group received an equal volume of phosphate-buffered saline.Six hours after the intratracheal instillation,the Lindera aggregata extract group was administered the extract at 5 g/(kg·d)by gavage for 5 consecutive days,and the dexa-methasone group received dexamethasone at 7.2 g/(kg·d)via intraperitoneal injection for 5 consecutive days.The normal group and the model group were given an equal volume of 0.9%sodium chloride solution by gavage for 5 consecutive days.Twenty-four hours after the last administration,the mice were anesthetized,and blood samples were collected via cardiac puncture.Bronchoalveolar lavage fluid(BALF)and lung tissues were harvested.The lung edema parameter,wet/dry(W/D)weight ratio,was calculated,and pathological changes in lung tissue were observed.The levels of interleukin-1β(IL-1β)and IL-6 were measured by ELISA.The positive expression rate of the M1 macrophage polarization marker CD86 in BALF was detected by flow cytometry.The expression levels of key proteins in the NF-κB signaling pathway,phosphorylat-ed p65(p-p65)and phosphorylated IκB(p-IκB),were determined by Western blotting.Results Compared with the normal group,the model group showed severe destruction of the alveolar structure,increased W/D ratio,elevated levels of IL-1β and IL-6 in serum and BALF,increased CD86 positive expression rate in BALF macrophages,and up-regulated ex-pression of p-p65 and p-IκB in lung tissues(all P<0.01).Compared with the model group,both the Lindera aggregata ex-tract group and the dexamethasone group exhibited alleviated alveolar structural damage,decreased W/D ratio,reduced levels of IL-1β and IL-6 in serum and BALF,declined CD86 expression rate in BALF,and down-regulated expression of p-p65 and p-IκB in lung tissues(all P<0.01).No statistically significant differences were observed between the Lindera ag-gregata extract group and the dexamethasone group in terms of serum IL-6 levels,BALF IL-1β levels,CD86 positive ex-pression rate in BALF macrophages,the expression of p-p65 or the expression of p-IκB in the lung tissues(all P>0.05).Conclusions The extract of Lindera aggregata can inhibit lung tissue inflammation and alleviate lung injury in LPS-in-duced ALI mice.The mechanism of action may be associated with the suppression of the NF-κB signaling pathway activa-tion.

Abstract:Objective To investigate the therapeutic effects of Adropin(ADR)on myocardial fibrosis in rats with di-abetic cardiomyopathy(DCM),and to explore its potential mechanisms.Methods Fifteen 8-week-old male SD rats were randomly divided into three groups:normal control group(CON group),high-glucose group(DCM group),and ADR intervention group(ADR group),with 5 rats in each group.The DCM models were established in the DCM group and ADR group through intraperitoneal injection of 1%streptozotocin,while the CON group received no treatment.After modeling,the ADR group was intraperitoneally injected with ADR at a dose of 10 μg/100 g,and the DCM group and CON group were intraperitoneally injected with normal saline at 1 mL/100 g,once daily for 8 consecutive weeks.After sacrific-ing the rats,myocardial tissues were collected to calculate the ratio of left ventricular weight(LVW)to body weight(LVW/BW),to observe pathological changes,and to detect the expression levels of inflammatory factors[tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)],myocardial fibrosis markers[collagen type Ⅰ(Col Ⅰ)and collagen type Ⅲ(ColⅢ)],transforming growth factor-β1(TGF-β1)/Smad signaling pathway proteins[TGF-β1,Smad3,phosphorylated Smad3(phos-Smad3)],and p38 mitogen-activated protein kinase(p38)signaling pathway-related proteins[p38,phosphorylat-ed p38(phos-p38)].Results Compared with the CON group,the LVW,LVW/BW,and the expression levels of TNF-α,IL-6,Col Ⅰ,Col Ⅲ,TGF-β1,phos-p38,and phos-Smad3 in the DCM group significantly increased(all P<0.05).After ADR intervention,compared with the DCM group,the LVW,LVW/BW,and the expression levels of TNF-α,IL-6,Col Ⅰ,Col Ⅲ,TGF-β1,phos-p38,and phos-Smad3 in the ADR group significantly decreased(all P<0.05).Conclu-sion Adropin alleviates myocardial fibrosis in DCM rats,potentially by down-regulating the activity of p38 MAPK and TGF-β1/Smad signaling pathway.

Abstract:Objective To observe and compare the cleaning effectiveness of three nickel titanium(NiTi)rotary instruments,PLEX-2.0,M3Pro,and EZ-PASS,in the root canal preparation of premolars with two root canals.Methods Thirty extracted human premolars with two root canals,which were indicated for extraction because of peri-odontal disease or orthodontic treatment and met the inclusion criteria,were randomly assigned into groups A,B and C(n=10 per group).Root canals in groups A,B and C were prepared mechanically using the PLEX-2.0,M3Pro and EZ-PASS NiTi rotary instruments,respectively,followed by chemical preparation with 3%sodium hypochlorite(NaOCl)and 17%ethylenediaminetetraacetic acid(EDTA).After preparation,the teeth were split longitudinally.The coronal third,middle third,apical third and root canal isthmus of each specimen were examined under a scanning electron microscope(SEM)to evaluate debris remaining on the canal walls and removal of the smear layer.Results In all three groups,dentinal tu-bules in the coronal third were clearly visible and regularly arranged,with almost no smear layer.In the middle third,part of the canal wall showed clearly visible and relatively well aligned dentinal tubules,whereas other areas were partly cov-ered by smear layer.In the apical third,the orifices of the dentinal tubules were clearly obstructed,with large clumps of debris on the canal walls and relatively poor cleanliness.In the root canal isthmus,almost no mechanical cutting marks were observed on the canal walls,and abundant debris occluded the surface with a widely scattered smear layer,indicating poor cleaning in this region.In all three groups,smear layer scores of the canal walls showed a gradual decrease from the apical third towards the coronal third.In the coronal third,smear layer scores decreased in the order of groups B,A and C.In the middle third,scores in the groups A and C were lower than those in the group B,and in the apical third,scores in the group C were lower than those in the groups A and B(all P<0.05).Smear layer scores in the root canal isthmus were high in all three groups,with no statistically significant differences among them.Conclusions When combined with chemical irrigation,the NiTi rotary instruments PLEX-2.0,M3Pro and EZ-PASS provide good cleaning in the coro-nal,middle and apical thirds of premolars with two root canals,whereas their cleaning effectiveness in the root canal isth-mus is relatively poor.For the coronal and apical thirds,EZ-PASS shows better cleaning ability than the other two instru-ments,while in the middle third M3Pro performs better.

Abstract:Objective To investigate the effect of tail vein injection of recombinant interleukin-35(pIL-35)on re-nal ischemia-reperfusion injury(IRI)in mice and to explore its potential mechanisms.Methods Forty-two C57BL/6J mice were randomly divided into the sham-operated group(sham group,n=6),model group(n=18),and pIL-35 group(n=18).Mice in the pIL-35 group received the tail vein injection of recombinant pIL-35(50 μg)plus 2 mL PBS,while those in the sham and model groups were given the empty vector(50 μg)plus 2 mL PBS.After injection,renal IRI models were established in the model and pIL-35 groups by clamping both renal pedicles for 40 min followed by 1 min reperfusion.The sham group underwent identical procedures without vascular clamping.Serum IL-35,creatinine(Cr),and blood urea nitrogen(BUN)levels were measured by ELISA before intervention and on day 1,3,and 5 after intervention.Renal tis-sue IL-16 and tumor necrosis factor-α(TNF-α)levels were determined by ELISA on day 1,3,and 5,and the expression of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway-related proteins was ana-lyzed by Western blotting.Results Compared with pre-intervention values,serum IL-35,Cr,and BUN levels increased in both the model and pIL-35 groups after intervention;however,the pIL-35 group showed significantly higher IL-35 and lower Cr and BUN levels than the model group at all time points(all P<0.05).Compared with the sham group,the expres-sion levels of IL-16,TNF-α,and JAK2/STAT3 pathway proteins were significantly elevated in the model and pIL-35 groups on day 1,3,and 5,while the expression levels of IL-16,TNF-α and the JAK2/STAT3 signaling pathway protein were lower in the pIL-35 group than in the model group at the same time point(all P<0.05).Conclusion Tail vein in-jection of pIL-35 can alleviate renal ischemia-reperfusion injury in mice,possibly by regulating the JAK2/STAT3 signaling pathway and reducing inflammatory responses.

Abstract:Objective To compare the therapeutic effects of hypoglycemic drugs in type 2 diabetes mellitus(T2DM)patients with different clinical characteristics.Methods A total of 4,911 patients with T2DM were retrospec-tively selected.Based on the K-means clustering method,the patients were classified according to six indicators at base-line:age,disease duration,body mass index(BMI),glycated hemoglobin(HbA1c),homeostasis model assessment of β-cell function index 2(HOMA2-β),and homeostasis model assessment 2-insulin resistance(HOMA2-IR)index.We compared the therapeutic effects of hypoglycemic agents in patients with different types,including the reduction of HbA1c,HbA1c achievement rate,body weight reduction,and body mass index(BMI)achievement rate.Results The results of cluster subtype characteristic analysis showed that 4,911 patients could be classified into 854 cases of obese insu-lin resistance type(type A),1,159 cases of elderly and long-course type(type B),1,069 cases of well-controlled blood glucose type(type C),and 1,829 cases of severe insulin deficiency type(type D).For type A patients,the reduction in HbA1c,the reduction in body weight,and the rate of reaching the HbA1c target in the group using glucagon-like peptide 1 receptor agonist(GLP-1RA)/sodium-glucose cotransporter 2 inhibitor(SGLT-2i)were higher than those in the non-use group(all P<0.05),while there was no statistically significant difference in the rate of reaching the BMI target(P>0.05).For patients with type B,the regimen of oral medication/GLP-1RA plus basal insulin had a higher weight reduction in com-parison with the regimen of adding basal insulin during meals(P<0.05).For patients with type C of using only one oral medication,there were no statistically significant differences in the four indicators between the biguanide group and the non-biguanide group(P>0.05).For type D patients,there were statistically significant differences in the reduction of HbA1c and body weight between the group receiving intensive insulin therapy(with basal insulin added during meals)and the non-treatment group(P<0.05),and no significant difference was found in the other parameters(all P>0.05).Conclusions During clinical diagnosis and treatment,GLP-1RAs or SGLT-2i should be incorporated into the therapeu-tic regimen for patients with T2DM characterized by obesity.For elderly patients with a long disease course,treatment with a single oral hypoglycemic agent/GLP-1RA combined with basal insulin confers higher safety.Patients with well-con-trolled blood glucose should be prioritized for biguanides,while those with poorly controlled blood glucose show favorable responses to intensive insulin therapy.

Abstract:Hepatoblastoma(HB)is the most common malignant liver tumor in children,predominantly affecting in-fants and young children aged under 5 years.With the adoption of multidisciplinary comprehensive treatment strategies,the survival rate of HB has been significantly improved;however,the prognosis of high-risk patients remains poor,and the adverse effects of traditional chemotherapy have become increasingly prominent.Current studies have demonstrated that the pathogenesis of HB is associated with dysregulation of signaling pathways including the Wnt/β-catenin pathway,PI3K/AKT/mTOR pathway,and LIN28B/RAN/AURKA pathway,as well as abnormal activation of proto-oncogenes such as CTNNB1,C-myc,and N-myc.Additionally,abnormalities of various enzymes(e.g.,Polo-like kinase 1,Gankyrin)and aberrant RNA editing are also involved in the development of HB.In-depth investigation of the molecular mechanisms un-derlying HB will provide crucial theoretical support for the development of novel targeted therapeutic regimens and the im-plementation of precision medicine.

Abstract:Objective To analyze the association between the C-reactive protein-triglyceride-glucose index(CTI)and cardiometabolic diseases(CMD)among middle-aged and elderly Chinese adults.Methods This cross-sectional study was based on data from the 2015 China Health and Retirement Longitudinal Study(CHARLS).Multicollinearity among variables was examined using the variance inflation factor(VIF).Multivariate Logistic regression was performed to evaluate the association between CTI and CMD.Subgroup analysis was conducted to assess the effect of CTI on CMD in dif-ferent subpopulations.Restricted cubic spline(RCS)models were used to explore nonlinear associations.Receiver operat-ing characteristic(ROC)curve analysis was applied to assess the predictive efficiency of CTI for CMD.Results A total of 7,316 middle-aged and elderly participants were included,among whom 2,397(32.76%)had CMD.After adjusting for potential confounders,elevated CTI was significantly associated with CMD(OR=2.53,95%CI:2.24-2.86,P<0.001).Subgroup analysis revealed a significant interaction between smoking history and the CTI-CMD association(P<0.05).RCS analysis indicated a significant nonlinear relationship between CTI and CMD(both P<0.001).The ROC curve showed that CTI had moderate predictive performance for CMD(area under the curve=0.633;cut-off value=3.839).Conclusion CTI is significantly associated with the presence of CMD in middle-aged and elderly Chinese adults and may serve as a useful indicator for CMD risk screening in this population.

Abstract:Objective To evaluate and compare the short-term clinical outcomes of gasless trans-subclavian endo-scopic thyroidectomy performed during the growth and mature phases of the learning curve with those of conventional open thyroidectomy.Methods A retrospective analysis was conducted on 126 patients who underwent thyroidectomy,includ-ing 60 cases of subclavian gasless endoscopic thyroidectomy(observation group)and 66 cases of open thyroidectomy(con-trol group).The learning curve was constructed using cumulative sum(CUSUM)analysis,and the growth and mature phases were identified.Surgical variables(total operative time,specimen extraction time,postoperative drainage,intraop-erative blood loss,parathyroid autotransplantation rate)and postoperative outcomes(length of stay,hospital cost,1-year recurrence,complications including hypocalcaemia,hypoparathyroidism,transient vocal cord palsy and persistent dyspho-nia)were compared between the two groups across both phases.Results The best-fitting equation for the surgical learn-ing curve was CUSUMn=-1.18n2+757+41.59n+185-3n3(R²=0.952,P<0.05),demonstrating a strong fit.During the learning phase,the observation group performed 20 cases of gasless trans-subclavian endoscopic thyroid surgery,while the control group conducted 24 cases of open thyroid surgery in the same timeframe.In the proficient phase,the observa-tion group completed 40 cases,and the control group completed 42 cases.In the learning phase,compared with the con-trol group,the observation group had longer operation time and longer thyroid specimen removal time,less intraoperative blood loss,higher postoperative drainage volumes,and a higher rate of parathyroid autotransplantation(all P<0.05).In the mature phase,the observation group experienced shorter postoperative hospital stay than the control group(P<0.01).There was no statistically significant difference in the rate of postoperative complications between the two groups during the learning phase(all P>0.05).However,in the mature phase,the observation group had a lower incidence of transient hy-pocalcemia than the control group(P<0.05).Conclusion Over the transition from the growth phase to the mature phase of the learning curve,subclavian gasless endoscopic thyroidectomy confers advantages of reduced intraoperative bleeding,shorter hospitalization and lower morbidity(especially transient hypocalcaemia)in comparison with the open surgery.

Abstract:Thyroid eye disease(TED)is an autoimmune disease characterized by inflammation and remodeling of or-bital tissues.Severe cases may present with optic nerve compression,proptosis,and exposure keratopathy.Traditional treatments for TED primarily include glucocorticoids and immunosuppressants;although they can alleviate the inflamma-tion,they are largely symptomatic and do not address the underlying pathogenesis.In recent years,with a deeper under-standing of the pathogenesis of TED,novel targeted therapies have been developed.Multiple clinical studies have shown that biologics such as teprotumumab,rituximab,and tocilizumab exhibit significant efficacy in treating TED;monoclonal antibodies targeting insulin-like growth factor 1 receptor(IGF-1R),thyroid-stimulating hormone receptor(TSHR),and tu-mor necrosis factor-α(TNF-α)have also shown therapeutic potential.Currently,TED drug treatment is evolving toward greater precision and safety,and multi-target combination therapy and biomarker-based personalized medicine may be-come future trends.

Abstract:Acute pancreatitis(AP)is a common clinical emergency within the digestive system,characterized by a complex pathological process and high mortality rates in severe cases.The proposal of the"gut-pancreatic axis"theory has provided novel research avenues for the prevention and treatment of AP,with dysbiosis of the gut microbiota,metabolic disorders,and immune inflammatory responses being closely interlinked in the pathogenesis and progression of AP.Sodi-um butyrate,as a representative short-chain fatty acid(SCFA),exerts multi-targeted regulation of the"gut microbiota-me-tabolism-immunity"network.It plays a crucial role in AP treatment through mechanisms including restoration of intestinal microecological balance,enhancement of mucosal barrier function,SCFA modulation,inhibition of histone deacetylase and NLRP3 inflammasome activation,and maintenance of Treg/Th17 balance.The combined application of sodium butyr-ate with prebiotics,probiotics,or traditional Chinese medicine may yield synergistic effects,offering novel approaches for multi-targeted precision interventions.In-depth exploration of the molecular mechanisms and clinical translational value of sodium butyrate in regulating the"gut microbiota-metabolism-immunity"axis for treating AP holds promise in providing new theoretical foundations and practical directions for the precise prevention and treatment of this disease.

Abstract:Objective To observe the effect of doxorubicin(DOX)on the integrity of the blood-brain barrier(BBB)in young mice and to explore its possible mechanism.Methods In vivo experiment:96 young mice were randomly divid-ed into the control group 1(C1 group),DOX group 1(D1 group),DOX+microRNA-155(miR-155)antagonist group 1(D+L1 group),DOX+activator protein 1(AP-1)inhibitor group 1(D+S1 group),miR-155 antagonist group 1(L1 group),and AP-1 inhibitor group 1(S1 group),with 16 rats in each group.The D1 group received intraperitoneal(i.p.)injection of DOX(4 mg/kg).The D+L1 group received i.p.injection of a locked nucleic acid(LNA)-modified miR-155 antagonist(LNA-antimiR-155)(5 mg/kg),followed by i.p.injection of DOX(4 mg/kg)1 h later.The D+S1 group re-ceived i.p.injection of the AP-1 inhibitor SP600125(10 mg/kg),followed by i.p.injection of DOX(4 mg/kg)1 h lat-er.The L1 group received i.p.injection of LNA-antimiR-155(5 mg/kg).The S1 group received i.p.injection of SP600125(10 mg/kg).All interventions were administered once a week for 5 weeks.BBB integrity was assessed using Evans Blue(EB)staining.The expression of tight junction proteins Occludin and Claudin-5 in hippocampal tissues was detected by Western blotting.In vitro experiment:The young mouse microvascular endothelial cell line bEnd.3 was divid-ed into groups corresponding to the in vivo experiment:C2,D2,D+L2,D+S2,L2,and S2 groups.The C2 group was rou-tinely cultured without drug intervention.The D2 group was treated with DOX(1 µmol/L)for 48 h.The D+L2 group was pretreated with LNA-antimiR-155(50 nmol/L)for 24 h,followed by intervention with DOX(1 µmol/L)for 48 h.The D+S2 group was pretreated with the AP-1 inhibitor SR11302(50 µmol/L)for 24 h,followed by intervention with DOX(1 µmol/L)for 48 h.The L2 group was treated with LNA-antimiR-155(50 nmol/L)alone for 24 h.The S2 group was treated with SR11302(50 µmol/L)alone for 24 h.Annexin A1 expression in the cells was detected by immunofluores-cence staining.MiR-155 expression was detected by real-time quantitative polymerase chain reaction(RT-qPCR).AP-1 activity was assessed by detecting c-Jun protein expression through Western blotting.Results In vivo experiment re-sults:Compared with the C1 group,the EB content in the hippocampal tissues of the D1 group was higher(P<0.05).Compared with the D1 group,the EB content in the hippocampal tissues of the D+L1,D+S1,L1,and S1 groups was lower(all P<0.05).Compared with the C1 group,the relative protein expression levels of Occludin and Claudin-5 in the brain tissues of the D1 group were lower(both P<0.05).Compared with the D1 group,the relative protein expression levels of Occludin and Claudin-5 in the brain tissues of the D+L1,D+S1,L1,and S1 groups were higher(all P<0.05).In vitro ex-periment results:Compared with the C2 group,the expression of Annexin A1 in the brain microvascular endothelial cells of the D2,D+L2,and D+S2 groups was lower(all P<0.05).Compared with the D2 group,the expression of Annexin A1 in the brain microvascular endothelial cells of the D+S2,D+L2,L2,and S2 groups was higher(all P<0.05).Compared with the C2 group,the relative expression of miR-155 in the microvascular endothelial cells of the D2 group was higher(P<0.05).Compared with the D2 group,the relative expression of miR-155 in the microvascular endothelial cells of the D+L2,D+S2,L2,and S2 groups was lower(all P<0.05).Compared with the C2 group,the relative expression of c-Jun pro-tein in the brain microvascular endothelial cells of the D2 and D+L2 groups was higher(both P<0.05),while that in the D+S2 and S2 groups was lower(P<0.05).Compared with the D2 group,the relative expression of c-Jun protein in the brain microvascular endothelial cells of the D+S2,L2,and S2 groups was lower(all P<0.05).Conclusion DOX may inhibit the expression of Annexin A1 and the synthesis of tight junction proteins by regulating the expression of AP-1 and miR-155,thereby disrupting BBB integrity of young mice.

Abstract:Valproic acid(VPA)is used in the clinical treatment of various diseases.However,due to its narrow ther-apeutic window and significant individual differences in pharmacokinetics and pharmacodynamics,precise clinical medica-tion faces challenges.Genetic polymorphisms(cytochrome P450 enzyme gene,UDP-glucuronosyltransferase gene mu-tants,and transport-related genes),age,gender,liver and kidney function,and concomitant medications are key factors affecting VPA metabolism,efficacy,and safety.These individual differences have an impact on the pharmacokinetics,blood drug concentration,efficacy,and adverse reactions of VPA.Therefore,individualized treatment plans should be for-mulated based on patient characteristics in clinical practice.