Objective:To discuss the effect of asiatic acid(AA)on the inflammation and oxidative stress damage induced by lipopolysaccharide(LPS)in the primary cultured hippocampus neurons,and to clarify its mechanism.Methods:The primary cultured rat hippocampus neurons(cell purity identified by immunofluorescence staining)were divided into control group,LPS(10 mg·L-1)group,and LPS+AA group(10 mg·L-1 LPS+10,20,and 40 μmol·L-1 AA),AA group(20 μmol·L-1 AA),ML385 group[10 μmol·L-1 nuclear factor erythroid 2-related factor(Nrf2)inhibitor],and LPS+ML385+AA group(10mg·L-1 LPS+10 μmol·L-1 ML385+20 μmol·L-1 AA).After drug treatment,methylthiazolyldiphenyl-tetrazolium bromide(MTT)method was used to detect the survival rates of the hippocampus neurons in various groups;lactate dehydrogenase(LDH)kit was used to detect the LDH leakage rates of the hippocampus neurons in various groups;enzyme linked immunosorbent assay(ELISA)kit was used to detect the expression levels of inflammatory factors[interleukin(IL)-1β and tumor necrosis factor(TNF)-α]and the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)levels in the hippocampus neurons in various groups;Griess method was used to detect the nitric oxide(NO)levels in supernatant of the hippocampus neurons in various groups;immunofluorescence staining was used to detect the expressions of Nrf2 and heme oxygenase-1(HO-1)proteins in the hippocampus neurons in various groups;Western blotting method was used to detect the expression levels of Nrf2,HO-1,nuclear factor-kappa B(NF-κB),and B-cell lymphoma 2(Bcl-2)proteins in the hippocampus neurons in various groups.Results:Compared with control group,the survival rate of the hippocampus neurons,SOD activity,and Bcl-2 expression level in the cells in LPS group were significantly decreased(P＜0.01),while the LDH leakage rate,expression levels of IL-1β and TNF-α,MDA level,and NO level,as well as the expression level of NF-κB protein,were significantly increased(P＜0.01);the fluorescence intensities and expression levels of Nrf2 and HO-1 proteins in hippocampus neurons were significantly decreased(P＜0.01).Compared with LPS group,the survival rates of hippocampus neurons,SOD activities,and expression levels of Bcl-2 in the cells in LPS+10 μmol·L-1 AA group and 20 μmol·L-1 AA group were significantly increased(P＜0.01),while the LDH leakage rates,expression levels of IL-1β and TNF-α,MDA levels,and NO levels,as well as expression levels of NF-κB protein,were significantly decreased(P＜0.05 or P＜0.01),and the fluorescence intensities and protein expression levels of Nrf2 and HO-1 in the cells were significantly increased(P＜0.01).Compared with LPS+20 μmol·L-1 AA group,the fluorescence intensities of Nrf2 and HO-1 in the cells in LPS+ML385+AA group were significantly decreased(P＜0.01),and the expression levels of Nrf2 protein in the nucleus and cytoplasm,the expression levels of HO-1 and Bcl-2 proteins in the cells were significantly decreased(P＜0.01),while the expression level of NF-κB protein was significantly increased(P＜0.01).Conclusion:AA can improve LPS-induced inflammation and oxidative stress damage in the primary cultured rat hippocampus neurons,and its mechanism may be related to the activation of the Nrf2/HO-1 signaling pathway.

Although in the treatment of extracranial vascular malformations the absolute ethanol used as an embolization agent has several advantages(such as low cost,reliable efficacy,no impact on subsequent treatments,etc.)and has already achieved significant progress in clinical practice,it is still regarded as a highly-selective liquid embolization agent in the sclerotherapy or embolization treatment of brain arteriovenous malformation(bAVM).At present,the indications of sclerotherapy and embolization therapy by using absolute ethanol include small AVM(＜3 cm)located at brain cortex or at non-eloguent area,and relatively low-flow AVM,in such case,the absolute ethanol acts as an effective supplement to other liquid embolization agents.Further studies are needed so as to improve the radiographic visualization and viscosity of absolute ethanol,to make the injection process more controlled,and to alleviate the edema caused by neurotoxicity and inflammation.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.

Objective:To investigate symptoms of anxiety and depression among primary and middle school students quarantined in hotels during the COVID-19 epidemic.Methods:Anxiety and depression symptoms among 726 primary and middle school students quarantined in hotels were investigated with The Screen for Child Anxiety Related Emotional Disorders(SCARED)and Depression Self-rating Scale for Children(DSRSC)from September to October 2022 in Chifeng City,Inner Mongolia Autonomous Region.There were 624 students completed investi-gation with response rate of 86％.The positive score of SCARED was ≥23 and DSRSC was ≥ 15.Results:The detection rates of anxiety and depression were 17.9％and 15.4％respectively.The detection rates of anxiety and depression were higherin middle school students than inprimary school students(Ps＜0.05).The scores of general-ized anxiety and social phobia factors were higher in female students than in male students(Ps＜0.05).The scores of dissociative anxiety factor and depression were higher in middle school students than in primary school students(Ps＜0.05).Conclusion:During the COVID-19 epidemic,middle school students quarantined in hotels are more likely to have anxiety and depression symptoms than primary school students,and female students are more likely to have anxiety symptoms than male students.

Objective:To analyze the association between sleep status and ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.Methods:It was a cross sentional study. Hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring from May 2021 to April 2023 in Shanghai Xinzhuang Town were enrolled. The demographic information and sleep status of patients were obtained from the questionnaire. A TM-2430 blood pressure monitor was used to measure 24-hour ambulatory blood pressure, and the relevant indicators, including blood pressure level and blood pressure coefficient of variation were documented. The association between sleep status and blood pressure indicators was analyzed with multivariate linear regression model.Results:A total 1 135 patients aged (65.07±12.61) years were enrolled, and 473 (41.67%) of whom were males. The sleep time was<7 hours in 76 cases, 7- 8 hours in 219 cases and >8 hours in 840 cases; the bedtime was earlier than 22∶00 in 415 cases, between 22∶00 and 23∶00 in 474 cases and later than 23∶00 in 246 cases; the wake-up time was before 6∶00 in 230 cases, between 6∶00 and 7∶00 in 521 cases and after 7∶00 in 384 cases. Multivariate linear regression analysis showed that after controlling for gender and age, the sleep time was negatively associated with diurnal, noctumal and 24-hour diastolic blood pressure levels (all P<0.05), and positively associated with diurnal and noctumal systolic blood pressure coefficient of variation, noctumal diastolic blood pressure coefficient of variation, and 24-hour systolic blood pressure coefficient of variation (all P<0.05).The bedtime was positively associated with diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), diastolic blood pressure (all P<0.05); and negatively associated with diurnal systolic blood pressure coefficient of variation, diurnal diastolic blood pressure coefficient of variation, noctumal systolic blood pressure coefficient of variation, 24-hour systolic blood pressure coefficient of variation, and 24-hour diastolic blood pressure coefficient of variation (all P<0.05). The wake-up time was positively associated with diurnal systolic blood pressure, diurnal, noctumal and 24-hour diastolic blood pressure (all P<0.05), and positively associated with diurmal systolic blood pressure and diastolic blood pressure (both P<0.05). Conclusion:Sleep status is closely associated with ambulatory blood pressure monitoring indicators in community-dwelling hypertensive patients.

Objective:To investigate the safety and effectiveness of endoscopic cold snare resection of small colorectal polyps and prophylactic hemostatic clip.Methods:A total of 260 patients diagnosed as having small colorectal polyps in Qinghai Provincial People's Hospital from January 2021 to March 2022 were randomly assigned to cold snare polypectomy (CSP) group (receiving CSP), CSP+hemostatic clip group (receiving CSP+prophylactic hemostatic clip), hot snare polypectomy (HSP) group, and HSP +hemostatic clip group (receiving HSP+prophylactic hemostatic clip). Each group had 65 cases. The treatment, incidence of bleeding, and other complications were compared.Results:There was no significant difference in the basic characteristics of patients or polyps among the four groups ( P>0.05). Immediate intraoperative bleeding occurred in 5 cases (7.69%), 4 cases (6.15%), 3 cases (4.62%), and 3 cases (4.62%) in the four groups respectively with no significant difference ( χ2=0.778, P=0.855), while only 1 delayed postoperative bleeding was observed in HSP group with no significant difference among the four groups ( χ2=3.012, P=0.390). The incidence of postoperative abdominal pain was the highest in the HSP group ( n=7, 10.77%) significantly different from those of the CSP group ( n=1, 1.54%) and the CSP+hemostatic clip group ( n=1, 1.54%) ( P<0.05). Polypectomy time of single polyp in CSP group was the shortest (2.18±1.07 min) , followed by HSP group (2.83±0.82 min), then CSP+hemostatic clip group (3.15±1.16 min), with HSP+hemostatic clip group (4.88±1.85 min) being the longest ( F=50.397, P<0.001). Conclusion:It is suggested to use CSP for small colorectal polyps. If there is no risk of bleeding or perforation during the operation, it is not necessary to use prophylactic hemostatic clips.

Objective To investigate the overweight and obesity of primary and middle school students in Sijing area of Shanghai from 2020 to 2022,so as to provide scientific basis for the intervention of childhood obesity.Methods In October 2020 and October 2022,all primary and middle school students in Sijing area underwent physical examination by cluster sampling method.A cross-sectional study was conducted to investigate the obesity and overweight in primary and middle school students of different ages and genders in Sijing area.Results In 2020 and 2022,7 766 and 10 594 students completed physical examination,respectively,and 4 626 of them underwent two consecutive physical examinations.The incidences of overweight and obesity were 15.14%and 21.89%in 2020,respectively.The incidences of overweight and obesity were 15.41%and 21.11%in 2022,respectively.There were no significant differences in the incidences of overweight or obesity between 2020 and 2022(P>0.05).In 2020,the incidences of overweight and obesity of male students were 14.91%and 24.70%;the incidences of overweight and obesity of female students were 15.40%and 18.80%,respectively.In 2022,the incidences of overweight and obesity of male students were 15.04%and 24.14%;the incidences of overweight and obesity of female students were 15.82%and 17.82%,respectively.There was no significant difference in the overweight rate between males and females(P>0.05).The incidence of obesity of male students was significantly higher than that of female students in both 2020 and 2022(P<0.05).In the students aged 12 years old,the incidence of obesity was 27.42%in 2022,which was significantly higher than that in 2020(P<0.05).There was no significant difference in the incidence of obesity between other age groups(P>0.05).Among the 4 626 children who participated in two consecutive physical examinations,the overweight/obesity rates were 14.46%/21.25%in 2020 and 16.04%/21.78%in 2022;there was significant difference in the overweight rates(P<0.05),while no significant difference was found in obesity rates(P>0.05).Among the 4 626 children,there were 2 402 boys and 2 224 girls.In 2020,the overweight/obesity rates were 13.70%/24.48%in these boys and 15.29%/17.76%in these girls.In 2022,the overweight/obesity rates were 16.07%/25.44%in these boys and 16.01%/17.72%in these girls.There was no significant difference in the incidence of overweight between these girls and boys in 2020 and 2022(P>0.05),but the obesity rate of boys was significantly higher than that of girls(P<0.05).Conclusion There are high incidences of overweight and obesity among primary and middle school students in Sijing area of Shanghai,and dietary and exercise guidances should be strengthened.Meanwhile,the incidences of overweight and obesity are higher among boys,and obesity prevention and control measures should be strengthened for boys.

Objective To investigate the effect of the loss of myeloid-derived growth factor(Mydgf)on the transformation of cardiac fibroblasts into myofibroblasts after myocardial infarction(MI).Methods Two adult mouse groups,including a wild-type(WT)group and another group with Mydgf knockout(Mydgf-KO),were examined in the study.The mice in these two groups were tested for their cardiac function by measuring left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(n=10).Quantitative real-time PCR(qRT-PCR)(n=3)was performed to determine the mRNA expression levels of myofibroblast markers,including α-smooth muscle actin(α-SMA),periostin(postn),type Ⅷ collagen(col8al),and connective tissue growth factor(ctgf).Western blot(n=3)was performed to verify the protein expression levels of α-SMA.MI modeling was performed on the WT and the Mydgf-KO mice.Postoperative LVEF and LVFS(n=10)were then measured.The hearts were harvested and Masson staining was performed to determine the infarcted area(n=10).The heart samples of Mydgf-KO and WT mice were collected at d 7 and d 14 after MI,respectively,to verify the expression of myofibroblast markers(n=3).Results Compared with WT mice,LVEF and LVFS in adult Mydgf-KO mice showed no significant changes(all P＞0.05).However,the mRNA levels of α-SMA and postn were upregulated,and α-SMA protein expression was also increased(all P＜0.05).After MI,compared with WT mice,LVEF and LVFS in Mydgf-KO mice decreased,and the infarcted area increased significantly(all P＜0.05).Furthermore,mRNA levels of α-SMA,col8al,postn,and ctgf were increased in Mydgf-KO mice.In addition,the α-SMA protein expression level was upregulated and α-SMA-positive fibroblasts were increased(P＜0.05).Conclusion Mydgf deletion promotes the transformation of cardiac fibroblasts into myofibroblasts and aggravates myocardial fibrosis after MI.

Objective:To investigate the relationship between spinal Mas-related gene receptor C (MrgC) and pathophysiological mechanism of bone cancer pain in mice.Methods:Forty male C3H/HeNCrlVr mice, aged 5-7 weeks, weighing 20-25 g, were selected and divided into 4 groups ( n=10 each) using a random number table method: sham operation group (group S), bone cancer pain group (group P), bone cancer pain + MrgC agonist group (group P-agonist) and bone cancer pain + Mrg C antagonist group (group P-Ab). Preparation of the bone cancer pain model: mouse fibrosarcoma cells (NCTC2472) were injected into the upper tibia of mice in P, P-agonist and P-Ab groups, and the equal volume of D-Hanks balanced salt solution was given instead in S group. Fourteen days later cerebrospinal fluid was intrathecally injected in S and P groups, and MrgC agonist and MrgC antibody were intrathecally injected in P-agonist and P-Ab groups. The mechanical paw withdrawal threshold (MWT) to von Frey stimuli was measured before developing the model (T 0), at 7 days after developing the model (T 1), at 14 days after developing the model (before intrathecal injection, T 2), and at 4, 8 and 12 h after intrathecal injection (T 3-5). Results:Compared with group S, no significant change was found in the MWT at T 0 ( P>0.05), and the MWT was significantly decreased at T 1-T 5 in the other groups ( P<0.05). Compared with group P, the MWT was significantly increased at T 3-T 5 in group P-agonist, and the MWT was significantly decreased at T 3-T 5 in group P-Ab ( P<0.05). Conclusions:Spinal MrgC plays an endogenous protective role in the pathophysiological mechanism of bone cancer pain to a certain extent in mice.

Purpose: The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). Materials and Methods: An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. Results: Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. Conclusion Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.