Epilepsy is a chronic neurological disease characterized by abnormal synchronous discharges of brain neurons. The mutation of GRIN1， a key gene encoding the essential GluN1 subunit of N-methyl-D-aspartate （NMDA） receptors， is closely associated with the pathogenesis and progression of epilepsy. This review summarizes research advances in GRIN1 mutation-related epilepsy， with a focus on its molecular mechanisms， clinical phenotypes， factors influencing phenotypic heterogeneity， and treatment strategies. In terms of molecular mechanisms， GRIN1 mutations affect NMDA receptor function through gain-of-function and loss-of-function mechanisms. Clinical phenotypes show significant heterogeneity， including seizure types， age of onset， and comorbid neurodevelopmental disorders. This heterogeneity may be related to the domain where the mutation is located， the mutation type， and the degree of impact on receptor function. Regarding treatment， gain-of-function mutations can be managed with NMDA receptor antagonists， while loss-of-function mutations may be treated with positive allosteric modulators. The ketogenic diet has also demonstrated potential therapeutic effects. This review aims to provide references for basic research and clinical translation in GRIN1 mutation-related epilepsy， and to promote the development of precision diagnosis and treatment.

Objective To analyze the diagnostic quality of imported malaria in Hubei Province from 2019 to 2022, and to further improve the diagnostic level and consolidate the achievements in eliminating malaria. Methods The samples of reported malaria cases in Hubei were collected by the provincial reference laboratory (PRL) from 2019 to 2022. The microscopy and fluorescent PCR were performed to confirm the infection of plasmodium species of each case．The positive coincidence rate and species coincidence rate were analyzed and compared． Results A total of 257 imported malaria cases were reported in Hubei Province from 2019 to 2022. Among 229 malaria cases were confirmed, the overall coincidence for malaria diagnosis was 91.24% (229/251), and the overall coincidence rate for parasite species identification was 86.03% (197/229). The difference in species coincidence rate among different years was statistically significant (χ²=10.458, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification in different cities (prefectures) of Hubei Province were 71.43% to 100.00% and 50.00% to 100.00%, respectively, with significant differences among different regions (χ²=29.283, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification were 72.73% to 100.00% and 0.00% to 100.00% in different diagnostic institutions, and the coincidence rate of species identification in hospitals (87.61%) was higher than that in Centers for Disease Control institutions (54.55%) (χ²=81.275, P<0.05). The coincidence rates of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale identification were 91.50%, 88.57%, 80.00%, and 58.06%, respectively (χ²=19.777, P<0.05). Conclusion The quality of the qualitative diagnosis of malaria cases reported online from 2019 to 2022 is generally high. However, the ability of Plasmodium typing needs to be improved. In the future, technical training and quality control should be strengthened to improve the malaria surveillance capability during the post-elimination stage.

Objective:To investigate the predictive value of neutrophil/lymphocyte ratio (NLR) at admission for stroke associated pneumonia (SAP) in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the First Affiliated Hospital of Kunming Medical University from January 2019 to June 2020 were retrospectively included. The demographic information, vascular risk factors, severity of stroke at admission, and NLR data of the patients were collected. Multivariate logistic regression was used to analyze the independent correlation between NLR and SAP. The NLR was divided into quartile groups to further analyze the trend relationship between NLR and SAP. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NLR for SAP. Results:A total of 316 patients with AIS were enrolled, including 200 males (63.29%) with an age of 63.86±13.78 years. The median baseline Nationanl Institutes of Health Stroke Scale score was 4 (interquartile range, 2-9), and the median NLR was 4.42 (interquartile range, 3.17-6.70). Ninety-three patients (29.43%) experienced SAP. Multivariate logistic regression analysis showed that NLR was an independent risk factor for SAP in patients with AIS (odds ratio 1.189, 95% confidence interval 1.077-1.313; P<0.001). Moreover, SAP risk increases with the increase of NLR ( Ptrend<0.001). Compared to the first quartile, the risk of SAP increased 9.991 times in the fourth quartile (95% confidence interval 2.912-34.279; P<0.001). ROC curve analysis showed that the area under the curve of NLR for SAP prediction was 0.793 (95% confidence interval 0.737-0.850), with an optimal cutoff value of 5.475. The sensitivity and specificity for predicting SAP were 66.67% and 79.82%, respectively. Conclusion:NLR at admission is an independent risk factor for SAP in patients with AIS and has certain predictive value for SAP.

Objective:To explore the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T cells (Tregs) by detecting the lncRNAs expression profiles in patients with systemic lupus erythematosus (SLE), then analyze the correlation between Tregs and lncRNAs and the clinical features of SLE patients. We also predict the mechanism by which lncRNAs regulate the differentiation and development of Tregs, and provid new approach for the treatment of SLE.Methods:Peripheral blood of 9 active SLE patients was collected and mononuclear cells (PBMCs) were extracted. The lncRNAs expression profiles of PBMCs was analyzed by whole transcriptome sequencing. Nine healthy people served as controls to screen the differentially expressed lncRNAs, and to analyze the correlation between lncRNAs and Tregs number. Pearson test was used to analyze the correlation between lncRNA and the number of Tregs, and the correlation between Treg-associated lncRNAs and systemic lupus erythematosus disease activity index(SLEDAI) score, erythrocyte sedimentation rate (ESR), C3, C4 in SLE patients. The targeted genes of Treg asso-ciated lncRNAs were predicted with miRcode and Targetscan databases and co-expression network.Results:There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs ( P<0.05) and 106 low expressed lncRNAs ( P<0.05). The expression of ANKRD44-AS1 ( r=0.74, P=0.022), LINC00200 ( r=0.70, P=0.037), AP001363.2 ( r=0.78, P=0.014) and LINC02824 (r=0.79, P=0.011) were positively correlated with the number of Tregs, and the expression of AP000640.1 ( r=-0.72, P=0.028), AC124248.1 ( r=-0.77, P=0.016), LINC00482 ( r=-0.83, P=0.005) and MIR503HG ( r=-0.96, P<0.001) were negatively correlated with the number of Tregs. Among these eight Tregs associated lncRNAs, the expression of LINC00482 ( r=-0.73, P<0.001) and MIR503HG ( r=-0.76, P<0.001) were negatively correlated with C3. LINC00200, ANKRD44-AS1 and AP000640.1 related to Tregs regulated the expression of STAT5, PLD1, HOPX and RUNX3 through competitively binding of miRNA or transregulatory mechanism, thereby regulating the differentiation and development of Tregs. Conclusion:The lncRNAs expression profiles are changed in SLE patients, the differentially expressed lncRNAs are associated with abnormal number and function of Tregs in SLE patients, and Treg associated lncRNAs are associated with SLE disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Tregs function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism.

Liddle syndrome and Gordon syndrome are two rare single-gene inherited hypertension diseases. In patients≤40 years, the prevalence of Liddle syndrome is about 1% and Gordon syndrome is uncertain all over the word, for which is often misdiagnosed and mistreated. The therapies of those diseases are targeted at gene mutation sites, as well as combined with modified lifestyle, and can achieve satisfactory diseases control. This paper reports a patient who is diagnosed with Liddle syndrome and Gordon syndrome at the same time. We aimed to consolidate and improve the diagnosis and accurate treatment of those two diseases by sharing, studying and discussing together with clinical doctors.

BACKGROUND: Health literacy is a public health goal which can be used as an independent factor of health outcomes. This study aimed to assess the association between health literacy and health status, as well as the two mediating factors of behavior and self-efficacy among residents aged 15-69 years in Qingdao. METHODS: A cross-sectional survey was implemented among residents aged 15-69 years (N = 3793) in Qingdao, China. A combination of stratified cluster random and proportional probability sampling methods was used to select subjects for this study. Data were collected using "The Chinese Citizen Health Literacy Questionnaire (2019)". We proposed a hypothetical model for the relationship between sociodemographic characteristics, health literacy, self-efficacy, health behavior, and health status, and used path analysis to validate the hypothesis. RESULTS: The path analysis showed that higher education (β = 0.293) and income (β = 0.135) are positively and directly associated with greater health literacy, which was positively associated with health status (β = 0.057). Health literacy is a direct influencing factor of health behavior (β = 0.070) and self-efficacy (β = 0.099). Health behavior (β = 0.041) and self-efficacy (β = 0.173) exerted a positive direct effect on health status. The model explained 14.1% of variance for health literacy, 3.8% for self-efficacy, 5.7% for health behavior, and 15.0% for health status. CONCLUSIONS Health literacy was identified to be a critical factor in health status. The results emphasized that the dissemination of health knowledge, development of healthy behavior, and cultivation of self-efficacy should be jointly promoted to reinforce the level of health status among residents in future work.
Adolescent ; Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; Health Behavior ; Health Knowledge, Attitudes, Practice ; Health Literacy/statistics & numerical data* ; Health Status ; Humans ; Male ; Middle Aged ; Young Adult

Objective:To investigate the distribution of the spherical aberration in age-related cataractous eyes using the Pentacam HR.Methods:A cross-sectional study was performed in Shanxi Eye Hospital from December 2014 to December 2015.The preoperative corneal spherical aberration of 1 319 eyes of 1 319 patients with age-related cataract over 40-years-old was analyzed.The mean average keratometry (Km value), and corneal posterior surface Km corneal astigmatism, posterior corneal astigmatism, and corneal thickness were measured with.Pentacam, and the Zernike coefficients of corneal spherical aberration were calculated.A correlation between spherical aberration and corneal parameters was evaluated by Pearson correlation analysis.The proportion of eyes qualifying for spherically neutral or negatively aspheric intraocular lens targeted residual spherical aberration level was evaluated.This study protocol was approved by Ethics Committee of Shanxi Eye Hospital and complied with Declaration of Helsinki.Results:The average age of all patients was (68.00±11.12) years old with an average spherical aberration (0.34±0.17)μm.The spherical aberration was lower than 0 μm in 22 eyes (1.67%), 0~0.4 μm in 842 eyes (63.84%), and greater than 0.4 μm in 455 eyes (34.50%). There was a weak positive correlation between spherical aberration and age ( r=0.398, P<0.001). There were very weak correlations between spherical aberration and corneal Km, posterior corneal surface Km, corneal thickness ( r=0.129, P<0.001; r=0.240, P<0.001; r=-0.068, P<0.05). No significant correlations were found between spherical aberration and corneal astigmatism or posterior corneal astigmatism ( r=-0.025, P=0.365; r=-0.008, P=0.771). Seven hundred and ten eyes (53.83%) could be qualified for implantation of negatively or neutrally aspheric intraocular lens based on postoperative targets of (0.10±0.05)μm residual spherical aberration. Conclusions:Corneal spherical aberration in Chinese patients is greater than that in other populations (+ 0.27 μm) in literature and shows individual differences.The appropriate aspheric intraocular lens should be selected according to individual corneal spherical aberration before cataract operation.

Objective: To analyze the molecular characteristics of Listeria monocytogenes strains from ready-to eat food in China. Methods: A total of 239 Listeria monocytogenes strains isolated from ready-to-eat food in 2017, all strains underwent whole-genome sequencing (WGS) , and comparisons uncovered population structure derived from lineages, clonal complex, serogroups, antimicrobial susceptibility and virulence, which were inferred in silico from the WGS data. Core genome multilocus sequence typing was used to subtype isolates. Results: All strains were categorized into three different lineages, lineage Ⅱ was the predominant types in food, and IIa was the main serogroups. CC8, CC101 and CC87 were the first three prevalent CCs among 23 detected CCs, accounting for 49.4%. Only 4.6% (11 isolates) of tested strains harbored antibiotic resistance genes, which were mostly trimethoprim genes (7 isolates, 2.9%). All strains were positive for LIPI-1, and only a part of strains harbored LIPI-3 and LIPI-4, accounting for 13.8% (33 isolates) and 14.2% (34 isolates), respectively. ST619 carried both LIPI-3 and LIPI-4. 51.5% (123 isolates) of strains carried SSI-1, and all CC121 strains harbored SSI-2. Different lineages, serogroups and CCs can be separated obviously through cgMLST analysis, and 24 sublineages were highly concordant with CCs. Conclusion Ⅱa was the main serogroups in ready-to-eat food isolates in China; CC8, CC101 and CC87 were the prevalent CCs, and CC87 isolates was hypervirulent isolates, cgMLST method can be adopted for prospective foodborne disease surveillance and outbreaks detection.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.