ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective To investigate the association between nonalcoholic fatty liver disease(NAFLD)and osteoporosis in elderly patients.Methods A total of 824 patients,aged≥60 years,who were hospitalized in Department of Gerontology,Peking University People's Hospital,from June 2016 to April 2023 were enrolled,with 398 patients in the osteoporosis group and 426 in the non-osteoporosis group.Related data were collected from all subjects,including general information,blood biochemical parameters,liver ultrasound,and bone mineral density measured by dual-energy X-ray examination.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical variables;a binary Logistic regression analysis was used to investigate the independent risk factors for osteoporosis.Results Compared with the non-osteoporosis group,the osteoporosis group had a significantly higher age,a significantly higher proportion of female patients or patients with diabetes,and a significantly lower body mass index(all P<0.05).The osteoporosis group had a significantly higher proportion of patients with NAFLD than the non-osteoporosis group(36.2%vs 24.6%,χ2=12.878,P<0.001).Compared with the non-osteoporosis group,the osteoporosis group had significantly lower levels of hemoglobin,uric acid,and albumin and significantly higher levels of total cholesterol,low-density lipoprotein cholesterol(LDL-C),bone-specific alkaline phosphatase,and tartrate-resistant acid phosphatase(all P<0.05).The binary Logistic regression analysis showed that old age(odd ratio[OR]=1.040,95%confidence interval[CI]:1.015-1.066,P=0.002),female sex(OR=4.089,95%CI:2.607-6.411,P<0.001),NAFLD(OR=1.697,95%CI:1.076-2.678,P=0.023),diabetes(OR=1.509,95%CI:1.008-2.260,P=0.046),and LDL-C(OR=1.431,95%CI:1.010-2.029,P=0.044)were independent risk factors for osteoporosis in elderly patients.Considering the impact of diabetes on the research findings,a subgroup analysis was performed for the patients without diabetes,and the results showed that NAFLD(OR=1.573,95%CI:1.015-2.439,P=0.043)was an independent risk factor for osteoporosis in the elderly patients without diabetes.Conclusion NAFLD,old age,and female sex are independent risk factors for osteoporosis in elderly patients.

Objective : To explore the type and control measure of black dot⁃like contaminants in cell cultures. Methods: The growth state of bacteria was investigated under an inverted microscope ; Their morphological characteristics were analyzed by Gram and auramine O staining as well as electron microscopy; 16S rDNA gene sequencing was used to analyze bacterial species ; Drug sensitivity test was used to screen antibiotics against the bacteria;Cryopreserved SH⁃SY5Y cells were resuscitated by cell culture supernatant of RAW264 cells. Results: Inverted microscopic real⁃time observations showed that black dot⁃like substances had two growth states : static and moving.They were negative for Gram staining while positive for auramine O staining. Electron microscopy revealed that they were short rod⁃shaped bacteria with a polar flagellum during moving phase. 16S rDNA gene sequencing showed that these bacteria were phenylobacterium zucineum HLK1. Ceftriaxone , carboxycillin and imipenem were screened by drug sensitivity test to have inhibitory effects on the bacteria , but cell culture experiments showed that they could not remove the bacteria from SH⁃SY5Y cells. Contaminated cells could not be cryopreserved for a long time , but resuscitation with RAW264. 7 cell culture supernatant significantly improved the survival rate of cells. Conclusion The black dot⁃like contaminants in cell cultures are a special type of oligotrophic bacterium with strong viability that can invade the cells and cannot be cleared with antibiotic treatment. RAW264. 7 cell culture supernatant seems contain some substances against bacteria , and resuscitating frozen cells with RAW264. 7 cell culture supernatant may significantly improve the survival rate of cells.

Objective:To investigate the association between nonalcoholic fatty liver disease(NAFLD)and mild cognitive impairment(MCI)in the elderly.Methods:Three hundred ninety-two study subjects aged 60 years and above visiting the geriatric department of Peking University People's Hospital for chronic disease management between July 2016 and January 2018 were enrolled, and population-based clinical data of the study subjects were collected.Participants' cognitive function was assessed, and the correlation between NAFLD and MCI was analyzed.Results:The detection rate of MCI in the NAFLD group(n=191)was significantly higher than that in the non-NAFLD group(n=201)[38(19.9%) vs.21(10.4%) χ2=6.837, P=0.009]. Multivariate analysis revealed that NAFLD was closely correlated with and was an independent risk factor for MCI( OR=2.625, 95% CI: 1.250-5.512, P=0.011)after adjusting confounding variables such as age, sex, education level, components of metabolic syndrome, medication, and conditions affecting biochemical and metabolic processes.In addition, the female sex( OR=2.775, 95% CI: 1.363-5.651, P=0.005), unstable carotid plaques( OR=2.736, 95% CI: 1.131-6.620, P=0.026), serum albumin( OR=0.908, 95% CI: 0.840-0.982, P=0.015), fasting serum glucose( OR=1.268, 95% CI: 1.076-1.493, P=0.004), and the serum AST/ALT ratio( OR=2.984, 95% CI: 1.370-6.500, P=0.006)were also independently associated with MCI, of which, the female sex, unstable carotid plaques, increased levels of fasting serum glucose and the AST/ALT ratio were independent risk factors for MCI. Conclusions:NAFLD is associated with and is an independent risk factor for MCI in the elderly.Assessment of cognitive function in elderly patients with NAFLD should be emphasized.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases worldwide and covers a series of pathological manifestations from hepatic steatosis to inflammation, fibrosis, and even liver cirrhosis. NAFLD is associated with a wide range of extrahepatic diseases, including metabolic syndrome, cardiovascular disease, chronic kidney disease, endocrine diseases, obstructive sleep apnea-hypopnea syndrome, psoriasis, and skeleton-muscle diseases. The major causes of death in patients with NAFLD include cardiovascular disease, malignancies, and liver-related complications, suggesting that extrahepatic diseases associated with NAFLD should be taken seriously by clinicians. This article reviews the research advances in extrahepatic diseases associated with NAFLD, so as to provide ideas for clinical assessment and treatment.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Objective:To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies.Methods:A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed.Results:The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old ( OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC ( OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein ( OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position ( OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level ( OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions:The CRT problem can′t be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

Objective:To explore the relationship between mild cognition impairment(MCI) and components of metabolic syndrome in the elderly.Methods:A total of 293 patients aged 65 years and older with an average age of (78.8 ± 7.5) years who met the inclusion criteria were included.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate cognitive function.The components of the metabolic syndrome were compared between the MCI and the normal cognitive function(NC) groups.Binary Logistic regression analysis was used to analyze the relationship between cognitive function and components of the metabolic syndrome.Results:The levels of body mass index(BMI)and tryglicerides(TG)were lower in the MCI group than in the NC group[BMI, (22.9±3.7)kg/m 2vs.(25.3±3.3)kg/m 2, t=3.124, P=0.002; TG, 1.2±0.6 mmol/L vs. 1.4±0.7 mmol/L, t=2.615, P=0.009]. The differences in proportions of hypertension and diabetes and in levels of fasting blood glucose and high-density lipoprotein cholesterol had no statistically significance between the MCI group and the NC group(all P>0.05). Binary multivariate Logistic regression analysis showed that after adjusting for age and education, BMI was independently associated with MCI, and as BMI increased, the risk of MCI decreased( OR=0.901, 95% CI: 0.838-0.968, P=0.004). In elderly men, after adjusting for age, education level and smoking history, TG was independently associated with MCI, and as TG increased, the risk of MCI decreased( OR=0.446, 95% CI: 0.249-0.874, P=0.017). While in elderly women, no independent correlation between TG and MCI was observed. Conclusions:BMI is independently associated with MCI.Screening for cognitive function among low-level BMI elderly is helpful to identify MCI.The relationship between TG and MCI is different between different genders, and different standards might be adopted for the management of TG in elderly MCI patients with different genders.

Objective: To investigate the correlation between nonalcoholic fatty liver disease(NAFLD)fibrosis score(NFS)and unstable plaques of carotid in elderly NAFLD patients. Methods: The clinical and carotid plaques data of 191 elderly(≥60 years old)admitted into our department between July 2016 and January 2018 were retrospectively collected.With NFS 0.676 as a cut-off point, the patients were divided into a liver fibrosis group(NFS ≥0.676, n=65)and a non-liver fibrosis group(NFS<0.676, n=126). Based on quartiles of NFS, the patients were divided into four groups: the Q1 group(NFS<-0.865, n=48), the Q2 group(-0.865≤NFS<0.100, n=48), the Q3 group(0.1≤NFS<1.070, n=47), the Q4 group(NFS≥1.070, n=48). The correlation of NFS with the property of carotid plaques was analyzed. Results: The detection rate of unstable carotid plaques was increased along with the increase of NFS(F=8.573, P=0.004). The detection rate of unstable carotid plaques was higher in the liver fibrosis group than in the non-liver fibrosis group(78.5% or 51/65 vs.60.3% or 76/126, χ²=5.883, P=0.015). Multiple logistic regression analysis showed that liver fibrosis(NFS≥0.676)was independently correlated with unstable carotid plaques(β=0.816, 95%CI: 1.110~4.607, OR=2.261, P=0.025)after adjusting for possible confounding factors including age, gender, diabetes mellitus, hypertension, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein. Conclusions NFS is correlated with unstable carotid plaques in elderly NAFLD patients, and the higher NFS is the independent risk factor for unstable carotid plaques for elderly NAFLD patients with NFS higher than 0.676.We should pay more attention to the evaluation of unstable carotid plaques.

Bone graft is an important basic condition for repairing skull defect caused by various reasons,but whether autologous bone graft or allograft bone transplantation,the clinical limitations was increasingly significant.With the development of bone tissue engineering,the introduction of bone progenitor cells and growth factors into composite scaffolds made from natural or synthetic materials,and as a substitute for bone graft has become a hot spot of research.It will review the research progress on bone graft substitute and bone biomimetic scaffold material,so as to provides reference on the further investigations.