BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Objective:To retrospectively analyze the changes in the proportion of refined lymphocyte subsets in peripheral blood of patients with Graves disease (GD), and their correlation with the clinical characteristics and efficacy of GD, and to explore the immunological pathogenesis of Graves disease for seeking new therapeutic targets.Methods:A total of 97 newly diagnosed GD patients (GD group), 27 patients after treatment (treatment group), and 31 healthy individuals (control group) who visited the Fifth Medical Center of the PLA General Hospital from 2018 to 2021 were included in this study. The data of refined lymphocyte subsets, thyroid function, blood routine and clinical treatment of the three groups were compared and analyzed. The t-test and rank sum test were used to compare the proportions of lymphocyte subsets among different groups, and Pearson correlation analysis was used to analyze the correlation between the proportions of lymphocyte subsets and thyroid function indicators.Results:The proportion of B cells in GD group was higher than that in the control group [16.2%(11.8%, 21.8%) vs 10.2%(8.1%,13.6%)], while the proportion of natural killer (NK) cells was lower [9.4%(4.9%, 13.6%) vs 14.6%(12.1%,18.8%)], and the differences were statistically significant ( P<0.05). Abnormal T cell differentiation: the proportions of functional cells, including activated T cells, memory T cells, clustering antigen(CD)4+memory T cells, Th1 cells, and Tc1 cells, were lower than that in the control group [3.2%(2.1%, 5.7%) vs 5.8%(3.0%, 9.3%), P<0.05; 36.7% (29.9%, 48.1%) vs 48.0%(39.2%,57.7%), P<0.05; 23.1%(17.4%, 30.1%) vs 28.9%(23.3%,34.6%), P<0.05; 16.4% (11.8%, 23.6%) vs 24.3%(16.9%,28.5%), P<0.05; 28.5% (14.7%, 39.2%) vs 46.3%(21.6%,69.2%), P<0.05]. The proportion of activated T cells in the treatment group was higher than that in the GD group [6.5% (4.6%, 13.6%) vs 3.2% (2.1%, 5.7%), P<0.05]. The total triiodothyronine results showed positive correlations with B cells ( r=0.356, P<0.01) and negative correlations with NK cells ( r=?0.416, P<0.01), while the total thyroxine values showed negative correlations with NK cells and activated T cells ( r=?0.318,?0.335; P<0.01). Thyroid stimulating hormone and CD8+initial T cells were positively correlated ( r=0.382, P<0.01). The proportion of B cells, cytotoxic T cells and suppressor T cells in CD8+cells of patients with complications [such as Graves orbitopathy (GO), thyroid toxic cardiomyopathy, etc.] was significantly different from that of the simple GD patients [18.3% (14.1%, 27.1%) vs 14.6% (10.8%, 21.4%), Z=2.54, P<0.05; 73.4%(65.6%,83.6%)vs 65.0%(50.3%,79.3%), Z=2.93, P<0.05; 26.6%(16.4%, 37.5%)vs 35.0%(20.7%,49.7%), Z=?2.74, P<0.05]. The proportion of suppressor T cells in GO patients was lower than that in non-GO patients [6.1% (3.4%, 8.1%) vs 8.5% (4.9%, 13.6%), Z=?3.20 P<0.05]. Conclusion:There are significant alterations in the circulating immune cells of GD patients, suggesting that immunological abnormalities play a crucial role in the onset and progression of the disease.

Objective:To investigate and summarize the chest CT imaging features of patients with novel coronavirus pneumonia (COVID-19), bacterial pneumonia and other viral pneumonia.Methods:Chest CT data of 102 patients with pulmonary infection due to different etiologies were retrospectively analyzed, including 36 patients with COVID-19 admitted to Hainan Provincial People's Hospital and the Second Affiliated Hospital of Hainan Medical University from December 2019 to March 2020, 16 patients with other viral pneumonia admitted to Hainan Provincial People's Hospital from January 2018 to February 2020, and 50 patients with bacterial pneumonia admitted to Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from April 2018 to May 2020. Two senior radiologists and two senior intensive care physicians were participated to evaluated the extent of lesions involvement and imaging features of the first chest CT after the onset of the disease.Results:Bilateral pulmonary lesions were more common in patients with COVID-19 and other viral pneumonia, and the incidence was significantly higher than that of bacterial pneumonia (91.6%, 75.0% vs. 26.0%, P < 0.05). Compared with other viral pneumonia and COVID-19, bacterial pneumonia was mainly characterized by single-lung and multi-lobed lesion (62.0% vs. 18.8%, 5.6%, P < 0.05), accompanied by pleural effusion and lymph node enlargement. The proportion of ground-glass opacity in the lung tissues of patients with COVID-19 was 97.2%, that of patients with other viral pneumonia was 56.2%, and that of patients with bacterial pneumonia was only 2.0% ( P < 0.05). The incidence rate of lung tissue consolidation (25.0%, 12.5%), air bronchial sign (13.9%, 6.2%) and pleural effusion (16.7%, 37.5%) in patients with COVID-19 and other viral pneumonia were significantly lower than those in patients with bacterial pneumonia (62.0%, 32.0%, 60.0%, all P < 0.05), paving stone sign (22.2%, 37.5%), fine mesh sign (38.9%, 31.2%), halo sign(11.1%, 25.0%), ground-glass opacity with interlobular septal thickening (30.6%, 37.5%), bilateral patchy pattern/rope shadow (80.6%, 50.0%) etc. were significantly higher than those of bacterial pneumonia (2.0%, 4.0%, 2.0%, 0%, 22.0%, all P < 0.05). The incidence of local patchy shadow in patients with COVID-19 was only 8.3%, significantly lower than that in patients with other viral pneumonia and bacterial pneumonia (8.3% vs. 68.8%, 50.0%, P < 0.05). There was no significant difference in the incidence of peripheral vascular shadow thickening in patients with COVID-19, other viral pneumonia and bacterial pneumonia (27.8%, 12.5%, 30.0%, P > 0.05). Conclusions:The probability of ground-glass opacity, paving stone and grid shadow in chest CT of patients with COVID-19 was significantly higher than those of bacterial pneumonia, and it was more common in the lower lungs and lateral dorsal segment. In other patients with viral pneumonia, ground-glass opacity was distributed in both upper and lower lungs. Bacterial pneumonia is usually characterized by single lung consolidation, distributed in lobules or large lobes and accompanied by pleural effusion.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Objective:To investigate the association between metabolically healthy obesity(MHO) and atherosclerosis risk among Chinese community population aged 40 or older.Methods:A total of 9 525 participants without cardiovascular diseases (3 621 men and 5 904 women) from Jiading community in Shanghai were enrolled to complete questionnaires, undergo extensive physical examination including brachial-ankle pulse wave velocity (baPWV) and blood pressure (BP) assessment, and laboratory screening. According to body mass index (BMI) and metabolic status, these participants were categorized into 4 groups including metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), MHO, and metabolically unhealthy obese (MUO). High baPWV was defined as baPWV>1 400 mm/s, and high pulse pressure (PP) was defined as PP above fourth quartile of the population. Multivariate logistic regression model was conducted to explore the relationship between MHO and high baPWV as well as high PP after adjusting for confounders. Results:After multivariable adjustment, such as sex, age, current smoking, current drinking, and education, logistic regression analysis showed that MHO was significantly correlated with high baPWV ( OR=1.18, 95% CI 1.02-1.37) and high PP ( OR=1.72, 95% CI 1.43-2.08) in comparison with MHNO. Otherwise, both MUNO and MUO subjects were at higher risk for suffering from high baPWV (MUNO: OR=3.02, 95% CI 2.60-3.50; MUO: OR=3.26, 95% CI 2.87-3.70) and high PP (MUNO: OR=2.56, 95% CI 2.17-3.02; MUO: OR=3.49, 95% CI 3.01-4.06). Conclusion:On the basis of Chinese community population, there was a pronounced correlation between the MHO phenotype and the increased risk of developing atherosclerosis.

1,2,3-trichloropropane (TCP) is an industrially synthesized aliphatic chlorinated hydrocarbon and an intermediate product in the industrial production of epichlorohydrin, which can be used as a precursor for the manufacture of soil fumigant and organic solvents. Due to its biological toxicity, environmental persistence and strong environmental migration ability, 1,2,3-TCP is listed as an emerging organochlorine pollutant in the environment and regulated by many international organizations. Currently, the degradation of 1,2,3-TCP and the remediation of 1,2,3-TCP-contaminated sites receive great attention, but the degradation mechanism of 1,2,3-TCP has not been summarized in depth. This article discussed the origin of 1,2,3-TCP, its environmental impact and ecological effects, and the physical and chemical degradation techniques. This was followed by summarizing the degradation mechanisms of 1,2,3-TCP (e.g., aerobic co-biodegradation, anaerobic biodegradation). Specially, the pathways and mechanisms of microbial biodegradation and transformation of 1,2,3-TCP in anoxic environments (e.g., groundwater) were thoroughly reviewed. The feasibility of using 1,2,3-TCP as an electron acceptor by organohalide-respiring bacteria under anoxic conditions was predicted based on thermodynamic analysis. Last but not least, in situ bioremediation of 1,2,3-TCP contaminated sites was summarized, and prospects for future research were discussed.
Biodegradation, Environmental ; Environmental Restoration and Remediation ; Hydrocarbons, Chlorinated ; Propane/analogs & derivatives* ; Technology

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.

? With the acceleration of the aging process, the problem of aged frailty has become prominent, which has aroused widespread concern. Actively and accurately assessing, identifying and intervening the weakened elderly are of great significance for improving the quality of life of the elderly, reducing adverse outcomes and predicting disability. The development and application of various frailty assessment tools in the world are getting matured gradually. Domestic enterprises have begun to use or sinicize foreign tools, and build local assessment tools. This paper reviews the application and adaptation of various assessment tools for frailty in China, and the research progress and prospects of localized assessment tools. The purpose is to provide reference for the assessment of frailty in China, hence to guide the follow-up intervention research.