Objective To evaluate the safety,tolerability and pharmacokinetic profiles of naldemedine in Chinese healthy adult subjects after single and multiple administrations.Methods After single and multiple oral administrations of naldemedine to 10 healthy Chinese subjects,the plasma concentrations of naldemedine and its metabolite(nor-naldemedine)were measured by liquid chromatography-mass spectrometry,and the pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.3.1 software.Results Compared with single administration,naldemedine showed no significant change in the tmax(1.06 h for single and 1.08 h for multiple)and Cmax(4.16 ng·mL-1 for single and 4.11 ng·mL-1 for multiple),higher AUC0-τ than that of single(23.88 ng·h·mL-1 for single and 28.93 ng·h·mL-1 for multiple),slightly prolonged t1/2(9.26 h for single,12.50 h for multiple),there was a slight drug accumulation after multiple doses(accumulation ratio of 0.99 for Cmax and 1.22 for AUC);t1/2(18.10 h for single,29.30 h for multiple),Cmax(0.19 ng·mL-1 for single,0.38 ng·mL-1 for multiple),and AUC0-τ(3.13 ng·h·mL-1 for single,6.02 ng·h·mL-1 for multiple)were all significantly elevated with nor-naldemedine,and the tmax(single was 3.49 h and multiple was 3.56 h)did not change significantly.The Cmax ratio and AUC ratio of metabolites to naldemedine were significantly elevated,and accumulation was present after multiple administrations(accumulation ratio of 2.01 for Cmax and 1.95 for AUC).All adverse events that occurred after treatment were mild.Conclusion After multiple oral administrations of 0.2 mg naldemedine tablets to Chinese healthy subjects(single dose on day 1 and once daily on days 4-13),the drug was eliminated rapidly with mild accumulation,and reached a steady state before the second dose of the multiple-dosing phase,and the product has a favorable safety and tolerability profiles.

A new alkaloid (1) and six known compounds (2-7) were isolated from the solid fermentation extract of the endophytic fungus Alternaria tenuissima Pas85 of Phragmites australis by silica gel column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and other chromatographic techniques. The structures of these compounds were determined by HREIMS, NMR, IR spectroscopy, and literature comparison, and the anti MRSA (methicillin-resistant Staphylococcus aureus) activity of 1-5 were tested. Compounds 1, 2, 3 and 4 exhibited certain inhibitory activity with MIC values of 64, 4, 32 and 32 μg·mL^-1, respectively, and compound 5 showed no significant inhibitory activity.

AIM: To observe the expression levels of pigment epithelium-derived factor(PEDF)and vascular endothelial growth factor(VEGF)in lens epithelial cells(LECs)of diabetic patients with age-related cataract, and explore the pathogenesis of diabetic with age-related cataract.METHODS: Retrospectively study. A total of 30 patients with age-related cataract(ARC group)and 30 patients with type 2 diabetes mellitus combined with age-related cataract(DC group)who treated at the Department of Ophthalmology of the First Affiliated Hospital of Bengbu Medical College from August 2020 to April 2021 were collected. Anterior capsule specimens with a diameter of 5.5-6.0mm in the central region of the intraoperative eye were collected during phacoemulsification. The protein expression levels of PEDF and VEGF in LECs were detected by Western-blot. Quantitative real-time PCR(qRT-PCR)was used to detect the relative mRNA expression levels of PEDF and VEGF.RESULTS:PEDF and VEGF were expressed in LECs of both groups, and the relative expression of VEGF mRNA in DC group was 1.364±0.062, which was higher than that of ARC group(1.000±0.0; P<0.01). The relative mRNA expression level of PEDF was 0.398±0.053, which was significantly lower than 1.000±0.0 in the ARC group(P<0.001). The expression of VEGF protein in LECs was 2.053±0.026 in DC group and 1.680±0.064 in ARC group, respectively. Meanwhile, the expression of PEDF protein was 0.579±0.045 in DC group and 1.058±0.007 in ARC group(all P<0.01).CONCLUSION:The changes of PEDF and VEGF expression levels in LECs may be related to the occurrence and development of cataract in diabetic patients.

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.

At present, the research of Moutan cortex carbonisata (MCC) mainly focuses on the changes of chemical composition before and after charcoal production, and there is a lack of material basic research directly related to the efficacy at home and abroad. In this study, Moutan cortex, as a precursor, and was calcined to MCC at high temperature. The Moutan cortex carbonisata nano-components (MCC-NCs) were extracted and separated from MCC to explore its cooling-blood and hemostatic effects. In the experiment, the MCC was calcined at a high temperature in a muffle furnace (350 ℃, 1 h), and then MCC-NCs were extracted for MCC, and characterized by transmission electron microscopy and UV-vis absorption spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. In addition, the study evaluated the blood-cooling and hemostatic effects of MCC-NCs. The results showed that MCC-NCs have a size distribution of 0.80-2.8 nm, a lattice spacing of 0.26 nm. MCC-NCs are mainly composed of C, O and N elements and have abundant surface functional groups such as OH, C=O, C-N and C=C. The fluorescence yield of MCC-NCs was 7.18%. The experiments complied with the Animal Ethics Committee of Beijing University of Chinese Medicine. The result indicated that pretreatment MCC-NCs can significantly (P < 0.05) reduce the high, medium, and low viscosity of whole blood and plasma viscosity, and reduce hematocrit, red blood cell distribution width, hemoglobin and red blood cell level. In addition, MCC-NCs significantly reduced the levels of activated partial thromboplastin time, thrombin time and fibrinogen (P < 0.05). The pathological examination results showed that MCC-NCs can significantly reduce lung tissue damage, reduce bleeding and inflammatory cell infiltration. At the same time, it can also significantly reduce the symptoms of gastric mucosal bleeding. In conclusion, the results indicated that MCC-NCs has significantly the effect of blood cooling and hemostasis, and its hemostatic effect is mainly related to the activation of endogenous coagulation pathway or fibrinogen system, which provided a novel strategy for exploring the material basis of traditional Chinese medicine for hemostasis.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective: To explore the relationship between fetal nuchal translucency (NT) in the first trimester and pregnancy outcome. Methods: A prospective cohort study was conducted in Nanjjing Drum Tower Hospital from December 2015 to December 2018, 4 958 singleton pregnant women were enrolled to screen fetal ultrasound structure and serology in the first trimester, ultrasound in the second trimester and neonatus physical examination 28 days after birth. According to the results of NT, 167 cases of fetus with increased NT (≥3.0 mm) and 4 791 cases of normal NT were divided, moreover, 86 cases with isolate increased NT and 81 cases of increased NT combined with structural abnormality. The prognosis of fetuses with different NT thickness was analyzed, and the pregnancy outcome of fetuses with isolate increased NT or combined with structural abnormality were analyzed. In the first trimester, if the fetal structure was abnormal or the serological screening result was high risk, the chromosomal microarray analysis (CMA) would be performed by chorionic villus sampling to determine the prenatal diagnosis. Results: (1) The pregnancy outcome for fetus of normal NT: there were 4 791 cases with normal NT. Totally, 4 726 cases with normal NT and no structural abnormalities were screened out in the firsttrimester. In this group, 5 cases of aneuploidies were diagnosed based on high risk of maternal serum biomarkers and 83 cases of structural abnormalities were screened out in the subsequent ultrasound scan and the neonatal examination. Another 65 cases with normal NT present complicated with structural anomalies were screened out in the first trimester and 4 cases were diagnosed as aneuploidies. (2) The pregnancy outcome for fetus of isolate increased NT: 66 (76.7%, 66/86) cases of isolated increased NT were performed CMA, 3 cases were diagnosed as trisomy 21 and terminated pregnancy. Another 4 cases were terminated pregnancy privately without cytogenetic diagnosis. No further anomalies were found in 79 cases till 6 to 21 months postnatally. (3) The pregnancy outcome for fetus of increased NT with structural anomalies: increased NT present with structural anomalies were screened out by detailed anomaly scan in the first trimester and 32 of them were confirmed as aneuploidies. In this group, 70 cases terminated pregnancy, 2 cases had spontaneous miscarriages and 9 cases had liveborns (1 newborn was found ventricular septal defect). (4) The pregnancy outcome for fetus of increased NT with or without structural anomalies: the percentage of aneuploidies in fetuses with isolated increased NT (3.5%, 3/86) was significantly lower than those with structural abnormalities (39.5%,32/81). The healthy survival rate in fetuses with isolated increased NT (91.9%,79/86) was significantly higher than those with structural abnormalities (9.9%, 8/81). Conclusions A detailed first-trimester anomaly scan could improve prenatal screening efficiency of birth defects. Compared to the fetuses with increased NT combined with structural abnormalities, the healthy survival rate of fetuses with isolated increased NT based on detailed first-trimester anomaly scan is higher and the percentage of fetal aneuploidies is lower.

BACKGROUND: Insomnia is a common complaint that is closely related to gastrointestinal symptoms, which is consistent with the traditional Chinese medicine classical theory of "stomach disharmony leading to restless sleep." Acupuncture is an effective complementary and alternative medicine therapy to improve gastrointestinal function and restore the normal sleep-wake cycle. However, studies on the effectiveness of acupuncture for insomnia due to spleen-stomach disharmony syndrome are limited to case reports and few randomized controlled trials; deeper research on its mechanism is still lacking. This randomized controlled trial aims to assess the treatment efficacy of "harmonizing stomach to tranquilize mind" acupuncture for insomnia and its influence on the intestinal microbiome. METHODS/DESIGN: This is a randomized, single-blind, parallel-group study. Sixty eligible patients with insomnia due to spleen-stomach disharmony syndrome will be randomly divided into two groups (1:1 allocation ratio). The intervention group will use "harmonizing stomach to tranquilize mind" acupuncture, and the control group will receive sham acupuncture. Participants will receive 5 acupuncture treatment sessions per week for 4 consecutive weeks. The Pittsburgh Sleep Quality Index will be used to evaluate the clinical efficacy of acupuncture treatment by making assessments at baseline, the end of treatment and the end of the follow-up. High-throughput 16S ribosomal ribonucleic acid gene sequencing will be performed to detect changes in the intestinal microbial composition before and after treatment. DISCUSSION: The results of this trial are expected to confirm that "harmonizing stomach to tranquilize mind" acupuncture can effectively relieve insomnia and alter the intestinal microbiome. TRIAL REGISTRATION Chinese Clinical Trials Registry: ChiCTR1800017092.

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of -0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. Trial Registration Clinicaltrials.gov, NCT02525497; https://clinicaltrials.gov/ct2/results?cond=&term=NCT02525497&cntry=& state=&city=&dist=.
Adult ; China ; Cross-Over Studies ; Female ; Humans ; Male ; Middle Aged ; Multicenter Studies as Topic ; Peritoneal Dialysis ; adverse effects ; instrumentation ; methods ; Quality of Life ; Temperature