Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

OBJECTIVE To investigate the efficacy and safety of different doses of zinc in the treatment of diarrhea in children， and to provide a reference for clinical safe and rational drug use. METHODS Retrieved from PubMed， Cochrane Library， Embase database， randomized controlled trials about zinc （zinc group） versus placebo or conventional treatment （control group） in the treatment of diarrhea in children were collected from the inception to October 2022. Then， the quality of the included literature was evaluated by the Cochrane Handbook 6.0， and meta-analysis and sensitivity analysis were performed by RevMan 5.3 software. RESULTS Finally， 25 RCTs were included， with a total of 8 618 children. The results of meta-analysis showed that in terms of duration of diarrhea， in zinc ＜20 mg group， the zinc group was significantly shorter than the control group [SMD＝ －0.39， 95%CI（－0.71， －0.08）， P＝0.01]， but in subgroups of ＜6 months old， there was no significant difference between the two groups [SMD＝0.01， 95%CI（－0.10， 0.11）， P＝0.88]. In zinc 20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.52， 95%CI（－0.80， －0.23）， P＝0.000 3]. In zinc ＞20 mg group， the zinc group was significantly shorter than the control group [SMD＝－0.83， 95%CI（－1.39， －0.27）， P＝0.004]. In zinc ＞10 mg （age ≤12 months） or zinc ＞ 20 mg （age ＞12 months） group （short for “constant dose group”）， the zinc group was significantly shorter than the control group [SMD＝－0.16， 95%CI（－0.27， －0.06）， P＝ 0.003]. In the aspect of diarrhea rate after 7 days of treatment，there was no significant difference in the diarrhea rate after 7 E-mail：lihuiying@etyy.cn days of treatment between the zinc group and the control group： in zinc ＜20 mg group[OR＝1.28，95%CI （0.96，1.70），P＝0.09]， in zinc 20 mg group [OR＝0.40， 95%CI （0.15，1.01），P＝ 0.05]， in constant dose group [OR＝0.64， 95%CI （0.28， 1.44）， P＝0.28]. In terms of vomiting rate， in zinc ＜20 mg group， the vomiting rate of zinc group was significantly higher than that of the control group [OR＝2.13， 95%CI （1.68， 2.70）， P＜0.001]； in constant dose group， vomiting rate of zinc group was significantly higher than that of the control group [OR＝1.84， 95%CI （1.44， 2.34）， P＜0.001]. CONCLUSIONS Zinc can significantly shorten the duration of diarrhea in children（6 months and above）， but low doses can increase the risk of vomiting， which should be taken attention in clinical.

Objective:To comprehensively analyze the current research status, hotspots, and development trends in the field of fatigue in maintenance hemodialysis patients both domestically and internationally in order to provide reference for future research directions.Methods:Relevant literature on the fatigue status of maintenance hemodialysis patients from the establishment of the database to the publication before December 30, 2022 was retrieved through CNKI, VIP database, Wanfang database, and Web of ScienceTM core collection database, and visualized using CiteSpace 6.1.R3 for analysis.Results:A total of 152 Chinese articles and 110 English articles were included. Analysis showed that foreign publications were first published in 1996, while domestic publications were first published in 2011, and the number of publications has shown a significant upward trend since 2017. The research focus at home and abroad mainly focuses on the influencing factors and intervention measures of fatigue in dialysis patients. Foreign researchers have paid more attention to the correlation between "depression" emotions and the positive intervention of aerobic exercise. In addition, China is actively exploring traditional Chinese medicine therapy aromatherapy to alleviate patient fatigue.Conclusions:In the future, clinical workers should pay attention to fatigue assessment in maintenance hemodialysis patients and explore the influencing factors of fatigue through large-scale longitudinal studies, in order to better provide intervention targets for the treatment of fatigue; Simultaneously conduct high-quality prospective intervention studies to maximize the improvement of fatigue status in such patients and form standardized guidelines for promotion and application.

Objective:To explore the effect of dialectical diet on traditional Chinese medicine (TCM) syndrome score of cirrhotic ascites patients based on "Gu Ben Kai Qu" theory.Methods:From March 2019 to January 2020, 84 patients with liver cirrhosis and ascites admitted to Shuguang Hospital Affiliated to Shanghai University of TCM were randomly divided into two groups according to the different dialectical types of the subjects, 14 cases in each group. Three non-syndrome differentiation diet groups were given routine nursing care of liver cirrhosis ascites. On the basis of routine nursing, the corresponding medicinal diet was selected according to syndrome differentiation based on "Gu Ben Kai Qu" theory. Patients with spleen and kidney yang deficiency syndrome selected Shenqi lean meat decoction. Patients with Yin deficiency of liver and kidney selected Wolfberry and ophiopogon spareribs decoction. Patients with qi stagnation and blood stasis syndrome selected Danggui Sanqi spareribs decoction. The TCM syndrome score scale for liver disease and the curative effect evaluation of cirrhosis ascites were used to evaluate the effect.Results:Eighty effective cases were included. On the first day of admission, the 14th day and the second week after discharge, the TCM syndrome scores of liver disease were as follows: the group (a1b1) with the spleen and kidney yang deficiency syndrome was 46.38±8.56, 34.20±8.42, 31.40±4.22, respectively. The group (a1b2) with the liver kidney yin deficiency syndrome was 41.50±8.71, 31.35±8.63, 31.12±4.94. The group(a1b3) with the qi stagnation and blood stasis syndrome was 45.92±7.86, 35.17±7.57, 30.83±7.32, respectively. The non-syndrome differentiation diet group (a2b1) with the spleen and kidney yang deficiency syndrome was 46.29±8.38, 39.79±7.65, 36.64±6.83, respectively. The non-syndrome differentiation diet group (a2b2) with the liver and kidney yin deficiency syndrome was 40.50±8.12, 38.10±8.93, 35.38±8.24, respectively. The non-syndrome differentiation diet group (a2b3) with the qi stagnation and blood stasis syndrome was 45.62±7.99, 41.83±7.31, 38.83±7.96, respectively. The comparison of TCM syndrome scores of liver disease at three time points was statistically significant ( χ2 value was 63.998, P<0.05), and the comparison between groups was statistically significant ( χ2 value was 20.993, P<0.05). On the 14th day and the second week after discharge, there were significant differences between the groups with the syndrome differentiation diet and another three groups with non-syndrome differentiation diet ( F values were 3.244, 3.489, all P<0.05). Conclusions:Based on the theory of "strengthening the foundation and opening channels", the syndrome differentiation group can effectively reduce the TCM syndrome score of patients with cirrhosis ascites, improve the symptoms and enhance the curative effect. With the development of time, the score of TCM syndrome in patients with liver disease become lower. On the 14th day of admission, patients with Yin deficiency of liver and kidney given medicated diets had significant effect; patients with spleen kidney yang deficiency syndrome or qi stagnation and blood stasis had significant effect in 2 weeks after discharge; which can effectively improve the clinical symptoms of patients with cirrhosis ascites to worthy of clinical application.

Objective:To investigate the sodium intake, potassium intake, sodium- potassium ratio and influencing factors of family cooks and members in six regions of China.Methods:Using the multistage random sampling method, a total of 1 576 family cooks and their family members were recruited from 6 regions in China. Questionnaire survey and physical examination were conducted to collect basic information. 24 h urine was collected to test 24 h urinary sodium and potassium levels.Results:After excluding unqualified urine samples, a total of 1 530 people were included in the study. For all participants, 24 h urine sodium value was (4.39±1.93) g, 24 h urine potassium value was (1.59±0.62) g and sodium-potassium ratio was 5.02±2.18. 24 h urinary sodium was negatively correlated with age, female, junior high school education or above, and annual family income ( P<0.05), and positively correlated with perceived salty taste, BMI and SBP ( P<0.05). The 24 h urine potassium value was negatively correlated with eating out almost everyday ( P<0.05), but positively correlated with BMI and unwillingness to reduct salt ( P<0.05). The sodium-potassium ratio was negatively correlated with age, female and junior high school education or above annual family income ( P<0.05), and positively correlated with perceived salty taste, SBP and eating out 3-5 d/week ( P<0.05). Conclusions:The 24 h urinary sodium value and sodium potassium ratio of family cooks and family members in six regions of China are still at high level, while the 24 h urine potassium value is low, with multiple factors. Therefore, it is necessary to carry out long-term comprehensive salt reduction intervention for family cooks and their members.

Objective To study the dynamic changes of blood carnitine and acylcarnitine levels in preterm infants during parenteral and enteral nutritional support,and the relationship between carnitine status and nutritional patterns,gestational age (GA) and weight gain.Method From January 2017 to December 2017,preterm infants admitted to the neonatal intensive care unit (NICU) within 24 hours after birth and received parenteral nutrition support were enrolled.They were assigned into 4 groups according to their GA:ultra-premature infants (＜ 28 weeks),very premature infants (28 ～ 31 weeks),mid premature infants (32 ～ 33 weeks) and late premature infants (34 ～ 36 weeks).They were assigned into 2 groups according to their average daily weight gain:＜ 15 g/(kg · d) group and ≥15 g/(kg · d) group.Blood samples were collected and examined as dried-blood spot specimens on filter paper for four times:after born,given total parenteral nutrition,given enteral combined parenteral nutrition,and given total parenteral nutrition.The concentrations of free carnitine and acylcarnitine were detected using liquid chromatographytandem mass spectrometry (LC-MS/MS).SPSS 21.0 statistical software was used for statistical analysis.Result A total of 124 preterm infants and 410 samples were collected.As the infants experienced gradual transition from parenteral nutrition to enteral nutrition,the free carnitine and most acylcarnitines levels were decreasing (C3,C4,C10DC,C12,C12∶1,C12DC,C14,C16,C16∶ 1,C16-OH and C18,P＜0.05).Preterm infants with small GA showed higher levels of C4-OH (P =0.001) and C5 (P =0.001).Preterm infants with lower velocity of weight gain showed lower concentration of C5-OH (P =0.006) in the early postnatal period.Conclusion Free carnitine and acylcarnitine in preterm infants during the early postnatal period are decreasing with the transition from parenteral nutrition to enteral nutrition,indicating that the exogenous nutrition is relatively insufficient.C4-OH and C5 levels are negatively correlated with GA.In addition,lower level of C5-OH may indicate slow weight gain during the early postnatal period.

Objective:To assess the relationship between body mass index (BMI) and death risk of cardiovascular disease (CVD) in rural male population.Methods:22 282 men aged 40 years older in Tanghe county and Fenghuang county from the cohort of the "Prospective Study on Adult Behavior and Health Risk Factors in China" were selected as subjects of this study. Cox regression model was used to calculate the hazard ratios ( HRs) of the death of CVD during the follow-up period with different BMI groups at baseline. Results:The average follow-up period in the two counties was (19.1±8.7) years and 10 828 (48.6%) people died during the follow-up period. 4 504 deaths were attributed to CVD. Among the deaths of CVD, 1 279 cases died of ischemic heart disease (IHD), ischemic stroke (IS) died in 1 201, cases died of died of 1 317 hemorrhagic stroke (HS), other 707 cases. Compared to population with BMI<18 kg/m 2, Cox regression model (adjusting factors of region, age, nationality, education level, occupation, smoking, drinking, blood pressure, blood pressure, etc.) showed that people with BMI between 20-22 kg/m 2 had the lowest risk of CVD death ( HR=0.95, 95 %CI: 0.83-1.09). But the difference was not statistically significant among each BMI group ( P>0.05). The risk of IHD death was the lowest in the population with BMI between 20-22 kg/m 2 ( P<0.05) ( HR=0.64, 95 %CI: 0.52-0.80). There was no statistically significant difference between the risk of IHD death in the population with BMI≥24 kg/m 2 and that in the population with BMI<18 kg/m 2 ( P>0.05). There was no statistically significant difference between the risk of IS death and BMI ( P>0.05). The death risk of HS in the population with BMI between 18-24 kg/m 2 was higher than that in the population with BMI<18 kg/m 2 ( P<0.05). The death risk of the population with BMI between 26-28 kg/m 2 was the highest ( HR=1.88, 95 %CI:1.18-2.99). Conclusions:The mortality risk of CVD and IHD was the lowest in lean or normal weight group, and HS was higher in overweight group. Maintaining a reasonable weight can reduce the risk of death in patients with CVD.