The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVES: To explore the predictive factors for non-response to intravenous immunoglobulin (IVIG) in children with Kawasaki disease (KD) and to establish an IVIG non-response prediction scoring model for the Sichuan region. METHODS: A retrospective study was conducted by collecting clinical data from children with KD admitted to four tertiary hospitals in Sichuan Province between 2019 and 2023. Among them, 940 children responded to IVIG, while 74 children did not respond. Multivariate logistic regression analysis was used to identify the predictive factors for non-response to IVIG and to establish a predictive scoring model. The model's effectiveness was assessed using the receiver operating characteristic curve (ROC) and validated with an independent dataset. RESULTS: Multivariate logistic regression analysis showed that the platelet-to-lymphocyte ratio (PLR), hemoglobin (Hb), serum creatinine, aspartate aminotransferase (AST), and platelet count (PLT) were closely related to non-response to IVIG in children with KD (P<0.05). Based on these indicators, a predictive scoring model was established: PLR > 199, 0.4 points; Hb ≤ 116 g/L, 4 points; AST > 58 U/L, 0.2 points; serum creatinine > 38 µmol/L, 3.9 points; PLT count ≤ 275 × 10⁹/L, 0.3 points. Using this model, children with KD were scored, and a total score greater than 4.3 was considered high risk of non-response to IVIG. The sensitivity of the model in predicting non-response to IVIG was 77.0%, specificity was 65.7%, and the area under the ROC curve was 0.746 (95%CI: 0.688-0.805). CONCLUSIONS The predictive scoring model based on PLR, Hb, serum creatinine, AST, and PLT demonstrates good predictive performance for non-response to IVIG in children with KD in the Sichuan region and can serve as a reference for clinical decision-making.
Humans ; Mucocutaneous Lymph Node Syndrome/blood* ; Immunoglobulins, Intravenous/therapeutic use* ; Male ; Female ; Retrospective Studies ; Child, Preschool ; Infant ; Logistic Models ; Child ; Platelet Count ; ROC Curve

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.

Objective To investigate the correlation between traditional Chinese medicine(TCM)syndrome elements and risk factors in patients with type Ⅱ cardio-renal syndrome(CRS).Methods A retrospective analysis was conducted on the medical records of 116 patients with type Ⅱ CRS.The distribution of TCM syndrome elements was analyzed,and the correlation between the syndrome elements and risk factors of gender,age,smoking history,alcohol consumption history,coronary heart disease,hypertension,diabetes,and anemia were evaluated.Results(1)The analysis of syndrome elements of 116 patients with type Ⅱ CRS showed that the main disease-location elements were heart(96 cases,82.76%),lung(89 cases,76.72%),kidney(81 cases,69.83%),spleen(71 cases,61.21%),and liver(25 cases,21.56%);the main disease-nature elements were qi deficiency(113 cases,97.41%),blood deficiency(96 cases,82.76%),yang deficiency(95 cases,81.89%),phlegm(94 cases,81.03%),yin deficiency(90 cases,77.59%),dampness(61 cases,52.59%),water retention(55 cases,47.41%),and blood stasis(47 cases,40.52%).(2)The analysis of age groups of 116 patients with type Ⅱ CRS showed that the majority of the patients were middle-aged and elderly individuals over 60 years old,and the age groups covered＜60 years old(4 cases,3.45%),61-70 years old(10 cases,8.62%),71-80 years old(28 cases,24.14%),81-90 years old(64 cases,55.17%),and>90 years old(10 cases,8.62%).(3)The analysis of gender of 116 patients with type Ⅱ CRS showed that 46 cases(39.66%)were male,and 70 cases(60.34%)were female,the female outnumbering the male.(4)The exploration of correlation between TCM syndrome elements and risk factors with Logistic regression analysis showed that blood deficiency was positively correlated with alcohol consumption,hypertension,and anemia(P＜0.05 or P＜0.01),yang deficiency was positively correlated with anemia(P＜0.05),yin deficiency was positively correlated with smoking and diabetes(P＜0.05),dampness was positively correlated with smoking and anemia(P＜0.01),water retention was positively correlated with gender and protein abnormalities(P＜0.05 or P＜0.01),and blood stasis was positively correlated with hypertension(P＜0.05).Conclusion The illness of type Ⅱ CRS is located in the heart,involving the five organs,and is closely related to the lungs and kidneys.The general pathogenesis of type Ⅱ CRS is characterized by being deficiency of qi and yang in the root cause,and having the symptom manifestations of phlegm and blood stasis.In type Ⅱ CRS patients,men are more likely to suffer water retention,smokers are more likely to suffer yin deficiency and dampness,drinkers are more likely to suffer blood deficiency,individuals with hypertension are more likely to suffer blood deficiency and blood stasis,individuals with diabetes are more likely to suffer yin deficiency,individuals with anemia are more likely to suffer blood deficiency,yang deficiency and dampness,and individuals with protein abnormalities are more likely to suffer water retention.

Objective To investigate the impact of different antibiotic courses on intestinal floras and immune function in 28-day-old premature infants.Methods A retrospective analysis was conducted on 120 premature infants admitted to the First People's Hospital of Nanyang City between March 2021 and March 2024.According to different courses of antibiotics,they were divided into short-course group(n=82,antibiotics use≤3 d)and long-course group(n=38,antibiotics use≥7 d).General data were collected,and intestinal floras and immune function were assessed at 28 days of age.Shannon and Simpson indexes of intestinal flora α-diversity,bacterial phylum and genus distribution of intestinal floras,and peripheral blood CD8+,CD4+T cell percentages,and CD4+/CD8+ratio were compared between the two groups.Pearson correlation analysis was used to explore the relationship between intestinal floras and immune function,and adverse outcomes were recorded.Results The Shannon and Simpson indexes of intestinal flora α-diversity in long-course group were lower than those in short-course group(P<0.05).No significant differences were found between the two groups in the distribution of Actinobacteria,Bacteroidetes,Firmicutes or Proteobacteria at the bacterial phylum level and Bacteroides,Enterococcus,or Veillonella at genus distribution level(P>0.05).However,the long-course group had lower proportions of Clostridioides,Clostridium sensu stricto 1,Escherichia and Klebsiella,and higher proportions of Enterococcus,Robinsoniella and Streptococcus than those in short-course group(P<0.05).After antibiotics use,levels of CD4+and CD4+/CD8+were decreased(P<0.05),while CD8+was increased in both groups(P<0.05).Compared with short-course group,levels of CD4+and CD4+/CD8+were lower,while CD8+was higher in short-course group(P<0.05).Pearson correlation analysis revealed that Clostridioides,Clostridium sensu stricto 1,Escherichia,Klebsiella were positively correlated with CD4+and CD4+/CD8+,while negatively correlated with CD8+(P<0.05).Conversely,Enterococcus,Robinsoniella and Streptococcus were negatively correlated with CD4+and CD4+/CD8+,while positively correlated with CD8+(P<0.05).No adverse outcomes occurred in two groups.Conclusion Compared with short-term antibiotic use,long-term use affects the colonization and diversity of intestinal floras in premature infants,and cause intestinal flora disturbance,potentially impairing immune function.

Early postoperative hypoxemia,a common adverse event following general anesthesia,is closely associated with pathophysiological changes in patients,prolonging stays in the post-anesthesia care unit(PACU)and intensive care unit(ICU),and correlating with increased one-year postoperative mortality rate.Nevertheless,due to differences in definitions of hypoxemia,heterogeneity of study populations,and variations in postoperative monitoring methods,the reported incidence and duration of early postoperative hypoxemia in the literature vary significantly.This review systematically summarizes relevant literature to elucidate the definition and characteristic indicators of early postoperative hypoxemia,and explores its correlations with postoperative respiratory complications,cardiovascular complications,and surgical site infections.By analyzing existing research evidence,this review aims to identify early-warning indicators of postoperative hypoxemia with predictive value,thereby providing a reference for future research in this field.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

BACKGROUND:Reducing the rate of abnormal fertilization is an effective approach to improving the efficacy of in vitro fertilization and reducing patients'financial strain.However,the current research on abnormal fertilization has focused on exploring the types of prokaryotic nuclei and their generation mechanisms,as well as analyzing embryos formed by abnormal fertilization,chromosomal ploidy and utilization value.There is a lack of clinical prediction models for abnormal fertilization based on retrospective studies. OBJECTIVE:To construct a nomogram model to predict abnormal female factors in in vitro fertilization. METHODS:A total of 5 075 patients undergoing treatment for conventional in vitro fertilization at Nanxishan Hospital of Guangxi Zhuang Autonomous Region from March 2017 to March 2022 were retrospectively analyzed.The male confounders were calibrated on a 1:1 propensity score with a match tolerance of 0.02,and 1 672 cases were successfully matched.According to the Vienna Consensus,patients with≥60%normal fertilization capacity were included in the normal fertilization group(n=836)and those with<60%normal fertilization capacity were included in the abnormal fertilization group(n=836).The model and validation groups were obtained by random sampling at a ratio of 7:3.Factors related to the occurrence of abnormal fertilization following conventional in vitro fertilization in the model group were screened using univariate analysis and the best matching factors were selected using the Least Absolute Shrinkage and Selection Operator(LASSO)and included in a multifactorial forward stepwise Logistic regression to identify their independent influencing factors and plot a nomogram.Finally,the prediction model was validated for discrimination,accuracy and clinical application efficacy using receiver operating characteristic curves,calibration curves,clinical decision curves and clinical impact curves. RESULTS AND CONCLUSION:The univariate analysis indicated the factors influencing the occurrence of abnormal fertilization were age,controlled ovarian hyperstimulation protocol,number of assisted pregnancies,years of infertility,infertility factors,anti-mullerian hormone,sinus follicle count,basal luteinizing hormone,luteinizing hormone concentration on the human chorionic gonadotropin day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).LASSO regression further identified the best matching factors,including age,microstimulation protocol,number of assisted pregnancies,years of infertility,anti-mullerian hormone,luteinizing hormone level on human chorionic gonadotropin injection day,and estradiol level on human chorionic gonadotropin injection day(P<0.05).Multifactorial forward stepwise Logistic regression results showed that age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day were independent influencing factors for the occurrence of abnormal fertilization following conventional in vitro fertilization.The receiver operating characteristic curves showed an area under the curve of 0.761(0.746,0.777)for the model group and 0.767(0.733,0.801)for the validation group,indicating that the model has good discrimination.The mean absolute error of the calibration curve was 0.044,and the Hosmer-Lemeshow test indicated that there was no significant difference between the predicted probability of abnormal fertilization and the actual probability of abnormal fertilization(P>0.05),indicating the prediction model has good consistency and accuracy.The clinical decision curves and clinical impact curves showed that the model and validation groups had the maximum net clinical benefit at valve probability values of 0.00-0.52 and 0.00-0.48,respectively,and there was a good clinical application efficacy in this valve probability range.To conclude,the nomogram model has good discrimination and accuracy as well as clinical application efficacy for predicting the occurrence of abnormal fertilization in women undergoing conventional in vitro fertilization based on age,microstimulation protocol,number of assisted conceptions,years of infertility,anti-mullerian hormone,and estradiol level on human chorionic gonadotropin injection day.

Objective To investigate the clinical application of perioperative human serum albumin(HSA)in cardiac surgery in multiple regions in China,and to evaluate the rationality of its clinical application in conjunction with the clinical guidelines,in order to provide a reference for promoting the rational application of HSA.Methods The medical records of patients who underwent cardiac surgery from April to June 2019 in eight hospitals across the country were retrospectively collected.The statistical information on patients'general information,the dosage,course of treatment,and cost of HSA,and the serum albumin level before and after medication was analyzed to evaluate the use of HSA.Relevant evaluation criteria were established,and the rationality of its medication was evaluated.Results Data from a total of 449 patients were included for analysis,the appropriate rate of medication was 81.1％.The course of medication was mostly＞2-5 days and the total amount of HSA was mostly 50-99 g.The main purpose of medicaiton were improving colloid osmotic pressure,reducing exudation to improve interstitial edema,postoperative volume expansion.Conclusion Clinical attention should be paid to ensure the rational application of HSA in cardiac surgery during the perioperative period and prevent the abuse of blood products.