Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Alzheimer’s disease (AD) is a neurodegenerative disorder involving multiple pathological processes, clinically characterized by memory loss and cognitive impairment. The pathological processes of AD are complex, and the etiology remains unclear. Currently, there are various hypotheses including β-amyloid (Aβ) deposition, tau protein hyperphosphorylation, neuroinflammation, and synaptic loss, upon which researchers base their drug development efforts. Prior to 2021, drugs approved by the U.S. Food and Drug Administration (FDA) had targeted neurotransmitter modulation, but their efficacy was limited. In recent years, the approval of two anti-Aβ monoclonal antibody drugs has brought some clinical benefits to patients, yet they have not fully met clinical needs, which had highlighted the urgent necessity for exploration of new mechanisms and targets in AD drug development. Presently, research on novel mechanisms and targets for AD drug development focuses primarily on several directions: anti-Aβ drugs, anti-Tau protein drugs, anti-neuroinflammation immunotherapies, mitochondrial function-improving drugs, neurogenesis-promoting drugs, and synapse-protective drugs. This paper provides an overview of AD drugs entering clinical trials in the past decade in these directions, details some representative drugs, and concludes with prospects, integrating findings from our research group.

Objective:To investigate the factors influencing fall risk scores in elderly individuals.Methods:A total of 4 419 individuals were randomly selected using the cluster sampling method from Beijing, Nanning(Guangxi), and Yinchuan(Ningxia).Data on demographic characteristics and fall-related incidents were gathered and analyzed for their correlation with fall risk scores.Results:The fall risk score showed significant associations with various factors, such as the history of falls within one year( β=-3.607, 95% CI: -3.881 to -3.332), care methods( β=2.442, 95% CI: 2.226 to 2.658), exercise( β=0.714, 95% CI: 0.443 to 0.986), retirement( β=-0.585, 95% CI: -0.819 to -0.351), age( β=0.173, 95% CI: 0.159 to 0.187), and use of walking aids( β=-3.737, 95% CI: -4.054 to -3.421). Conclusions:Fall risk scores in older adults are influenced by a variety of factors.Factors such as no history of falls within the past year, living independently, engaging in physical activity, and being employed may contribute to lower fall risk scores in older adults.

The reform on the outpatient coordination of Employee Medical Insurance is very important in the field of medical secu-rity.It sorts out the design of outpatient treatment in areas where general outpatient coordination has been carried out before the na-tional reform of outpatient security launched in 2021,summarizes the institutional design and main characteristics of"two lines and one ratio",and provides a decision-making basis for further promoting the reform of total outpatient security in various regions.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.

Studies suggest that synaptic damage is closely associated with cognitive dysfunction, and lemur tyrosine kinase 1 (LMTK1) is a key kinase that affects synaptic growth. Dihydroergotamine (DHE) is an ergot alkaloid derivative with high biological activity, which could regulate cognition, memory processing and motor control.This study aims to investigate the effect of DHE on synapse atrophy and plasticity as well as cognition in Alzheimer’s disease (AD) model animals.SAMR1 mice were selected as control group (n = 12).SAMP8 mice were randomly divided into 3 groups (n = 12 for each group):AD group, DHE low-dose group and high-dose group.The DHE groups were injected DHE intraperitoneally daily for 8 weeks.Immunofluorescence experiments, Golgi staining experiment, electrophysiological experiment, Morris water maze experiment (MWM) and Western blot experiment were conducted to investigate the effect of DHE on synaptic morphology, synaptic plasticity, cognitive function as well as the phosphorylation level of LMTK1 downstream TBC1D9B in AD model mice.Subsequently, the LMTK1 silencing and overexpression cells were constructed.Immunofluorescence experiments were used to study the effect of DHE on synaptic length of nerve cell after LMTK1 silencing and overexpression.In the hippocampus of AD mice, the postsynaptic marker PSD95 was significantly increased after DHE administration, which suggested that DHE could increase the synaptic density. In Golgi staining experiment, synaptic atrophy was observed in the hippocampal of AD mice, which could be improved by high-dose DHE.Compared with normal mice, the long-term potentiation (LTP) level of AD model mice was significantly reduced (P < 0.000 1), DHE could increase LTP significantly.The MWM experiment further showed that DHE could improve cognitive function in AD mice.WB experiments showed that the level of P-LMTK1 in the hippocampus of AD mice increased significantly, and the level of downstream P-TBC1D9B decreased significantly after DHE administration.Cell immunofluorescence experiments in vitro had shown that DHE significantly improved synaptic atrophy in overexpressed C17.2 cells, while its improvement disappeared when LMTK1 was silenced. This research suggests DHE may improve synaptic atrophy and cognitive dysfunction in AD by targeting on LMTK1.

To study the prognosis-related regulation mechanism of miR-452-5p and its influence on the proliferation and migration of hepatocellular carcinoma (HCC) cells, liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas (TCGA) was used to validate the differential expression of miR-452-5p and perform the Kaplan-Meier analysis of overall survival (OS).Target genes of miR-452-5p from TargetscanHuman and miRDB databases were predictived; and differentially expressed genes(DEGs) and weighted gene co-expression network analysis (WCGNA) were completed with GSE14520.Lipofectmine-2000 was used to transfect miR-452-5p mimics, mimics negative control, miR-452-5p inhibitor and inhibitor negative control into Huh7 cells,respectively.The mRNA and protein expression level of RORα in 4 groups were determined by RT-qPCR and Western blot.CCK-8 assay and Transwell assay were conducted to testify the capabilities of proliferation and migration.The regulation between miR-452-5p and RORα was confirmed by the dual luciferase reporter assay.After analysis in the TCGA-LIHC dataset, miR-452-5p had higher expression in HCC tissue than that in normal tissue, which was also associated with a shorter OS.RORα and LAMC1 were discriminated by intersecting of DEGs, WGCNA module genes, and predictive target genes.Survival analysis exhibited that dysregulation of RORα was significantly related to the OS.Overexpression of miR-452-5p in HCC cells suppressed the expression of RORα both in mRNA and protein, and also enhanced the viability and migration of HCC cells.The results of the dual luciferase reporter assay showed that miR-452-5p targeted 3′UTR of RORα.Up-regulated miR-452-5p inhibited the expression of RORα, facilitated the proliferation and migration of HCC cells, and promoted the progression and poor prognosis of HCC.

Objective:To summarize the clinical features and treatment of pneumocystis jirovecii pneumonia(PCP) in children with non-human immunodeficiency virus(HIV) infection.Methods:A retrospective study was performed on seven cases of severe PCP children with non-HIV infection who were admitted to PICU of The University of Hong Kong-Shenzhen Hospital and PICU of Xianyang Rainbow Hospital from May 1, 2015 to May 1, 2021.The risk factors, clinical manifestations, laboratory results, pulmonary radiological features, treatment and outcomes were observed.Results:Seven children with PCP, including four males and three females, aged from 13 months to 85 months[(42.4±26.8) months], were all associated with underlying diseases, and most of which was hematological malignancies.Six children had a history of using TMP-SMX for PCP prevention, but four of them stopped by themselves and infected PCP in 2 to 4 weeks.All children had hypoxic respiratory failure, whose OI was 30.6±3.4, and presented with fever, dry cough, progressive dyspnea but no lung rales in the early stage.LDH[(745.7±317.0) U/L] and β-D-glucan[(513.8±225.0) pg/mL] increased in all patients.Chest CT showed diffused interstitial changes in bilateral lung fields associated with multiple exudative lesions.Among the anti-Pneumocystis Jirovecii treatment regimens, all cases began the treatment in the first three days during the admission, five cases were treated with intravenous TMP-SMX, and two cases were treated with oral TMP-SMX + caspofungin, with a course of 21 days.All children were also treated with glucocorticoid at the same time.Three days after the treatment of PCP, two children were worsened and one of them died, while another one started to recover on the 6th day of the regimen.The remaining five cases began to show clinical improvement after 3~7 days of PCP treatment.Finally six children were cured and one was died.Conclusion:PCP infection of children without HIV has high risk of destruction in immune system.TMP-SMX can prevent PCP effectively.In the severe PCP cases, early commencement of intravenous TMP-SMX can reduce the mortality rate.In the absence of intravenous TMP-SMX, oral TMP-SMX can be used with caspofungin.