Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
Mice ; Animals ; Gastrointestinal Microbiome ; Tripterygium ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Mice, Inbred C57BL ; Arthritis, Experimental/drug therapy*

Objective:To discuss the protective effect of Syringin (SYR) on myotube cell atrophy induced by lipopolysaccharide (LPS) and its molecular mechanism.Methods:After C2C12 myoblasts were differentiated into myotubes, they were divided into normal control group, model group and syringin group according to the random number table method. The cultured medium of model group and syringin group were added with LPS with a concentration of 200 ng/ml; the cultured medium of the syringin group was also added with 10 μmol/L syringin for 24 h. CCK8 was used to detect cell viability. In cell supernatant, NO release was detected with Griess and TNF-α level was detected by ELISA kit. The expression of NF-κB, PPAR γ1, MyHC were detected by Western blot.Results:Compared with the model group, the viability of cells [(101.08±8.92)%, (79.53±5.19)% vs. (69.07±7.16)%] in the 10 μmol/L and 100 μmol/L syringin groups were significantly increased ( P<0.01 or P<0.01), of which 10 μmol/L syringin had better effect. Compared with the model group, the level of NO [(2.92±0.33) μmol/L vs. (3.57±0.41) μmol/L] in the syringin group was significantly decreased after 6 hours of intervention ( P<0.01), and the cells in the syringin group after 24 hours of intervention, the level of TNF-α [(2.73±0.29) pg/ml vs. (4.15±0.29) pg/ml] was significantly decreased ( P<0.01), and the protein expression of cellular NF-κB (0.95±0.24 vs. 1.16±0.28) was significantly decreased ( P<0.05), the protein expression of MyHC (0.79±0.15 vs. 0.70±0.16) was increased ( P<0.05). Conclusion:SYR could inhibit the inflammatory response induced by LPS, promote the activity of myotubes, and antagonize the damage of LPS to myotube cells.

Paraneoplastic neurological syndromes (PNS) are a rare group of immune-mediated disorders that affect the central and peripheral neuromuscular system in association with cancer.If the limbal lobe system of the brain is involved,it will show paraneoplastic limbal encephalitis(PLE).The discern of patients with PNS is challenging since tumors causing paraneoplastic neurologic disorders are often asymptomatic and sometimes occult.We report a case of PLE with double positive anti-Hu and Yo antibodies,and further analyze and discuss it in conmbination with relevant literature to improve the understanding of the disease.

Sepsis is caused by maladjustment of host response to infection, resulting in life-threatening organ dysfunction, which is equivalent to infection + sequential organ failure score (SOFA) > 2 scores, and it is the out of control of the host's responses to infection leading to an imbalance of the pro-inflammatory-anti-inflammatory responses. In recent years, besides the antibiotics, etiological treatment, fluid resuscitation and organ functional support, there has been no single adjuvant therapy for sepsis. The focus of previous treatments has been on immunosuppression, however immune paralysis induced by sepsis was playing an increasingly important role in the processes of patient's disease onset and death, leading to a shift in the field of research to enhancing immune responses. Therefore, it is crucial to identify a septic patient with a severely suppressed or hyperactive immune system, and accurately monitor both immune and therapeutic responses. This review outlines the advances and challenges of precision immunotherapy in patients with sepsis.

Objective To investigate the effect of endoplasmic reticulum stress on sensitivity of glioma cell line U87 to temozolomide (TMZ) and underlying mechanism.Methods (1) Glioma U87 cells were routinely cultured for 24 h in vitro;different concentrations of TMZ (0,12.5,25,50,100 μmol/L) were added to intervene the cell proliferation of U87 cells for 24 h;MTT method was used to detect the cellular proliferation inhibition rate,and half maximal inhibitory concentration (IC50) of TMZ was calculated;tunicamycin (TM) treatment (0,2,4,8 μmol/L) was given to the cells for 6 h,and then,50 μmol/L TMZ was given for 24 h,and cellular proliferation inhibition rate of U87 was detect by MTT method.(2) U87 cells were randomly divided into control group,TM group,TMZ group and TM+TMZ group;pretreatment of TM for 6 h was given to cells from TM group and TM+TMZ group;and 50 μmol/L TMZ was given to cells from TMZ group and TM+TMZ group;same amount of medium was given to cells from control group;24 h after treatment,the apoptotic rate was examined by flow cytometry;Westem blotting was used to detect the protein expressions of caspase-3,B-cell lymphoma 2 associated X protein (Bax),O-6-methlguanine-DNA methyltransferase (MGMT),glucose-regulated protein 78 (GRP78),and inositol-requiring enzyme 1 (IRE-l).Results (1) MTT showed that IC50 of TMZ was 50 μmol/L.As compared with that of 0 μmol/L TM+50 μmol/L TMZ group or 2 μmol/L TM+50 μmol/L TMZ group,the cellular proliferation inhibition rate of 4 μmol/L TM+50 μmol/L TMZ group and 8 μmol/L TM+50 μmol/L TMZ group was significantly decreased (P＜0.05).(2) As compared with TMZ group,TM+TMZ group had significantly decreased apoptotic rate (46.98％±4.79％ vs.35.74％ ±4.09％),significantly decreased caspase-3 and Bax protein expressions,and significantly increased MGMT,GRP78 and IRE-1 protein expressions (P＜0.05).Conclusion Endoplasmic reticulum stress can increase the resistance gene MGMT expression,decrease the chemotherapy sensitivity to TMZ,and induce chemoresistance ofglioma cell line U87.

Objective To investigate the effect ofeicosapentaenoic acid (EPA) on sensitivity of glioma cell line U87 to temozolomide (TMZ) and its underlying mechanism.Methods (1) U87 cells were routinely cultured in vitro,and 0,25,50,100 and 200 μmol/L EPA was given to these cells for 12,24,and 48 h;MTT assay was used to detect the cell viability.(2) U87 cells were randomly divided into control group,EPA group,TMZ group and EPA+TMZ group (concentrations of EPA and TMZ were 25 and 100 mol/L;EPA pretreatment for 12,24 and 48 h was given;TMZ was given for 24 h);MTT assay was used to evaluate the inhibition ratio of cell proliferation.(3) U87 cells were randomly divided into control group Ⅰ,EPA group Ⅰ,TMZ group Ⅰ and EPA+TMZ group Ⅰ (concentrations of EPA and TMZ were 25 and 100 mol/L;EPA pretreatment for 6 h was given;TMZ was given for 24 h);the apoptotic ratio was examined by fiow eytometry (FCM);Western blotting was used to detect the protein expressions ofcleavedcaspase-3,Bax,O-6-methlguanine-DNAmethyltransferase (MGMT),nuclear factor (NF)-κB signaling pathway related protein p65,and NF-κB inhibitor IKBα;immunofluorescent staining was employed to detect the MGMT and NF-κB p65 expressions;methylated specific PCR (MSP)was used to detect the MGMT gene promoter methylation.Results (1) The 50,100 and 200 μmol/L EPA caused concentration-dependent and time-dependent proliferation inhibition of U87 cells.(2) The inhibition ratio of cell proliferation in EPA+TMZ group was significantly higher as compared with that in the TMZ group (P＜0.05).(3) As compared with that in the TMZ group Ⅰ (34.58％±4.35％),the apoptotic ratio of U87 cells in the EPA+TMZ group Ⅰ was significantly increased (53.28％±5.05％,P＜0.05);Western blotting showed that as compared with those in TMZ group Ⅰ,the protein expressions of activated caspase-3,Bax and IKBα were significantly increased,and MGMT and NF-κB p65 protein expressions were significantly decreased in EPA+TMZ group Ⅰ (P＜0.05);immunofluorescent staining indicated that the MGMT and NF-κB p65 protein expressions in EPA+TMZ group Ⅰ were significantly lower than those in TMZ group Ⅰ (P＜0.05);the MGMT gene promoter methylaion in EPA+TMZ group Ⅰ was higher than that in TMZ group Ⅰ.Conclusion EPA enhances the sensitivity of glioma cell line U87 to TMZ,which may inhibit the MGMT expression by NF-κB dependent pathway.

OBJECTIVE: To evaluate the safety and feasibility of neoadjuvant chemotherapy prior elective surgery following self-expanding metallic stents (SEMS) for complete obstructive left hemicolon cancer. METHODS: This prospective, multicenter, open-labelled trial was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University(2016-ke-161-1) and registered in Clinicaltrials.gov (NCT02972541). INCLUSION CRITERIA: (1)age between 18 and 75 years old;(2) adenocarcinoma confirmed by pathology;(3) left hemicolon cancer confirmed by clinical manifestations and imaging examinations with the distance to anal verge > 15 cm; (4) resectable cancer evaluated by imaging examination without distant metastasis; (5) Eastern Cooperative Oncology Group (ECOG) score ≤ 1 or Karnofsky Performance Scale (KPS) > 70, indicating tolerance of neoadjuvant chemotherapy and operation; (6) absence of chemotherapy or radiotherapy within past six months; (7) bone marrow system and hepatorenal function: hemoglobin ≥ 90 g/L, neutrophil ≥ 1.5×10/L, platelet ≥ 80×10/L, total bilirubin ≤ 1.5×ULN(upper limits of normal), serum transaminase ≤ 2.5×ULN, serum creatinine ≤ 1.0×ULN, endogenous creatinine clearance rate > 50 ml/min; (8) sign for informed consent. EXCLUSION CRITERIA: (1) multiple primary colorectal cancer; (2) rejection of operation;(3) presenting peritonitis or bowel perforation before SEMS; (4) unqualified conditions proved by inspector from registration data. According to inclusion criteria, 62 consecutive patients receiving neoadjuvant chemotherapy prior to elective surgery following SEMS for complete obstructive left hemicolon cancer from Beijing Chaoyang Hospital of Capital Medical University (n=31), Qilu Hospital of Shandong University (n=14), the Third Xiangya Hospital of Central South University (n=13), Zhongnan Hospital of Wuhan University (n=2), the Fourth Hospital of Hebei Medical University (n=2) between December 2015 and December 2017 were prospectively enrolled in this study. Patients were divided into neoadjuvant chemotherapy group and elective surgery group according to the investigator's clinical experience and patient's preference. Patients in the elective surgery group received surgery within one to two weeks after SEMS placement without neoadjuvant chemotherapy. Those in the neoadjuvant chemotherapy group received 2 cycles of CapeOX or 3 cycles of mFOLFOX6 neoadjuvant chemotherapy within one to two weeks after SEMS placement, and then underwent surgery within 3 weeks after finishing neoadjuvant chemotherapy. Data between groups were compared using Student t-test, chi-square analysis or Fisher exact test analysis, including basic clinical informations, operational conditions and postoperative complications. The adverse reactions during the neoadjuvant chemotherapy were recorded. Surgical difficulty was assessed using visual analog scales ranging from 1 to 10, where 1 represented the lowest and 10 the highest degree of surgical difficulty, as judged by the surgeon. RESULTS: The study included 38 males and 24 females with mean age of (64.8±8.8) years. The clinical baseline data between 2 groups were not significantly different (all P>0.05) except the average time interval between SEMS and surgery was significantly longer in neoadjuvant chemotherapy group [(61.6±13.5) days vs. (10.4±5.2) days, t=16.679, P<0.001]. There was no stent migration in either group. Three patients had perforation in the elective surgery group; one patient had perforation and one had obstruction in the neoadjuvant chemotherapy group; and all these patients received emergent surgery. Adverse reactions of neodajuvant chemotherapy were mainly degree 1 and 2 except one patient with degree 3 diarrhea. Patients in neoadjuvant chemotherapy group had significantly lower rate of stoma [4.8%(1/21) vs. 34.1%(14/41), χ²=6.538, P=0.011], higher rate of laparoscopic surgery [71.4%(15/21) vs. 36.6%(15/41), χ²=6.751, P=0.009], shorter mean operative time (147 minutes vs. 178 minutes, t=-3.255, P=0.002), less mean intraoperative blood loss (47 ml vs. 127 ml, t=-4.129, P<0.001), lower degree of surgical difficulty(3.3 vs. 5.6, t=-5.091, P<0.001), shorter mean postoperative exhausting time (56.2 hours vs. 69.0 hours, t=-2.891, P=0.006), and shorter mean postoperative hospital stay (8.5 days vs. 13.5 days, t=-2.246, P=0.028) as compared with patients in the elective surgery group. Surgical site infection rate and anastomotic leakage rate did not differ significantly between two groups(all P>0.05). CONCLUSION Neoadjuvant chemotherapy prior elective surgery following SEMS is a relatively safe and feasible approach in the treatment for obstructive left hemicolon cancer, and is associated with less stoma, more laparoscopic surgery, shorter operative time, less blood loss, lower surgical difficulty, and faster postoperative recovery as compared with conventional elective surgery.
Aged ; Colorectal Neoplasms ; surgery ; therapy ; Female ; Humans ; Intestinal Obstruction ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prospective Studies ; Stents ; Treatment Outcome

Objective To investigate the effect of Eicosapentaenoic scid (EPA) on the sensitivity of glioma cell line U87 to temozolomide (TMZ) and the mechanism behind this effect.Methods U87 cells were randomly divided into four groups:control group,TMZ group,EPA+TMZ group and endoplasmic reticulum stress (ERS) activation tunicamycin group (EPA+TMZ+TM group).MTT method was used to evaluate inhibition ratio of cell proliferation.The apoptotic ratio was examined by flow eytometry.Western blot was used to detect the protein expressions of apoptosis cytokines (caspase-3 and Bax) and ERS cytokines [glucose-regulated protein 78 (GRP78) and inositol-requiring enzyme 1 (IRE-1)].Results EPA causes concentration-dependent and time-dependent inhibition of the cell proliferation (all P=0.00).EPA significantly enhanced the sensitivity of glioma cell line U87 to temozolomide.Compared to TMZ treatment alone,the inhibition ratio [(56.27+6.15)％ vs.(42.32±4.12)％,P=0.03] and apoptotic ratio [(49.78±5.94)％ vs.(37.74± 4.24)％,P=0.04] of U87 cells were enhanced by EPA+TMZ treatment.Western blot showed that the expression of apoptotic factor caspase-3 and Bax proteins were increased by EPA+TMZ treatment,while the protein expressions of ERS-related factors (GRP78 and IRE-1) were significantly inhibited (P=0.01).However,the salutary effects of EPA were reversed by ERS activation tunicamycin.Conclusion EPA enhances the sensitivity of glioma cell line U87 to temozolomide,the mechanism of which may be the suppression of ERS response.

Objective To investigate the relationship between the plasma neutrophil gelatinase-associated lipocalin (NGAL)and endothelin-1 (ET-1) levels and cognitive dysfunction in chronic obstructive pulmonary disease (COPD) patients.Methods A case-control study was performed,consisting of 128 patients with COPD(68 patients without cognitive dysfunction and 60 patients with cognitive dysfunction) and 70 normal controls.All patients with COPD were diagnosed by pulmonary function tests and plasma levels of NGAL and ET-1 were determined by enzyme immunoassay.The cognitive function was evaluated by the MMSE and MoCA.Results ①Compared with normal control,the levels of plasma NGAL and ET-1 were increased(NGAL:(2.20±0.60) μg/L vs (1.69±0.73) μg/L,P＜0.05;ET-1:(26.19± 10.55)pg/ml vs (13.05±2.37) pg/ml,P＜0.05) in COPD patients without cognitive dysfunction and in COPD patients with cognitive dysfunction(NGAL:(3.80±2.75) μg/L vs (1.69±0.73) μg/L,P＜0.01;ET-1:(37.82±0.29) pg/ml vs (13.05±2.37) pg/ml,P＜0.01).Compared with the COPD patients without cognitive dysfunction,the levels of plasma NGAL and ET-1 were also increased in COPD patients with cognitive dysfunction (all P＜0.05).②The plasma NGAL levels were correlated negatively with MMSE scores(r=-0.524,P＜0.05),and negatively correlated with MoCA scores (r=-0.527,P＜0.05).The plasma ET-1 levels were negatively correlated with MMSE scores(r=-0.549,P＜0.05),and negatively correlated with MoCA scores(r=-0.558,P＜0.05).The levels of NGAL and ET-1 were positively correlated(r=0.564,P＜0.05).Conclusion NGAL and ET-1 may be involved in the pathophysiological process of cognitive dysfunction in patients with COPD,which provides a certain clinical value for the assessment of cognitive dysfunction in patients with COPD.