Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective:To investigate the effects of self-made Gujin Xiaoji Mixture combined with warming needle therapy on the clinical efficacy and immune function of patients with advanced non-small cell lung cancer (NSCLC) with qi and yin deficiency syndrome.Methods:This experiment was a randomized controlled trial study. 180 patients with advanced NSCLC qi and yin deficiency syndrome in the oncology centre of Qingdao Hospital of Traditional Chinese Medicine were selected as the observation subjects from March 2021 to August 2022, and were divided into 2 groups using the random number table method, with 90 cases in each group. The control group received conventional chemotherapy combined with Sintilimab injection, 21 days as a cycle, with a total of 4 cycles of treatment; and the observation group received Gujin Xiaoji Mixture combined with warming needle therapy based on the control group, 7 days as one course of treatment, with a total of 12 courses. Both groups were followed up for 12 months. The TCM syndrome scores were performed before and after treatment. The functional assessment of cancer therapy-lung (FACT-L) was used to evaluate the quality of life of patients; flow cytometry was used to detect the levels of CD3 +, CD4 +, CD8 + and NK cell, and the CD4 +/CD8 + ratio was calculated; adverse drug reactions and progression free survival of patients during treatment were observed and recorded, the efficacy of TCM syndrome and objective efficacy of solid tumors were evaluated. Results:After treatment, the observation group's post-treatment TCM syndrome score (5.67±1.99 vs. 7.12±2.31, t=-4.53) was lower than that of the control group ( P<0.001); mobility (23.03±2.80 vs. 20.69±2.46, t=5.96), daily living (23.06±2.56 vs. 20.71± 2.33, t=6.42), emotional status (18.44±2.32 vs. 16.12±2.71, t=6.18), and other factors (33.14±4.11 vs. 27.39±4.64, t=8.81) and total score (97.68±7.23 vs. 84.91±7.49, t=11.64) were higher than those in the control group ( P<0.01). In the observation group, after treatment, the levels of CD3 + [(65.14±6.06)% vs. (59.84±5.74)%, t=6.02], CD4 + [(40.09±4.09)% vs. (35.69±3.86)%, t=7.43], NK cell [(29.11±4.81)% vs. (22.38±4.51)%, t=9.68] and CD4 +/CD8 + [(1.52±0.27) vs. (1.14±0.12), t=12.63] were higher than those in the control group ( P<0.01), and CD8 + [(26.82±3.79)% vs. (31.76±4.65)%, t=-7.81] level was lower than that of the control group ( P<0.01). After treatment, the objective remission rate in the observation group was 7.8% (7/90), and the disease control rate was 87.8% (79/90), while the objective remission rate after treatment in the control group was 5.5% (5/90), and the disease control rate was 82.2% (74/90), and there were no statistical significance in the comparison of objective remission rate and disease control rate of the 2 groups ( χ2=0.09, 0.70, P=0.765, 0.407). The total effective rate after treatment was 62.2% (56/90) in the observation group and 34.4% (31/90) in the control group, and the difference between the 2 groups was statistically significant ( Z=-3.89, P<0.001). WBC [(4.27±1.12)×10 9/L vs. (3.84±1.11)×10 9/L, t=2.58] and haemoglobin [(119.93±17.25)g/L vs. (109.76±15.61)g/L, t=4.15] levels of the observation group were higher than those in the control group after treatment ( P<0.01). During follow-up, the median progression-free survival was 6.2 months in the observation group and 5.5 months in the control group patients, and the difference between the 2 groups was not statistically different ( t=0.11, P>0.05). Conclusion:The combination of Gujin Xiaoji Mixture with warming needle therapy can effectively improve the clinical symptoms of patients with advanced NSCLC with deficiency of qi and yin syndrome, improve the immunity and clinical efficacy of patients, alleviate the adverse effects of drugs, and prolong the progression-free survival period.

Objective To establish a scoring model for predicting the prognosis and drug sensitivity of colorectal cancer(CRC)based on the expression of disulfidptosis-related genes by bioinformatics analyses combined with the validation with CRC patient-derived organoids(CRC-PDOs).Methods NMF(non-negative Matrix Factorization)algorithm,Cox and LASSO regression analyses were used to identify disulfidptosis-related genes with predictive value for CRC prognosis,and disulfidptosis-related risk scoring formula was constructed.The differential genes and enrichment pathways among different clusters were analyzed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes).The sensitivity of the high/low-risk clusters of CRC patients to chemotherapy drugs was predicted using the GDSC database and validated using CRC-PDOs.Results The results of NMF algorithm showed that CRC patients could be grouped into two clusters based on the disulfidptosis-related genes.COX regression analysis demonstrated that LRPPRC and SLC7A11 were the only two genes with significance to predict the prognosis of CRC patients(P=0.047,0.033).Low expression of SLC7A11 or high expression of LRPPRC in tumors of CRC patients was significantly correlated with overall survival(OS)(P=0.004,0.003).Based on LASSO regression analysis,the mortality risk scoring formula for disulfidptosis was as follows:Risk score=LRPPRC×(-0.670 5)+SLC7A11×0.311 2,and the GSE161158 dataset could be re-grouped into high-risk and low-risk clusters accordingly.There were 125 differentially expressed genes(DEGs)between the two clusters.According to the GO and KEGG results,the up-regulated genes in high-risk cluster were mainly enriched in immune regulation,such as leukocyte chemotaxis,granulocyte migration and toll-like receptor binding.Low-risk cluster was characterized by pathways associated with sulfide metabolism,such as sulfur compound transmembrane transporter activity.Based on the GDSC database,the expression level of SLC7A11 and LRPPRC could predict chemotherapy drug sensitivity.As a representative,the efficacy of chemotherapy drug(irinotecan)on inhibiting the growth of CRC-PDOs was shown to be linearly correlated with the relative gene expression levels of SLC7A11 and LRPPRC in CRC tissues of patients(P=0.007,0.040).Conclusion According to the results based on the bioinformatics analyses and drug sensitivity testing on CRC-PDOs,disulfidptosis risk score could predict the prognosis and drug sensitivity of CRC patients,with potential clinical application prospect.

Objective To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).Methods A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022.Results Among the AAV children,there were 5 males and 20 females,with a median age of onset of 11.0 years.Involvement of the urinary system was seen in 18 cases(72%);respiratory system involvement in 10 cases(40%);skin involvement in 6 cases(24%);eye,ear,and nose involvement in 5 cases(20%);joint involvement in 4 cases(16%);digestive system involvement in 2 cases(8%).Eleven cases underwent kidney biopsy,with 5 cases(46%)showing focal type,2 cases(18%)showing crescentic type,2 cases(18%)showing mixed type,and 2 cases(18%)showing sclerotic type.Immune complex deposits were present in 5 cases(45%).Seven cases reached chronic kidney disease(CKD)stage Ⅴ,with 2 cases resulting in death.Two cases underwent kidney transplantation.At the end of the follow-up period,2 cases were at CKD stage Ⅱ,and 1 case was at CKD stage Ⅲ.Of the 16 cases of microscopic polyangiitis(MPA)group,13(81%)involved the urinary system.Of the 9 cases of granulomatosis with polyangiitis(GPA),6 cases(66%)had sinusitis.Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group(P<0.05),while red blood cell count and glomerular filtration rate were lower in the MPA group(P<0.05).Conclusions AAV is more common in school-age female children,with MPA being the most common clinical subtype.The onset of AAV in children is mainly characterized by renal involvement,followed by respiratory system involvement.The renal pathology often presents as focal type with possible immune complex deposits.Children with MPA often have renal involvement,while those with GPA commonly have sinusitis.The prognosis of children with AAV is poor,often accompanied by renal insufficiency.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

ObjectiveTo analyze the HIV infection characteristics and influencing factors among the spouses of HIV/AIDS patients in Shanghai. MethodsA cross-sectional survey was conducted to collect demographic， behavioral， epidemiological and spousal HIV detection information of newly reported and married patients with HIV/AIDS in Shanghai from January 2018 to July 2022 in the comprehensive HIV prevention and control information system of Chinese Center for Disease Prevention and Control. Descriptive analysis was used to analyze the HIV positivity rate of the spouses of HIV patients and the influencing factors were analyzed by univariate and multivariate logistic regression models. ResultsA total of 1 233 subjects were investigated， and the first HIV-testing positivity rate of the spouses of HIV/AIDS patients was 29.3% （361/1 233）. There were statistically significant differences in the HIV-testing positivity rate among spouses of HIV/AIDS patients by different age， gender， education level， occupation， transmission route， quantity of non-marital sexual activities， quantity of homo-sexual activities， and baseline CD4 cell count level （P<0.05）. Spouses of the HIV/AIDS patients aged ≥65 years old， female， heterosexual transmission， less non-marital sex， and no history of homosexual sex had relatively high HIV positive rate. The HIV-positive detection rate of spouses in the ≥65 age group was 1.81 times higher than that in the <45 age group. The HIV-positive detection rate of spouses in the female group was 3.66 times higher than that in the male group， and the HIV-positive detection rate of spouses in the homosexual transmission group was 0.25 times higher than that of the heterosexual transmission group. ConclusionRisk awareness of HIV infection among married people with spouses should be improved. The key populations with the characteristics such as females as the first HIV-positive reporter， and heterosexual transmission should be paid special attention.Their spouses should be mobilized to conduct HIV-testing as early as possible

Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.

Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People's Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.
Female ; Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/genetics* ; Leukocytes, Mononuclear ; Carcinoma, Transitional Cell ; Antagomirs ; Cell Line, Tumor ; Urinary Bladder Neoplasms ; Cell Proliferation ; Endometrial Neoplasms/genetics* ; Apoptosis/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.
Animals ; Cell Differentiation ; Disease Models, Animal ; Ischemic Stroke ; Proteomics ; Rats ; Stem Cell Transplantation/methods* ; Stroke/therapy*