Objective To compare the bioavailability and bioequivalence of pivastatin calcium dispersive tablets in healthy Chinese subjects.Methods A single dose of pitavastatin calcium(2 mg)was orally administered to the test preparation or reference preparation under fasting and postprandial conditions,respectively.The plasma concentrations of pitavastatin calcium were measured at different time points before and after administration by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The bioequivalence of the two formulations was evaluated.Results Subjects received pitavastatin calcium test preparation and reference preparation in fasting condition,the Cmax were(47.79±23.99)and(46.03±21.82)ng·L-1;AUC0_,were(96.56±42.64)and(97.96±35.40)ng·h·L-1;AUC0_∞ were(102.09±43.01)and(103.46±35.62)ng·h·L-1,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0_t and AUC0-∞ of pitavastin-calcium test formulation and reference formulation were 96.28％-111.16％,94.46％-101.19％and 94.77％-101.31％,respectively.Subjects received pitavastatin calcium test preparation and reference preparation in fasting condition,the Cmax were(27.32±10.68)and(28.58±11.39)ng·L-1;AUC0_t were(82.76±27.58)and(84.06±29.12)ng·h·L-1;AUC0_∞ were(87.88±26.93)and(89.29±29.18)ng·h·L-1,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the test formulation and the reference formulation of pitavastatin calcium were 87.39％-102.10％,94.62％-101.34％and 94.88％-101.47％,respectively.All of them were within the bioequivalence range of 80.00％to 125.00％.Conclusion Two pivastatin calcium dispersion tablets were bioequivalent and safe in healthy Chinese adult subjects.

Objective:To establish a predictive scoring model for bladder neck contracture(BNC)after laparoscopic enuclea-tion of the prostate with preservation of the urethra(Madigan surgery)and explore the preventive measures against this postoperative complication.Methods:We included 362 cases of BPH treated by laparoscopic Madigan surgery from January 2019 to March 2022(45 with and 317 without postoperative BNC)in the training group and another 120 cases treated the same way in the verification group,collected the clinical data on the patients and evaluated the results of surgery.Using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression,we analyzed the risk factors for postoperative BNC and constructed a predictive scoring model for evaluation of the factors.Results:Compared with the baseline,the IPSS,quality of life(QOL)score and postvoid residual urine volume(PVR)were significantly decreased(P＜0.05)while the maximum urinary flow rate(Qmax)remarkably in-creased(P＜0.05)in the BPH patients at 3 months after surgery.Eight non-zero characteristic predictors were identified by LASSO regression analysis.Multivariate logistic regression analysis showed that short clinical experience of the surgeon,concurrent prostatitis,bladder rinse solution temperature＜34℃,catheter blockage,urethral balloon injection volume＞40 ml and postoperative constipation were independent risk factors for postoperative BNC(P＜0.05).The best cut-off value was 2.36 points in both the training and the verification groups.The results of evaluation exhibited a high discriminability of the predictive scoring model.Conclusion:Laparo-scopic Madigan surgery is a safe and effective method for the treatment of BPH.Short clinical experience of the surgeon,concurrent prostatitis,bladder rinse solution temperature＜34℃,catheter blockage,water injected into the urethral balloon＞40 ml and postop-erative constipation were independent risk factors for postoperative BNC.The predictive scoring model constructed in this study has a good discriminability and is simple and feasible,contributive to the prediction of postoperative BNC in BPH patients undergoing laparo-scopic Madigan surgery.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Neurodegenerative diseases are a collective term for a large group of diseases caused by degenerative changes in nerve cells. Aging is the main risk factor for neurodegenerative diseases. The neurovascular unit(NVU) is the smallest functional unit of the brain, which regulates brain blood flow and maintains brain homeostasis. Accelerated aging of NVU cells directly impairs NVU function and leads to the occurrence of various neurodegenerative diseases. The intrinsic mechanisms of NVU cell aging are complex and involve oxidative stress damage, loss of protein homeostasis, DNA damage, mitochondrial dysfunction, immune inflammatory response, and impaired cellular autophagy. In recent years, studies have found that traditional Chinese medicine(TCM) can inhibit NVU aging through multiple pathways and targets, exerting a brain-protective effect. Therefore, this article aimed to provide a theoretical basis for further research on TCM inhibition of NVU cell aging and references for new drug development and clinical applications by reviewing its mechanisms of anti-aging, such as regulating relevant proteins, improving mitochondrial dysfunction, reducing DNA damage, lowering inflammatory response, antioxidant stress, and modulating cellular autophagy.
Humans ; Medicine, Chinese Traditional ; Neurodegenerative Diseases/drug therapy* ; Brain ; Aging ; Neurons ; Blood-Brain Barrier

OBJECTIVE: To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. METHODS: A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. RESULTS: A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (P_trend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. CONCLUSIONS In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.
Female ; Humans ; Middle Aged ; Adolescent ; Young Adult ; Adult ; Aged ; Aged, 80 and over ; Diagnosis, Differential ; Retrospective Studies ; Case-Control Studies ; Breast/pathology* ; Breast Neoplasms/pathology*

Objective To explore the spatiotemporal distribution pattern, and identify risk cluster of esophageal cancer in Huai’an City so as to provide evidence for control and prevention of esophageal cancer. Methods Data of esophageal cancer incidence at township level in Huai’an City from 2011 to 2015 was collected. Spatial autocorrelation and local indications of spatial autocorrelation (LISA) were implemented to evaluate the spatial pattern of esophageal cancer incidence. Spatial scan statistics was used to examine spatio-temporal clustering of risk areas. Results The average incidence of esophageal cancer in Huai’an from 2011 to 2015 was 67.12/10 million, the incidence of male was significantly higher than that of female. The results of Moran’s I values implyed the spatial autocorrelation at township level. The results of LISA indicated that there were local hot spots and cold spots. The significant high-risk clusters included townships in Huai’an County, Huaiyin County and Jinhu County. The low-risk clusters were located in the main urban area and Xuyi County. Conclusions There are significant spatio-temporal aggregation for the distribution of incidence of esophageal cancer in Huai’an City and same spatiotemporal high-risk clusters between male and female. Our findings have a foundation to explore the multi-factorial etiology of esophageal cancer and have vital practical value for health services and policies implementation.

OBJECTIVETo develop a risk model for predicting later development of diabetic nephropathy (DN) in Chinese people with type 2 diabetes mellitus (T2DM) and evaluate its performance with independent validation.

METHODSWe used data collected from the project 'Comprehensive Research on the Prevention and Control of Diabetes', which was a community-based study conducted by the Jiangsu Center for Disease Control and Prevention in 2013. A total of 11,771 eligible participants were included in our study. The endpoint was a clear diagnosis of DN. Data was divided into two components: a training set for model development and a test set for validation. The Cox proportional hazard regression was used for survival analysis in men and women. The model's performance was evaluated by discrimination and calibration.

RESULTSThe incidence (cases per 10,000 person-years) of DN was 9.95 (95% CI; 8.66-11.43) in women and 11.28 (95% CI; 9.77-13.03) in men. Factors including diagnosis age, location, body mass index, high-density-lipoprotein cholesterol, creatinine, hypertension, dyslipidemia, retinopathy, diet control, and physical activity were significant in the final model. The model showed high discrimination and good calibration.

CONCLUSIONThe risk model for predicting DN in people with T2DM can be used in clinical practice for improving the quality of risk management and intervention.

Aged ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Nephropathies ; pathology ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Reproducibility of Results ; Risk Factors ; Urban Population

Purpose: To evaluate the use of signal intensity index (SII) of skull-base invasion in nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI), select a best cut-off SII value to predict the outcome of NPC. Materials and Methods: One hundred and twenty-two NPC patients (92 men, 30 women) with skull-base invasion were included. All patients underwent MRI, signal intensities on T1-weighted imaging (T1WI) were measured for each invaded site and its contralateral normal counterpart. The SIIs were calculated, receiver operating characteristic curves were constructed. The optimal cut-off values were extracted. The overall survival (OS) rates of 5-year follow-up were performed. Results: Sensitivities for differentiating skull-base invasion from normal contralateral anatomy were 98.9%, 88.5% and 70.0%, and specificities were 98.9%, 96.0% and 74.4%, respectively. There were three cut-off values for differentiating invasion from normal anatomy of skull-base, 49%, 98%, and 60%. Significant difference in OS rates (84.2% vs. 57.1%, p=0.007) was seen for SII threshold values > 60% and those ≤ 60%. Conclusions: The SII might be a useful means of differentiating invasion from normal tissue at the skull-base in NPC. The cut-off value of quantitative SII at the skull-base may aid in monitoring the response to treatment of NPC patients.

Ginsenoside Rb3 (GRb3) is one of the main components in plasma of Panax quinquefolius Saponin of stem and leaf (PQS), which can be into human plasma. Previous studies have found PQS has estrogen-like vascular protective effects. In the present study, we investigated the estrogen-like protective effect of GRb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein. The activities of SOD, NOS and the contents of MDA in the cell lysate were examined by enzyme method or spectrophotometry. The NO and ET-1 concentrations in the cell culture supernatant were measured by ELISA method. The iNOS and eNOS mRNA expression were measured by real time RT-PCR, while the phosphorylation levels of Akt was measured by Western blotting. The results showed that GRb3 could enhance the activity of SOD, reduce the content of MDA, increase the level of NOS, NO, ET-1 and iNOS mRNA expression while decrease the eNOS mRNA expression and the phosphorylation level of Akt. These effects were blocked by estrogen receptor antagonist ICI182780. GRb3 can play a role in protecting vascular endothelial cells by estrogen receptors, the protective mechanism is similar to 17-β estrodiol.
Cells, Cultured ; Endothelial Cells ; drug effects ; Endothelin-1 ; metabolism ; Estradiol ; analogs & derivatives ; Estrogens ; pharmacology ; Ginsenosides ; pharmacology ; Humans ; Lipoproteins, LDL ; adverse effects ; Nitric Oxide Synthase Type II ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Oxidative Stress ; Panax ; chemistry ; Phosphorylation ; Saponins ; pharmacology ; Superoxide Dismutase ; metabolism