Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

Objective To assess the clinical efficacy of sodium hyaluronate （0.3%） eye drops combined with herbal self-heating steam eye mask in the treatment of dry eye disease. Methods A prospective randomized controlled clinical trial was performed on 60 patients diagnosed with dry eye at the ophthalmic clinic of a Grade A, Class Ⅲ hospital in Shanghai from June 2023 to September 2024. Specifically, patients were randomly divided into control group and study group. Patients in the control group were treated with sodium hyaluronate （0.3%） eye drops for six weeks; while in the study group, patients received the eye drops combined with the herbal self-heating steam eye mask mainly containing powders of Flos Buddlejae. Subsequently, comparisons and analysis were performed before and after treatment between the two groups in the clinical symptom questionnaire score traditional Chinese medicine （TCM syndrome score），the Chinese dry eye questionnaire score and determination of tear film fluorscein breakup time （FBUT）, and curative effect. Results The quality control standard of the herbal powder in the self-heating steam eye mask was established through TLC and HPLC, and good heating behavior of the herbal self-heating steam eye mask was ascertained heating temperature （43±5）℃; heating duration （≥20 min）, meeting requirements of the product quality control. After treatment for 6 weeks, FBUT was increased, while TCM syndrome score and the Chinese dry eye questionnaire score were both decreased in the study group （P<0.001）. Besides, compared with the control group, TCM syndrome score and the Chinese dry eye questionnaire score were much lower, while the FBUT were higher in the study group （P<0.001）. Moreover, the overall response rate in the study group （81.7%） was much better than that in the control group （25.9%）. Conclusion The combination of sodium hyaluronate （0.3%） eye drops with herbal self-heating steam eye mask could be applied to the clinical treatment of dry eye disease due to its good clinical effects on relieving dry eye symptoms.

This narrative review examines the challenges, strategies, and future directions in the development of young teachers within the pathophysiology departments of Chinese medical colleges. A thorough review of 49 studies published between 2013 and 2024 was carried out using PubMed, Web of Science, and various Chinese databases. The primary challenges identified include teaching innovation (cited in 84.2% of the studies), research pressure (91.2%), disciplinary characteristics (87.7%), and career development (80.7%). Medical schools have responded by enhancing training systems (94.7%), innovating teaching methods (93.0%), and bolstering research support (96.5%). Looking ahead, trends are shifting toward the application of new technologies, interdisciplinary integration, and international collaboration. The focus on cultivating young teachers is increasingly geared towards personalization and diversification, which are essential for advancing education in pathophysiology. High-quality young teachers are pivotal in raising teaching standards, fostering research innovation, and facilitating interdisciplinary exchanges. Based on these insights, we recommend several practical measures to enhance the quality of pathophysiology education in China. These include establishing comprehensive training programs that integrate teaching innovation and research skills; developing structured mentorship systems with clear pathways for career advancement; creating platforms that support technology-enhanced teaching and international collaboration; and implementing systematic evaluation mechanisms to assess teaching effectiveness. These targeted interventions will require a coordinated effort from department heads, educational institutions, and policymakers to ensure a sustained improvement in the quality of pathophysiology education.

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

Discoidin domain receptor 1(DDR1)is overexpressed in various tumors,such as triple-negative breast cancer(TNBC),and is rarely expressed in normal tissues.These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate(ADC)for targeted therapy.Here,we investigated the preparation and preclinical efficacy of DDR1-DX8951,an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly(GGFG)linker.The anti-DDR1 monoclonal antibody was coupled to DX8951(i.e.,DDR1-DX8951),producing the targeted ther-apy ADC.The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models.DDR1-DX8951 can specifically target DDR1,be quickly internal-ized by TNBC cells,and reduce the viability of TNBC cells in vitro.The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models.Importantly,our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvi-ronment(TME)of TNBC.Taken together,this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.

Objective:To explore the efficacy and prognosis of hepatectomy via Laennec membrane approach in patients with hepatocellular carcinoma (HCC).Methods:The data of 98 patients with HCC who underwent hepatectomy in the First Affiliated Hospital of Soochow University from January 2016 to December 2022 were retrospectively analyzed, including 76 males and 22 females, aged 61.0 (55.0, 66.0) years. Forty-eight patients treated with Laennec membrane approach hepatectomy were included in the study group and 50 patients treated with traditional approach hepatectomy were included in the control group. The age, gender, combined hypertension and diabetes, aspartate transaminase, alanine transaminase, albumin, total bilirubin, prealbumin, platelet, alpha-fetoprotein, carbohydrate antigen 19-9 and carbohydrate antigen 125 were compared between the two groups. The surgical bleeding, operation time and complications (abdominal bleeding, bile leakage, poor incision healing, etc.) were compared between the two groups. The prognosis of the two groups was compared.Results:There were no significant differences in gender, age, underlying diseases, preoperative biochemical and tumor serological indexes between the two groups (all P>0.05). The operation time of the study group was 180.0 (141.3, 227.3) min, which was lower than that of the control group 221.5 (187.5, 256.3) min ( Z=-0.41, P=0.002). The intraoperative blood loss in the study group was 295.0 (127.5, 350.0) ml, which was lower than that in the control group 300.0 (200.0, 500.0) ml, and the difference was statistically significant ( Z=-1.97, P=0.003). The levels of aspartate transaminase and alanine transaminase 1 week after surgery in the study group were 33.4 (24.0, 43.8) U/L and 64.5 (38.3, 119.1) U/L, respectively, which were lower than those in the control group 41.3 (29.7, 63.0) U/L and 102.8 (50.1, 140.7) U/L, the differences were statistically significant ( Z=-2.09, -2.38, P=0.035, 0.028). Postoperative complications occurred in 8 cases (16.7%) in the study group and 10 cases (20.0%) in the control group, with no significant difference between the two groups ( χ2=0.18, P=0.670). The median overall survival was 16 months in the study group and 18 months in the control group, respectively. There was no significant difference in cumulative survival between the two groups ( χ2=1.41, P=0.130). Conclusion:Laennec membrane approach hepatectomy can not only shorten the operation time and reduce the amount of blood loss, but also promote the recovery of liver function.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

HIV infection remains a critical global health challenge due to the virus’s high mutation rate enabling immune evasion and persistent transmission. While antiretroviral therapy（ART）effectively suppresses viral replication，it fails to eradicate latent viral reservoirs. Chimeric antigen receptor T cell（CAR-T）therapy，revolutionary in hematologic malignancies，shows emerging potential for HIV functional cure. Preclinical and clinical studies demonstrate that anti-HIV CAR-T cells specifically target and eliminate HIV-infected cells，yet challenges persist regarding efficacy，persistence，and safety. This review synthesizes recent advances in CAR-T cell design，clinical trial outcomes，and translational challenges，proposing novel strategies to achieve functional HIV cure.