ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective:To systematically evaluate the correlation between chronic periodontitis and postmenopausal osteoporosis (PMOP).Methods:Electronic searches were conducted on Cochrane Library, Pubmed, Embase, Ovid, CNKI, CBM, VIP, and WF databases to collect research literature on the correlation between chronic periodontitis and PMOP. The Newcastle Ottawa Scale (NOS) criteria were used to evaluate the quality of the included literature, and RevMan 5.3 software was used for meta-analysis. The outcome measures were clinical attachment loss (CAL), probing depth (PD), plaque index (PI), calculus index (CI), bleeding on probing (BOP), and simplified oral hygiene index (OHI-S).Results:A total of 16 articles were included, with a total of 1587 patients. Compared with the postmenopausal non osteoporosis group, the osteoporosis group showed significant abnormalities in CAL [standardized mean difference (SMD)=1.09, 95% CI: 0.62-1.57, P<0.001], PD(SMD=0.71, 95% CI: 0.28-1.14, P<0.001), PI(SMD=0.43, 95% CI: 0.29-0.56, P<0.001), and OHI-S(SMD=0.28, 95% CI: 0.22-0.35, P<0.001) indicators, as well as in BOP(SMD=0.01, 95% CI: -0.48-0.49, P=0.97) and GI(SMD=0.01, 95% CI: -0.48-0.49, P=0.97). At the level of 0.24 and 95% CI: -0.34 to 0.81, P=0.42, there was no statistically significant difference. Conclusions:Women with PMOP exhibit more significant changes in indicators such as CAL, PD, PI, and OHI-S, suggesting that postmenopausal women with osteoporosis are more likely to suffer from periodontitis.

In order to establish a rapid,specific and sensitive detection method for Streptococcus equi subspecies zooepidemicus(SEZ)and to understand the infection status of SEZ in horses ente-ring China,specific primers were designed and synthesized based on the conserved gene comB of standard strain SEZ(ATCC 43079)in this work.Then,the pMD19-T-comB recombinant plasmid was constructed and used as a standard positive template.After that,the fluorescence-based quantitative PCR(qPCR)detection method based on SYBR Green Ⅰ dye was established.Totally,477 equine entry serum samples from 6 countries,including Netherlands,Belgium,Japan,Germa-ny,Argentina and New Zealand,during 2018 to 2023,were randomly selected and detected for SEZ by the qPCR method.Results showed that the established qPCR method had specific amplification for only SEZ,which illustrated a good specificity.Sensitivity test of the method showed that the limited detection amount was 4.58 X101 copies/μL.And the repeatability test showed that the coef-ficient of variation of intra-batch repeatability was less than 0.5％,while the inter-batch repeat-ability was less than 3.0％,which indicated good repeatability and high stability.Retrospective a-nalysis showed that totally 11 of 477 positive samples were detected,with a relatively low positive rate of 2.31％(11/477).Among them,all the 40 samples from Netherlands in 2018 were negative(0/40).In the samples of 2019,one positive was detected from Belgium(1/20),while all other 36 samples which form Japan and Germany were negative.In the samples of 2021,three samples(3/34)from Japan and one sample(1/20)from Argentina were positive,and all the other 40 samples from the Netherlands were negative.In the samples of 2022,76 samples from Netherlands were all negative.While in the 2023,5(5/126)of 126 samples from Netherlands and one(1/88)of 88 from New Zealand were found positive with SEZ.To summarize,The SYBR Green Ⅰ qPCR method for the diagnosis of SEZ was successfully established,and it could provide necessary technical support for the rapid quarantine of China's entry-exit and port departments,as well as the epidemiological investigation of the disease.

OBJECTIVES: To achieve the ambitious goal of eliminating schistosome infections, the Chinese government has implemented diverse control strategies. This study explored the progress of the 2 most recent national schistosomiasis control programs in an endemic area along the Yangtze River in China. METHODS: We obtained village-level parasitological data from cross-sectional surveys combined with environmental data in Anhui Province, China from 1997 to 2015. A convolutional neural network (CNN) based on a hierarchical integro-difference equation (IDE) framework (i.e., CNN-IDE) was used to model spatio-temporal variations in schistosomiasis. Two traditional models were also constructed for comparison with 2 evaluation indicators: the mean-squared prediction error (MSPE) and continuous ranked probability score (CRPS). RESULTS: The CNN-IDE model was the optimal model, with the lowest overall average MSPE of 0.04 and the CRPS of 0.19. From 1997 to 2011, the prevalence exhibited a notable trend: it increased steadily until peaking at 1.6 per 1,000 in 2005, then gradually declined, stabilizing at a lower rate of approximately 0.6 per 1,000 in 2006, and approaching zero by 2011. During this period, noticeable geographic disparities in schistosomiasis prevalence were observed; high-risk areas were initially dispersed, followed by contraction. Predictions for the period 2012 to 2015 demonstrated a consistent and uniform decrease. CONCLUSIONS The proposed CNN-IDE model captured the intricate and evolving dynamics of schistosomiasis prevalence, offering a promising alternative for future risk modeling of the disease. The comprehensive strategy is expected to help diminish schistosomiasis infection, emphasizing the necessity to continue implementing this strategy.

Objective: To understand the status of pinworm infection in rural children aged 3-9 years in Anhui Province, and to provide scientific basis for the prevention and control strategy of pinworm disease. Methods: According to the National Surveillance Program of Liver Fluke Disease and Soil Transmitted Nematodiasis(Trial), no less than 10% counties(cities and districts) in Anhui Province were selected as mobile surveillance sites every year. Each surveillance site was divided into 5 areas on the basis of geographical location(east, west, south, north and middle), from each of the areas, one administrative village was selected from one township(town, community) for conducting surveillance. Children at age 3-9 years from each site were examined for pinworm infection with the modified Kato-Katz thick smear method and the adhesive cellophane tape perianal swab method. Chi square test was used to compare the infection rate. Results: From 2017 to 2021, the 5 year average infection rate of pinworm in rural Anhui was 1.34%(128/9 557), and there was no significant difference in the infection rate over the years( P >0.05). The detection rates of the modified Kato-Katz thick smear method and the adhesive cellophane tape perianal swab method were 0.28% and 1.23%, respectively, the difference was statistically significant( χ 2=72.97, P <0.01). In different regions, the 5 year average infection rate of Fuyang City was the highest(4.27%), and the rate of each city was positively correlated with the number of local resident population( r =0.54, P <0.05). There was no significant sex difference in the 5 year average infection rates( P >0.05). The 5 year average infection rate of children aged 3 to 9 years in rural areas were 0.62%, 1.10%, 1.44%, 1.57%, 0.94%, 2.09% and 1.57%, respectively, showed an increasing trend with the increase of age( χ 2=14.41, χ 2 trend =6.70, P <0.05). There was no significant difference in the average infection rate between scattered children and collectively living children( P >0.05). Conclusion From 2017 to 2021, the infection rate of pinworm among children in rural Anhui province remains at a low level. In the future, health education and monitoring should be strengthened.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg^-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.

Objective To evaluate the application and effect of signature verification technology in children's vaccination clinics (CVC) of Jiangsu Province in 2020. Methods The signature verification data were derived from the Jiangsu Provincial Vaccination Integrated Service Management Information System, and the inquiry and registration, informed consent, vaccine traceability code scanning and observation information of children's vaccination clinics in different regions were analyzed. 210 doses of vaccination information were randomly selected from CVCs in each county, and the length of vaccination services in different regions was compared. Results During 2020, all of CVCs in Jiangsu were equipped with signature verification technology, and the signature verification rate of each vaccination sector was more than 99.90%. The length of outpatient vaccination service and overall length of stay in southern Jiangsu were slightly shorter than those in other regions. Conclusion The introduction of electronic signature verification technology in CVCs can effectively standardize the vaccination. It is necessary to expand the functions of electronic signature verification equipment, strengthen data analysis and utilization, and guide vaccination scientifically.

Objective To observe the effect of pre-hospital and intra-hospital collaborative ther-apeutic model in the treatment of patients with acute cerebral infarction.Methods A total of 67 pa-tients with acute cerebral infarction were selected as the research objects,and they were divided into observation group(n=37)and control group(n=30)according to the therapeutic model.The con-trol group was conducted with the traditional therapeutic model,while the observation group was con-ducted with the pre-hospital and intra-hospital collaborative therapeutic model.The time efficiency of intravenous thrombolysis,early recovery of nerve function and oxidative stress indexes were compared between the two groups.Results There was no significant difference in the time from onset to visit between the two groups(P＞0.05);the time from seeing a doctor to thrombolysis and the time from seeing a doctor to signing the informed consent for intravenous thrombolysis in the observation group were significantly shorter than those in the control group(P＜0.05).On the hospital admission,there was no significant difference in the National Institutes of Health Stroke Scale(NIHSS)score be-tween the two groups(P＞0.05);at the time points of 7 days after admission and 90 days after thrombolysis,the NIHSS scores of patients in the observation group were significantly lower than that in the control group(P＜0.05).There were no significant differences in the levels of serum glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)between the two groups(P＞0.05);the level of serum superoxide dismutase(SOD)in the observation group was significantly higher than that in the control group(P＜0.05).One patient died in the control group,with a mortality rate of 3.33％;no patient died in the observation group.Conclusion Pre-hospital and intra-hospital collaborative therapeutic model can effectively improve the time efficiency of intravenous thrombolysis for patients with acute cerebral infarction,alleviate the neurological damage,and reduce degree of oxidative stress reaction and death risk.

Objective To observe the effect of pre-hospital and intra-hospital collaborative ther-apeutic model in the treatment of patients with acute cerebral infarction.Methods A total of 67 pa-tients with acute cerebral infarction were selected as the research objects,and they were divided into observation group(n=37)and control group(n=30)according to the therapeutic model.The con-trol group was conducted with the traditional therapeutic model,while the observation group was con-ducted with the pre-hospital and intra-hospital collaborative therapeutic model.The time efficiency of intravenous thrombolysis,early recovery of nerve function and oxidative stress indexes were compared between the two groups.Results There was no significant difference in the time from onset to visit between the two groups(P＞0.05);the time from seeing a doctor to thrombolysis and the time from seeing a doctor to signing the informed consent for intravenous thrombolysis in the observation group were significantly shorter than those in the control group(P＜0.05).On the hospital admission,there was no significant difference in the National Institutes of Health Stroke Scale(NIHSS)score be-tween the two groups(P＞0.05);at the time points of 7 days after admission and 90 days after thrombolysis,the NIHSS scores of patients in the observation group were significantly lower than that in the control group(P＜0.05).There were no significant differences in the levels of serum glutathione peroxidase(GSH-Px)and malonaldehyde(MDA)between the two groups(P＞0.05);the level of serum superoxide dismutase(SOD)in the observation group was significantly higher than that in the control group(P＜0.05).One patient died in the control group,with a mortality rate of 3.33％;no patient died in the observation group.Conclusion Pre-hospital and intra-hospital collaborative therapeutic model can effectively improve the time efficiency of intravenous thrombolysis for patients with acute cerebral infarction,alleviate the neurological damage,and reduce degree of oxidative stress reaction and death risk.