Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

Artificial neural network(ANN)is a simulation of a biological neural network.It is an adaptive,non-linear,dynamic network system formed by interconnections.The advantages of ANN include easy optimization,simple modeling,and ac-curate results.This review examines the application of ANN in therapeutic drug monitoring for immunosuppressants,antibacteri-als,and anti-epileptic drugs.It discusses the advantages and disadvantages of the current ANN models and highlights future de-velopment directions.The aim is to provide valuable reference information for future researchers.The use of ANN for therapeutic drug monitoring shows great potential and holds promise as an effective method of personalizing patient medication.

Objective:To explore the optimal blood glucose-lowering strategies for patients with diabetic ketoacidosis (DKA) to enhance personalized treatment effects using machine learning techniques based on the United States Critical Care Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ).Methods:Utilizing the MIMIC-Ⅳ database, the case data of 2 096 patients with DKA admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center from 2008 to 2019 were analyzed. Machine learning models were developed, and receiver operator characteristic curve (ROC curve) and precision-recall curve (PR curve) were plotted to evaluate the model's effectiveness in predicting four common adverse outcomes: hypoglycemia, hypokalemia, reductions in Glasgow coma scale (GCS), and extended hospital stays. The risk of adverse outcomes was analyzed in relation to the rate of blood glucose decrease. Univariate and multivariate Logistic regression analyses were conducted to examine the relationship between relevant factors and the risk of hypokalemia. Personalized risk interpretation methods and predictive technologies were applied to individualize the analysis of optimal glucose control ranges for patients.Results:The machine learning models demonstrated excellent performance in predicting adverse outcomes in patients with DKA, with areas under the ROC curve (AUROC) and 95% confidence interval (95% CI) for predicting hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stays being 0.826 (0.803-0.849), 0.850 (0.828-0.870), 0.925 (0.903-0.946), and 0.901 (0.883-0.920), respectively. Analysis of the relationship between the rate of blood glucose reduction and the risk of four adverse outcomes showed that a maximum glucose reduction rate > 6.26 mmol·L -1·h -1 significantly increased the risk of hypoglycemia ( P < 0.001); a rate > 2.72 mmol·L -1·h -1 significantly elevated the risk of hypokalemia ( P < 0.001); a rate > 5.53 mmol·L -1·h -1 significantly reduced the risk of GCS score reduction ( P < 0.001); and a rate > 8.03 mmol·L -1·h -1 significantly shortened the length of hospital stay ( P < 0.001). Multivariate Logistic regression analysis indicated significant correlations between maximum bicarbonate levels, blood urea nitrogen levels, and total insulin doses with the risk of hypokalemia (all P < 0.01). In terms of establishing personalized optimal treatment thresholds, assuming optimal glucose reduction thresholds for hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stay were x1, x2, x3, x4, respectively, the recommended glucose reduction rates to minimize the risks of hypokalemia and hypoglycemia should be ≤min{ x1, x2}, while those to reduce GCS score decline and extended hospital stay should be ≥ max{ x3, x4}. When these ranges overlap, i.e., max{ x3, x4} ≤ min{ x1, x2}, this interval was the recommended optimal glucose reduction range. If there was no overlap between these ranges, i.e., max{ x3, x4} > min{ x1, x2}, the treatment strategy should be dynamically adjusted considering individual differences in the risk of various adverse outcomes. Conclusion:The machine learning models shows good performance in predicting adverse outcomes in patients with DKA, assisting in personalized blood glucose management and holding important clinical application prospects.

Objective:To explore the correlation between the methylation of sclerostin (SOST) promoter and glucocorticoid-induced osteoporosis (GIOP) in children.Methods:Children with GIOP ( n=66) were selected as the experimental group. At the same time, children treated with glucocorticoid whose bone mass were selected as the control group ( n=72). The general clinical information of all children was compared, and the data collected by CT were detected by lumbar QCT, and the levels of bone metabolism related indexes were detected by biochemical analyzer. The mRNA expression of SOST was detected by fluorescence quantitative PCR, and the protein content of SOST was detected by enzyme-linked Immunosorbent Assay (ELISA). Methylation status of SOST gene promoter was detected by methylation-specific PCR (MSP), and the risk factors affecting GIOP were compared and analyzed, and the diagnostic and therapeutic value of each index for children with GIOP was evaluated. Results:Compared with the control group, the duration of hormone application and the current dose of hormone in the experimental group were higher, and the expression levels of bone metabolism indexes β-collagen carboxy terminal peptide ( β-CTX) ( t=9.87, P<0.01), typeⅠprocollagenamino-terminal peptide (P1NP) ( t=16.09, P<0.001), osteopontin (OPN) ( t=21.32, P<0.001) and N-MID ( t=15.21, P<0.01) were significantly increased, with statistical significance. However, in terms of bone mineral density, the related level of children in the experimental group was low ( t=22.49, P<0.001), and the expression of SOST mRNA ( t=9.48, P<0.01) and protein content ( t=7.70, P<0.01) was significantly decreased, and the children in the experimental group showed methylation status of SOST. Pearson analysis showed that the level of serum SOST protein in the experimental group was negatively correlated with the levels of β-CTX ( r=-0.16, P=0.012), P1NP ( r=-0.35, P=0.021), OPN ( r=-0.25, P=0.043) and N-MID ( r=-0.09, P=0.036). At the same time, the Logistic regression analysis showed that the high expression of P1NP ( SE=0.35, P<0.001), OPN (S E=0.37, P<0.001) and SOST ( SE=0.33, P<0.001) were risk factors for glucocorticoid-induced osteoporosis in children. The receiver operating characteristic (ROC) curve showed that the area under the curve of SOST was 0.874 (95% CI: 0.824-0.934), with higher sensitivity and specificity. Conclusions:There is a correlation between the methylation of SOST promoter and the GIOP of children. Besides, SOST can be used as a potential diagnostic index of GIOP with high value among many factors affecting children’s GIOP. In this case, the medical industry needs to further strengthen the prevention and treatment of children’s GIOP.

Objective To screen ischemia and hypoxiarelated genes(IAHRGs)after spinal cord injury(SCI)and analyze their immune infiltration patterns by bioinformatics methods.Methods The expression profiles of SCI-related GSE5296,GSE47681 and GSE217797 were downloaded from the Gene Expression Omnibus(GEO)database,where GSE5296,GSE47681 samples were used as the test set and GSE217797 samples as the validation set,and the differentially expressed genes(DEGs)between SCI and healthy samples were obtained.IAHRGs were screened in GeneCards and MSigDB databases.The intersection of DEGs and IAHRGs yielded ischemic and hypoxia related differentially expressed genes(IAHRDEGs).Based on the IAHRDEGs,the key genes were jointly screened by LASSO model and SVM analysis.The key genes were subjected to logistic regression analysis and a diagnostic model was constructed.The diagnostic ability of the diagnostic model was analyzed by Nomogram and the column line graph of Logistic predictive values was plotted.The diagnostic value of the diagnostic model and key genes for SCI was evaluated using the receiver operating characteristics(ROC).Immune cell infiltration patterns of the disease were analyzed using the CIBERSORT tool.Results A total of 388 IAHRGs were screened,313 differentially expressed genes were detected between SCI and healthy samples,among which 312 were up-regulated and 1 was down-regulated.A sum of 27 up-regulated IAHRDEGs genes were obtained.Five key genes related to ischemia and hypoxia after SCI(Abca1,Caspl,Lpl,Procr,Tnfrsf1a)were screened by LASSO model and SVM analysis based on IAHRDEGs.Nomogram analysis confirms the effect of logistics diagnosis model.ROC curve analysis showed that Casp1,Lpl and Tnfrsf1a had higher diagnostic efficacy(AUC＞0.9),followed by Abca1 and Procr(AUC:0.7～0.9),and the logistics linear predictors had the best diagnostic effect(AUC=0.964).CIBERSORT analysis showed that five key genes were associated with the infiltration of eight types of immune cells(neutrophil cells,B cells naive,plasma cells,M0 macrophage,T cells CD4 naive,T cells CD4 follicular,Th17 cells,and NK resting).Conclusion The five key genes of Abcal,Caspl,Lpl,Procr,and Tnfrsfla,may be closely related to ischemic-hypoxic pathogenesis after SCI,and can be used as candidate molecular markers for the diagnosis and treatment after SCI.

Objective:To investigate clinical features and current treatment status of patients with physical urticaria (PU) in China.Methods:A questionnaire survey was carried out in patients diagnosed with PU at the first visit at the Department of Dermatology of 12 tertiary hospitals in China from January to December 2019. Physicians filled out the survey questionnaires, which included demographic characteristics, pruritus intensity, the number of wheals, concomitant symptoms (such as pain in skin rashes, arthralgia, and fever), subtypes of PU, treatment regimens, etc. Differences between groups were analyzed using one-way analysis of variance, Kruskal-Wallis test or chi-square test.Results:Overall, 612 PU outpatients were enrolled, including 268 males and 344 females; they were aged 37.4 ± 16.4 years, their age at the onset was 35.1 ± 16.4 years, and the disease duration ( M [ Q1, Q3]) was 0.50 (0.25, 2.00) years. Of these patients, 500 were diagnosed with symptomatic dermographism (SD), 54 with heat contact urticaria (HCU), 43 with cold contact urticaria (CCU), and 15 with delayed pressure urticaria (DPU). There were no significant differences in the gender distribution, age, age at onset, or disease duration among the 4 subtypes of PU patients (all P > 0.05), but the proportions of patients with arthralgia, with eczema/dermatitis, and with elevated total serum IgE levels significantly differed among the 4 subtypes (all P < 0.05). Concretely, the proportion of patients with arthralgia was significantly higher in the DPU group (4/15, 26.7%) than in the SD group (64/500, 12.8%), HCU group (1/54, 1.9%), and CCU group (5/43, 11.6%) (all P < 0.05) ; the proportion of patients with eczema/dermatitis was significantly lower in the HCU group (2/54, 3.7%) than in the SD group (96/500, 19.2%), CCU group (7/43, 16.3%), and DPU group (3/15, 20.0%) (all P < 0.05) ; the proportion of patients with elevated total serum IgE levels was significantly higher in the SD group (185/500, 37.0%) than in the HCU group (9/54, 16.7%), CCU group (11/43, 25.6%), and DPU group (4/15, 26.7%) (all P < 0.05). Among the PU patients, 307 (50.3%) chose dietary avoidance, and only 95 (15.5%) considered that the dietary avoidance was effective for the treatment of PU. At the initial visit, a single second-generation H1 antihistamine (sgAH) was prescribed in 271 cases (44.3%), two or more sgAHs in combination were prescribed in 258 cases (42.2%), and sgAHs were administered at double doses in 17 cases (2.7%) . Conclusion:The PU patients were predominantly young and middle-aged adults, and PU frequently occurred in females; the clinical characteristics varied among the subtypes of PU.

Objective:To investigate clinical features of patients with chronic spontaneous urticaria (CSU) in China.Methods:A questionnaire survey was carried out in CSU patients at the first visit and 4 follow-up visits in Departments of Dermatology of 12 third-grade hospitals in northern and southern China from January to December 2019. The survey content included demographic characteristics, pruritus intensity, the number of wheals, concomitant symptoms (such as pain in skin lesions, arthralgia, fever) during the last week prior to the admission, classification and subtypes of urticaria, and previous and current treatment regimens, etc., and the 7-day urticaria activity score (UAS7) was used to evaluate the therapeutic effect. Patients from 9 hospitals in Sichuan, Hubei and Fujian provinces were enrolled into the southern China group, and patients from 3 hospitals in Beijing municipality and Liaoning province were enrolled into the northern China group. Differences between groups were analyzed by two-independent-sample t-test, Mann-Whitney U test or chi-square test. Results:Overall, 1 396 CSU outpatients were enrolled, including 592 males and 804 females; their age was 38.32 ± 16.13 years, 1 109 (79.5%) were aged between 20 and 60 years, and 660 (47.3%) were aged between 20 and 40 years. Their age at onset was 35.85 ± 16.03 years, and the disease duration was 0.50 (0.25, 2.00) years. Allergic diseases were the most common concomitant diseases, 269 (19.3%) patients were diagnosed with accompanied allergic rhinitis or conjunctivitis, 169 (14%) with accompanied eczema/dermatitis, 39 (2.8%) with accompanied asthma; only 19 (1.4%) CSU patients had a history of thyroid diseases, but 133 (9.5%) were positive for anti-thyroid peroxidase (TPO) or anti-thyroglobulin (Tg) antibodies at the visit; elevated serum total IgE levels were observed in 437 (31.3%) patients, and 104 (7.4%) were positive for autoantibodies. There were 1 078 (77.2%) patients in the southern China group and 318 (22.8%) in the northern China group, and the southern China group showed significantly longer disease duration (2.16 ± 4.76 years vs. 1.53 ± 2.80 years, P < 0.001) , and significantly higher proportions of patients with family history (10.7% vs. 3.5%) , with painful lesions (5.8% vs. 0.9%) , and those with arthralgia (10.7% vs. 0) compared with the northern China group (all P < 0.05) . The three most prevalent urticaria subtypes were CSU (835 cases, 49.9%) , symptomatic dermographism (437 cases, 31.3%) , and angioedema (138 cases, 9.9%) , and the proportion of patients with the single diagnosis of CSU was significantly higher in the southern China group (53%) than in the northern China group (38.9%, P < 0.001) . In terms of treatment, 1 365 (97.8%) patients received conventional-dose second-generation H1 antihistamines alone or in combination, and only 31 (2.2%) were treated with antihistamines at high doses; other medicines were mostly administered in combination, and compound glycyrrhizin was most frequently prescribed (36.6%) , while omalizumab was only administered in 7 patients (0.5%) . Conclusions:Significant differences in the clinical features of CSU were observed between northern and southern China. Nowadays traditional modalities are inadequate for the treatment of CSU, and new therapeutic drugs are somewhat promising.

ObjectiveTo explore the effect and underlying mechanism of alcohol extract of Phyllanthi Fructus on silicosis mice induced by silicon dioxide （SiO₂）. MethodThirty-six male Kunming mice of SPF grade were randomly divided into a blank group，a model group，high-， medium， and low-dose Phyllanthi Fructus groups （800， 400， 200 mg·kg^-1），and a tetrandrine group （0.039 mg·kg^-1），with six mice in each group. The silicosis model was induced by static SiO₂ exposure in mice except for those in the blank group. After 28 days of administration by gavage，the lung tissues were collected and the organ coefficient was calculated. Hematoxylin-eosin（HE）staining and Masson staining were used to detect the morphology of lung tissues. The content of hydroxyproline （HYP），superoxide dismutase （SOD），malondialdehyde （MDA）， and catalase （CAT） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and Real-time polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of nuclear factor E₂-related factor 2 （Nrf2），heme oxygenase-1 （HO-1），NAD（P）H：quinone oxidoreductase 1 （NQO1），and Kelch-like ECH-associated protein 1 （Keap1）， respectively. ResultCompared with the blank group，the model group showed seriously damaged morphological structure of lung tissues with inflammatory cell infiltration and fibrous tissue proliferation， reduced serum content of SOD and CAT（P<0.01），increased content of HYP and MDA（P<0.01）， down-regulated protein and mRNA expression of Nrf2，HO-1， and NQO1（P<0.01），and up-regulated protein and mRNA expression of Keap1 （P<0.05，P<0.01）. Compared with the model group，the high- and medium-dose Phyllanthi Fructus groups showed significantly restored morphological structure of lung tissues with reduced collagen deposition， increased serum content of SOD and CAT（P<0.05，P<0.01），decreased content of HYP and MDA（P<0.01）， up-regulated protein and mRNA expression of Nrf2，HO-1， and NQO1 （P<0.05，P<0.01），and down-regulated protein and mRNA expression of Keap1（P<0.05，P<0.01）. ConclusionThe alcohol extract of Phyllanthi Fructus can inhibit pulmonary fibrosis in silicosis mice，and the underlying mechanism may be related to the regulation of the Nrf2/antioxidant response element （ARE） signaling pathway.

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
Rats ; Animals ; Vascular Endothelial Growth Factor A/pharmacology* ; Brain Ischemia/metabolism* ; Ischemic Stroke ; Signal Transduction ; ARNTL Transcription Factors/pharmacology* ; Neovascularization, Physiologic/physiology*

Objective:To observe any effect of long-distance application of Oral Reading for Language with Aphasia (ORLA) training on patients with post-stroke aphasia.Methods:A total of 42 stroke survivors with aphasia were randomly divided into an inpatient group, and two online groups, each of 14. All three groups had their routine rehabilitation treatment supplemented with ordinary multimodal language therapy and ORLA. The inpatient group completed the routine in the rehabilitation treatment room, while the online groups completed it at home using Tencent video conferencing software. The conventional multimodal language therapy was conducted once daily, 5 days a week for 4 weeks. For the inpatient group and online group 2 the daily session lasted 30 minutes, while for the online 1 groups the daily length was doubled. The ORLA therapy was also conducted once daily, 5 days a week for 4 weeks, for the inpatient group and online group 2 the daily session lasted 1h, while for the online 1 groups the daily length was 30min.The speech function, reading ability and life quality of the three groups were evaluated before and after the intervention using the Western Aphasia Battery, the Chinese Standard Aphasia Examination Scale and the Chinese version of the Stroke Aphasia Quality of Life Scale.Results:After treatment, the average aphasia quotient (AQ), reading, naming and quality of life scores in all three groups had improved significantly compared with those before treatment. And related language ability scores (such as retelling, fluency, information volume, listening comprehension, etc.) had also improved significantly in all three groups. However, the average AQ, reading, and oral fluency scores of the inpatient group and online group 2 were significantly higher than those of online group 1. Significant improvement was also observed in the reading aloud and life quality of all three groups, but the average improvement in reading aloud was significantly greater in the inpatient group and in online group 2 compared to online group 1. The average life quality of the online groups was significantly superior to that of the inpatient group.Conclusion:Medium- and high-intensity ORLA synchronous remote speech rehabilitation can significantly improve the speech ability, reading ability and life quality of aphasic stroke survivors.