Objective:To analyze the clinical blood bile acid spectrum detection results of patients with biliary atresia（BA）and non-BA cholestasis,and to clarify the distribution changes of major bile acids in the serum of BA patients and their potential differential diagnostic value.Methods:The serum bile acid concentrations of BA and other non-BA cholestasis patients in the same age who underwent clinical bile acid spectrum testing at Children's Hospital of Fudan University from September 2019 to September 2020 were retrospectively analyzed.Non-BA patients were divided into the low gamma-glutamyl transpeptidase (GGT) cholestasis group (33 cases) and the high GGT cholestasis group (19 cases) based on serum GGT levels.ROC curve was used to analyze the differences in bile acid concentration levels between BA and non-BA patients,and their potential differential diagnostic value for BA.Results:(1) A clinical bile acid spectrum was collected from 74 BA patients and 52 non-BA patients.The median level of primary bile acid concentration in the BA group increased,ranging from 4.8 to 46.7 times the upper limit of the normal reference value.In the BA group,the median levels of all secondary bile acid concentrations decreased,ranging from 1/660 to 1/1.1 of the upper limit of the normal reference value.(2) The concentrations of glycocholic acid(GCA) and taurocholate (TCA) in the BA group were higher than those in the high GGT cholestasis group and the low GGT cholestasis group( P<0.05).(3) ROC curve analysis showed that when the GCA concentration>8 690 nmol/L,the AUC value was 0.706 (95% CI 0.609-0.803),with a sensitivity of 0.811,specificity of 0.538,positive predictive value of 0.714,and negative predictive value of 0.667. Conclusion:An obstruction of bile salt secretion in the bile duct,leading to a decrease in secondary bile acid production in the intestine.A significant decrease in secondary bile acid levels,accompanied by a significant increase in GCA concentration may suggest BA.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective:By sequencing and analyzing the biliary flora by 16S rDNA high-throughput sequencing technology,to identify the main flora associated with gallbladder stone formation and the main flora regulated by the Dahuang lingxian(DHLX),pre-liminary investigation the effect of DHLX on the biliary flora.Methods:The 50 male guinea pigs were randomly divided into Normal group,Model group,DHLX group.There were 15 guinea pigs in the normal group and 20 guinea pigs in the DHLX group,and 20 guin-ea pigs in the model group:the guinea pig model of gallstone was replicated with high-fat lithogenic diet,which was simultaneously ad-ministrated by gavage.After continuous intervention for 8 weeks,bile and gallbladder tissue samples were collected,and the gallstone formation rate of guinea pigs in each group was calculated,the pathological morphological changes of gallbladder tissue were detected by HE,T-CHO,TBA,LPS,IL-6,TNF-α were detected by ELISA,and the changes of biliary flora were detected by 16S rDNA;the correlation between biliary flora and bile index was detected by Pearson statistical method.Results:The stone formation rate of guinea pigs in the normal group was 8.3%,the rate of model stone composition was 90.8%,and the stone composition rate of DHLX group was 36.4%,and the HE staining results showed that compared with the normal group,the mucous membrane of the guinea pig in the model group was thickened,the columnar epithelial cells were arranged in a large number of inflammatory cells,and the columnar epi-thelial cells of the gallbladder mucosa in the chinese medicine group were arranged neatly compared with the model group,the thick-ness of the mucosa was reduced compared with the model group,and some inflammatory cells were infiltrated;ELISA results showed that compared with the normal group,the expressions of T-CHO,LPS,IL-6 and TNF-α in the bile of guinea pigs in the model group were significantly increased(P<0.01),while the content of TBA was significantly reduced(P<0.01);compared with the model group,the expression of LPS and IL-6 in the bile of the DHLX group were significantly reduced(P<0.01).The results of 16S rDNA showed that compared with the normal group the Ace index and Chao1 index of the model group were significantly reduced(P<0.01),and the Chao1 index of the DHLX group was significantly higher than that of the model group(P<0.05);biliary flora at the genera level was mainly composed of Burkholderia,Sphingomycetes,Breghamus,Delfortella,Pseudomonas;correlation analysis showed that total cholesterol was negatively correlated with the abundance of Methyloversatilis(P<0.05),and total bile acids were positively corre-lated with the abundance of Burkholderia(P<0.05),and Pseudomonas erythrocytes,Rhizobia,the abundance of Phreatobacter was negatively correlated(P<0.01)and LPS was positively correlated with the abundance of Pseudomonas erythrocytes(P<0.01).Conclu-sion:Biliary microflora disorder exists in the formation of biliary stones,and biliary microflora may participate in the formation of stones by regulating cholesterol,bile acids and LPS.DHLX can regulate the changes in the abundance of the microflora,make the structure of the microflora become normal,reduce the inflammation of the gallbladder,and prevent the formation of gallstones.

Metastatic castration-resistant prostate cancer (mCRPC) is often resistant to conventional therapies, and prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy has emerged as a promising therapeutic strategy. Ligands such as 177Lu-PSMA and 225Ac-PSMA have demonstrated clinical benefits in ongoing studies and show potential when combined with endocrine therapy, chemotherapy, immunotherapy, and radiotherapy. Additionally, novel therapeutic approaches, including PSMA-targeted antibody-drug conjugates (ADCs), chimeric antigen receptor T-cell (CAR-T) therapy, and bispecific T-cell engagers (BiTEs), are being actively explored. This review summarizes the recent advancements in PSMA-targeted treatment and their clinical applications.

This study was aimed at evaluating the characteristics of H9N2 subtype avian influenza viruses(AIVs)origina-ting from wild birds in major wetlands in Fujian.Five H9N2 subtype AIVs isolated from fecal samples from wild birds in wet-lands of the Minjiang River,Jiulong River,Sandu Bay,Xinghua Bay,and Quanzhou Bay in Fujian were sequenced.Sequence a-nalysis of the HA genes of the five H9N2 subtype AIVs indicated that the five isolates shared 89.8％-99.4％nucleotide se-quence identity.All five isolates belonged to the same h9.4.2.5c evolutionary branch.The cleavage site motifs of HA were all PSRSSR ↓ GLF,thus indicating molecular characteristics of AIVs with low pathogenicity.The HA proteins of the viruses orig-inating from wild birds bore eight identical potential glycosylation sites,among which the glycosylation site at position 313 was located near the HA protein cleavage site.The 226th amino acid of HA in the receptor binding site was leucine in each virus,thus indicating that HAs of the five H9N2 subtype AIVs had mammalian sialic acid α-2,6 receptor binding affinity.In conclu-sion,the five H9N2 subtype AIVs originating from wild birds in Fujian had low pathogenicity,and the HAs had mammalian sialic acid α-2,6 receptor binding affinity.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

Metastatic castration-resistant prostate cancer (mCRPC) is often resistant to conventional therapies, and prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy has emerged as a promising therapeutic strategy. Ligands such as 177Lu-PSMA and 225Ac-PSMA have demonstrated clinical benefits in ongoing studies and show potential when combined with endocrine therapy, chemotherapy, immunotherapy, and radiotherapy. Additionally, novel therapeutic approaches, including PSMA-targeted antibody-drug conjugates (ADCs), chimeric antigen receptor T-cell (CAR-T) therapy, and bispecific T-cell engagers (BiTEs), are being actively explored. This review summarizes the recent advancements in PSMA-targeted treatment and their clinical applications.

Porcine arthritis,one of the common chronic diseases in large-scale pig farms,can signifi-cantly reduce the production performance of meat pigs.In this study,a strain of Haemophilus pa-rasuis(HPS)was isolated from the joint fluid of a lame pig.The HPS was analyzed in terms of se-rotypes,virulence genes,and resistance genes.Additionally,it was treated with sensitive antibiotics to provide a theoretical basis for the comprehensive prevention and treatment of arthritis in meat pigs in future production settings.A strain of HPS type 14 was isolated from the joint fluid of dis-eased pigs.The HPS isolate demonstrated sensitivity to β-lactams and tetracyclines,while florfeni-col and polymyxin effectively inhibited its growth at low concentrations.However,the bacteria ex-hibited resistance to sulfonamides and ciprofloxacin.The treatment of affected pigs with clinical ar-thritis using doxycycline and enrofloxacin injections proved effective.Compared to the infected group,in which the sick pigs experienced difficulty flexing their carpal and tarsal joints and exhibi-ted significant lameness,the pigs in the treatment group showed marked improvement.Their joints were only slightly swollen,and the clinical symptoms of arthropathy were alleviated.

Objective:To analyze the clinical blood bile acid spectrum detection results of patients with biliary atresia（BA）and non-BA cholestasis,and to clarify the distribution changes of major bile acids in the serum of BA patients and their potential differential diagnostic value.Methods:The serum bile acid concentrations of BA and other non-BA cholestasis patients in the same age who underwent clinical bile acid spectrum testing at Children's Hospital of Fudan University from September 2019 to September 2020 were retrospectively analyzed.Non-BA patients were divided into the low gamma-glutamyl transpeptidase (GGT) cholestasis group (33 cases) and the high GGT cholestasis group (19 cases) based on serum GGT levels.ROC curve was used to analyze the differences in bile acid concentration levels between BA and non-BA patients,and their potential differential diagnostic value for BA.Results:(1) A clinical bile acid spectrum was collected from 74 BA patients and 52 non-BA patients.The median level of primary bile acid concentration in the BA group increased,ranging from 4.8 to 46.7 times the upper limit of the normal reference value.In the BA group,the median levels of all secondary bile acid concentrations decreased,ranging from 1/660 to 1/1.1 of the upper limit of the normal reference value.(2) The concentrations of glycocholic acid(GCA) and taurocholate (TCA) in the BA group were higher than those in the high GGT cholestasis group and the low GGT cholestasis group( P<0.05).(3) ROC curve analysis showed that when the GCA concentration>8 690 nmol/L,the AUC value was 0.706 (95% CI 0.609-0.803),with a sensitivity of 0.811,specificity of 0.538,positive predictive value of 0.714,and negative predictive value of 0.667. Conclusion:An obstruction of bile salt secretion in the bile duct,leading to a decrease in secondary bile acid production in the intestine.A significant decrease in secondary bile acid levels,accompanied by a significant increase in GCA concentration may suggest BA.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.