Direct compression is an ideal method for tablet preparation, but it requires the powder's high functional properties. The functional properties of the powder during compression directly affect the quality of the tablet. 15 parameters such as Py, FES-8KN, FES-12KN, FES-16KN, CR-8KN, CR-12KN, and CR-16KN were used as the characteristic variables in this paper. Unsupervised learning methods like principal component analysis, cluster analysis, and factor analysis were applied to analyze and classify the compression behavior data of 36 traditional Chinese medicine powders. The results showed that both different dimensionality reduction classification methods could effectively differentiate the compression behavior characteristics of 36 traditional Chinese medicine compound powders. The hierarchical cluster analysis results showed a better agreement with the actual compression phenomena of the powders, where group 1 was high elasticity and low compressibility, group 2 was easily compressed and hard to break, group 3 was excellent compressibility and compactibility. This study is expected to provide references and ideas for predicting the behavior of traditional Chinese medicine powders and the screening of tablet formulations.

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Objective To evaluate the bioequivalence of test and reference mirabegron sustained release tablets under fasting/postprandial conditions.Methods A randomized,open,single dose,four cycle,two sequence,self-crossover trial design was used.32 healthy subjects respectively for fasting and fed study were enrolled,who were randomized to a single oral dose of 50 mg of either reference or test preparation of mirabegron sustained release tablets.The plasma concentration of mirabegron in healthy subjects after oral administration was detected by liquid chromatography tandem mass spectrometry,and Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of mirabegron.The main pharmacokinetic parameters of mirabegron in the fasting study were asfollows:Cmaxwere(43.91±21.40)and(40.82±24.94)ng·mL-1,AUC0-t were(464.45±149.01)and(452.67±157.63)h·ng·mL-1,AUC0-∞were(501.64±162.39)and(488.70±173.81)h·ng·mL-1.The main pharmacokinetic parameters of mirabegron in the fed study were as follows:Cmax were(16.90±8.94)and(16.90±9.66)ng·mL-1,AUC0-t were(247.09±82.53)and(243.22±78.20)h·ng·mL-1,AUC0-∞ were(269.58±86.52)and(265.66±81.89)h·ng·mL-1.The 90％confidence intervals for the geometric means of Cmax,AUC0-t and AUC0-∞ for reference and test preparations in the fasting and fed groups were in the range of 80.00％to 125.00％.Conclusions The test and reference formulation of mirabegron sustained release tablets were bioeguivalence.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Objective:To investigate the effects of Jianpi Huatan Prescription on a rat model of polycystic ovary syndrome (PCOS) with insulin resistance (IR) induced by letrozole combined with high fat diet based on the liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK) signaling pathway; To discuss its mechanism.Methods:A total of 40 SD female rats were divided into model group (30 rats) and blank group (10 rats). The model group rats were fed with high-fat feed from the first week of modeling for 8 consecutive weeks, and from the fourth week onwards, were given a daily gavage of letrozole solution for 5 consecutive weeks; the blank group was fed normally, and from the 4th week onwards, an equal amount of sodium carboxymethyl cellulose solution was administered. After the completion of modeling, the modeling group was divided into Jianpi Huatan Prescription group, Metformin group, and model group according to random number table method. The Jianpi Huatan Prescription group and the metformin group were given corresponding drug interventions, while the other two groups were simultaneously administered an equal amount of physiological saline for a total of 4 weeks. Ovarian morphological changes were observed using HE staining; intraperitoneal glucose tolerance test (IPGTT) was used to detect glucose tolerance in rats; Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E 2), total testosterone (T), fasting blood glucose (FBG), and fasting insulin (FINS) in rats; Real time fluorescence quantitative PCR and Western blot techniques were used to detect changes in LKB1, AMPK mRNA and protein expression in the LKB1/AMPK signaling pathway of rat ovarian tissue. Results:Compared with the model group, the polycystic changes in the ovaries of rats in the Jianpi Huatan Prescription group were improved, and the growth rate of body weight decreased. The levels of FBG, FINS, HOMA-IR, and IPGTT decreased ( P<0.05 or P<0.01), while serum FSH and HDL-C levels were significantly up-regulated ( P<0.05 or P<0.01). The levels of T, LH, LH/FSH, TC, TG, and LDL-C decreased ( P<0.05 or P<0.01); The mRNA and protein expression levels of LKB1 and AMPK in ovarian tissue increased ( P<0.05). Conclusion:Jianpi Huatan Prescription can improve PCOS-IR in rats caused by the combination of letrozole and high-fat diet, regulate various levels of sex hormones, and improve glucose and lipid metabolism disorders by regulating the LKB1/AMPK signaling pathway, which has a repairing effect on polycystic ovary disease in rats.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

A boy,aged 7 months,presented with severe global developmental delay(GDD),refractory epilepsy,hypotonia,nystagmus,ocular hypertelorism,a broad nasal bridge,everted upper lip,a high palatal arch,and cryptorchidism.Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K)in the EEF1A2 gene,and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation.This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy,genetic testing for EEF1A2 gene mutations should be considered.This is particularly important for those exhibiting hypotonia,nonverbal communication,and craniofacial deformities,to facilitate a confirmed diagnosis.

This study was aimed at creating an engineered strain of Bacillus subtilis for efficient expression of biologically active type 2 toxin B(TcdB2)derived from a highly virulent strain of Clostridium difficile.The TcdB2 gene was cloned from ST1/RT027 strain genome DNA,incorporated into the PHT01 vector,and then transformed into B.subtilis strain WB800N for prokaryotic expression.Cell toxicity assays revealed that the recombinant TcdB2 exhibited cytotoxic effects in various cells.The engineered B.subtilis strain effectively expressed biologically active TcdB2,thus providing a basis for further exploration of the pathogenic mechanisms of highly virulent strains of C.difficile and establishing a foundation for potential vaccine can-didate targets.

Objective:To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia(TDT),and reveal the changes of metabolic pattern in children with TDT.Methods:23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected,and 11 healthy children who underwent physical examination during the same period were selected as the control group.The routine indexes between children with TDT and the control group were compared,and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry.An OPLS-DA model was established to perform differential analysis on the detected metabolites,and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites.Results:The results of routine testing showed that the indexes of ferritin,bilirubin,total bile acid,glucose and triglycerides in children with TDT were significantly higher than those in healthy controls,while hemoglobin and total cholesterol were significantly lower(all P＜0.05).However there was no significant difference in lactate dehydrogenase between the two groups(P＞0.05).Compared with the control group,190 differential metabolites(VIP＞1)were identified in TDT children.Among them,168 compounds such as arginine,proline and glycocholic acid were significantly increased,while the other 22 compounds such as myristic acid,eleostearic acid,palmitic acid and linoleic acid were significantly decreased.The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism.Conclusion:The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group.This finding is helpful to optimize the treatment choice for children with TDT,and provides a new idea for clinical treatment.