ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To analyze the efficacy of Astragalus membranaceus and Draba nemorosa in the treatment of chronic heart failure(CHF),the change of cardiac color ultrasound parameters and its predictive value for adverse end events.Methods A total of 92 patients with Qi-deficiency and blood-stasis combined with Shuiyin CHF treated in Wenzhou Hospital of Traditional Chinese Medicine from September 2019 to September 2021 were randomly selected and divided into two groups by random number table method,with 46 cases in each group.Patients in control group were received conventional Western medicine treatment,and patients in observation group were received the addition and subtraction treatment of Yiqi Huoxue Lishui prescription based on Astragalus membranaceus and Draba nemorosa.The clinical efficacy,TCM syndrome score,heart color ultrasound parameters and the incidence of adverse endpoint events within 6 months were compared between the two groups.Cardiac color doppler ultrasound parameters were compared between the occurrence group and the non-occurrence group,and receiver operating characteristic curve was drawn to analyze the predictive value of cardiac color Doppler ultrasound parameters for adverse end events.Results The total clinical effective rate of the observation group(95.65%)was higher than that of the control group(71.74%)(P<0.05).After treatment,palpitation,weakness,shortness of breath,lethargy and lip purple score in observation group were lower than those in control group(P<0.05).The left ventricular end-diastolic diameter(LVEDD)and left arial diameters(LAD)of the observation group were lower than those of the control group after treatment(P<0.05).After treatment,the left ventricular ejection fraction(LVEF)of the observation group was higher than that of the control group(P<0.05);The incidence of adverse endpoint events within 6 months in the observation group(2.17%)was lower than that in the control group(19.57%)(P<0.05).The LVEDD and LAD in the adverse end point event group were higher than those in the without adverse end point event group(P<0.05),and the LVEF was lower than that in the without adverse end point event group(P<0.05).The area under the curve(AUC)of LVEDD,LAD and LVEF combined to predict the occurrence of adverse endpoint events was 0.812,and the 95%CI confidence interval was 0.734-0.968;The sensitivity of combined detection(93.42%)was higher than that of single detection(71.52%,75.11%,79.62%)(P<0.05).The specificity of combined detection(82.27%)compared with that of single detection(70.19%,73.07%,77.28%)(P>0.05).Conclusion Supplementing qi and promoting blood circulation and rehydrating water based on Astragalus membranaceus and Draba nemorosa can effectively improve the cardiac function of CHF patients,alleviate symptoms such as palpitations and fatigue,and reduce the incidence of adverse endpoint events.In addition,the combined detection of cardiac ultrasound parameters can improve the prediction efficiency of adverse endpoint events,which has certain clinical value.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective To evaluate the efficacy of endovascular treatment for ruptured descending thoracic aortic aneurysm(rDTAA),and to summarize the treatment experience.Methods The clinical data of 8 patients with rDTAA,who were admitted to the Department of Vascular Interventional Surgery,Zhangjiajie Municipal People's Hospital of China to receive treatment between January 2016 and June 2023,were retrospectively analyzed.The patients included 4 males and 4 females,with a median age of 70.5 years(61-78 years).Preoperative computed tomography angiography(CTA)was performed in all the 8 patients,and the diagnosis of rDTAA complicated by hematoma in the thoracic cavity and/or mediastinum was confirmed.Emergency thoracic endovascular aortic repair(TEVAR)was carried out in all the 8 patients.Results Complete isolation of the thoracic descending aortic aneurysm was achieved in 6 patients,and 2 of them received reconstruction of left subclavian artery by using chimney stent technique.The remaining two patients had a small amount of type Ⅰa endoleak,which disappeared after implantation of a cuff stent at the proximal site.During hospitalization,one patient died of septic shock caused by thoracic aortic-esophageal fistula,and 3 patients developed respiratory failure after operation,which was recovered after thoracic drainage,anti-infection medication and ventilator-assisted breathing therapy.Two patients developed postoperative ischemic stroke,one of them presented as grade Ⅲ motor muscle weakness on the affected side accompanied by speech impairment,and the another patient presented as grade Ⅳ motor muscle weakness on the affected side accompanied by speech impairment.During the follow-up period,one patient died of sudden chest pain 7 months after surgery,and another patient who had not received chimney stent implantation developed type Ⅰa endoleak 18 months after operation,which disappeared after implantation of a cuff stent at the proximal site.The remaining 5 patients showed good clinical condition during the follow-up period.Conclusion For the treatment of rDTAA,TEVAR is clinically safe and effective.

Intestinal pathogenic bacteria utilize their own virulence factors to interfere with the nor-mal function of intestinal epithelial cells and evade clearance by the host immune system through precise gene regulation and expression strategies,thereby causing a variety of diseases.It has been found that the mechanisms affecting the gene expression strategies of pathogens include the toxin-antitoxin system,secretory system,and quorum sensing system.Novel antimicrobial strategies are being developed to interfere with the inherent gene regulatory system of bacteria and inhibit the expression of virulence genes,thus enabling a modest approach to the treatment of intestinal disea-ses.This paper initially discusses the components of innate immunity in the gut,followed by a dis-cussion of the common gene regulatory system of intestinal pathogenic bacteria.This article aims to clarify the mechanisms by which intestinal pathogenic bacteria evade clearance by the innate im-mune system through gene regulation and expression strategies,and to provide new ideas for the treatment of intestinal bacterial diseases.

Objective:To assess the mental health status of anesthesiology residents and identify its influencing factors during standardized training, and to enhance the attention and understanding of standardized training management personnel regarding the mental health of residents.Methods:All on-duty residents in the anesthesiology departments of ten standardized anesthesiology training bases, including The Second Affiliated Hospital of Harbin Medical University, were selected as subjects. Self-designed questionnaires were distributed, which included a general information survey, the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Fatigue Severity Scale (FSS), and the Self-Rating Scale of Sleep (SRSS), to investigate the psychological state and sources of stress. Based on the questionnaire results, residents from the Department of Anesthesiology at The Second Affiliated Hospital of Harbin Medical University were purposively and heterogeneously selected as interviewees. One-on-one semi-structured in-depth interviews were conducted to understand the major life events that triggered emotional or psychological issues and their connections with standardized training or the profession. This survey also aimed to understand the support that anesthesiology residents hoped to receive and their suggestions for the standardized training program. The chi-square test, t-test, and one-way analysis of variance were performed using Graphpad Prism 9.0. Interview content was coded and categorized using data analysis software NVivo12. The Colaizzi's seven-step method was used to analyze the data and extract interview themes. Results:A total of 157 valid questionnaires were recovered, with a response rate of 100.00%. The mean scores of SAS, SDS, FSS, and SRSS were (50.60±14.16), (56.31±12.90), (44.49±13.88), and (27.78±9.40), respectively, all meeting the diagnostic criteria for mild conditions. Of them, 16 (10.19%), 18 (11.46%), 47 (29.94%), and 19 (12.10%) residents met the diagnostic criteria for severe conditions. Compared with Grade 1 residents, Grade 3 residents showed increased scores in anxiety [(54.24±13.83) vs. (47.02±12.04), P=0.030] and depression [(59.66±12.74) vs. (51.53±10.76), P=0.005]. In total, 24 anesthesiology residents were selected for semi-structured interview and three themes were identified: psychological stress related to the training bases, psychological stress related to personal issues, and psychological stress related to career prospects. Conclusions:The anesthesiology residents during standardized training have high prevalence of psychological disorders, which are closely related to work overload, financial stress, occupational exposure, and personal factors. Psychological counseling and crisis intervention should be regarded as integral components of standardized training management, and attention is needed in monitoring the psychological fluctuations of anesthesiology residents and helping them to complete their rotations on time.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa