Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80％and 125％.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.

Heart failure with preserved ejection fraction(HFpEF)may be a main form of heart failure,with a high mortality and an increasing incidence,which is a significant problem in cardiovascular disease.Although some important advancements in HFpEF has been made in recent years,its pathogenesis remains unclear,and the prognosis and mortality of patients have not significantly improved.Due to a large number of complications and complex pathological mechanism of HFpEF,and traditional treatment medicines of heart failure cannot effectively improve the prognosis of HFpEF patients,it is still lack of accurate diagnostic methods and effective clinical treatment strategies.Exploring and developing effective diagnostic and therapeutic approaches are of great clinical significance.This review summarizes the progress and future research direction in the diagnosis and treatment of HFpEF.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

Objective:To explore the diagnostic value of quantitative 99Tc m-hydrazinonicotinamide(HYNIC)-prostate specific membrane antigen (PSMA) SPECT/CT in patients with prostate cancer. Methods:From November 2018 to March 2021, the data of 56 patients ((69.8±8.0) years) with clinically suspected prostate cancer, who had elevated radioactive uptake in prostate on 99Tc m-HYNIC-PSMA SPECT/CT images in Henan Provincial People′s Hospital, were retrospectively analyzed. According to the pathological results, patients were divided into prostate cancer group ( n=45) and non-prostate cancer group ( n=11). The xSPECT-QUANT software was used to quantitatively analyze the high uptake area of the prostate, and SUV max was measured. The independent-sample t test, Mann-Whitney U test, ROC curve and Spearman correlation analysis were used for data analysis. Results:The prostate cancer group had higher SUV max than non-prostate cancer group (10.79±5.96 vs 3.60±1.27; t=7.43, P<0.001). When SUV max≥6.46, the AUC of prostate cancer was 0.887, with the diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 73.3%(33/45), 11/11, 100%(33/33), 47.8%(11/23), 78.6%(44/56), respectively. The SUV max of prostate cancer group was positively correlated with Gleason score ( rs=0.632, P<0.001). The SUV max of 29 patients with Gleason score≥8 was higher than that of 16 patients with Gleason score≤7 ( z=-3.89, P<0.001). There was no statistical difference in PSA level between patients with Gleason score≤ 7 and patients with non-prostate cancer ( z=-1.63, P=0.110), but the SUV max was significantly different ( z=-2.22, P=0.026). The SUV max of 23 patients with metastases was higher than that of 22 patients without metastasis (12.99±5.85 vs 8.50±5.28; t=2.69, P=0.010). ROC analysis showed that the AUC was 0.709; with SUV max≥13.02 as the threshold, the sensitivity for diagnosing prostate cancer metastases was 56.5%(13/23), the specificity was 86.4%(19/22), and the accuracy was 71.1%(32/45). Conclusions:The 99Tc m-HYNIC-PSMA SPECT/CT quantitative analysis is feasible in patients with prostate cancer. SUV max of 99Tc m-HYNIC-PSMA can be used in the diagnosis of prostate cancer, assessment of the malignancy and prediction of metastasis.

In recent years, the number of autoimmune hepatitis cases in the world has shown a significant upward trend, but its etiology and pathogenesis is still unclear. At present, it is generally considered to be caused by abnormal immune regulation mechanism of the body, especially the lymphocytes and their cytokines, which has attracted widespread concern and thus is reviewed here.
Cytokines ; Hepatitis, Autoimmune ; Humans ; Lymphocytes

The development of quality Chinese medicine is an important way to improve the quality of Chinese medicine, and ensure the safety and effectiveness of Chinese medicine. This article systematically elaborates the definition, classification, standard and mana-gement certification strategy of quality Chinese medicine. We present the quality Chinese medicine which is higher quality than that of eligible Chinese medicine based on quality control standards. Quality Chinese medicine is strictly in accordance with management procedures, likely GAP and GMP et al, during the productive process, which quality indicators is higher than that of the current relevant national quality standards, such as Chinese Pharmacopoeia(ChP) et al; its limited indicators such as exogenous pollutants and endogenous toxic substances are lower than that of the current relevant national quality standards, likely ChP et al; meanwhile these Chinese herbal medicine, medicinal pieces, patent medicines, and health products and foods with Chinese medicine raw materials are been certificated by quality Chinese medicine. At the same time, this article systematically expounds the five major management systems of quality Chinese medicine, including technical training management for practitioners, productive process management, standard mana-gement, quality inspection and certification management, and product traceability management. And we put forward strategies to improve the supervision and management system, and promote the standardization and development of quality Chinese medicine by improving the technical management system of quality Chinese medicine, strengthening the quality management system and six sigma(6σ) management in the company. These strategies will provide a reliable basis and effective way to improve the quality of Chinese medicine.
Drugs, Chinese Herbal ; Food ; Medicine, Chinese Traditional ; Quality Control ; Reference Standards

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.
Acute Disease ; Aneurysm, Dissecting/diagnosis* ; China ; Hematoma ; Humans ; Male ; Middle Aged ; Registries ; Retrospective Studies ; Time Factors ; Treatment Outcome

Air Pollution ; Asthma/drug therapy* ; China ; Humans ; Treatment Adherence and Compliance

Differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. The process of reprogramming requires the interaction of various transcription factors to regulate the transformation of cell fate. Hoxd12 (Homeobox D12) is one of the transcription factors regulating the embryonic development of vertebrates, and it plays an outstanding role in the development of the limb, body axis formation, and cell signal transduction. However, any roles of Hoxd12 may play in the somatic cell reprogramming and the pluripotency of embryonic stem cells (ESCs) have not been reported. In this study, we firstly used 7 factors (Sall4-Esrrb-Jdp2-Glis1-Mkk6-Nanog-Kdm2b) and Yamanaka factors (Oct4-Klf4-Sox2) as the research model, combined with RNA interference (shRNA) and gene overexpression, to explore the mechanism of Hoxd12 in somatic cell reprogramming. Moreover, we used CRISPR/Cas9 gene editing to construct Hoxd12 knockout embryonic stem cell lines, and combined embryoid body formation (EB) and RNA sequencing (RNA-seq) to explore the function of Hoxd12 in the pluripotency of ESCs. The conclusions are as follows: (1) Knocking down of Hoxd12 inhibits 7 factor-induced reprogramming (

BACKGROUND: Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions. METHODS: Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes. RESULTS: A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04-8.62, P = 0.042). CONCLUSION Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.