BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Objective·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein(COMP)in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment.Methods·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS(GEO)database,and differentially expressed genes(DEGs)were obtained via GEO2R.The molecular functions and signaling pathways related to differential genes were summarized.The most correlated key genes(hub genes)were acquired by Weighted Gene Co-Expression Network Analysis(WGCNA)and the protein-protein interaction network(PPI)of DEGs was constructed with STRING database.The enrichment analysis was performed again.Conditionally immortalized mouse podocyte cells were cultured in vitro.After being fully differentiated,they were stimulated with high glucose,and the expressions of COMP,mammalian target of rapamycin(mTOR),microtubule-associated protein 1 light chain3(LC3)and other proteins in podocytes were detected by Western blotting.The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP,and the stable cell strains were screened by puromycin.The expression of COMP,mTOR,and LC3 of stable strains were detected by Western blotting,in order to observe the effect of COMP on autophagy.Results·A total of 362 DEGs were filtered for subsequent analysis.Among these DEGs,284 genes were up-regulated and 78 genes were down-regulated.The results of Gene Onotology(GO)term analysis showed that DEGs in diabetic nephropathy(DN)were mainly enriched in cell surface receptor signaling pathway,receptor binding,etc.The main enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways included phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway,extracellular matrix(ECM)-receptor interaction,etc.Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes,and the hub genes with significantly increased or decreased expression were sifted.The hub genes were annotated with KEGG again,and it was found that most of the hub genes were enriched in"ECM-receptor interaction"and"PI3K/AKT signaling pathway".The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway,and COMP was absolutely overexpressed(logFC>2)in the 64 hub genes,suggesting that it may affect autophagy through this pathway.Western blotting showed that compared with the mannitol control group and the low glucose group,the expression of COMP in podocytes was significantly increased under high glucose stimulation.Compared with the control group,the expression of LC3-Ⅱ in the high glucose group was significantly decreased,indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment.Compared with the negative control,the expression of LC3-Ⅱ in renal podocytes of mice with knockdown of COMP was significantly increased,and the mTOR decreased with the decrease of the expression of COMP,indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes.Conclusion·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway.Autophagy in mouse renal podocytes is inhibited under high glucose conditions,and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition.Inhibiting COMP helps to restore autophagy in mouse renal podocytes.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the screening scheme of gastric cancer in large-scale natural population in Wuxi.Methods:From December 2016 to December 2019, 105 865 residents of 19 communities (villages) in six streets of Xinwu District, Wuxi were randomly enrolled in this study by random number table. A household epidemiological questionnaire survey was conducted among 50 063 target population subjects (aged 40-69), and then, respondents were divided into four categories, category Ⅰ: HP (-), PG (-); category Ⅱ: HP (+ ), PG (-); category Ⅲ: HP (+ ), PG (+ ); category Ⅳ: HP (-), PG (+ )according to the serological Helicobacter pylori ( HP) antibodies and pepsinogen (PG) test results. People in category Ⅲ and Ⅳ were all selected into group C and group D respectively, then individuals 3 times of group D were randomly selected from category Ⅰ to assign to group A, and individuals 3 times of group C from category Ⅱwere assigned to group B in the same way. Remaining individuals in category Ⅰ and Ⅱ who had first-degree family history of gastric cancer were also included in group A and group B, respectively. Endoscopic and pathological examination were performed on the above enrolled subjects for high grade intraepithelialneoplasia (HGIN), early gastric cancer and gastric cancer. Results:Of the 50 063 target subjects, 31 508 questionnaires were finally collected, with a participation rate of 62.9%. A total of 19 745 people were tested for serology, and the participation rate was 39.4% (19 745/50 063). Serological results showed that there were 11 152 people (56.48%) in category Ⅰ, 8 170 (41.38%) in category Ⅱ, 124 (0.63%) in category Ⅲ, and 299 (1.51%) in category Ⅳ. According to the exclusion criteria and principle of voluntariness, 3 400 individuals were candidates to undergo gastroscopy. Finally, a total of 2 389 people came to the hospital for gastroscopy, 1 263 in group A, 814 in group B, 86 in group C and 226 in group D, with an overall response rate of 70.3% (2 389/3 400), target population participation rate of 4.8% (389/50 063), and the overall population participation rate of 2.3% (2 389/105 865). In the 2 389 cases, there were 32 cases (1.34%) of HGIN and gastric cancer by gastroscopy and biopsy pathology, among which 1 case (3.125%) aged 40-49, 9 (28.125%) aged 50-59, and 22 (68.750%) aged 60-69. Among the 32 cases, 25 cases (78.13%)were pathologically confirmed as having HGIN or early gastric cancer by endoscopic submucosal dissection or surgical operation. By eliminating 810 people (including 3 gastric cancer) without first-degree family history with gastric cancer in group Ⅰ and Ⅱ, and increasing the gastroscopy screening age to 50 years (exluding 214 people aged 40-49, including 1 gastric cancer), the number of people who should undergo gastroscopy could be reduced from 2 389 to 1 365, and 28 cases of HGIN or gastric cancer were still detected, including 22 HGIN or early gastric cancer.Conclusion:Gastroscopy after the screening with epidemiological, serological tests, age and first-degree relative with gastric cancer family history is suitable for gastric cancer screening in Wuxi. Based on Chinese national conditions, a new community gastric cancer screening program is recommended in Wuxi considering cost-effectiveness, which includes those over 50 years old, serological PG (+ ) and first-degree relatives with family history of gastric cancer.

Objective:To evaluate the sedative effect of remimazolam for induction of general anesthesia in elderly patients.Methods:One hundred patients of both sexes, aged 65-75 yr, with American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective general anesthesia requiring tracheal intubation, were divided into 4 groups ( n=25 each) using a random number table method: propofol group (group P) and three different doses of remimazolam groups (group R1, group R2 and group R3). In group P, general anesthesia was induced with propofol 1.5 mg/kg intravenously injected over 30 s, cisatracurium 0.2 mg/kg and fentanyl 4 μg/kg were intravenously injected when bispectral index (BIS) value ≤ 60, and endotracheal intubation was performed.In R1, R2 and R3 groups, general anesthesia was induced with 0.2, 0.3 and 0.4 mg/kg of remimazolam intravenously injected over 30 s, respectively, cisatracurium 0.2 mg/kg and fentanyl 4 μg/kg were intravenously injected when BIS value ≤ 60, and endotracheal intubation was performed.When the BIS value was > 60 during the induction of anesthesia, propofol 0.5 mg/kg was intravenously injected per time for rescue sedation in group P, and remimazolam 0.05 mg/kg was intravenously injected per time for rescue sedation until the BIS value ≤ 60, with the interval between the two injections > 1 min in R1, R2, and R3 groups.The onset time of propofol or remazolam was recorded.The occurrence of hypertension, hypotension, bradycardia, hypoxemia, injection pain and rescue sedation during the induction of anesthesia was recorded.The occurrence of intraoperative awareness was recorded during follow-up at 1 day after surgery. Results:Compared with group P, the rate of rescue sedation was significantly increased in group R1, the incidence of hypoxemia was significantly reduced in R1 and R2 groups, the onset time was significantly prolonged, and the incidence of hypotension, bradycardia and injection pain was decreased in R1, R2 and R3 groups ( P<0.05). Compared with group R1, the rate of rescue sedation was significantly decreased in R2 and R3 groups ( P<0.05). Compared with R1 and R2 groups, the incidence of hypoxemia was significantly increased in group R3 ( P<0.05). There was no significant difference in the incidence of hypotension, hypoxemia and injection pain among R1 group, R2 group and R3 group ( P>0.05). No hypertension and intraoperative awareness was found in the four groups. Conclusion:Remimazolam can be safely and effectively used for sedation during induction of general anesthesia in elderly patients, and the optimal dose is 0.3 mg/kg.

Objective To assess the association between early adiposity rebound (AR) and indices of obesity and metabolic risk in 5-year-old children. Methods Based on Ma’anshan Birth Cohort Study (MABC), single live births born in Ma'anshan of Anhui province from October 2013 to April 2015 were followed for up to 5 years consecutively. As of August 2019, 720 children with continuous measurements (≥8 times) and metabolic indicators were obtained. Physical examination and laboratory tests were used to obtain information on the birth status, length/height, weight, waist circumference, body composition and metabolic indicators of children. The 2 test, F test, t-test, non-parametric test, general linear model and logistic regression model were used for statistical analysis. Results 43.5% of the children had AR≤4 years. After controlling for gender, it was found that earlier AR was associated with overweight/obesity (OR=2.71, 95%CI: 1.81~4.05), larger waist circumference (OR=1.88, 95%CI: 1.25~2.82), and body fat percentage ≥90th percentile (OR=2.09, 95%CI: 1.26~3.48). In the earlier AR group, the insulin resistance and metabolic score were higher, but the difference was not statistically significant. At 5 years of age, the prevalence of obesity and overweight was 6.0% and 12.8%, respectively. Children with overweight/obesity, larger waist circumference, higher waist-to-weight ratio and body fat percentage ≥ 90th percentile were associated with higher insulin resistance and metabolic score, and all the differences were statistically significant (all P<0.001). Conclusion Earlier AR increased the risk of overweight/obesity, larger waist circumference, and body fat percentage ≥90th percentile at age of 5 years. Each index of the commonly used measures of childhood obesity was closely related with insulin resistance and metabolic risk factors at 5 years old.