Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Objective : To investigate the role of enhancer of zeste homolog 2(EZH2)-trimethylated lysine 27 of histone H3(H3K27me3) axis in the dedifferentiation of thyroid cancer and its clinical value as a potential target for the treatment of anaplastic thyroid cancer(ATC). Methods : Immunohistochemical SP method was used to detect the expression of EZH2, H3K27me3, paired box gene 8(PAX8), thyroglobulin(TG) and thyroid transcription factor 1(TTF1) in ATC and papillary thyroid carcinoma(PTC) and their adjacent tissues. The relationship between EZH2 and thyroid differentiation markers(PAX8, TTF1, TG) was further analyzed by gene expression omnibus(GEO) database. ATC cell lines 8305C and BHT-101 were culturedin vitro. Real-time reverse transcription PCR(RT-qPCR) was used to detect the expression of thyroid differentiation markers(TTF1, PAX8) mRNA in ATC cell lines treated with EZH2 inhibitor(GSK126), and evaluate the potential therapeutic effect of GSK126in vitro. The effects of GSK126 and BRAF inhibitor vemurafenib on the proliferation of ATC cell lines were observed by cell proliferation assay. Results : The expression of EZH2 in ATC tissues was significantly higher than that in papillary thyroid carcinoma and adjacent tissues(P<0.05). The expression of H3K37me3 in ATC tissues was significantly lower than that in PTC tissues(P<0.05). EZH2 was negatively correlated with PAX8 and TG expression levels, but not with TTF1 expression level.In vitroexperiments, GSK126 could reverse the expression of thyroid differentiation markers PAX8 and TTF1 in ATC cell lines. GSK126 combined with BRAF inhibitor vemurafenib could significantly inhibit the growth of ATC cell lines. Conclusion The EZH2-H3K27me3 axis plays an important role in regulating thyroid specific markers, and the inhibition of EZH2 by small molecular compounds is a promising target for ATC treatment in the future.

[摘 要] 目的：探讨免疫检查点抑制剂（ICI）治疗非小细胞肺癌（NSCLC）患者发生免疫检查点抑制剂相关性肺炎（CIP）的发生情况和免疫治疗疗效的关系，分析接受ICI治疗的NSCLC患者的预后相关因素。方法：回顾性分析2020年3月至2023年3月在新疆医科大学附属肿瘤医院接受ICI治疗145例NSCLC患者的临床资料，将患者分为CIP组和非CIP组，随后将发生CIP的患者分为轻度（1、2级）CIP和重度（3、4级）CIP两个亚组，通过Kaplan-Meier法比较生存曲线，分析CIP的发生及严重程度对于患者PFS及OS的影响。通过单因素及多因素COX风险比例回归模型分析与PFS和OS相关的预后因素。结果：145例患者中有26例患者出现CIP，发生率为17.93％，重度CIP发生率为3.45%。CIP组患者PFS明显长于非CIP组患者（12.3 vs 7.6个月，P<0.05），CIP组与非CIP组的OS比较差异无统计学意义（16.2 vs 15.8个月，P>0.05)。亚组分析显示，轻度CIP和重度CIP相比，PFS（12.2 vs 12.9个月）及OS（16.1 vs 17.8个月）均无统计学意义（均P>0.05）。多因素COX回归分析显示，CIP[HR=0.55，95%CI（0.33, 0.90），P=0.02]、免疫疗程>6个[HR=0.51，95%CI（0.31, 0.85），P=0.01]是影响患者PFS的有利预后因素，免疫疗程>6个[HR=0.4，95%CI（0.18, 0.88），P=0.02]是影响OS的有利预后因素。结论：CIP的发生率为17.93％，CIP的发生与PFS的延长密切相关。免疫疗程>6个是影响NSCLC患者PFS、OS的有利预后因素。

ObjectiveTo investigate the pathogenic spectrum and molecular characteristics of infectious diarrhea among children in Putuo District of Shanghai from 2018 to 2023， and to provide scientific basis for the prevention and control of infectious diarrhea in children. MethodsFecal samples from the cases visited sentinel hospitals for children’s diarrheal disease in Putuo District， Shanghai， were collected from January 2018 to December 2023. A total of 11 species of bacteria were isolated and cultured， and 5 species of viruses were detected by real-time fluorescent polymerase chain reaction （PCR）. The molecular typing of some positive strains was analyzed by the standard pulsed-field gel electrophoresis （PFGE） method. The polymerase-capsid protein linkage region of some norovirus-positive samples was amplified by reverse transcription PCR， and was sequenced and analyzed by bioinformatics software. The Chi-square test and Fisher’s exact probability test were used to compare the pathogen-positive rates in 2018‒2019 and 2020‒2023. ResultsOf the 707 cases of children with infectious diarrhea， the total positive rate was 47.67%， with a single bacterial positivity rate of 16.27%， a single viral positivity rate of 22.63%， and a mixed positivity rate of 8.77%， respectively. The dominant pathogens were rotavirus （10.75%）， norovirus （10.33%）， enteropathogenic Escherichia coli （8.06%）， Salmonella （6.36%）， enteroaggregative Escherichia coli （5.52%）， and Campylobacter （5.23%）. Bacterial infections were predominant in summer and fall， and viral infections were predominant in winter and spring. The total positive rate decreased in 2020‒2023 compared with that of 2018‒2019 （χ²=5.753，P<0.05）. Thirty-seven strains of Salmonella， 81 strains of diarrheagenic Escherichia coli， and 19 strains of Campylobacter were completed for the molecular typing analysis by PFGE， which were classified into 28， 80 and 18 banding types， respectively， with a wide range of banding similarity. Nineteen copies of norovirus GⅡ group gene sequences were analyzed and classified into 5 genotypes， which were mainly GⅡ.Pe-GⅡ.4 and GⅡ.P16-GⅡ.2 types. ConclusionRotavirus， norovirus， diarrheagenic Escherichia coli， Salmonella， and Campylobacter are the dominant pathogens of infectious diarrhea in children in Putuo District of Shanghai. The pathogen spectrum shows a trend of seasonal epidemic characteristics， with a diversity of molecular characteristics of some pathogens. Surveillance and monitoring on molecular characteristics of the pathogens of infectious diarrhea in children should be strengthened in different seasons， so as to provide a laboratory basis for the prevention and control of infectious diarrhea.

OBJECTIVE: To analyze the accuracy of prosthesis size selection in Naton robot-assisted medial unicondyle knee arthroplasty by comparing the actual prosthesis size used during operation and the preoperative planning. METHODS: The clinical data of 100 patients (110 knees) who underwent Naton robot-assisted medial unicondylar knee arthroplasty between June 2023 and July 2024 was retrospectively analyzed, including 47 knees on left side and 63 knees on right side. There were 37 males (40 knees) and 63 females (70 knees) with a mean age of 65.4 years (range, 59-71 years). Body mass index was 22.2-28.6 kg/m ² (mean, 25.4 kg/m ²). The disease duration ranged from 1 to 8 years (mean, 3.4 years). Preoperative planning was performed by Naton robotic surgical system based on lower limb CT data. The final prosthesis size after osteotomy was recorded and compared with the preoperative plan to analyse whether it was consistent with the preoperative plan, as well as the situation of knee flexion and extension gaps (<0.5 mm, >2.0 mm) corresponding to the different models of prostheses. RESULTS: During operation, 5 patients (5 knees) were treated with traditional UKA due to mechanical arm failure, software obstacles, significant bone amputation bias, or loose reference frame, and were excluded from the final analysis. The remaining 95 patients (105 knees) successfully received Naton robot-assisted surgery, and no related complications occurred. The prosthesis size was consistent with the preoperative plan in 101 knees (96.2%) on the femur side, 100 knees (95.2%) on the tibia side, and 97 knees (92.4%) on both femur and tibia sides. The prosthesis size was inconsistent in 3 cases (2.86%) on the femur side alone, 4 cases (3.81%) on the tibial side alone, and 1 case (0.95%) on both femur and tibial sides. Among the prostheses with different models, the flexion and extension gaps were less than 0.5 mm in 3 knees, the flexion gap was less than 0.5 mm and the extension gap was more than 2.0 mm in 3 knees, and the flexion gap was more than 2.0 mm and the extension gap was less than 0.5 mm in 2 knees. CONCLUSION The accuracy of prosthesis size selection for Naton robot-assisted medial unicondylar knee arthroplasty is relatively high.
Humans ; Arthroplasty, Replacement, Knee/instrumentation* ; Female ; Male ; Middle Aged ; Aged ; Knee Prosthesis ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Prosthesis Design ; Knee Joint/surgery* ; Osteoarthritis, Knee/surgery* ; Range of Motion, Articular

Objective:To investigate the clinical application value and safety of magnetically controlled capsule gastroscopy (MCCG) in gastric and duodenal examination of children in comparison with conventional gastroscopy.Methods:Data of 160 outpatients or inpatients with abdominal pain accompanied by Helicobacter pylori infection aged 8-16 who underwent either MCCG or conventional gastroscopy in Shanghai Children's Hospital from March 2020 to March 2022 were retrospectively analyzed. Children were divided into the MCCG group ( n=80) and the conventional gastroscopy group ( n=80) according to different examination methods. The detection and examination time of lesions in upper gastrointestinal tract, tolerance and safety between the two groups were analyzed. Results:MCCG was successfully performed in 79 children and conventional gastroscopy was successfully performed in 78 children, respectively. The positive detection rates were 1.3% (1/79) and 1.3% (1/78) in the esophagus ( χ2=0.000, P>0.999), 87.3% (69/79) and 91.0% (71/78) in the stomach ( χ2=0.552, P=0.327) , 15.2% (12/79) and 19.2% (15/78) in duodenum ( χ2=0.450, P=0.533) with no significant difference between the two groups. There was no significant difference in the examination time [72.0 (41.0, 109.5) min VS 6.0 (4.3, 7.0) min, U=24, P<0.001] in the MCCG group and the conventional gastroscopy group. No adverse event occurred in either group. Conclusion:There is no significant difference in the detection rate of gastric and duodenal lesions between the MCCG group and the conventional gastroscopy group. MCCG is safe and stable, and can be used as an diagnostic tool for gastric and duodenal diseases in children.

Objective:To explore the application value of humanistic literacy and clinical practice ability training in postgraduate courses of geriatrics.Methods:Postgraduates in Zhejiang University School of Medicine were taken as research objects. The teaching curriculum combining humanistic literacy and clinical practice ability training was set as the course of experimental group, and the teacher-led teaching course was set as the course of control group. The questionnaire survey was conducted to the evaluate the teaching effect among the postgraduates from three aspects: classroom situation, knowledge application and ability training. SPSS 17.0 was used for t-test. Results:The teaching of combining humanistic literacy and clinical practice ability training in classroom atmosphere, participation, teacher-student communication, helping memory, knowledge comprehension, knowledge application, collaboration ability, expression ability, organizational ability, knowledge acquisition ability, and autonomous learning ability scores of the experimental group were (3.96±0.20), (3.92±0.28), (3.75±0.44), (3.92±0.28), (3.96±0.20), (3.96±0.20), (3.83±0.38), (3.92±0.28), (3.79±0.41), (3.88±0.34), and (3.83±0.38), which were better than those of the control group, especially in classroom atmosphere, participation, knowledge application, expression ability, and autonomous learning ability.Conclusion:The combination of humanistic literacy and clinical practice ability training can significantly improve the classroom atmosphere of geriatric postgraduate courses, enhance students' medical humanistic literacy, familiarize students with the core skills of geriatrics, and improve students' ability to express and learn independently.

To investigate the diagnostic value of narrow-band imaging (NBI) endoscopy for esophageal polyps in children. Microscopic morphology of various polyps in 35 children with esophageal polyps in Children's Hospital of Shanghai from January 2016 to June 2020 were observed under both traditional white light endoscopy and NBI endoscopy. The sensitivity and specificity of traditional white light endoscopy and NBI endoscopy were compared with the pathological results as the gold standard. A total of 70 esophageal polypoid lesions were found in 35 children, including 27 single polyps. Pathological results indicated that the majority of polyps were non-neoplastic polyps (52.9%, 37/70).The sensitivity of NBI endoscopy in the diagnosis of esophageal neoplastic polyps was significantly higher than that of white light endoscopy [93.9% (31/33) VS 90.9% (30/33), P < 0.001], and the specificity was also higher [89.2% (33/37) VS 78.4% (29/37), P=0.864]. By observing the microscopic structure of esophageal polyps, NBI endoscopy contributes to the clinical prediction of the pathological properties of polyps. Its sensitivity is superior to the white light endoscopy.

Objective:To establish a three-dimensional spheroid expansion model of human glioma stem cells with spontaneous sphere forming and multilineage differentiation potential in vitro and investigated the contents of the proteins and lipids and their secondary components, so as to lay a foundation for further study of sphere metabolism. Methods:Human glioma stem cells GSC23 and SU3 were cultured in serum-free stem cell culture medium, respectively, and the cell spheres were harvested for about 2-3 weeks. After fixation in paraformaldehyde solution, dehydration, paraffin embedding, and sectioning, glioma-associated marker proteins were detected by immunohistochemical staining, and the protein and lipid and their secondary components contents in the spheroid tissues were analyzed by Raman imaging. One-way ANOVA was used to compare the protein, lipid and phenylalanine contents in the large sphere, medium sphere and small sphere groups.Results:Both stem cells were able to form stem cell expansion spheres resembling solid tumors within the culture dish. Immunohistochemical staining showed that the regular marker proteins of glioblastoma multiforme, CD133, nestin, epidermal growth factor receptor (EGFR), S100, Olig2, p53, Ki-67, glial fibrillary acidic protein (GFAP), vimentin, CXC chemokine receptor 4 (CXCR4), and CD34, were all expressed. Raman imaging revealed that the constructed expanded spheres of human glioma stem cells contained protein (2 930, 1 685 and 1 586 cm -1), lipid (2 845 and 1 444 cm -1), phenylalanine (1 003 cm -1) amide Ⅲ (1 250 cm -1), while there were no significant differences of protein, lipid and phenylalanine contents among the large sphere, medium sphere and small sphere groups ( P>0.05). Conclusions:We have successfully established an expanded spheroid model of human glioma stem cells in vitro, which not only exhibits the topographical characteristics and unlimited expansion ability of three-dimensional solid tumors, but also has the ability to stably store metabolically obligatory energy sources of tumor cells such as proteins and lipids, and is expected to serve as a promising tool for human glioma research in vitro.