OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.

Objective:To examine the validity and reliability of the DSM-5 Social Anxiety Disorder Severity Scale(SAD-D)in a Chinese adult population.Methods:The Chinese version of the DSM-5 Social Anxiety Disor-der Severity Scale was administered via online data collection platform Credamo to 300 adults(Sample 1,for item analysis,exploratory factor analysis and item selection of brief version of SAD-D)and 528 adults(Sample 2,for confirmatory factor analysis,criterion validity test,measurement invariance analysis and internal consistency reliabil-ity analysis for both SAD-D and its brief version).Criterion validity was tested with the Social Phobia Scale(SPIN)and Personal Report of Confidence as a Speaker(PRCS).A brief version of the scale was developed by u-sing the Ant Colony Optimization(ACO).A retest was conducted with 152 participants from Sample 2 after three weeks.Results:Exploratory factor analysis indicated that the SAD-D was a unidimensional scale with factor load-ings ranging from 0.49 to 0.82,and the results of the confirmatory factor analysis also supported the unidimension-al structure(x2/df=3.49,RMSEA=0.069,CFI=0.971,TLI=0.962,SRMR=0.028).The scores of Chinese version of the SAD-D were positively correlated with the SPIN scores(ICC=0.70,P＜0.001)and PRCS scores(ICC=0.73,P＜0.001).The Cronbach'α of the scale was 0.92,and the retest reliability was 0.85.The scale dem-onstrated cross-gender measurement invariance(△CFI＜0.01,△RMSEA＜0.01).The brief version of the SAD-D was selected as items 2,5,and 6,and its Cronbach'α coefficient was 0.86.Conclusion:The Chinese version of the SAD-D has satisfactoryvalidity andreliability,making it suitable for the assessment of social anxiety symptoms with Chinese adults.

Objective:To examine the validity and reliability of the DSM-5 Social Anxiety Disorder Severity Scale(SAD-D)in a Chinese adult population.Methods:The Chinese version of the DSM-5 Social Anxiety Disor-der Severity Scale was administered via online data collection platform Credamo to 300 adults(Sample 1,for item analysis,exploratory factor analysis and item selection of brief version of SAD-D)and 528 adults(Sample 2,for confirmatory factor analysis,criterion validity test,measurement invariance analysis and internal consistency reliabil-ity analysis for both SAD-D and its brief version).Criterion validity was tested with the Social Phobia Scale(SPIN)and Personal Report of Confidence as a Speaker(PRCS).A brief version of the scale was developed by u-sing the Ant Colony Optimization(ACO).A retest was conducted with 152 participants from Sample 2 after three weeks.Results:Exploratory factor analysis indicated that the SAD-D was a unidimensional scale with factor load-ings ranging from 0.49 to 0.82,and the results of the confirmatory factor analysis also supported the unidimension-al structure(x2/df=3.49,RMSEA=0.069,CFI=0.971,TLI=0.962,SRMR=0.028).The scores of Chinese version of the SAD-D were positively correlated with the SPIN scores(ICC=0.70,P＜0.001)and PRCS scores(ICC=0.73,P＜0.001).The Cronbach'α of the scale was 0.92,and the retest reliability was 0.85.The scale dem-onstrated cross-gender measurement invariance(△CFI＜0.01,△RMSEA＜0.01).The brief version of the SAD-D was selected as items 2,5,and 6,and its Cronbach'α coefficient was 0.86.Conclusion:The Chinese version of the SAD-D has satisfactoryvalidity andreliability,making it suitable for the assessment of social anxiety symptoms with Chinese adults.

OBJECTIVE To investigate the effects of potassium channel Kv1.3knockout(Kv1.3 KO)on neurological dysfunction and neuroinflammation in C57BL/6 mice following traumatic brain injury(TBI).METHODS C57BL/6 mice and homozygous Kv1.3 KO C57BL/6 mice were subjected to the classic controlled cortical impact model to establish a TBI model.The experimental groups included the sham surgery group,C57BL/6 TBI model group(TBI group),and a Kv1.3 KO C57BL/6 TBI model group(TBI+Kv1.3 KO group).At 1,2,and 3 weeks post-modeling,real-time quantitative PCR was used to measure the mRNA expression levels of Kv1.3,interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),and IL-10 in hippocampal tissues.At 1 and 3 weeks post-modeling,Western blotting was performed to detect Kv1.3 protein expressions in the hippocampus.At 3 weeks post-modeling,Western blotting was used to assess the protein levels of IL-1β,IL-6,TNF-α,and IL-10 in hippocampal tissues.Additionally,immunofluorescence was employed to quantify cells co-labeled with the microglial marker ionized calcium-binding adapter molecule 1(IBA1)and Kv1.3,IL-1β,or TNF-α in the hippocampus.Patch-clamp recordings were conducted to measure Kv1.3 channel currents in primary microglia at 3 weeks post-modeling.Neurological function was evaluated at 1 and 3 weeks post-modeling using the neurological severity score(NSS),pole climbing,and rotarod tests.Cognitive function was assessed at 3 weeks post-modeling via open field,Morris water maze,and Y-maze tests.RESULTS Compared with the sham group,the TBI group exhibited significantly elevated mRNA expression levels of Kv1.3 and IL-1β in the hippocampus at 1,2 and 3 weeks post-modeling,while IL-6 and IL-10 mRNA levels showed no significant changes.Notably,TNF-α mRNA expressions demonstrated a significant increase only at 2 and 3 weeks post-modeling.At 1 and 3 weeks post-modeling,Kv1.3 protein expres-sions in the hippocampus were significantly higher in the TBI group.At 3 weeks post-modeling,hippo-campal IL-1β and TNF-α protein levels were markedly increased in the TBI group,whereas IL-6 and IL-10 protein levels did not change significantly.Moreover,Kv1.3 current density in primary microglia was signifi-cantly enhanced in the TBI group at 3 weeks post-modeling.Immunofluorescence analysis revealed that the number of IBA1-positive microglia co-labeled with Kv1.3,IL-1β,or TNF-α in the hippocampus was significantly larger in the TBI group than in the sham group at 3 weeks post-modeling.Behaviorally,the TBI group exhibited significantly higher NSS scores,lower success rates in full turn attempts,and longer times taken to descend the pole at 1 and 3 weeks post-modeling compared with the sham group.At 3 weeks post-modeling,TBI mice also demonstrated reduced total movement distance in the open field,decreased time spent in the central zone,fewer platform crossings,less time in the target quadrant,and lower spontaneous alternation rates.In contrast,the TBI+Kv1.3 KO group showed signifi-cantly improved outcomes compared with the TBI group:lower NSS scores,higher success rates in full turns,and shorter time taken to descend the pole at 1 and 3 weeks post-modeling.At 3 weeks post-modeling,the TBI+Kv1.3 KO group displayed longer rotarod endurance,increased total movement dis-tance in the open field,more time spent in the central zone,higher platform crossings,greater target quadrant exploration time,and improved spontaneous alternation rates.Furthermore,at 1 and 3 weeks post-modeling,the TBI+Kv1.3 KO group exhibited significantly reduced mRNA expression levels of the inflammatory cytokines IL-1β and TNF-α in the hippocampus compared with the TBI group.CONCLU-SION Potassium channel Kv1.3 knockout mitigates neurological dysfunction and neuroinflammation in C57BL/6 mice following TBI.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Humans ; Stroke ; Phagocytosis/physiology* ; Inflammation ; Apoptosis/physiology* ; Animals ; Phagocytes/physiology* ; Brain/metabolism* ; Efferocytosis

Tuberculous meningitis is the most common and serious type of central nervous system tuberculosis, with high mortality and disability rate, which has attracted extensive attention of global public health. The high mortality rate and disability rate of tuberculosis meningitis may be related to its lack of specific clinical and imaging characteristics, insufficient attention from clinicians, lack of early sensitive and specific diagnostic testing techniques, delay in treatment, and restricted penetration of anti-TB drugs into the blood-brain barrier or/and MDR-TB, etc. This article reviews the disease burden of TBM, chemotherapy drugs and regimens, anti-inflammatory agents, aspirin, interventional and surgical treatment to provide reference for clinical management of this disease.

OBJECTIVE：To improve the quality standard of M ongolian med icine Artemisia sacrorum ，and to provide scientific basis for comprehensive quality evaluation. METHODS ：The appearance and microscopic characteristics of A. sacrorum were identified；scopoletin，chlorogenic acid ，caffeic acid ，scopoletin and 3，5-dicaffeoylquinic acid were identified quantitatively by TLC；the contents of above 5 components were determined by HPLC. The water content ，total ash and extract were examined. RESULTS：The stem of A. sacrorum was cylindrical ，and its surface was purple or purple-brown or cyan-brown ；the leaves were ovate or oblong-ovate ，fragrant；the flowers were yellow ，head-shaped，subglobose or hemispherical. The powder was green or yellow-green，its pollen grain had three germination ；the parenchymal cell clusters with sharp edges and numerous threaded ducts ， occasionally having marginal pitted ducts ；its wood fibers were in bundles mostly. Results of TLC showed that the spots of the same color were found in the corresponding positions of chromatogram for 5 substance control and samples. The linear range of scopoletin， chlorogenic acid ， caffeic acid ， scopolactone and 3，5-dicaffeoylquinic acid were 85.60-428.00， 10.16-101.60， 10.20-102.00，40.84-408.40 and 40.80-408.00 μg/mL（all r＞0.999 0）. RSDs of precision ，stability，repeatability tests were all less than 3.00％（n＝6）. The average recoveries were 103.07％，99.66％，98.37％，97.78％，98.40％（all RSDs ＜3.00％，n＝6）. The contents of the above-mentioned 5 compounds in 10 batches of samples were 0.36％-1.23％，0.09％-0.51％，0.04％-0.13％， 0.61％ -1.13％ ，0.12％ -1.11％ ，respectively；the average com contents of water ，total ash and water soluble extract were 6.25％，5.86％，26.50％，respectively. CONCLU SIONS：O the basis of the original quality standard of A. sacrorum ， microscopic identification，TLC identification ，content determination and examination items of water ，total ash and extract are added. The method shows good precision ，accuracy and stability ，which can provide reference for more scientific and standardized evaluation of the quality of this medicinal material.

Currently, tuberculosis, including both pulmonary tuberculosis (PTB) and extra pulmonary tuberculosis (EPTB) still widely spread worldwide. EPTB has become one of research hotspots, changes in the incidence of EPTB and its composition in TB have occurred, the situation varied with country and region. The age and gender distributions of EPTB cases were different, even contradicted, indicated by different studies. The incidence rate and prevalence rate of EPTB might be underestimated due to insufficient attention paid to EPTB, inadequate diagnostic methods and low diagnosis rate. The cure rate of EPTB is always lower than PTB, posing challenges to global TB control. This paper summarizes the progress in research of EPTB epidemiology in recent years in terms of EPTB definition, epidemiological characteristics of EPTB in the world, correlation of different EPTB and related risk factors to provide reference for the prevention and control of EPTB.

Objective:To investigate the effect of virus inactivation on weak positive result of 2019 novel coronavirus(2019-nCoV) nucleic acid test.Methods:A retrospective study was conducted on the nasopharyngeal swabs of three patients with positive PCR nucleic acid test for 2019-nCoV at different concentrations in the Second affiliated Hospital of Zhejiang University Medical College from January to February 2020.The virus in nasopharyngeal swab specimens were inactivated by water bath at 56 ℃ for 30 min, dry bath at 56 ℃ for 60 min and dry bath at 60 ℃ for 30 min respectively. After treatment, these samples RNA were extracted and then detected by three new commercial quantitative real-time polymerase chain reaction reagent kits for 2019-nCoV.Cycle threshold (Ct) value was used to evaluate the effect of virus inactivation on nucleic acid detection of 2019-nCoV.Results:There was no significant difference between the groups before and after inactivation. Ct values of ORF1ab gene before inactivation were 23.28±0.28, 25.25±0.25, 28.93±0.44, 32.06±0.47, 35.20±0.38, 32.89±0.38, 36.24±0.23, 33.30±0.46, and those after inactivation were, group 1:23.60±0.20, 27.29±0.30, 31.83±0.51, 37.41±0.46, group 2: 24.25±0.34, 27.18±0.42, 31.84±0.61, 34.99±1.01, 34.89±0.45,group 3: 23.37±0.17, 26.89±0.52, 32.05±0.50.Ct value of N gene before inactivation were 24.38±0.09, 26.64±0.11, 30.35±0.12, 33.29±0.33, 36.93±0.11, 34.50±0.12, 35.63±0.12, those after inactivation were, group 1: 24.66±0.11, 28.52±0.14, 32.71±0.14, 37.00±0.13;group 2: 25.41±0.10, 28.79±0.15, 33.29±0.28; group 3: 23.37±0.11, 28.68±0.11, 33.54±0.13, 37.18±0.23(ORF1ab gene: t=-1.416; N gene: t=-1.379, P>0.05). There was no significant difference among the three inactivation groups, the specific Ct values are shown above(ORF1ab gene: t=-0.460; N gene: t=-0.132, P>0.05). However, the Ct values of the inactivated groups (1,2,3) and the non-inactivated group at different dilution times were different (10 ×:Ct value of ORF1ab was 25.25±0.25 in the non-inactivated group, and 27.29±0.30, 27.18±0.42 and 26.89±0.52 in the inactivated group1,2 and 3, t(ORF1ab)=-7.327, P<0.01.Ct value of N gene in the non-inactivated group was26.64±0.11, those in inactivated group 1, 2 and 3 were 28.52±0.14, 28.79±0.15 and 28.68±0.11, respectively, t (N)=-19.340, P<0.01. 100 ×:Ct value of ORF1ab was 28.93±0.44 in the non-inactivated group, and 31.83±0.51,31.84±0.61 and 32.05±0.50 in the inactivated group1,2 and 3, t (ORF1ab)=-9.462, P<0.01. Ct value of N gene in the non-inactivated group was 30.35±0.12, those in the inactivated group 1, 2 and 3 were 32.71±0.14, 33.29±0.28 and 33.54±0.13, respectively, t (N)=-18.583, P<0.01. The positive detection rate of the non-inactivated group (7/11, 8/11, 5/11) was significantly different from that of the inactivated group (inactivated group 1:4/11, 4/11, 3/11, inactivated group 2:3/11, 3/11, 3/11, and inactivated group 3:3/11, 3/11, 2/11) ( Z=-2.670, P<0.01). There were no significant difference among the inactivated groups(inactivated group 1:4/11, 4/11, 3/11, inactivated group 2:3/11, 3/11, 3/11, inactivated group 3:3/11, 3/11, 2/11) ( Z=4.413, P>0.05) and among the three reagents(reagent 1:7/11, 4/11, 3/11, 3/11, reagent 2:8/11, 4/11, 3/11, 3/11, reagent 3:5/11, 3/11, 3/11, 2/11)(χ 2=1.199, P>0.05). Conclusion:The virus inactivation can degrade the nucleic acid of the 2019-nCoV, resulting in the decrease of the Ct value and the false negative results of the low-concentration specimens.

OBJECTIVETo explore the value of nutrition management in obese patients with type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG).

METHODSClinical data of 22 obese T2DM patients undergoing LSG from March 2013 to July 2015 in Fudan University Pudong Medical Center were collected. All the patients strictly followed the specialized instruction by nutritionists: diabetic and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation for promoting gastric emptying; fasting diet before postoperative ventilation; clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to 3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6 months after operation on time. Changes of body weight, waist circumference, hip circumference, body mass index(BMI), blood glucose indexes induding fasting blood glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and analyzed before and 1 week, 1, 3, 6 months after operation.

RESULTSThe average age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The duration of diabetes varied from 1 month to 15 years. Comorbidity included 12 patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease, 1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was performed successfully in all the patients and no severe complications and transference to laparotomy occurred. As compared to pre-operation, at 6 months after operation, the average body weight decreased from (103.9±20.2) kg to (80.9±12.6) kg (t=6.294, P=0.000), waist circumference from (118.6±13.8) cm to (96.4±8.0) cm (t=6.331, P=0.000), hip circumference from (116.9±12.6) cm to (104.0±7.7) cm (t=3.854, P=0.000), BMI from (36.2±5.9) kg/mto (27.9±3.5) kg/m(t=5.630, P=0.000), showing a decreasing trend over time. There was no underweight patient after 6 months follow-up. As compared to pre-operation, at 6 months after operation, the average FBG reduced from (7.4±1.4) mmol/L to (6.0±0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1±4.9) mmol/L to (7.5±2.2) mmol/L (t=7.026, P=0.000), FINS from (160.0±71.9) mIU/L to (43.8±20.8) mIU/L (t=7.259, P=0.000), 2-hour postprandial INS from (437.6±261.4) mIU/L to (140.5±104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1±0.6) μg/L to (0.7±0.3) μg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from (2.5±0.9) μg/L to (1.5±0.7) μg/L (t=3.865, P=0.000), HbAlc from (8.0±1.6)% to (5.9±0.6)% (t=5.953, P=0.000), showing a decreasing trend over time except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG of 16 patients returned to normal 3 months after the operation. Blood pressure and trigly ceride decreased obviously 6 months after operation compared to pre-operation with significant difference(P<0.05). At 6 months after operation, blood pressure of 8 comorbidity patients with high blood pressure became normal (8/12, 66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the menstruation of the menstrual disorder patient returned to normal 3 months and 1 month after the operation respectively.

CONCLUSIONAs for obese patients with T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body weight, and to obtain an ideal improvement of blood glucose and blood lipid levels.

Adolescent ; Adult ; Aged ; Bariatric Surgery ; Blood Glucose ; physiology ; Body Weights and Measures ; C-Peptide ; blood ; physiology ; Caloric Restriction ; Combined Modality Therapy ; Comorbidity ; Coronary Disease ; complications ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Diet Therapy ; methods ; Diet, Diabetic ; Endoscopy ; Fatty Liver ; complications ; surgery ; Female ; Food, Formulated ; Gastrectomy ; Glycated Hemoglobin A ; physiology ; Gout ; complications ; surgery ; Hashimoto Disease ; complications ; Humans ; Hypertension ; complications ; surgery ; Insulin ; blood ; physiology ; Lipids ; blood ; physiology ; Male ; Menstruation Disturbances ; complications ; surgery ; Middle Aged ; Obesity ; complications ; therapy ; Perioperative Care ; methods ; Thyroiditis ; complications ; Treatment Outcome ; Triglycerides ; blood ; physiology