Objective:To investigate the relationship between serum miR-501 and miR-195 levels and sensitivity to concurrent chemoradiotherapy in patients with locally advanced cervical cancer (LACC).Methods:Clinical data of 96 patients with LACC admitted to Nanyang Central Hospital from January 2020 to June 2022 were retrospectively analyzed and compared with those of 96 healthy subjects during physical examination in our hospital during the same period to compare the differences of serum miR-501 and miR-195 levels. Tumor status was reviewed at 6 months after concurrent chemoradiotherapy. Patients were divided into the sensitive and resistant groups according to the evaluation criteria of solid tumor efficacy. The relationship between serum miR-501 and miR-195 levels and the sensitivity to concurrent chemoradiotherapy in LACC patients was analyzed by univariate and multivariate analyses. The receiver operating characteristic (ROC) curve was also drawn to predict differential efficacy of concurrent chemoradiotherapy sensitivity in LACC patients. Multivariate analysis was conducted by binary logistic regression analysis. P<0.05 indicated statistically significant differences. Results:In LACC patients, serum miR-501 level was significantly higher, whereas serum miR-195 level was significantly lower than those in physical examination subjects (both P<0.05). Univariate analysis showed that serum miR-501 level at admission in the resistant group was significantly higher, whereas serum miR-195 level was significantly lower than those in the sensitive group (both P<0.05). Multivariate analysis showed that serum miR-501 and miR-195 levels were significantly correlated with the sensitivity to concurrent chemoradiotherapy in LACC patients. The area under the ROC curve (AUC) was 0.736 and 0.913, respectively. Conclusions:The higher the serum miR-501 level and the lower the serum miR-195 level before treatment, the higher the probability of resistance to concurrent chemoradiotherapy in LACC patients. Serum miR-501 and miR-195 levels of LACC patients before treatment have certain predictive value for the sensitivity to concurrent chemoradiotherapy.

OBJECTIVES: To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (V_acetonitrile∶V_methanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring. RESULTS: The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively. CONCLUSIONS This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.
Chromatography, Liquid/methods* ; Tandem Mass Spectrometry ; Methanol ; Carbamazepine/analysis* ; Benzodiazepines/analysis* ; Solvents ; Chromatography, High Pressure Liquid ; Solid Phase Extraction

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.
Medicine, Chinese Traditional ; Cross-Sectional Studies ; Treatment Outcome ; Case-Control Studies ; Narrative Medicine

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.
Medicine, Chinese Traditional/adverse effects* ; Social Change

Coronary Angiography ; Coronary Disease ; Humans ; Liver ; Non-alcoholic Fatty Liver Disease/complications*

Objective: To investigate the effects of glucose-6-phosphatase catalytic subunit (G6PC) recombinant adenovirus on proliferation and cell cycle regulation of liver cancer cells. Methods: Recombinant adenovirus AdG6PC was constructed. Huh7 cells and SK-Hep1 cells were set as Mock, AdGFP and AdG6PC group. Cell proliferation and clone formation assay were used to observe the proliferation of liver cancer cells. Transwell and scratch assay were used to observe the invasion and migration of liver cancer cells. Cell cycle flow cytometry assay was used to analyze the effect of G6PC overexpression on the proliferation cycle of liver cancer cells. Western blot was used to detect the effect of G6PC overexpression on the cell-cycle protein expression in liver cancer cells. Results: The recombinant adenovirus AdG6PC was successfully constructed. Huh7 and SK-Hep1 cells proliferation assay showed that the number of proliferating cells in the AdG6PC group was significantly lower than the other two groups (P < 0.05). Clone formation assay showed that the number of clones was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression could significantly inhibit the proliferation of liver cancer cells. Transwell assay showed that the number of cell migration was significantly lower in AdG6PC than the other two groups (P < 0.05). Scratch repair rate was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression can significantly inhibit the invasion and migration of liver cancer cells. Cell cycle flow cytometry showed that G6PC overexpression had significantly inhibited the Huh7 cells G(1)/S phase transition. Western blot result showed that G6PC overexpression had down-regulated the proliferation in cell-cycle related proteins expression. Conclusion: G6PC inhibits the proliferation, cell-cycle related expression, and migration of liver cancer cells by inhibiting the G(1)/S phase transition.
Catalytic Domain ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glucose-6-Phosphatase/metabolism* ; Humans ; Liver Neoplasms/genetics*

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
Adult ; COVID-19/pathology* ; China/epidemiology* ; Comorbidity ; Cough ; Cross-Sectional Studies ; Diarrhea ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg^-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg^-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg^-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg^-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, geraniin can reduce activities or contents of ALT, AST, ALP, TBIL in serum and MDA in liver of mice (P<0.05, P<0.01), but increase activities of T-SOD and GSH-Px in liver (P<0.05,P<0.01), while inhibiting the contents of TNF-α, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (P<0.05,P<0.01). HE staining showed that acute liver injury of mice was alleviated obviously by geraniin. Conclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.

In order to solve the problem of long-term (>9 months) efficacy in the treatment of Alzheimer's disease (AD) by conventional therapy (CT), a staged and multiply-targeted sequential therapy based on the evolvement of patterns (STEP) was developed. Its main innovations include: (1) the time order of evolution of patterns defined by Chinese medicine (CM) in AD was found, that is, "the orderly pattern evolution starting from Shen (Kidney) deficiency, progressing to phlegm, stasis and fire, and worsening to severe toxin as well as functional collapse"; (2) the cascade hypothesis of Shen deficiency in AD and its sequential therapy based on Shen-reinforcing was proposed, that is, "reinforcing Shen in the early stage and throughout the whole process, resolving phlegm, activating blood and purging fire in the middle stage, detoxifying and replenishing vitality to stop the collapse in the advanced stage", and through meta-analysis, clinical drug use was optimized, thus the leap from "inferential selection" to "evidence-based selection" was realized; (3) the STEP regimen combined with CT maintained cognitive and behavioral stability in AD patients for at least 12 months, with cognitive enhancement and behavioral synergy after 9 months, and cognitive benefit was superior to CT at 9, 12, 15, 18, 21, and 24 months, respectively. The 2-year cognitive improvement rate was increased by 25.64% (P=0.020) and the cognitive deterioration rate was decreased by 48.71% (P=0.000). Among them, the cognitive and functional benefits of Shen-reinforcing therapy for very early AD (350 cases) for 1 year were better than the placebo (P<0.001), and the dementia conversion rate was reduced by 8.85% (P=0.002). The behavioral symptomatic relief of patients with vascular dementia received fire-purging therapy (540 cases) was superior to those received CT (P=0.016). These data suggested that the STEP regimen has synergistic effects on CTs at least in terms of cognitive benefit, and the earlier the use, the greater the benefit will have. Therefore, the STEP regimen should be considered as one of the clinical options, particularly for the dearth of effective pharmaceutical or immunological interventions that are currently available for AD.

Objective Few clinical studies have been reported on the reversibility of uremic cardiomyopathy (UC) after renal transplantation. This article aimed to investigate the cardiac structure and function of end-stage renal disease (ESRD) patients undergoing renal transplantation using cardiac magnetic resonance (CMR). Methods This study included 38 ESRD patients undergoing renal transplantation in the National Clinical Research Center for Kidney Diseases, General Hospital of Eastern Theater Command, from September 2015 to February 2017. All the patients received initial CMR examination at 1－2 days before renal transplantation and during the postoperative follow-up. At the median follow-up time of 3.5 (3.4-3.7), 7.0 (3.7-9.5) and 8.4 (7.1-12.7) months, we recorded the CMR parameters, including the left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic mass (LVEDM), end-systolic mass (LVESM), ejection fraction (LVEF), and native myocardial T1 relaxation time, and compared the parameters obtained before and after surgery. Results Twenty-five of the patients completed the postoperative follow-up, who averaged 27.5 years of age, with no history of diabetes mellitus or ischemic heart disease, and treated by dialysis for 1.7 (1.5-2.2) years. At 7.0 months after renal transplantation, as compared with the baseline, the patients showed significant decreases in the LVEDV ([96.7 ± 22.8] vs [83.4 ± 17.4] mL/m², P < 0.05), LVESV ([44.3 ± 14.8] vs [33.0 ± 10.9] mL/m², P < 0.05) and LVEDM ([67.1 ± 24.2] vs [59.0 ± 17.0] mL/m², P < 0.05), but an increase in the LVEF ([54.1 ± 10.6] % vs [60.9 ± 9.6] %, P < 0.01). The LVEDV and LVESV were also remarkably lower at 3.5 and 8.4 months than the baseline (P < 0.001), and so were the left ventricular at basal, mid, apical and global native T1 relaxation times at 3.5, 7.0 and 8.4 months (P < 0.05). Conclusion For young ESRD patients with no history of diabetes mellitus or ischemic heart disease and on short-term dialysis, left ventricular dilatation, systolic dysfunction and diffuse myocardial fibrosis are reversible after renal transplantation. Native T1 relaxation time can be used as a sensitive indicator to evaluate the degree of diffuse myocardial fibrosis in ESRD patients.