Ubiquitin-specific proteases (USPs) regulate the deconjugation of ubiquitin tag from substrate proteins. Dysregulation of USPs has been linked to many diseases. Despite extensive efforts by academia and industry,high quality chemical molecules targeting the USPs family of ubiquitin enzymes are still scarce. In this commentary,I propose the criteria of a high quality chemical probe and the strategies to target USPs.

Objective:The purpose of this study is to evaluate the frequency of MDSCs in peripheral blood of hepatocellular carcinoma patients and to investigate the clinical significance of change of MDSCs in the peripheral blood and provide new ways for e-valuating immune state and prognosis of hepatocellular carcinoma patients.Methods: Blood samples were obtained from 62 patients with HCC and 20 healthy donors.The phenotype of CD3,CD4,CD33,HLA-DR and Th1,Th2 immune subsets in peripheral blood of each group were observed by FCM methods.Results:There were statically different frequencies in the peripheral blood between hepato-cellular carcinoma and healthy control group,which the proportion of total CD3+T lymphocytes and CD3+CD4+T cells were lower and the proportion of CD33+HLA-DR-MDSCs was higher in hepatocellular carcinoma patients.( P<0.05 ).The increase of percentage of MDSCs was greater in patients at Stage C and D than in patients at stage A and B.Conclusion:The Th1/Th2 ratio in the PBMC were of imbalance and MDSCs was significantly increased in peripheral blood of hepatocellular carcinoma patients.The increase of MDSCs was significantly correlated with clinical stage.CD33+HLA-DR-MDSCs may play an important role in prediction in prognosis and tumor immune status of hepatocellular carcinoma.

Objective To study the effects of tonifying kidney therapy on pathology in chronic hepatitis B virus carriers.MethodsWith the multi-center, randomized, double-blinded and placebo-controlled methods, 600 cases of chronic hepatitis B virus carriers were divided intoBushen Qingtou group,Bushen Jianpi group and control group, 200 cases in each group, and were treated withBushen Qingtou prescription,Bushen Jianpi prescription and placebo prescription respectively for 52 weeks. The pathological changes of the liver biopsy were observed by liver biopsy examination before and after treatment. Inflammatory active degree and fibrosis were scored with Knodell HAI and Ishak.Results The number of decreasing more than 2 points on Knodell HAI inBushen Qingtou group,Bushen Jianpi group and control group was 21, 18, and 6 respectively (P<0.05); the number of increasing more than 2 points on Knodell HAI in three groups was 3, 2, and 8 respectively (P<0.05). The curative effect ofBushen Qingtou prescription,Bushen Jianpi prescription were significantly obviously better than control group, without statistical significnce between the two treatment groups (P>0.05). The number of decreasing more than 1 points on Ishak in Bushen Qingtou group,Bushen Jianpi group, and control group was 13, 12, and 9 respectively (P>0.05); the number of increasing more than 1 points on Ishak inBushen Qingtou group,Bushen Jianpi group and control group was 8, 3, and 11 respectively, with statistical significance betweenBushen Jianpi group and controlled group (P<0.01), without statistical significance betweenBushen Qingtou group and control group (P>0.05), which meantBushenJianpi prescription could prevent the deterioration of liver tissue fibrosis more significantly than placebo prescription did. ConclusionTonifying kidney therapy, includingBushen Qingtou prescription andBushen Jianpi prescription, can inhibit the inflammatory activity and slow down the fibrosis progression of the chronic HBV carriers.

Objective:To investigate the efficacy of modified surgery in the treatment of breast abscess and its effects on inflammatory reaction and pain-related factors.Methods:A total of 100 patients with breast abscess who were treated in Zhoushan Women and Children's Hospital from December 2019 to October 2022 were included in this study. They were divided into an observation group and a control group ( n = 50 per group) using the random number table. The control group received vacuum assisted rotary resection, while the observation group underwent modified surgery. Operation conditions, postoperative complications, and postoperative conditions were recorded in each group. Before and 24 hours after surgery, inflammatory reaction and pain-related factors were compared between the two groups. Results:There was no significant difference in operative time between the two groups ( P > 0.05). The intraoperative bleeding volume in the observation group was (23.14 ± 4.53) mL, which was significantly lower than (36.52 ± 7.18) mL in the control group ( t = 11.14, P < 0.001). The incidence of complications in the observation group was 6.00% (3/50), which was significantly lower than 20% (10/50) in the control group ( χ2 = 4.33, P < 0.05). The observation group had significantly lower postoperative visual analogue scale score [(2.42 ± 0.78) points], fewer dressing changes [(5.26 ± 1.34) times], and lower scar degree [(6.82 ± 1.27) mm] compared with the control group [(3.56 ± 0.89) points, (7.43 ± 1.62) times, (9.12 ± 1.54) mm, t = 6.81, 7.30, 8.15, all P < 0.001]. At 24 hours after surgery, high-sensitivity C-reactive protein, interleukin-1 β, and tumor necrosis factor-α in the observation group were (14.52 ± 3.37) mg/L, (182.13 ± 23.32) ng/L, and (20.08 ± 2.89) ng/L, respectively, which were significantly lower than (29.94 ± 5.45) mg/L, (231.24 ± 16.56) ng/L, and (29.98 ± 4.36) ng/L in the control group ( t = 17.02, 12.14, 13.38, all P < 0.001). At 24 hours after surgery, prostaglandin E 2 and substance P in the observation group were (97.14 ± 18.78) ng/L and (175.18 ± 24.37) μg/L respectively, which were significantly lower than (148.65 ± 20.06) ng/L and (265.41 ± 27.86) μg/L in the control group ( t = 13.26, 17.24, both P < 0.001). Conclusion:The modified surgical treatment for breast abscess shows significant effects with fewer complications and minimal impact on inflammatory response, effectively inhibiting the release of pain-related factors.

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of the low molecular weight polypeptide (LMP) gene with chronic hepatitis C virus (HCV) infection among ethnic Han population from Yunnan.

METHODSA total of 427 patients with chronic HCV infection and 412 healthy controls were recruited. SNPs rs1351383, rs17587 and rs2127675 from the promoter region of the LMP2 gene and rs2071543 from the promoter region of the LPM7 gene were genotyped using a TaqMan probe. The haplotypes were constructed. Frequencies of various alleles, genotypes and haplotypes of the selected SNPs were calculated, and their association with chronic HCV infection was analyzed.

RESULTSThe frequencies of rs1351383 and rs2127675 alleles of the LMP2 gene, as well as the A-G-A and C-G-G haplotypes of the rs1351383/rs17587/rs2127675 loci, had differed significantly between the two groups (P<0.05).

CONCLUSIONThe C allele of the rs1351383 locus and G allele of the rs2217675 locus of the LMP2 gene may be susceptible factors for chronic HCV infection among ethnic Han people from Yunnan. The A-G-A haplotype of the rs1351383/rs17587/rs2127675 loci may confer a protective effect, while the C-G-G haplotype may be a susceptible factor for chronic HCV infection in this population.

Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; genetics ; Hepatitis C ; genetics ; Humans ; Male ; Peptides ; genetics ; Polymorphism, Single Nucleotide ; genetics

Chronic HBV infection is an important phase in the natural history of HBV, but there are still controversies over the treatment of this stage. Traditional Chinese medicine has had unique advantages in the prevention and treatment of viral hepatitis since ancient times and plays an important role in prevention and treatment of viral hepatitis in China. Based on the pathological process of chronic HBV infection, the team of Department of Hepatology in Shenzhen Hospital of Traditional Chinese Medicine believes that the core pathogenesis of chronic HBV infection is "kidney deficiency and epidemic toxin lurking in liver blood" and established kidney-tonifying therapy for the treatment of chronic HBV infection. Under the support of the project of Prevention and Treatment of Major Infectious Diseases such as AIDS and Viral Hepatitis in The Eleventh Five Year Plan, The Twelfth Five Year Plan, and The Thirteenth Five Year Plan, the team has conducted studies on the regularity of syndromes and a series of clinical studies and investigated the clinical efficacy of kidney-tonifying therapy through multicenter, randomized, double-blind, placebo-controlled studies, thereby exploring the application and mechanism of traditional Chinese medicine treatment in patients with chronic HBV infection. However, there are still difficulties in the pathogenesis and treatment of chronic HBV infection, and with the inheritance, innovation, and modernization of traditional Chinese medicine, it is believed that traditional Chinese medicine can provide reliable regimens for the treatment of chronic HBV infection.

Objective: To detect and analyze the differential expression profile of long non-coding RNA (lncRNA) in aggressive periodontitis (AgP) and healthy gingival tissues, in order to explore the role of lncRNA in AgP. Methods: After the informed consents were obtained, gingival tissues from AgP patients (n=40) and healthy volunteers (n=40) were collected in Department of Periodontology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (from Mar. 2012 to Aug. 2012) and Department of Periodontology, Hospital of Stomatology, Tianjin Medical University (from Oct. 2016 to Apr. 2017). The differential expression of lncRNA of tissues from AgP patients (n=20) and healthy volunteers (n=20) were examined via microarray assay. Bioinformatics was applied to analyze the expression data of lncRNA and correlative mRNA. Two lncRNAs (lncRNA-TNFRSF13C and lncRNA-API5) were chosen to verify the microarray results by using real time quantitative polymerase chain reaction (PCR) in the other gingival tissues. Results: Compared with the result of healthy gingival tissues, totally 8 632 lncRNAs were differentially expressed in tissues from AgP patients. From these data, 1 986 lncRNAs were significantly upregulated while 6 646 lncRNAs were downregulated, amongst which 48 lncRNAs were upregulated (>10 times) (P<0.05), 14 lncRNAs were downregulated (>10 times) (P<0.05). Furthermore, totally 5 519 correlative mRNAs were differentially expressed, amongst which 1 676 mRNAs were upregulated (≥2 times, P<0.05) and 3 843 mRNAs were downregulated≤0.5 (P<0.05). The selected lncRNA-TNFRSF13C and lncRNA-API5 were up-regulated in AgP (P<0.05), which confirmed the results of microarray. From bioinformatics, differential expression lncRNAs were in association with many signal pathways including toll-like receptor signaling pathway, cell cycle and apoptosis pathway, and tumor necrosis factor receptor superfamily pathway. Conclusions LncRNA may be involved in the pathogenesis of AgP through various pathways, which need to be further explored.

Objective To understand the situation and the influencing factors of life quality in diabetic patients in Shanghai， and to develop effective intervention measures. Methods A total of 212 diabetic patients in Baoshan District， Shanghai were selected as the research objects. Diabetes specific quality of life scale （DSQL） was used to investigate the basic situation and quality of life of patients. Combined with biochemical detection indexes and questionnaire survey， data were analyzed by variance analysis and multiple linear stepwise regression analysis. Blood glucose level was assessed according to the 1999 WHO diagnostic criteria for type 2 diabetes. Results The overall quality of life score in the patients was 4.31±7.82， which was higher than the domestic norm. The best quality of life was in the dimension of physiological function with the score of 1.84±6.00， which was lower than the domestic norm. The next was the dimension of social relationship， and the worst was the dimension of treatment. The single factor analysis and multivariate analysis identified the following influence factors of quality of life in the patients： family history， educational level， exercise habit， blood glucose control and diet control. There was a negative correlation with educational level and blood glucose control， and a positive correlation with diet control. Conclusion The quality of life in the middle-aged diabetic patients was affected by the education level， blood glucose control and diet control. We suggest to strengthen the community management， health education， and improve the living habits.

Improving the reproducibility of biomedical research results is a major challenge.Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org). The fourth part of the article includes the items 1-5 of ARRIVE 2.0 Recommended 11 section, which covers "Abstract" "Background" "Objectives" "Ethical statement" and "Housing and husbandry". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China.

Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at https://arriveguidelines.org). This section includes the items 6-11 of Recommended 11 section, covering "Animal Care and Monitoring", "Interpretation/Scientific Implications", "Generalisability/Translation", "Protocol Registration", "Data Access" and "Declaration of Interests". Its aim is to promote a comprehensive understanding and use of the ARRIVE 2.0 guidelines among domestic researchers, to enhance the standardization of experimental animal research and reporting, and to promote high-quality development of experimental animal sciences and comparative medicine research in China.