Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC_0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC_0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).
Alkaloids ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Double-Blind Method ; Glycated Hemoglobin A ; Humans ; Hypoglycemic Agents/therapeutic use* ; Morus ; Tablets/therapeutic use* ; Treatment Outcome

Objective: To examine the associations of childhood obesity, assessed by genetic variations of childhood body mass index (BMI), with the risk of adult ischemic heart disease (IHD) and major coronary event (MCE). Methods: More than 69 000 participants from the China Kadoorie Biobank were genotyped. After excluding those with coronary heart disease, stroke, or cancer at baseline, a total of 64 454 participants were included in this study. Based on genome-wide significant single nucleotide polymorphisms (SNPs), childhood BMI genetic risk score were constructed for every participant and divided into quintiles, with the lowest quintile as the low genetic risk group and the highest quintile as the high genetic risk group. Cox proportional hazards regression models were used to estimate the association between genetic predisposition to childhood obesity and the risk of ischemic heart disease. Results: During a median of 10.7 years of follow-up, 7 073 incident cases of IHD and 1 845 cases of MCE were documented. After adjusting for sex, age, region, and the first ten genetic principal components, the HRs (95%CIs) for IHD and MCE in the high genetic risk group were 1.10 (1.02-1.18) and 1.10 (0.95-1.27), compared with the low genetic risk group. IHD risk increased by 4% (2%-6%) for each one standard deviation increase in genetic risk score (trend P=0.001). After further adjustment for baseline BMI, the differences between genetic risk groups were not statistically significant, but there was still a linear trend between genetic risk score and IHD risk (trend P=0.019). Conclusions: IHD risk increased with genetic predisposition to childhood obesity, suggesting that childhood obesity is an important risk factor for the development of IHD in China. As an easily identifiable feature, changes of childhood BMI should be monitored regularly to realize early intervention of IHD in adults.
Adult ; Body Mass Index ; Child ; China/epidemiology* ; Genetic Predisposition to Disease ; Humans ; Myocardial Ischemia/genetics* ; Pediatric Obesity/genetics* ; Prospective Studies ; Risk Factors

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Angiogenesis Inhibitors/therapeutic use* ; Endothelial Growth Factors/therapeutic use* ; Hemorrhage ; Hypertension, Pregnancy-Induced ; Oxygen/therapeutic use* ; Retinopathy of Prematurity/drug therapy* ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A

OBJECTIVE: To observe the clinical therapeutic effect of the combination of electroacupuncture (EA) at METHODS: A total of 58 patients after uterine curettage of incomplete abortion were randomized into an EA group and a western medication group, 29 cases in each one. In the western medication group, mifepristone tablets were administered orally, 2 tablets each time, once daily. In the EA group, on the base of the treatment as the western medication group, EA was applied to RESULTS: After treatment, the intrauterine residue area and CDFI blood flow signal positive rate were all reduced as compared with the values before treatment in patients of the two groups ( CONCLUSION The combined treatment of electroacupuncture at
Abortion, Incomplete/therapy* ; Abortion, Induced ; Acupuncture Points ; Curettage ; Electroacupuncture ; Female ; Humans ; Pregnancy

Objective:To investigate the differences of main components of prepared Morindae Officinalis Radix，Morindae Officinalis Radix processed with steaming and salt. Method:A total of 83 batches samples were collected in the market， including 41 batches of prepared Morindae Officinalis Radix，32 batches of Morindae Officinalis Radix processed with steaming and 10 batches of Morindae Officinalis Radix processed with salt. The contents of main components were determined with high performance liquid chromatography coupled with four-pole tandem time-of-flight mass spectrometry（UPLC-Q-TOF-MS），and the differences were analyzed. Result:The main components of prepared Morindae Officinalis Radix and Morindae Officinalis Radix processed with salt were fructo-oligosaccharides （GFn），monotropein. The main components of Morindae Officinalis Radix processed with steaming were fructose，glucose，sucrose，and monotropein. The main differences of prepared Morindae Officinalis Radix and Morindae Officinalis Radix processed with steaming and salt were the contents of fructose，glucose，sucrose and GF2-GF11. The contents of GF2-GF11 in Morindae Officinalis Radix processed with steaming and salt were all lower than those in prepared Morindae Officinalis Radix，with extremely significant differences（P<0.01）. The contents of fructose，glucose and sucrose in Morindae Officinalis Radix processed with steaming were significantly higher than those in prepared Morindae Officinalis Radix. The content of GF3 in each batch was higher than 40.0 mg·g^-1 in prepared Morindae Officinalis Radix and Morindae Officinalis Radix processed with salt，and significantly higher than the limit in Chinese Pharmacopoeia. However，there were only a few batches of Morindae Officinalis Radix processed with steaming in line with the requirements of Chinese Pharmacopoeia. The contents of monotropein in processing Morindae Officinalis Radix and Morindae Officinalis Radix processed with steaming and salt were 42.6，39.8，32.3 mg·g^-1，respectively. The content of monotropein in prepared Morindae Officinalis Radix was higher than that in Morindae Officinalis Radix processed with steaming. The content of monotropein in Morindae Officinalis Radix processed with steaming was higher than that in Morindae Officinalis Radix processed with salt. Compared with the components of GF2-GF11，the effect of processing with steaming process and/or salt on monotropein content was relatively less. Conclusion:The contents of GF2-GF11 components in prepared Morindae Officinalis Radix were converted into fructose，glucose and sucrose after processing with steaming and/or salt. The results showed that the content limit of Morindae Officinalis Radix processed with steaming needs to be revised in line with the requirements of Chinese Pharmacopoeia for the quality control of Morindae Officinalis Radix. The results provide a reference basis for revising the quality standards and studying the pharmacodynamic material basis of prepared Morindae Officinalis Radix，Morindae Officinalis Radix processed with steaming and salt.

: Aim To explore the role and possible mechanism of forked transcription factor (FoxO1) in hepatocyte apoptosis induced by homocysteine (Hey) . Methods The male cbs

Objective:Through phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR） signaling pathway， explore the effect of Zhigancao Tang on myocardial ischemia-reperfusion injury（MIRI）The role and mechanism of arrhythmia（ventricular tachycardia and ventricular fibrillation）. Method:The 72 SD rats were randomly divided into sham operation group，model group， Zhigancao Tang low，medium and high dose group（11.43，22.86，45.72 g·kg^-1），Wenxin granule group（2.43 g·kg^-1），continuous drug intervention for 10 days. Two hours after the last administration，the MIRI model of rat was prepared by ligating the left anterior descending coronary artery，and the changes of electrocardiogram were recorded. After successful modeling，blood and heart tissue were collected to detect the content of creatine creatine（CK），lactate dehydrogenase（LDH）and aspartate aminotransferase（AST）in the serum, the enzyme-linked immunoassay（ELISA） method was used to detect cardiac troponin（CtnI）content, immunohistochemical detection of myocardial PI3K，Akt，mTOR expression. Western blot was used to detect the myocardial autophagy-related protein microtubule-associated protein 1 light chain 3（LC-3），autophagy markers Beclin1 and PI3K/Akt/mTOR signaling pathway related protein expression and phosphorylated p-PI3K，p-Akt，p-mTOR levels. Result:In model group， 100% of ventricular tachycardia and 91.67% of ventricular fibrillation occurred. Compared with sham operation group， the serum levels of CK，LDH，AST，and CtnI in the model group were significantly increased（P<0.01），PI3K，Akt，mTOR AOD values in myocardial tissue were significantly increased （P<0.01），the relative expression of the ratio of LC3-Ⅱ/LC3-Ⅰ and Beclin1 was significantly increased（P<0.01），p-PI3K/PI3K，p-Akt/Akt，and p-mTOR/mTOR were significantly reduced （P<0.01）. Compared with model group， the incidence of ventricular tachycardia and ventricular fibrillation in the high-dose Zhigancao Tang group was significantly reduced （P<0.01），and the duration was the shortest compared with other administration groups（P<0.01）， CK，LDH，AST level and CtnI content were significantly reduced（P<0.01）， the expression of PI3K，Akt and mTOR of Zhigancao Tang group was significantly decreased with increasing dose（P<0.01）， the expression of LC-3 and Beclin1 was accompanied by Zhigancao Tang increase of each dose group of soup had different degrees of decrease （P<0.01），while the expression ratio of PI3K/Akt/mTOR-related protein was significantly increased （P<0.05，P<0.01）. Conclusion:Pretreatment of Zhigancao Tang can reduce the abusually elevated cardiac enzymes CK, LDH, AST and CtnI, inhibit excessive autophagy of cells, and up-regulate the expression of PI3K, Akt and mTOR, indicating that the anti-MIRI arrhythmia effect of Zhigancao Tang may be related to the PI3K/Akt/mTOR signaling pathway.