This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Objective:To analyze the distribution characteristics of Rh phenotype in pregnant and postpartum women in Chongqing area,and to explore the clinical significance of Rh phenotype in pregnant and postpartum women and the feasibility of Rh phenotype compatible blood transfusion.Methods:The ABO blood group and Rh phenotype of 65 161 pregnant and postpartum women were detected by microcolumn gel method,and 48 122 males in the same period were taken as controls.The data were analyzed by Chi-square test.Results:There were 112 870 cases(99.64％)of RhD+in 113 283 samples.In RhD+cases,CCDee(48.39％)and CcDEe(32.88％)were the main phenotypes.The first case of D--phenotype in Chongqing area was detected.413 cases(0.36％)of RhD-were detected,with ccdee(52.78％)and Ccdee(33.41％)as the main phenotypes.Compared with RhD-group,RhD+group showed statistically significant difference in Rh phenotype distribution(P＜0.01).Among 65 161 maternal samples,the positive rate of 5 antigens of Rh blood group from high to low was D＞e＞C＞c＞E,and there was no significant difference compared with male samples(P＞0.05).There was no significant difference in the distribution of Rh phenotype between males and pregnant/postpartum women,as well as between pregnant/postpartum women with different ABO blood groups(P＞0.05).In pregnant and postpartum women,there was no significant difference in distribution of Rh phenotype among the normal pregnancy population,the population with adverse pregnancy history,the population using human assisted reproductive technology(ART)and the population with infertility(P＞0.05).There was no significant difference in the distribution of Rh phenotype between the 4 populations mentioned above and the inpatients in the local general Grade A hospitals and the blood donors(P＞0.05).In RhD positive pregnant and postpartum women,the probability of finding compatible blood for CcDEe phenotype was 100％,the probability of finding compatible blood for CCDee,CcDee and CCDEe phenotypes was 45％-60％,the probability of finding compatible blood for ccDEE,ccDEe and CcDEE phenotypes was 5％-10％,and the probability of finding compatible blood for other phenotypes was lower than 0.5％.The supply of blood with CCDee and ccDEE phenotypes can meet the compatible transfusions requirements of 7 Rh phenotypes in more than 99％of patients.Conclusion:Rh phenotype detection should be carried out for pregnant and postpartum women,and it is feasible to carry out Rh phenotype-matched or compatible blood transfusion for pregnant and postpartum women who need blood transfusion.

Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Francisella philomiragia(F.philomiragia)infection is a rare infectious disease.This article repor-ted one case of bloodstream infection of F.philomiragia.Relevant literatures from at home and abroad were sys-tematically reviewed,and clinical characteristics of infected patients were summarized and analyzed.The research found that people with chronic granulomatous disease,drowning,blood system diseases,diabetes,kidney trans-plantation,rheumatism,alcoholism,and other immunocompromised or immune barrier damaged people are suscep-tible to F.philomiragia.Salt water exposure is a risk factor.The combined anti-infection scheme based on amino-glycosides,fluoroquinolones and doxycycline can improve the success rate of treatment.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective To explore the protective mechanism of honey-processed Hedysari Radix in regulating intestinal mucosal injury in rats with spleen qi deficiency.Methods The three-factor composite modeling method of bitter cold diarrhea,overwork and hunger and satiety disorder was used to construct a spleen qi deficiency model rats.After the model was successfully made,they were randomly divided into model group,honey-processed Hedysari Radix group and probiotic group,with 15 animals in each group.Another 15 normal rats were taken as the blank group.The honey-processed Hedysari Radix group was given 12.6 g·kg-1 water decoction of honey-processed Hedysari Radix by gavage,the probiotics group was given Bifidobacterium Lactobacillus triple viable tablets suspension at a dose of 0.625 g·kg-1,and the blank group and the model group were given the same dose of distilled water.The rats in the four groups were administered once a day for 15 days.Enzyme-linked immunosorbent assay was used to detect diamine oxidase(DAO)in serum,D-lactic acid(D-LA),secretory immunoglobulin A factor,and Western blotting was used to detect the expression levels of AMP-activated protein kinase(AMPK),zonula occludens-1(ZO-1)and occludin in colon tissues.Results The serum levels of DAO in the blank group,model group,honey-processed Hedysari Radix group and probiotic group were(138.93±9.78),(187.95±12.90),(147.21±6.92)and(166.47±3.37)pg·mL-1;the contents of D-LA were(892.23±49.17),(1 099.84±137.64),(956.56±86.04)and(989.61±51.75)μg·L-1;the contents of SIgA in colon tissues were(14.04±1.42),(11.47±2.39),(11.84±1.49)and(12.93±1.65)μg·mL-1;the relative expression levels of ZO-1 protein in colon tissues were 1.18±0.11,0.42±0.04,0.77±0.05 and 0.95±0.07;the relative expression levels of occludin protein were 1.35±0.31,0.61±0.17,1.19±0.19 and 0.88±0.13;the relative expression levels of AMPK protein were 0.91±0.02,0.35±0.09,0.74±0.08 and 0.59±0.11.Compared with the model group,there were significant differences in the serum content of DAO and D-LA,SIgA content in colon,and the content of ZO-1,occludin and AMPK protein in the honey-processed Hedysari Radix group(P＜0.01,P＜0.05).Conclusion Honey-processed Hedysari Radix can enhance the protective effect on the intestinal mucosa of rats with spleen qi deficiency by regulating the expression of related inflammatory cytokines,intestinal mucosal upper cell enzymes and tight junction proteins in rats with spleen qi deficiency.