Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective: To investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

Objective : To investigate the diagnostic value of linear array endoscopic ultrasonography ( EUS) for common bile duct microlithiasis． Methods : Data of patients who attended in the hospital and diagnosed as common bile duct microlithiasis and biliary sludge by EUS were selected．A total of 85 patients with magnetic resonance cholangiopancreatography ( MRCP) examination and ERCP treatment during hospitalization were enrolled．The results of endoscopic retrograde cholangiopancreatography / endoscopic sphincterotomy ( ERCP / EST) were the gold standard for diagnosis．The results of EUS，MRCP，and diagnostic ERCP were compared with the gold standard， and the sensitivity，specificity，positive predictive value，negative predictive value，and diagnostic accuracy of the three methods were calculated，respectively．The chi-square test was used for comparison of the above indices． Results : Of all 85 patients，63 had positive EUS results，among whom 5 had false positive results; 22 had negative EUS results，among whom 1 had false negative results．Of all 85 patients，49 had positive MRCP results，among whom 4 had false positive results; 36 had negative MRCP results，among whom 14 had false negative results．Of all 85 patients，59 had positive diagnostic ERCP results，among whom 10 had false positive results; 26 had negative diagnostic ERCP results，among whom 10 had false negative results．The sensitivity，specificity，positive predictive value( PPV) ，negative predictive value ( NPV) ，and accuracy of EUS in diagnosing common bile duct microlithia- sis were 98. 3% ，80. 8% ，92. 1% ，95. 4% and 92. 9% ，respectively． For MRCP，these values were 76. 3% ， 84. 6% ，91. 8% ，61. 1% and 78. 8% ，respectively．For diagnostic ERCP，these values were 83. 1% ，61. 5% ， 83. 1% ，61. 5% and 76. 5% ，respectively．The EUS group had a significantly higher accuracy than the MRCP group ( χ2 = 6. 986，P ＜0. 05) and diagnostic ERCP group ( χ2 = 8. 900，P ＜0. 05) ．The areas under the ROC curves ( AUC) and 95% CI of EUS group，MRCP group and diagnostic ERCP were 0. 895 ( 95% CI: 0. 802 - 0. 988，P＜0. 001) ，0. 804 ( 95% CI: 0. 702 －0. 907，P ＜0. 001) and 0. 723 ( 95% CI: 0. 598 －0. 848，P = 0. 001) ，respectively． Conclusion EUS has a high diagnostic value in the diagnosis of common bile duct microli- thiasis and thus can be used as the preferred examination before therapeutic ERCP．

Taking chronic atrophic gastritis （CAG） as an example， the frontier technologies in data science have been introduced into the inheritance， innovation and development of traditional Chinese medicine （TCM）， providing reference for conducting real-world clinical research on specialized diseases of TCM. This paper put forward the construction of CAG data science system by elaborating the connotation of data science and its application value in TCM， and discussed the path to build CAG data science system， namely through "data acquisition-knowledge expression-knowledge reasoning" to establish CAG database， knowledge base and develop diagnosis platform differentiating diseases and syndromes. Besides， this paper analyzed the prospects of CAG data science in improving data governance ability and knowledge discovery efficiency， deepening the level of knowledge sharing， promoting interdisciplinary integration， and strengthening the integration process of industry， academia and research.

OBJECTIVE To investigate the role of solute carrier family 1 member 4(SLC1A4) in platinum-based chemotherapy resistance in ovarian cancer. METHODS The expression of SLC1A4 in ovarian cancer or platinum-resistant ovarian cancer was analyzed by GEO and TCGA database analysis tools. The expression of SLC1A4 in platinum-treated ovarian cancer cell lines was analyzed by GEO database. The relation of SLC1A4 expression and overall survival(OS) or progression free survival(PFS) in ovarian cancer patients were analyzed by Kaplan Meier-plotter. Correlation between SLC1A4 gene effect and sensitivity to chemotherapeutic agents in ovarian cancer was analyzed through DepMap platform. Low expression of SLC1A4 mediates cisplatin resistance in ovarian cancer cells as verified by flow cytometry and tumor cell clone colony formation assays; prediction of microRNAs(miRNA) targeting SLC1A4 was conducted using TargetScan then validated their correlation in TCGA ovarian cancer samples. Used COREMINE tool to analyze the biological processes of SLC1A4 mediating chemoresistance in ovarian cancer. RESULTS SLC1A4 was significantly reduced in ovarian cancer patients and platinum-resistant ovarian cancer(P<0.05) and significantly correlated with OS and PFS in ovarian cancer patients(P<0.05). SLC1A4 expression was increased in ovarian cancer cells with platinum treatment. The genetic effect of SLC1A4 on ovarian cancer was positively correlated with platinum drug sensitivity. Overexpression of SLC1A4 increased cisplatin-induced apoptosis and reduced tumor cell colony formation in ovarian cancer cells. Hsa-let-7c-5p was targeted to SLC1A4 and significantly negatively correlated in samples from drug-resistant ovarian cancer patients. CONCLUSION Low expression of SLC1A4 mediates platinum drug resistance in ovarian cancer and is potentially associated with hsa-let-7c-5p regulation.

Objective To investigate the role of knockdown of peroxiredoxin-6(PRDX6)in injury and adaptive expression of bile acid transporter in human hepatoellular carcinomas(HepG2)cells induced by rifampicin(RFP).Methods Cells in logarithmic growth phase were uniformly inoculated in six-well plates,and HepG2 cells were transiently transfected with specific PRDX6-siRNA and control-siRNA to construct the knockdown group and control group.After 24 h of induction with 100 μmol/L RFP,Western blot and qRT-PCR were performed to detect the protein and gene expression levels of PRDX6,multidrug resistance protein 1(MDR1),multidrug resist-ance-associated proteins 2,3 and 4(MRP2,MRP3 and MRP4),and Na+/taurine taurocholate cotransporter pro-tein(NTCP).Annexin V-FITC/PI double staining assay was used to detect the apoptosis rate of cells in each group;CCK-8 assay was used to detect the changes of cell proliferation in each group;The relative contents of ala-nine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),indirect bilirubin(IBIL)and total bile acid(TBA)in the supernatant of cell culture medium of each group were detected by kits.Results RFP increased the protein and gene expression levels of MRP2,MRP3,MRP4,MDR1,NTCP and PRDX6 in HepG2 cells(P<0.05),while the protein and gene expression levels of MRP2,MRP3,MRP4,MDR1 and NTCP decreased to different degrees after PRDX6 knockdown(P<0.05).In addition,PRDX6 knockdown re-sulted in increased apoptosis rate of HepG2 cells(P<0.05),decreased cell proliferation ability(P<0.05),and increased levels of cell injury markers(ALT,AST,TBIL,DBIL,TBA)in cell culture supernatants(P<0.05).Conclusion RFP increased the protein and gene expression of bile acid transporter and PRDX6 to increase in HepG2 cells.However,following knockdown of PRDX6 and treatment with RFP,the protein and gene expression levels of the bile acid transporter decreased and cell injury was aggravated,suggesting that PRDX6 played a protec-tive role in RFP-induced adaptive response in HepG2 cells.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective : To analyze the clinical characteristics of patients with abdominal type allergic purpura(HSP), to improve their diagnostic level, and to explore the risk factors for gastrointestinal bleeding in HSP patients. Methods : A retrospective analysis was conducted on the clinical manifestations, laboratory data, imaging, endoscopic, and pathological characteristics of 98 patients with abdominal type HSP. Based on the occurrence of gastrointestinal bleeding, 98 patients were divided into a bleeding group and a non-bleeding group, and the risk factors for gastrointestinal bleeding in HSP patients were analyzed. Results : Abdominal HSP often presented with abdominal pain, vomiting, vomiting blood, black stools, and bloody stools. Imaging often showed edema and thickening of the duodenum and jejunum, as well as enlargement of surrounding lymph nodes. Under endoscopy, the descending part of the duodenum and jejunum mucosa were commonly congested and edematous with erosion, and ulcers were seen in the distal ileum. Pathology commonly involved acute and chronic inflammation of the mucosa with congestion, edema, and local erosion. Patients with gastrointestinal bleeding had significantly higher levels of white blood cell count(WBC), neutrophil count(NEUT), C-reactive protein(CRP), D-dimer(D-D), and fibrinolytic products(FDP) compared to non-bleeding patients(P<0.05), while levels of red blood cell count(RBC), hemoglobin(HGB), and albumin(ALB) were significantly lower than those of non bleeding patients(P<0.05). Logistic regression analysis showed that decreased ALB and increased FDP were independent risk factors for gastrointestinal bleeding in patients with abdominal HSP(P<0.05). The areas under the ROC curves of ALB and FDP were(AUC=0.877, 95%CI:0.794-0.960,P<0.01) and(AUC=0.806, 95%CI:0.722-0.890,P<0.01), respectively. The maximum value of the Jordan index for ALB was 0.734, with sensitivity and specificity of 89.6% and 83.9%, respectively, and had a critical value of 38.2 g/L. The maximum value of the Jordan index for FDP was 0.577, with sensitivity and specificity of 64.2% and 93.5%, respectively, and had a critical value of 18.14 μg/ml. There was no statistically significant difference in the ROC curves between ALB and FDP. Conclusion For HSP with abdominal pain as the initial symptom, imaging and endoscopic examination are helpful for early diagnosis. Decreased ALB and elevated FDP are independent risk factors for gastrointestinal bleeding in adult patients with abdominal HSP.

Objective:To investigate the related factors and prognosis of invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The in-patients diagnosed with Klebsiella pneumoniae liver abscess in the Department of Infectious Diseases, Huashan Hospital, Fudan University from January 2015 to February 2021 were retrospectively enrolled. The patients were divided into IKLAS group and non-IKLAS group according to whether they had IKLAS or not. The clinical data between the two groups were compared, including the prevalence of diabetes mellitus, the details of liver abscess, clinical symptoms such as fever and abdominal pain, as well as laboratory tests such as glycosylated hemoglobin and hemoglobin. Statistical analysis was performed using chi-square test or independent sample t test. Multivariate logistic regression analysis was used to analyze the factors influencing the occurrence of IKLAS. Results:A total of 75 patients with Klebsiella pneumoniae liver abscess were enrolled, including 55 patients (73.33%) in the IKLAS group and 20 patients (26.67%) in the non-IKLAS group. Fifty-two point seven three percent (29/55) of the patients had diabetes mellitus and 12.73%(7/55) of the patients had abdominal pain in the IKLAS group, which were 20.00%(4/20) and 45.00%(9/20) in the non-IKLAS group, respectively, and the differences were both statistically significant ( χ2=6.38 and 7.28, respectively, both P<0.05). Most of liver abscesses were single (50/75, 66.67%), and more likely to occur in the right liver (50/75, 66.67%). The maximum diameter of liver abscess in the IKLAS group was (4.58±2.04) cm, which was smaller than that in the non-IKLAS group ((6.49±3.11) cm), and the difference was statistically significant ( t=2.82, P=0.011). Compared with those in the non-IKLAS group, patients in the IKLAS group had higher glycosylated hemoglobin (8.69%±2.64% vs 6.18%±1.31%) and hemoglobin ((112.25±22.04) g/L vs (100.05±18.59) g/L), and the differences were both statistically significant ( t=-4.25 and -2.21, respectively, both P<0.05). The proportion of patients using antibiotics combined with abscess drainage in the IKLAS group was 38.18%(21/55), and that in the non-IKLAS group was 85.00%(17/20). The difference between the two groups was statistically significant ( χ2=12.86, P<0.001). A total of 16 patients (21 eyes) were diagnosed as endogenous Klebsiella pneumoniae endophthalmitis (EKPE), and all of them were IKLAS patients, and 14 patients underwent monocular/binocular eyeball injection and/or vitrectomy and silicone oil filling. The visual acuity of 13 patients decreased significantly. Multivariate logistic regression analysis showed that complicated with diabetes mellitus was an independent risk factor for IKLAS (odds ratio ( OR)=5.02, 95% confidence interval (95% CI) 1.01 to 25.03, P=0.049). The large diameter of liver abscess was a protective factor for IKLAS ( OR=0.64, 95% CI 0.47 to 0.86, P=0.003). Conclusions:The patients with IKLAS have less abdominal pain, and most of them complicate with diabetes mellitus. Diabetes mellitus is an independent risk factor for the occurrence of IKLAS, while the large diameter of liver abscess is a protective factor. EKPE is associated with poor visual prognosis.

Objective To prepare indocyanine green(ICG)-loaded platelet membrane biomimetic liposome(ICG-PLP)for tumor photothermal therapy,and to preliminarily evaluate its in vitro characteristics.Methods ICG-PLP was prepared by an ultrasound method,and its particle size and zeta potential were determined using a laser particle size analyzer.The encapsulation efficiency of ICG-PLP was detected by ultraviolet spectrophotometry.The photothermal properties of ICG-PLP were investigated under 808 nm near-infrared ray irradiation(2 W/cm2),and the retention of platelet membrane proteins was observed by sodium dodecylsulfate-polyacrylamide gel electrophoresis.The uptake of ICG-PLP by mouse macrophage RAW264.7,human non-small cell lung cancer cell A549,mouse melanoma cell B16-F10,and mouse breast cancer cell 4T1 was observed by a laser confocal microscope.Furthermore,the phototoxicity of ICG-PLP was detected by methyl thiazolyl tetrazolium assay,and the safety of ICG-PLP was preliminarily evaluated according to hemolysis rate and cytocompatibility.Besides,the in vivo retention time of ICG,ICG-loaded liposome and ICG-PLP in healthy SD rats was observed after tail vein injection.Results ICG-PLP was successfully prepared and its encapsulation efficiency,particle size,zeta potential,and the polydispersity index were(97.68±0.01)％,(109.77±0.76)nm,(-21.23±0.84)mV,and 0.22±0.01,respectively.ICG-PLP well retained the proteins on platelet membrane and showed good photothermal properties.Platelet membrane enhanced the uptake of biomimetic nanoparticles by tumor cells A549,B16-F10,and 4T1,and reduced the phagocytosis of biomimetic nanoparticles by macrophages.ICG-PLP exhibited a favorable photothermal therapy effect and could kill tumor cells.Additionally,ICG-PLP displayed a good safety.After intravenous administration,ICG-PLP prolonged the in vivo retention time of ICG in healthy SD rats.Conclusion ICG-PLP has been successfully constructed.It has a great potential in targeted drug delivery and tumor photothermal therapy.