Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0％to 69％,severe stenosis as a stenosis rate of 70％to 99％,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score＞2 indicating a poor outcome.Variables with P＜0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4％)were in the END group and 707 patients(85.6％)were included in the non-END group.At 90days after stroke,744 patients(90.1％)had a favorable outcome,while 82 patients(9.9％)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P＜0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P＜0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95％CI2.32-14.91,P＜0.01),occlusion of the culprit vessel(OR,5.74,95％CI 2.25-14.62,P＜0.01),history of alcohol consumption(OR,5.59,95％CI3.41-9.17,P＜0.01),elevated HbA1c(OR,1.67,95％CI 1.35-2.08,P＜0.01),and higher baseline NIHSS motor score(OR,1.43,95％CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95％CI 1.89-3.57,P＜0.01)and the occurrence of END(OR,18.42,95％CI 5.13-66.18,P＜0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95％CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective To observe the clinical effect of doing Huatuo five-animal play treating blood-stasis-type silent myocardial ischemia(SMI)and its influence on coronary hemodynamics.Methods Ninety patients diagnosed as silent myocardial ischemia were randomly divided into a five-animal play group(n=45,age:51.56±11.00 years,24 males and 21 females)and a regular exercise group(n=45,age:52.44±7.19 years old,24 males and 21 females)according to a random number table.The five-animal play group practised the traditional five-animal play,while the regular exercise group con-ducted daily 30-minute moderate-intensity treadmill aerobic exercise,five times a week,for 4 weeks.The changes in the number of abnormal ST-T segment occurrences,myocardial oxygen consumption(CMO),coronary ischemia threshold(CIT),and blood smoothness index(BSD)within 24-hour ambu-latory electrocardiogram before and after the intervention were observed in both groups,with the thera-peutic effect and hemodynamic characteristics of both groups evaluated.Results The average number of ST-T segment abnormalities decreased after intervention in both groups(P<0.001),with significantly greater improvement in the five-animal play group than the regular exercise group(P<0.001).More-over,the average CMO decreased significantly,while the average CMR and BSD increased significant-ly in both groups after intervention(P<0.05),with significantly greater improvement in the five-ani-mal play group than the other group.Meanwhile,the total effective rate in the five-animal play group was significantly higher than the regular exercise group(P<0.01).Conclusion Undergoing the five-ani-mal play and moderate intensity treadmill aerobic exercise both are effective in treating silent myocardi-al ischemia.However,the former therapy is superior to the latter in bettering CMO,CIT and BSD.

Objective:To observe the clinical efficacy of acupuncture at the front-Mu points and the lower He-sea points combined with Western medication in the treatment of diarrhea induced by anti-tuberculosis drugs,as well as the effects on clinical symptoms and serum albumin.Methods:Seventy patients with diarrhea caused by anti-tuberculosis drugs were divided into an observation group and a control group according to the different treatment methods,with 35 cases in each group.Both groups were treated with the same Western medication,and the observation group was additionally treated with acupuncture at the front-Mu points and the lower He-sea points.After treatment,changes in the Hart score,traditional Chinese medicine(TCM)symptom score,and serum albumin were observed in both groups.Results:There was no statistically significant difference in the Hart score,TCM symptom score,and serum albumin level between the two groups before treatment(P>0.05).No adverse reactions occurred during treatment in either group.After 3 d of treatment,the total effective rate of the observation group was 68.6%,which was higher than 25.7%of the control group(P<0.01);after 7 d of treatment,the total effective rate of both the observation group and the control group was 100.0%,but the cured rate of the observation group was 80.0%,which was significantly higher than 2.9%of the control group(P<0.01).The Hart score and TCM symptom score of both groups after 3 d and 7 d of treatment were significantly lower than those before treatment(P<0.05),and the scores of the observation group were lower than those of the control group(P<0.05).After 7 d of treatment,the albumin level of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The addition of acupuncture at the front-Mu points combined with lower He-sea points to routine Western mediation treatment for diarrhea induced by anti-tuberculosis drugs is more effective than Western medication alone and can improve the clinical symptoms and nutritional status of the patients at an early stage.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

Objective:To evaluate the efficacy of defocus incorporated multiple segments (DIMS) on spherical equivalent (SE) and axial length (AL) in myopic children.Methods:Clinical studies on the progress of DIMS lens intervention in myopia reported in CNKI, Wanfang Data, VIP, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, and Web of Science from the establishment of the database to June 2023 were searched.The experimental group and control group used DIMS lens and single vision lens (SVL) for intervention, respectively.Two researchers independently conducted the literature search, screening and data extraction based on the inclusion and exclusion criteria.Literature quality and risk of bias were evaluated in accordance with the requirements of the Cochrane Manual.Meta-analysis was performed using Revman 5.4 software.Results:A total of 7 clinical studies using DIMS lenses to intervene in the development of myopia were included .Seven studies provided complete SE data for analysis, with sample sizes of 1 164 eyes and 1 140 eyes for the DIMS group and SVL group, respectively.Five studies provided complete AL data for analysis, with sample sizes of 339 eyes and 315 eyes for the DIMS group and SVL group, respectively.There were statistically significant differences in SE and AL between DIMS group and SVL group (SE: WMD=0.40, 95% CI: 0.32-0.47, P<0.001; AL: WMD=-0.14, 95% CI: -0.17--0.11, P<0.001).DIMS lens could effectively delay SE progression and AL growth in myopic patients. Conclusions:DIMS lenses could delay the increase of SE and AL to a certain extent.

Objective:To compare the efficacy of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunnotherapy and transarterial chemoembolization (TACE) combined with targeted therapy and immunnotherapy in the treatment of unresectable hepatocellular carcinoma HCC.Methods:We retrospectively analyzed the clinical data of 40 patients with unresectable HCC treated with HAIC combined with targeted therapy and immunnotherapy and TACE combined with targeted therapy and immunnotherapy in Tongde Hospital of Zhejiang Province and Zhejiang Provincial People's Hospital.The patients were divided into HAIC group ( n=14) and TACE group ( n=26) according to the different treatment methods. Baseline data, surgical conversion and intraoperative situation, tumor response, portal vein cancer thrombus control rate, leukocyte reduction rate, platelet reduction rate, incidence of liver function abnormalities, objective remission rate, and disease control rate were compared between the two groups. Results:The HAIC group had a later baseline tumor staging than the TACE group (higher percentage of portal vein cancer thrombus, CNLC stage Ⅲa).The surgical conversion rate of the HAIC and TACE groups were 28.6%(4/14) and 26.9%(7/26), respectively, with the difference of no statistical significance ( P>0.05);The operation time and intraoperative bleeding were (329.5±19.9) min vs.(413.4±26.4) min, (272.2±49.9) ml vs.(536.0±123.6) ml, and the differences were statistically significant ( P<0. 05); The maximum tumor diameter reduction rate [(30.7%±15.1%) vs.(7.2%±12.6%)] and portal vein cancer thrombus control rate [100% (12/12) vs. 64.3% (9/14)], the differences were statistically significant ( P<0.05);The incidences of leukocyte and platelet decrease in the two groups during the course of treatment were 71.4%(10/14) vs. 34.6%(9/26)、78.5%(11/14) vs. 38.5%(10/26), and the incidences of liver function abnormalities were 35.7%(5/14) vs. 69.2%(18/26), the differences were statistically significant ( P<0.05);The objective response rate and disease control rate were 57.1%(8/14) vs. 30.8% (8/26)、71.4% (10/14) vs. 53.8%(14/26), all statistically significant. Conclusion:HAIC combined with targeted therapy and immunnotherapy is a safe and effective treatment for middle and advanced HCC, especially suitable for patients with portal vein tumor thrombus(PVTT), large tumor, or poor liver function.

Objective:To evaluate the efficacy of defocus incorporated multiple segments (DIMS) on spherical equivalent (SE) and axial length (AL) in myopic children.Methods:Clinical studies on the progress of DIMS lens intervention in myopia reported in CNKI, Wanfang Data, VIP, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, and Web of Science from the establishment of the database to June 2023 were searched.The experimental group and control group used DIMS lens and single vision lens (SVL) for intervention, respectively.Two researchers independently conducted the literature search, screening and data extraction based on the inclusion and exclusion criteria.Literature quality and risk of bias were evaluated in accordance with the requirements of the Cochrane Manual.Meta-analysis was performed using Revman 5.4 software.Results:A total of 7 clinical studies using DIMS lenses to intervene in the development of myopia were included .Seven studies provided complete SE data for analysis, with sample sizes of 1 164 eyes and 1 140 eyes for the DIMS group and SVL group, respectively.Five studies provided complete AL data for analysis, with sample sizes of 339 eyes and 315 eyes for the DIMS group and SVL group, respectively.There were statistically significant differences in SE and AL between DIMS group and SVL group (SE: WMD=0.40, 95% CI: 0.32-0.47, P<0.001; AL: WMD=-0.14, 95% CI: -0.17--0.11, P<0.001).DIMS lens could effectively delay SE progression and AL growth in myopic patients. Conclusions:DIMS lenses could delay the increase of SE and AL to a certain extent.

To report the first case of congenital ichthyosis with woolly hair in China, and to elucidate its genetic variant profile. A 28-year-old female patient presented with rashes on the trunk and limbs for 28 years. Dermatological examination revealed dry and rough skin over the entire body, with well-defined, polygonal, dark brown, adherent scales densely distributed over the trunk and extremities. No significant abnormalities were observed in the mucous membranes, teeth, or nails. The patient exhibited uniformly distributed, woolly and curly hair with a soft, dry texture and normal density; no significant hair breakage or brittleness was observed, while the eyebrows appeared sparse. Hair microscopy showed irregular axial twisting of hair strands at varying intervals; scanning electron microscopy (SEM) revealed irregular hair shafts with some segments appearing flat in a belt-like pattern, and magnified SEM images further demonstrated hair cuticle damage on the surface of hair shafts, manifesting as localized upward curling and longitudinal grooves, indicating structural damage to the hair shafts. Whole-exome sequencing identified a homozygous variant c.124dupC in exon 3 of the PRSS8 gene in the proband, resulting in a frameshift mutation (p.Gln42Profs*24) in the PRSS8 protein. According to the guidelines of the American College of Medical Genetics and Genomics as well as the patient's clinical manifestations, this variant could be preliminarily classified as pathogenic. A diagnosis of syndromic ichthyosis was made. This case represents the first report of syndromic ichthyosis caused by PRSS8 variants in China and the second report in the world, and this condition is proposed to be tentatively named as "ichthyosis-woolly hair syndrome".

Objective:To investigate the level of rehabilitation exercise adherence in patients undergoing anterior cruciate ligament (ACL) reconstruction within 6 months post-surgery, analyze its trajectory, and provide a reference for clinical nursing interventions.Methods:Using a convenience sampling method, 150 patients who underwent arthroscopic ACL reconstruction at the First Affiliated Hospital of Zhengzhou University from June 2022 to August 2023 were selected. Rehabilitation exercise adherence was assessed monthly from postoperative 1 month (M 1) to 6 months (M 6) using the Orthopedic Functional Exercise Adherence Scale. A latent class growth model was employed to analyze adherence trajectory categories, and Logistic regression was used to identify influencing factors for different adherence trajectories. Results:A total of 144 patients completed follow-up (follow-up rate was 96.00%). Exercise adherence scores gradually declined over the 6 months post-surgery, with scores of (50.30±5.39), (45.92±3.85), (39.48±5.27), (35.83±6.19), (31.85±7.59), and (29.88±7.88) from M 1 to M 6, respectively. The difference in scores across time points was statistically significant ( F=85.467, P<0.01). Three potential categories were identified through the latent class growth model: the moderate-high level rapid decline group ( n=65, 45.14%), the moderate-low level stable group ( n=32, 22.22%), and the moderate-low level slow decline group ( n=47, 32.64%). Logistic regression analysis revealed that gender and age were significant factors influencing adherence trajectory categories ( P<0.05) . Conclusions:Dynamic declines in rehabilitation exercise adherence are common among ACL reconstruction patients, with varying degrees of decline. Gender and age may influence adherence trajectories, suggesting that targeted management strategies could be implemented in clinical practice.