Objective:The differentially expressed genes(DEGs)and activated signaling pathways in systemic sclerosis(SSc)were screened by bioinformatics methods,and Chinese medicines for potential treatment of SSc were explored,providing a new theoretical basis for the study of SSc and the screening of potential markers.Methods:The data sets GSE58095,GSE130953,GSE33463 and GSE58613 were selected from GEO database and divided into skin group and peripheral blood group according to the sample source.The DEGs of SSc patients was analyzed by R language,and the Wayne diagram was drawn to take the intersection of the two groups.Metascape was used for GO enrichment analysis and KEGG pathway enrichment analysis,and STRING and Cytoscape were used for protein interaction network analysis to find key pathways and hub genes.The core genes were mapped to the medical on-tology information retrieval platform,and related Chinese medicines for SSc treatment were screened.The effective components of Chi-nese medicines were obtained through TCMSP and HERB databases,and the target letters of active ingredients were obtained through swiss database.The"drug-active ingredient-target"network was constructed by Cytoscape.Results:Total 218 DEGs were identified from the skin group of patients with SSc,and 283 DEGs were screened from peripheral blood of patients with SSc.Among them,there were 7 DEGs co-upregulated in skin and peripheral blood,namely ISG15,LGALS3BP,BST2,C1QB,IFI27,CEACAM1 and FBP1.CAMK2N1 was up-regulated in skin but down-regulated in peripheral blood,ARG1 was down-regulated in skin but up-regulated in pe-ripheral blood.GO and KEGG analysis of SSc DEGs showed that these genes were significantly enriched in inflammatory response,he-moglobin complex,immune receptor activity and extracellular matrix.The results of protein interaction network suggest that more than 10 genes such as COL1A1,CTGF12,IL1B,IFNG and JUN may be potential markers of SSc and core genes of therapeutic targets.The potential Chinese medicines screened for SSc treatment include ginseng,sanguisorba,convolvula,wolfberry,safflower,etc.The main components of these herbs were β-sitosterol,quercetin,kaempferol,stigmasterol,luteolin,sitosterol,Spinasterol,and the target were AKR1B1,AR,CYP1B1,XDH,etc.Conclusion:This study uses bioinformatics to screen out core genes that may be potential markers and therapeutic targets for SSc,which is expected to be a new target for the early diagnosis and mechanism research of SSc.Meanwhile,the mapped Chinese medicine and its effective components can provide ideas for the research and development of Chinese medicine compounds for the treatment of SSc.

Objective:The differentially expressed genes(DEGs)and activated signaling pathways in systemic sclerosis(SSc)were screened by bioinformatics methods,and Chinese medicines for potential treatment of SSc were explored,providing a new theoretical basis for the study of SSc and the screening of potential markers.Methods:The data sets GSE58095,GSE130953,GSE33463 and GSE58613 were selected from GEO database and divided into skin group and peripheral blood group according to the sample source.The DEGs of SSc patients was analyzed by R language,and the Wayne diagram was drawn to take the intersection of the two groups.Metascape was used for GO enrichment analysis and KEGG pathway enrichment analysis,and STRING and Cytoscape were used for protein interaction network analysis to find key pathways and hub genes.The core genes were mapped to the medical on-tology information retrieval platform,and related Chinese medicines for SSc treatment were screened.The effective components of Chi-nese medicines were obtained through TCMSP and HERB databases,and the target letters of active ingredients were obtained through swiss database.The"drug-active ingredient-target"network was constructed by Cytoscape.Results:Total 218 DEGs were identified from the skin group of patients with SSc,and 283 DEGs were screened from peripheral blood of patients with SSc.Among them,there were 7 DEGs co-upregulated in skin and peripheral blood,namely ISG15,LGALS3BP,BST2,C1QB,IFI27,CEACAM1 and FBP1.CAMK2N1 was up-regulated in skin but down-regulated in peripheral blood,ARG1 was down-regulated in skin but up-regulated in pe-ripheral blood.GO and KEGG analysis of SSc DEGs showed that these genes were significantly enriched in inflammatory response,he-moglobin complex,immune receptor activity and extracellular matrix.The results of protein interaction network suggest that more than 10 genes such as COL1A1,CTGF12,IL1B,IFNG and JUN may be potential markers of SSc and core genes of therapeutic targets.The potential Chinese medicines screened for SSc treatment include ginseng,sanguisorba,convolvula,wolfberry,safflower,etc.The main components of these herbs were β-sitosterol,quercetin,kaempferol,stigmasterol,luteolin,sitosterol,Spinasterol,and the target were AKR1B1,AR,CYP1B1,XDH,etc.Conclusion:This study uses bioinformatics to screen out core genes that may be potential markers and therapeutic targets for SSc,which is expected to be a new target for the early diagnosis and mechanism research of SSc.Meanwhile,the mapped Chinese medicine and its effective components can provide ideas for the research and development of Chinese medicine compounds for the treatment of SSc.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Background/Aims:  Rituximab is known to be associated with high hepatitis B virus (HBV) reactivation rate in patients with resolved HBV infection and hematologic malignancy. However, data regarding HBV reactivation (HBVr) in rheumatic patients receiving rituximab is limited. To assess the HBVr rate in hepatitis B surface antigen (HBsAg)-negative patients receiving rituximab for autoimmune diseases in a large real-world cohort. Methods:  From March 2006 to December 2019, 900 patients with negative HBsAg receiving at least one cycle of rituximab for autoimmune diseases in a tertiary medical center in Taiwan were retrospectively reviewed. Clinical outcome and factors associated with HBVr were analyzed. Results: After a median follow-up period of 3.3 years, 21 patients developed HBVr, among whom 17 patients were positive for hepatitis B core antibody (anti-HBc) and four were negative. Thirteen patients had clinical hepatitis flare, while eight patients had HBsAg seroreversion without hepatitis. Old age, anti-HBc positivity, undetectable serum hepatitis B surface antibody level at rituximab initiation and a higher average rituximab dose were associated with a higher HBVr rate. There was no significant difference in the HBVr risk between rheumatoid arthritis and other autoimmune diseases. Among anti-HBc-negative patients, subjects without HBV vaccination at birth had an increased risk of HBVr (4/368, 1.1%) compared with those who received vaccination (0/126, 0%). Conclusions In HBV endemic areas where occult HBV is prevalent, anti-HBc-negative patients, may still be at risk for HBVr after rituximab exposure. HBVr may still be considered in HBsAgnegative patients developing abnormal liver function after rituximab exposure, even in patients with negative anti-HBc.

[Abstract] Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’ s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP

Tumor metastasis is an important cause of tumor treatment failure. Its molecular mechanism is closely related to tumor cells remodeling immune cells and immunosuppressive microenvironment, so as to create a suitable soil for tumor cell invasion and growth. "Huoxue Huayu" is one of the important therapeutic principles in cancer treatment, but the influence of Huoxue drugs on tumor metastasis has been controversial in clinical application. In this paper, we systematically summarized the comparative study of Huoxue drugs and Yiqi Huoxue drugs in tumor metastasis in recent years, and discussed the differences of molecular mechanisms of Huoxue drugs and Yiqi Huoxue drugs in anti-tumor metastasis from the perspective of immune remodeling, so as to provide scientific basis for clinical rational application of Huoxue drugs and Yiqi Huoxue drugs.

Objective: Cytoreductive surgery followed by adjuvant chemotherapy is a standard frontline treatment for epithelial ovarian cancer (EOC). We aimed to develop an ovarian cancer risk score (OVRS) based on the expression of 10 ovarian-cancer-related genes to predict the chemoresistance, and outcomes of EOC patients. Methods: We designed a case-control study with total 149 EOC women including 75 chemosensitives and 74 chemoresistants. Gene expression was measured using the quantitative real-time polymerase chain reaction. We tested for correlation between the OVRS and chemosensitivity or chemoresistance, disease-free survival (DFS), and overall survival (OS), and validated the OVRS by analyzing patients from the TCGA database. Results: The chemosensitive group had lower OVRS than the chemoresistant group (5 vs.15, p≤0.001, Mann-Whitney U test). Patients with disease relapse (13 vs. 5, p<0.001, MannWhitney U test) or disease-related death (13.5 vs. 6, p<0.001) had higher OVRS than those without. OVRS ≥10 (hazard ratio=3.29; 95% confidence interval=1.94–5.58; p<0.001) was the only predictor for chemoresistance in multivariate analysis. The median DFS (5 months vs. 24 months) and OS (39 months vs. >60 months) of patients with OVRS ≥10 were significantly shorter than those of patients with OVRS <9). The high OVRS group also had significantly shorter median OS than the low OVRS group in 255 patients in the TCGA database (39 vs. 49 months, p=0.046). Conclusions Specific genes panel can be clinically applied in predicting the chemoresistance and outcome, and decision-making of epithelial ovarian cancer.

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load