BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in the patients with acute cerebral infarction,and to analyze the correlation of TCM syndromes with collateral circulation,cerebral blood perfusion and prognosis.Methods A total of 300 patients with acute cerebral infarction were selected.All patients underwent head-neck CT angiography(CTA)and CT perfusion imaging(CTP),and then were followed up for 30 days.The prognosis was evaluated by modified Rankin Scale(MRS)score.In addition,the dynamic evolution of TCM syndromes was observed to explore the correlation of TCM syndromes with collateral circulation,cerebral blood flow perfusion in the lesion area and prognosis.Logistic regression analysis was used to explore the influences of TCM syndromes,blood flow perfusion and collateral circulation establishment on stroke outcomes.Results(1)Highest incidences of syndrome elements of phlegm,blood stasis and wind were presented in ACI patients.The syndrome element of qi deficiency was predominated in the patients with anterior/posterior communicating artery opening and extracranial-to-intracranial collateral circulation establishment.On the first day of onset,the incidence of qi deficiency syndrome element in the good collateral circulation group was lower than that in the poor collateral circulation group(P＜0.05).On the 30th day after onset,the incidences of qi deficiency syndrome element and phlegm syndrome element in the good collateral circulation group were significantly lower than those in the poor collateral circulation group(P＜0.01).The results of correlation analysis showed that the score of qi deficiency was negatively correlated with regional cerebral blood volume(rCBV)of region of interest(r=-0.472,P＜0.05),and the score of yin deficiency was positively correlated with rCBV(r=-0.557,P＜0.01)on the first day of onset.The incidence of qi deficiency in the lesion area was relatively high in the patients of decreased rCBV(rCBV＜1.0 score)group(P＜0.01),while the incidence of yin deficiency in the lesion area was relatively high in the patients of elevated rCBV(rCBV＞1.0 score)group(P＜0.05).(2)The distribution of syndrome elements on the first day of onset showed that the incidence of qi deficiency syndrome element in the poor prognosis group was significantly higher than that in the good prognosis group(P＜0.01);on the 30th day after onset,the incidences of qi deficiency syndrome element and phlegm syndrome element in the good prognosis group was significantly lower than those in the poor prognosis group(P＜0.05 or P＜0.01).The incidence of phlegm syndrome element in the good prognosis group was significantly reduced on the 30th day after onset compared with that on the first day of onset(χ2=7.409,P＜0.01),while there was no significant difference shown in the poor prognosis group(P＞0.05).(3)Logistic regression analysis showed that syndrome elements(qi deficiency,phlegm),collateral circulation grading,and rCBV in the lesion area were the independent risk factors for stroke outcomes.Conclusion The acute cerebral infarction patients with poor collateral circulation,decreased blood perfusion and poor prognosis are predominated by qi deficiency syndrome element.Moreover,phlegm syndrome element is presented in the patients with poor prognosis throughout the course of disease.It is indicated that qi deficiency syndrome element and phlegm syndrome element play an important role in the pathogenesis and progression of acute cerebral infarction.

Objective To study the effects of scutellarin on endometrial carcinoma Ishikawa cells,and analyze the correlation between the effects and phosphatidyl inositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway.Methods Ishikawa cells were divided into blank group and experimental-L,-M,-H groups,each group was treated with complete medium containing 0,5,10 and 20 μmol·L-1 scutellarin,respectively.Cell viability,clonal formation ability,metastatic ability,invasion,apoptosis and protein expression were detected by cell counting kit-8(CCK-8),plate cloning,scratch,Transwell,flow cytometry and Western blot assay,respectively.Results The cell viability of blank group and experimental-L,-M,-H groups at 48 h were(100.00±0.00)％,(78.51±7.54)％,(52.93±4.91)％and(41.62±5.33)％;the clone formation rate were(100.00±0.00)％,(56.59±6.34)％,(35.23±4.62)％and(10.66±1.91)％;the scratch healing rate were(53.70±6.19)％,(40.59±4.75)％,(34.25±4.40)％and(15.78±2.14)％;the number of invasive cells were 189.70±14.06,106.82±12.67,84.37±8.13 and 53.74±6.78;the relative expression levels of matrixmetallo proteinase-2 were 0.96±0.10,0.73±0.06,0.68±0.08 and 0.42±0.05;tissue inhibitor of MMP-1(TIMP-1)were 0.35±0.04,0.51±0.05,0.74±0.08 and 1.20±0.14;the apoptosis rates were(4.21±0.53)％,(15.83±2.42)％,(22.72±3.85)％and(34.41±4.67)％;the relative expression levels of B cell lymphoma-2(Bcl-2)were 1.38±0.15,0.90±0.10,0.56±0.06 and 0.24±0.03;Bcl-2 associated X protein(Bax)were 0.31±0.02,0.44±0.04,0.93±0.11 and 1.26±0.14;the relative expression levels of PI3Kp85 were 0.67±0.05,0.42±0.04,0.36±0.02 and 0.28±0.03;phosphorylated Akt(p-Akt)were 0.78±0.06,0.53±0.04,0.46±0.05 and 0.42±0.03.Compared with the blank group,the above indexes in the experimental-L,-M,-H groups were statistically significant(P＜0.05 or P＜0.01).Conclusion Scutellarin can inhibit the proliferation,metastatic ability and invasion of endometrial carcinoma Ishikawa cells and promote apoptosis by regulating PI3K/Akt signaling pathway.

In recent years, with the policy reform of new drug review and approval, China has ushered in a surge of innovative drug development. Based on the Pharnexcloud database and the Pharmcube database, we analyzed the innovative drugs approved for marketing and entered clinical trials in China, sorted out the major research and development (R&D) institutions and enterprises, the distribution of innovative drug target types, and the primary therapeutic areas of the approved innovative drugs, and compared with the global innovative drug R&D landscape. Since 2020, China's innovative drug development has shown a rapid growth trend, with intense competition among biopharmaceutical companies, and the emergence of a number of leading biopharmaceutical enterprises. Popular targets for clinical-stage and approved drugs include protein tyrosine kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, and others. Oncological diseases are the most active domain for new drug R&D in China, followed by infectious diseases and neurological diseases. Suggestions for future development are proposed to increase policy support, enhance R&D innovation investment, optimize pipeline layout, strengthen international cooperation, and focus on innovative targets. This review provides a reference for pharmaceutical R&D enterprises, scientific researchers, and government administrators.
China ; Drug Development/trends* ; Drug Approval ; Pharmaceutical Research

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

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

Objective: To explore the phonological processes in initial consonants of Putonghua-speaking children in Jiangsu urban areas. Methods: A status survey was applied. From December 2014 to September 2015, a stratified random sampling method was used to select 958 children aged 1 to 6 years with Putonghua as their mother tongue in the urban area of Nanjing, Changzhou, Yangzhou and Xuzhou to examine their phonological performance. Speech samples were collected by the method of picture naming. The children were divided into 9 age groups (1.5-<2.0, 2.0-<2.5, 2.5-<3.0, 2.5-<3.0, 3.0-<3.5, 3.5-<4.0, 4.0-<4.5, 5.0-<6.0, 6.0-<7.0 years). Descriptive analysis method was used to analyze the phonological processes in initial consonants at different age groups. Results: Among the 958 children, there were 482 boys and 476 girls. The age of the children was (3.8±1.4) years. The number of children in the 9 age groups (1.5-<2.0, 2.0-<2.5, 2.5-<3.0, 2.5-<3.0, 3.0-<3.5, 3.5-<4.0, 4.0-<4.5, 5.0-<6.0, 6.0-<7.0 years) is 100, 110, 110, 114, 114, 114, 111, 119, and 66, separately. The process of substitution was found in the speech of 701 children (73.2%), syllable structure simplification was found in 194 children (20.3%), distortion was found in 41 children (4.3%), and assimilation was found in 17 children (1.8%). Among these 4 types of processes, the occurrence of substitution was highest in all the age groups, ranging from 30.3% (20/66) to 94.5% (104/110). The occurrence of syllable structure simplification ranged from 27.3% (30/110) to 91.0% (91/100) in the age groups of 1.5-<3.0 years and 0.9% (1/114) to 7.9% (9/114) in the age groups of 3.0-<7.0 years. The occurrence of distortion ranged from 7.3% (8/110) to 19.1% (21/110) in the age groups of 1.5-<3.0 years and 0 (0/114) to 2.7% (3/111) in the age groups of 3.0-<7.0 years. The occurrence of assimilation was very low in all age groups, ranging from 0 (0/114) to 3.0% (3/100) among all age groups. For substitution, the occurrence order of mainly individual processes from high to low was listed as follows: retroflexion 35.4% (339/958), deretroflexion 31.6% (303/958), lateralization 27.9% (267/958), stopping 17.8% (171/958), backing 14.2% (136/958), palatalization 10.9% (104/958), fronting 10.6% (102/958), and nasalization 5.8% (56/958). From the 4.0-<4.5 years of age group onwards, the phonological processes in initial consonants all met suppression criteria (the occurrence of processes was reduced to<10%) except retroflexion, deretroflexion, and lateralization. Conclusions: The processes of syllable structure simplification and distortion mainly appears in the early stage of speech sound development, while substitution is the major form of phonological pattern in initial consonants found in developmental speech errors. By 4 years of age, phonological processes in initial consonants almost disappear. The remaining processes that persisted for a longer period of time are retroflexion, deretroflexion, and lateralization.
Male ; Female ; Humans ; Child ; Child, Preschool ; Phonetics ; Surveys and Questionnaires