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OBJECTIVE To evaluate the therapeutic effects of Fuzheng jiedu therapy of traditional Chinese medicine (TCM) in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS Randomized controlled trials on the treatment of NSCLC with Fuzheng jiedu therapy of TCM+conventional chemotherapy (trial group) versus conventional chemotherapy (control group) were collected by searching PubMed, CBM, China Periodicals Full Text Database, VIP and Wanfang data service platform during the inception-Oct.Two researchers respectively screened the literature and extracted data, evaluated the quality according to Cochrane 5.4 tool, and used RevMan 5.3 software to perform meta-analysis on the data. RESULTS Nineteen pieces of literature were finally included in the study; meta-analysis showed disease control rate [RR=1.15, 95%CI (1.07, 1.23), P= 0.000 1], objective remission rate [RR=1.47, 95%CI (1.29, 1.67), P<0.000 01], Karnofsky performance scores [WMD=6.11, 95%CI (2.97, 9.25), P=0.000 1], the levels of immune function indexes (CD3+, CD4+, CD4+/CD8+), inflammatory factor indicators [interleukin-2 (IL-2), interferon-γ (IFN-γ)] and lung function indexes (forced vital capacity, forced expiratory volume in the first second and peak expiratory flow) in the trial group were higher than control group (P<0.05). The symptomatic score [WMD=-2.83, 95%CI (-4.42, -1.24), P=0.000 5], the levels of IL-6 [WMD=-11.20, 95%CI (-21.75,-0.64), P= 0.04], and the incidence of ADRs (myelosuppression, hepatic and renal injury, gastrointestinal reactions in trial group were all lower than control group (P<0.05). In addition, the levels of natural killer cells in the trial group were higher than the control group, but the results were not statistically significant (P>0.05). CONCLUSIONS Compared with conventional chemotherapy, Fuzheng jiedu therapy of TCM combined with conventional chemotherapy has obvious advantages in increasing the disease control rate and objective remission rate, improving the quality of life, promoting TCM syndrome and inflammatory status,enhancing immunity and lung function, and decreasing the incidence of ADRs in NSCLC patients.
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Background The staff in centers for disease control and prevention (CDC) were at a great risk for psychological distress when they were faced with outbreak-related prevention and control work and routine tasks during the COVID-19 period. Psychological resilience and burnout are two key influencing factors on psychological distress. Objective To explore the status and mechanisms of psychological resilience, burnout, and psychological distress among CDC staff. Methods From September to October 2022, a cross-sectional survey was conducted in all CDC staff in Beijing, and 2228 CDC staff from 17 units (including 1 municipality-level CDC and 16 district-level CDCs) participated the questionnaire survey. The basic information questionnaire, Connor-Davidson Resilience Scale (CD-RISC-10) Chinese version, Maslach Burnout Inventory-General Survey (MBI-GS) Chinese version, and the 10-item Kessler Psychological Distress Scale (Kessler10) Chinese version were selected in our study. Mann-Whitney U test or Kruskal-Wallis H test was used to analyze the differences in the scores of psychological resilience, burnout, and psychological distress by demographic and sociological characteristics. The correlations among the three elements were analyzed by Spearman correlation analysis. Potential influencing factors of psychological distress of the CDC staff were evaluated by multiple linear regression. A potential mediating effect of psychological resilience-burnout-psychological distress was analyzed by the mediation package of R 4.2.0, and validated by Bootstrap method. Results Of 2228 questionnaires distributed, 2022 valid questionnaires were collected, and the recovery rate was 90.75%. The median (P25, P75) psychological distress score of CDC staff was 13.00 (8.00, 24.00), and the number of participants with psychological distress levels of 1, 2, 3, and 4 was 358 (17.71%), 546 (27.00%), 362 (17.90%), and 756 (37.39%), respectively. The median (P25, P75) psychological resilience score was 24.00 (20.00, 30.00) and the median (P25, P75) burnout score was 38.00 (25.00, 50.00). The results of the multiple linear regression showed that psychological resilience, burnout, caring for the elderly, having a chronic disease, and monthly income had independent influences on psychological distress (P<0.05), and emotional exhaustion, cynicism, and reduced personal accomplishment (reversed) in the case of burnout had a great effect on psychological distress (P<0.05). After controlling general demographic characteristic variables, total burnout score exerted a partial mediation effect on the relationship between psychological resilience and psychological distress, with a mediation effect value of −0.439 (95%CI: −0.483, −0.397), and a total mediation effect contribution rate of 60.89%. The two dimensions of burnout (emotional exhaustion and cynicism) played a partial mediating role between psychological resilience and psychological distress, with mediating effect contribution rates of 42.44% and 41.41%, respectively. Conclusion Psychological distress among CDC staff in Beijing was prominent during COVID-19. Psychological resilience can act directly on psychological distress or indirectly on psychological distress through burnout. Both emotional exhaustion and cynicism dimensions of burnout have a partial mediating role between psychological resilience and psychological distress. Increasing psychological resilience and decreasing burnout may reduce the occurrence of psychological distress.
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Objective Screening of modified Foshou San to improve cerebral ischemia,determine the best prescription composition and the proper dose.Methods Using data mining method,the traditional Chinese medicine for hypertensive intracerebral hemorrhage(HICH)were screened,and cluster analysis was carried out to obtain Jiawei Foshou San combinations;According to the mixed uniform design U14(42×33×22),the auricular artery dilatation experiment and acute cerebral ischemia induced by saturated magnesium chloride in mice were used to observe the auricular artery dilatation index and survival time of mice,and the pharmacological effects of each prescription to improve cerebral ischemia were evaluated.On the basis of visual analysis of pharmacodynamics,stepwise multiple regression analysis was carried out,and the regression equation was used to calculate the best prescription composition and dose of Jiawei Foshou San.The optimized prescription was verified by acute cerebral ischemia experiment in mice.Results A total of 51 prescriptions that may be used for the treatment of HICH were selected by data mining,including 103 Chinese herbs,with a total frequency of 535 times.The results of mixed uniform design U14(42×33×22)test showed that the auricular artery index of mice in each prescription group of Jiawei Foshou San increased to varying degrees.The differences between prescription 4,8,12 and 13 were significant(P<0.05),and the differences between prescription 3,7,9,11 and 14 were extremely significant(P<0.01).The survival time of acute cerebral ischemia in mice was prolonged to varying degrees in each group of Jiawei Foshou San,and the difference between prescription 2-14 groups and the blank group was statistically significant(P<0.01).The prescription of the new Jiawei Foshou San was determined as 60 g of Astragalus membranaceus,60 g of Angelica sinensis,24 g of Ligusticum chuanxiong,15 g of Paeonia lactiflora and 9 g of Dilong from the intuitive analysis.The validation results showed that the high and middle dosage of the new Jiawei Foshou San could significantly prolong the breathing time,increase the number of breaths,and prolong the time of normal pressure hypoxia tolerance in mice with acute cerebral ischemia(P<0.01,P<0.05).Conclusion Using mixed uniform design combined with improving cerebral ischemia effect index can determine the best prescription composition and the best dose of Jiawei Foshou San,and the effect of improving cerebral ischemia is certain.
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Primary aldosteronism(PA) is a common cause of secondary hypertension, with adrenal vein sampling(AVS)being the gold standard for etiological typing diagnosis. This retrospective study analyzed data from patients diagnosed with PA who underwent AVS or unilateral adrenalectomy at Nanjing Drum Tower Hospital′s Endocrinology Department from July 2018 to August 2021. Using multivariate logistic regression analysis, factors associated with unilateral aldosterone hypersecretion were identified. Based on these factors, a predictive model for diagnosing unilateral primary aldosteronism(UPA)was established: age <40 years, plasma aldosterone concentration(PAC)>15 ng/dL, adrenal CT indicating an unilateral typical adenoma, and spontaneous hypokalemia. This predictive model could help 14% of PA patients avoid unnecessary AVS procedures.
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Objective:To identify the clinical and pathological characteristics of adrenocortical carcinoma(ACC) with hypercortisolism and analyze the prognostic factors.Methods:Clinical data of ACC patients between January 2003 and December 2022 from Nanjing Drum Tower Hospital were collected retrospectively. Clinical and pathological characteristics were compared between ACC patients with hypercortisolism and nonfunctional ACCs. Kaplan-Meier method was used for survival analyses and Cox regression models were performed to analyze prognostic factors for ACC patients.Results:In 61 cases of ACC patients, the average age was (49.33±16.32) years. After a median follow-up of 77 months(95% CI 47.49-106.51 months), median overall survival and progression-free survival were 50 months(95% CI 20.44-79.56 months) and 29 months(95% CI 22.87-35.13 months), respectively. Among 36 patients with complete endocrinologic evaluations, 19(52.77%) were diagnosed with hypercortisolism. Compared with nonfunctional ACC, patients with hypercortisolism had more hypokalemia(42.11% vs 6.25%, P=0.022), capsular invasion(68.42% vs 25.00%, P=0.018), and distant metastases(73.68% vs 25.00%, P=0.007). Median overall survival and progression-free survival were significantly shorter than nonfunctional ACC(overall survival: 39 months vs 67 months, P=0.009; progression-free survival: 30 months vs 51 months, P=0.040) as well. Multivariate Cox regression analyses indicated that Ki67 index( HR=1.078, P=0.024) was an independent risk factor for overall survival. Hypercortisolism( HR=71.112, P=0.006), Ki67 index( HR=1.345, P=0.003), adjuvant therapy( HR=176.652, P=0.012), and operation( HR=0.020, P=0.003), were associated with disease progression. Conclusion:ACC accompanied by hypercortisolism is more prone to invasion and distant metastasis, resulting in shorter survival. Hypercortisolism is an independent prognostic factor for ACC patients.
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ObjectiveTo investigate the psychological tendency characteristics of vocational selection for college students with disabilities. MethodsA total of 155 college students with disabilities in four colleges and universities were investigated using Psychological Tendencies of Vocational Selection for College Students with Disabilities (PTVS). ResultsA total of 151 questionnaires returned finally. The principal component analysis extracted four factors, namely profession, capability, parental occupation and parental education, with a cumulative contribution rate of 74.98%. Clustering analysis clustered three categories, namely vocational capability and parental education dominated, profession and capability dominated, and profession dominated, which accounted for 20.5%, 31.1% and 48.3%, respectively. There were significant differences among the three categories in the dimensions of personal cognition, employment tendency, employment affect and employment will of PTVS (F > 7.021, P < 0.01). ConclusionThere are four dimensions of PTVS, i.e., the dimension of profession, the dimension of capability, the dimension of parental occupation and the dimension of parental education; while the PTVS could be divided into three categories, i.e., vocational capability and parental education dominated, profession and capability dominated, and profession dominated. For college students with disabilities, accurate career counseling and guidance should be provided according to the psychological structure of vocational selection and PTVS.
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Objective:To identify the risk factors for simple congenital ptosis.Methods:A case-control study was performed.A total of 106 children diagnosed with simple congenital ptosis at the Second Affiliated Hospital of Zhejiang University School of Medicine from October 2018 to January 2021 were recruited as a case group, and 106 sex-matched children without congenital abnormalities were enrolled as a control group at the same period.Ophthalmic examinations, including interpalpebral fissure height and margin reex distance 1, were performed on all participants.A questionnaire survey was administered to their mothers.The questionnaire included demographic information, prenatal maternal diseases, medical treatments and environmental exposures during pregnancy.Univariate analysis was used to compare the differences in variables between the case and control groups.Variables with P<0.20 were retained for multivariate logistic regression analysis to identify the risk factors for simple congenital ptosis.The goodness of fit of the model was evaluated by the Hosmer-Lemeshow test, and collinearity was assessed by the variance inflation factor (VIF). This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (No.2019-136). The method and purpose of the study were fully explained to the children's guardians and written informed consent was obtained. Results:Comparisons of gestational age <37 weeks, birth order ≥2, maternal age, antibiotic use in the first trimester, paternal smoking ≥half a pack per day, and prenatal maternal passive smoking between the two groups were all with P<0.20.Multivariate logistic regression analysis showed that gestational age <37 weeks (odds ratio [ OR]=4.58; 95% confidence interval [ CI]: 1.24-16.85), paternal smoking ≥half a pack per day ( OR=2.28; 95% CI: 1.22-4.28) and prenatal maternal passive smoking ( OR=3.13; 95% CI: 1.16-8.41) were risk factors for simple congenital ptosis.No significant collinearity was found among these identified factors (all VIF<5). Conclusions:Preterm birth, paternal smoking, and prenatal maternal passive smoking are risk factors for simple congenital ptosis.
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SARS-CoV-2, responsible for the COVID-19 pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of COVID-19 associated cell injury and immunopathogenesis processes, we investigated Hippo pathway dynamics in SARS-CoV-2 infection by utilizing COVID-19 lung samples, and human cell models based on pluripotent stem cell-derived cardiomyocytes (PSC-CMs) and human primary lung air-liquid interface (ALI) cultures. SARS-CoV-2 infection caused activation of the Hippo signaling pathway in COVID-19 lung and in vitro cultures. Both parental and Delta variant of concern (VOC) strains induced Hippo pathway. The chemical inhibition and gene knockdown of upstream kinases MST1/2 and LATS1 resulted in significantly enhanced SARS-CoV-2 replication, indicating antiviral roles. Verteporfin a pharmacological inhibitor of the Hippo pathway downstream transactivator, YAP, significantly reduced virus replication. These results delineate a direct antiviral role for Hippo signaling in SARS-CoV-2 infection and the potential for this pathway to be pharmacologically targeted to treat COVID-19.
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With the rapid development of immunotherapy, an increasing number of immune checkpoint inhibitors have been used in clinical settings. Immunotherapy provides a new treatment option for patients with advanced colorectal cancer metastasis. Studies have confirmed that patients with metastatic colorectal cancer with dMMR/MSI-H status are more sensitive to immunotherapy and have a more objective and sustained clinical response than their counterparts. Gut microbiome has been proved to play a certain regulatory role in tumor immunotherapy response, and some bacteria can affect the efficacy of immune checkpoint inhibitors through the immune system or metabolic function of the body. With the progress of the study, the gut microbiome is expected to become not only the predictive biomarkers of curative effect of colorectal cancer immunotherapy, but it can also be a key regulatory factor influencing the results of colorectal cancer immunotherapy. For future clinical treatment, the use of immune checkpoint inhibitors may benefit patients with advanced colorectal cancer.
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Objective:To explore the value of adrenocorticotrophic hormone (ACTH) stimulation in adrenal vein sampling (AVS) with its effect on the sampling success rate and lateralization determination.Methods:The clinical data of 54 patients with primary aldosteronism (PA) who underwent AVS in Nanjing Drum Tower Hospital from July 2018 to June 2020 were collected retrospectively. Blood samples from bilateral adrenal veins were collected simultaneously at baseline and after ACTH stimulation. The selectivity index (SI), lateralization index (LI), and relative aldosterone secretion index (RASI) were examined.Results:The concentration of serum cortisol level in left and right adrenal vein and peripheral vein increased significantly after ACTH stimulation ( P<0.001). SI of left adrenal vein increased from 18.00 (2.29, 20.29) to 34.76 (12.10, 46.86) , and the SI of right adrenal vein increased from 26.61(5.24, 31.85) to 28.40 (27.65, 56.05, P<0.001). The bilateral vein sampling success rate increased from 80%(43/54) to 93%(50/54). LI decreased from 2.85(1.78, 6.20) at baseline to 2.45(1.40, 6.10) after ACTH stimulation without significant difference( P>0.05). Eleven patients who identified unilateral secretion at baseline demonstrated bilateral after ACTH stimulation, and the RASI of these patients decreased from 0.50 (0.38, 1.25 ) to 0.37 (0.22, 0.84, P=0.019). Conclusion:ACTH stimulation significantly increased SI and the AVS success rate in patients with PA: ACTH stimulation decreased the relative aldosterone secretion in the dominant side of some patients with aldosterone producing adenoma, thus reduced the proportion of identified unilateral PA.
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Objective:To establish the quality standard for Sancao Anshen capsules. Methods:Valerian, Spica Prunellae, Radix Scutellariae and Rhizoma Coptidis were indentified by TLC. The content of rosmarinic acid was determined by HPLC. The column was Hypersil ODS2 C18 with mobile phase of acetonitrile-0. 1% trifluoroacetic acid(30:70,V/V) at a flow rate of 1. 0 ml·min-1 , the col-umn temperature was 25 ℃ ,the detection wavelength was 330 nm,and the sample size was 20 μl. Results: The characteristic spots could be detected by TLC with good reproducibility. The linear range of rosmarinic acid was 0.105-2.104 μg·ml-1(r=0.9993). The average recovery was 99. 5% and the RSD was 0. 80% (n=6). Conclusion:The developed method is simple and accurate, and suitable for the quality control of Sancao Anshen capsules.
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Objective To explore the early diagnosis and risk factors for judging prognosis of acute respiratory distress syndrome (ARDS),and to provide references for clinical intervention.Methods Using the method for prospective cohort study,clinical data were collected from 64 ARDS and 66 high-risk ARDS patients in Department of Respiratory Diseases of Xinqiao Hospital from January 2013 to March 2016.They included patients' demographic data,Acute Physiology and Chronic Health Evaluation system Ⅱ (APACHE Ⅱ) score,oxygenation index,blood routine test,coagulation function and inflammatory markers (procalcitonin,C-reaction protein,tumor necrosis factor and interleukin-6) within 24h and the state of survival or death of the 24th day.Risk factors for predicting progression of the high-risk ARDS patients into ARDS patients and influencing the prognosis of the ARDS patients were analyzed by using logistic regression.Results Univariate logistic regression analysis found that the independent risk factors for progression of ARDS were APACHE Ⅱ score (OR=6.764,P=0.001),hypoproteinemia (OR=10.54,P=0.002),white blood cell count (OR=3.912,P=0.012),fibrinogen (OR=9.953,P=0.064),and D-dimer (OR=4.239,P=0.029).The mortality rate was 43.75% (36/64) in ARDS group,and the oxygenation index (OR=6.573,P=0.014),platelet count (OR=9.376,P=0.003),hypoproteinemia (OR=10.738,P=0.056) were the independent risk factors of death in ARDS patients.Multivariate logistic regression showed that combination of multiple indicators for predicting ARDS improved the specificity,but reduce the sensitivity.APACHE Ⅱ and hypoproteinemia (sensitivity 62.50%,specificity 92.42%) and APACHE Ⅱ and D dimmer (sensitivity 62.07%,specificity 93.33%) had better specificity and sensitivity.The specificity and sensitivity of combining hypoproteinemia and platelet count to predict the risk of death in these patients were 77.78% and 60.71%.Conclusions In high-risk ARDS patients,combining hypoproteinemia or APACHE Ⅱ score with D-dimer to judge the development of ARDS has good specificity but poor sensitivity.For ARDS patients,low oxygenation index,thrombocytopenia and hypoproteinemia indicate a poor prognosis.
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Objective To detect the signal pathways through which IL-4 regulates expression of DC-SIGN in THP-1 cells.Methods We used phorbol 12-myristate 13-acetate(PMA) differentiated THP-1 cells as the in vitro model of monocyte/macrophage cells to study the signal pathways involved in IL-4 regulated expression of DC-SIGN.DC-SIGN mRNA expression was detected by RT-PCR.Cytoplasmic DC-SIGN protein was tested by Western blot.Flow cytometry was used to detect cell surface expression of DC-SIGN.Cytoplasm and nuclear protein of PMA stimulated THP-1 cells induced by IL-4 for 0,10,20,30,60 and 120 min was extracted and detected by Western blot for signal pathway signaling protein and phosphoprotein.Results We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein.Up-regulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway,and partly reduced by the specific inhibitors of JAK-STAT and NF-κB pathways.The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time.Conclusion Multiple signaling pathways are involved in IL-4 induced high expression of DC-SIGN on THP-1 cells,in which ERK pathway is the main signal pathway.
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A magnetoelastic Staphylococcus aureus (S.aureus) wireless sensor was fabricated to detect S.aureus in different liquid medium.After 0.2 mL bacteria with proper concentration was taken into the tes ting cuvette containing 2 mL liquid medium, the resonance frequency of magnetoelastic sensor changed with the bacteria growth.Via changing the concentration of beef extract and peptone, sensor had the most frequen cy response in culture medium CM2-2 incubated with 2 × 10~5 cells/mL S.aureus.The results indicated that this sensor can be used to determine S.aureus concentrations of 3 × 10~3 to 2×10~7 cells/mL in culture medium and 10~4 to 10~7 cells/mL in milk, with the detection limits of 10~3 cells/mL and 104 cells/mL, respectively.The sensor frequency shift was correlated to the logarithmic value of the S.aureus concentration, and the correlation coefficient was 0.98 in milk and 0.99 in culture medium.
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Objective To investigate the effects of IL-12 coexpression level on antigen expression and immune responses induced by HBsAg DNA vaccination. Methods DNA vaccine plasmid pHBV carrying codon-optimized preS2-S gene of reference sequence CHN-HBV07-C in China was constructed. Three DNA vaccine plasmids pHBV-12i, pHBV-12l and pHBV-12h were also constructed by subcloning three different IL-12 expression cassettes with various expression strengths to plasmid pHBV, respectively. Expression levels of IL-12 and HBsAg in vaccine plasmid-tranfected 293T cells were measured by quantitative ELISA. DNA vaccines were administered intramuscularly to BALB/c mice and HBsAg-specific cellular immune responses were determined by IFN-γ ELISPOT. HBsAg-specific antibodies were tested by Chemiluminescence Quantitative Immunoassay. Results The HBsAg expression level in 293T cells was 70 ng/ml when transfected by plasmid pHBV without IL-12 expression cassette, and the HBsAg level was 18 ng/ml when transfected by plasmid pHBV-12l carrying low-level IL-12 expression cassette, whereas the HBsAg level was only 6 ng/ml when transfected by plasmid pHBV-12h carrying high-level IL-12 expression cassette.Results of DNA vaccination revealed that HBsAg-specific humoral and cellular immune responses were significantly decreased in mice administering vaccine pHBV-12h carrying high-level IL-12 expression cassette. Although HBsAg-specific antibody responses in mice inoculated with pHBV-12l were also decreased when compared with those in pHBV-vaccinated mice without IL-12 expression, the HBsAg-specific cellular immune responses were significantly increased. Conclusion High-level coexpression of IL-12 may suppress the expression of HBsAg, Whereas modest coexpression of IL-12 significantly enhanced the HBsAg-specific T cell responses induced by DNA vaccination. Therefore, it is so important to balance the expression between adjuvant and antigen to enhance the immune response.