Background and Aims:Complex choledocholithiasis often coexists with stenosis of the ampulla of Vater,which increases the difficulty and complexity of treatment.If only the stones in the bile duct are removed without addressing the ampullary stenosis,the disease is prone to recurrence.Previously,most treatments involved the use of endoscopic retrograde cholangiopancreatography(ERCP)to guide the wire for sphincterotomy and stone extraction,followed by laparoscopic cholecystectomy.However,ERCP has limitations in handling complex cases.In response,our team pioneered a new method of treating choledocholithiasis combined with stenosis of the ampulla of Vater via a transabdominal approach.This study was performed to investigate the feasibility and efficacy of this method,aiming to provide a new therapeutic option for clinical practice.Methods:A randomized controlled study was conducted with 120 patients treated at Chengdu Second People's Hospital from 2021 to 2023 for gallbladder stones and choledocholithiasis with stenosis of the ampulla of Vater.Patients were divided into an observation group and a control group,with 60 cases in each group.The observation group underwent laparoscopic cholecystectomy with choledochotomy for stone extraction,followed by retrograde guidance of duodenal papillary sphincterotomy through the opened bile duct,simultaneously treating gallbladder,bile duct stones,and stenosis of the ampulla of Vater.The control group underwent traditional ERCP approach for sphincterotomy,stone extraction,and laparoscopic cholecystectomy.Perioperative variables were collected for both groups and the surgical outcomes were compared.Results:Among the 120 patients,54 were male and 66 were female.There were no statistically significant differences between the two groups in terms of stone extraction success rate,intraoperative blood loss,postoperative 24-h total bilirubin,direct bilirubin,transaminases,white blood cell count,jaundice relief time,or incidence rates of bile leakage,retroperitoneal bleeding/infection,and severe pancreatitis(all P>0.05).The observation group had significantly shorter average operative time and postoperative hospital stay compared to the control group(98.67 min vs.110.8 min,P<0.05;3.81 d vs.5.61 d,P<0.05).Additionally,the observation group had a significantly lower incidence of postoperative hyperamylasemia and/or hyperlipasemia and mild pancreatitis(1.67%vs.25.00%,P<0.001;0 vs.10%,P=0.027).Conclusion:The novel transabdominal approach is superior to the ERCP approach in terms of reducing surgery time and hospitalization time,and it carries a lower risk of postoperative mild pancreatitis and hyperamylasemia and/or hyperlipasemia.The stone extraction success rate is comparable to that of ERCP,making it a viable alternative treatment option.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.

Objective·To explore the antitumor effects and potential mechanisms of combining phosphoinositide 3-kinase,FYVE-type zinc finger containing(PIKfyve)inhibitor YM201636 with the stimulator of interferon genes(STING)agonist diABZI in STING pathway-deficient melanoma.Methods·The mRNA and protein expression levels of STING in human cancer cell lines were obtained from the Cancer Cell Line Encyclopedia(CCLE)and UniProt databases.Based on median expression values,melanoma cell lines with high STING mRNA but low protein expression were identified.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to validate STING mRNA and protein expression in human melanoma cells.The murine melanoma cell line YUMM1.7,characterized by low STING protein expression,was selected through Western blotting.The ability of YM201636 to restore STING protein expression in YUMM1.7 cells was evaluated.STING agonist diABZI was then applied in combination with YM201636 to analyze the synergistic tumor cell-killing effect through CCK-8 assay.Western blotting was used to detect the phosphorylation of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3),and qRT-PCR was used to evaluate type Ⅰ interferon expression.A mouse melanoma model was established and treated with YM201636,diABZI,or their combination.Tumor volume was measured,and treatment efficacy was assessed.RNA sequencing and immunofluorescence staining were performed to analyze immune cell infiltration in the tumor microenvironment.Results·Database analyses,qRT-PCR,and Western blotting confirmed that some human melanoma cell lines exhibited high STING mRNA expression but low STING protein levels.YM201636 significantly increased STING protein expression in YUMM1.7 cells(P<0.001).Combined treatment with YM201636 and diABZI significantly enhanced phosphorylation of TBK1 and IRF3(P<0.05),indicating effective activation of the STING signaling pathway.This combination also promoted the expression of type Ⅰ interferons(P<0.001)and enhanced tumor cell killing in vitro.In vivo,the combination therapy markedly suppressed melanoma growth compared to monotherapy.Immune profiling of the tumor microenvironment revealed significantly increased infiltration of CD4? T cells and CD8? T cells in the combination treatment group(P<0.05).Conclusion·The PIKfyve inhibitor YM201636 could restore STING protein expression in STING-deficient melanoma and enhance the antitumor efficacy of the STING agonist diABZI,offering a promising therapeutic strategy for tumors with defective STING signaling.

Background and Aims:Complex choledocholithiasis often coexists with stenosis of the ampulla of Vater,which increases the difficulty and complexity of treatment.If only the stones in the bile duct are removed without addressing the ampullary stenosis,the disease is prone to recurrence.Previously,most treatments involved the use of endoscopic retrograde cholangiopancreatography(ERCP)to guide the wire for sphincterotomy and stone extraction,followed by laparoscopic cholecystectomy.However,ERCP has limitations in handling complex cases.In response,our team pioneered a new method of treating choledocholithiasis combined with stenosis of the ampulla of Vater via a transabdominal approach.This study was performed to investigate the feasibility and efficacy of this method,aiming to provide a new therapeutic option for clinical practice.Methods:A randomized controlled study was conducted with 120 patients treated at Chengdu Second People's Hospital from 2021 to 2023 for gallbladder stones and choledocholithiasis with stenosis of the ampulla of Vater.Patients were divided into an observation group and a control group,with 60 cases in each group.The observation group underwent laparoscopic cholecystectomy with choledochotomy for stone extraction,followed by retrograde guidance of duodenal papillary sphincterotomy through the opened bile duct,simultaneously treating gallbladder,bile duct stones,and stenosis of the ampulla of Vater.The control group underwent traditional ERCP approach for sphincterotomy,stone extraction,and laparoscopic cholecystectomy.Perioperative variables were collected for both groups and the surgical outcomes were compared.Results:Among the 120 patients,54 were male and 66 were female.There were no statistically significant differences between the two groups in terms of stone extraction success rate,intraoperative blood loss,postoperative 24-h total bilirubin,direct bilirubin,transaminases,white blood cell count,jaundice relief time,or incidence rates of bile leakage,retroperitoneal bleeding/infection,and severe pancreatitis(all P>0.05).The observation group had significantly shorter average operative time and postoperative hospital stay compared to the control group(98.67 min vs.110.8 min,P<0.05;3.81 d vs.5.61 d,P<0.05).Additionally,the observation group had a significantly lower incidence of postoperative hyperamylasemia and/or hyperlipasemia and mild pancreatitis(1.67%vs.25.00%,P<0.001;0 vs.10%,P=0.027).Conclusion:The novel transabdominal approach is superior to the ERCP approach in terms of reducing surgery time and hospitalization time,and it carries a lower risk of postoperative mild pancreatitis and hyperamylasemia and/or hyperlipasemia.The stone extraction success rate is comparable to that of ERCP,making it a viable alternative treatment option.

Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.

Objective·To explore the antitumor effects and potential mechanisms of combining phosphoinositide 3-kinase,FYVE-type zinc finger containing(PIKfyve)inhibitor YM201636 with the stimulator of interferon genes(STING)agonist diABZI in STING pathway-deficient melanoma.Methods·The mRNA and protein expression levels of STING in human cancer cell lines were obtained from the Cancer Cell Line Encyclopedia(CCLE)and UniProt databases.Based on median expression values,melanoma cell lines with high STING mRNA but low protein expression were identified.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to validate STING mRNA and protein expression in human melanoma cells.The murine melanoma cell line YUMM1.7,characterized by low STING protein expression,was selected through Western blotting.The ability of YM201636 to restore STING protein expression in YUMM1.7 cells was evaluated.STING agonist diABZI was then applied in combination with YM201636 to analyze the synergistic tumor cell-killing effect through CCK-8 assay.Western blotting was used to detect the phosphorylation of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3),and qRT-PCR was used to evaluate type Ⅰ interferon expression.A mouse melanoma model was established and treated with YM201636,diABZI,or their combination.Tumor volume was measured,and treatment efficacy was assessed.RNA sequencing and immunofluorescence staining were performed to analyze immune cell infiltration in the tumor microenvironment.Results·Database analyses,qRT-PCR,and Western blotting confirmed that some human melanoma cell lines exhibited high STING mRNA expression but low STING protein levels.YM201636 significantly increased STING protein expression in YUMM1.7 cells(P<0.001).Combined treatment with YM201636 and diABZI significantly enhanced phosphorylation of TBK1 and IRF3(P<0.05),indicating effective activation of the STING signaling pathway.This combination also promoted the expression of type Ⅰ interferons(P<0.001)and enhanced tumor cell killing in vitro.In vivo,the combination therapy markedly suppressed melanoma growth compared to monotherapy.Immune profiling of the tumor microenvironment revealed significantly increased infiltration of CD4? T cells and CD8? T cells in the combination treatment group(P<0.05).Conclusion·The PIKfyve inhibitor YM201636 could restore STING protein expression in STING-deficient melanoma and enhance the antitumor efficacy of the STING agonist diABZI,offering a promising therapeutic strategy for tumors with defective STING signaling.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

Objective·To investigate the effect of F-box only protein 38(FBXO38)on the ocular melanoma proliferation and the potential regulatory pathway.Methods·Human skin cutaneous melanoma A375 and human uveal melanoma OMM2.3 cell lines with FBXO38 knockdown and overexpression were constructed by FBXO38 short hairpin RNA(shRNA)and FBXO38 overexpression plasmids respectively.Knockdown and overexpression efficiency of FBXO38 at transcription and protein levels were verified by using quantitative real-time PCR(qRT-PCR)and Western blotting.The effects of FBXO38 on melanoma cell proliferation were detected through clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay.By using The Cancer Genome Atlas(TCGA)database,differentially expressed genes were analyzed in the high and low expression groups of FBXO38.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment was performed to reveal the signaling pathways associated with FBXO38.CCK8 cell proliferation assay was used to detect the inhibition rates of the signaling pathway inhibitors on cells with different FBXO38 expression levels.qRT-PCR and Western blotting were used to detect whether the signaling pathway was activated after knocking down FBXO38.Results·qRT-PCR and Western blotting verified that mRNA and protein expression levels of FBXO38 in FBXO38 knockdown A375 and OMM2.3 cell lines decreased compared with the control group,while the expression levels of FBXO38 in the overexpression cell lines increased compared with wild type group(P＜0.05).Clonal formation assay,BrdU immunofluorescence staining and CCK8 cell proliferation assay showed that FBXO38 knockdown significantly enhanced the proliferation of A375 and OMM2.3 cells(P＜0.05),while overexpression of FBXO38 inhibited melanoma cell proliferation(P＜0.05).Enrichment analysis showed that in skin cutaneous melanoma and uveal melanoma,FBXO38 expression influenced the phosphoinositide 3-kinase/protein kinase B(PI3K-Akt)pathway activation.Compared with those in the control group,the inhibition rates of P13K inhibitor LY294002 and mTOR1 inhibitor Everolimus in the FBXO38 knockdown group significantly improved(P＜0.05),while their inhibition rates of the overexpression group significantly decreased compared with those of control cells(P＜0.05).Western blotting results showed that after knocking down FBXO38,expression levels of PTEN,P21 and P53 proteins decreased,while expression level of MDM2 protein increased.The qRT-PCR results showed a significant decrease in P53 transcription level(P＜0.05)and a significant increase in MDM2 transcription level in FBXO38 knockdown cells(P＜0.05).Conclusion·FBXO38 plays a role in regulating the proliferation of ocular melanoma,and this regulatory effect is related to the PI3K-Akt signaling pathway.

Objective:The present study was designed to strengthen the education of research integrity, and to improve the awareness of academic misconduct and academic literacy of medical post-graduate students.Methods:A questionnaire survey was conducted with master post-graduate students of a university affiliated hospital, and statistical analysis on the education of research integrity and the perception of academic misconduct among the survey respondents was performed.Results:Academic master post-graduate students′ cognitions of the misconduct in scientific research process and overall academic misconduct were better than that of professional master post-graduate students, and there were significant differences ( P<0.05). The more times of participation in research integrity training, the better cognition of misconduct of scientific research process, research results publication process, and overall academic misconduct, with significant differences ( P<0.05). Conclusions:The education on scientific research integrity of medical post-graduates should be carried out systematically, while the content should be improved and the form should be enriched for scientific research integrity education, so that the medical post-graduates can have a deeper understanding of the code of academic practices, and an education model of scientific research integrity for medical post-graduate which is suitable for China′s national conditions can be gradually developed.