A network meta-analysis of 5 Chinese patent medicines combined with conventional western medicine in the treatment of coronary heart disease complicated with anxiety and depression / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of five different Chinese patent medicines combined with conventional western medicine therapy in the treatment of coronary heart disease with anxiety and depression.Methods:Randomized controlled trials (RCTs) of Chinese patent medicine combined with conventional western medicine therapy and conventional western medicine therapy in the treatment of coronary heart disease with anxiety and depression were retrieved from China Academic Journal Database (Wanfang Data), China Biomedical Literature Service System (SinoMed), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (Chongqing VIP), Cochrane Library, PubMed and Embase databases from January 1, 2010 to December 31, 2020. The Jadad score and Cochrane bias risk assessment tool were used to assess the bias risk of the included literature. The RevMan 5.3, Stata 16.0 and GeMTC 14.3 software were used for network meta-analysis.Results:A total of 32 articles involving 3 494 patients were included. In terms of clinical efficacy, the clinical efficacy of conventional western medicine combined with Zhenyuan Capsule [ OR (95% CI)=16.64 (6.38, 43.44)], Xinkeshu Tablets [ OR (95% CI)=4.67 (3.26, 6.68)], Wuling Capsule [ OR (95% CI)=4.65 (2.48, 8.72)], Guanxinjing Capsule [ OR (95% CI)=2.93 (1.37, 2.64)] weres better than that of conventional western medicine alone. The clinical efficacy of combined Zhenyuan Capsule was better than that of combined Xinkeshu Tablets [ OR (95% CI)=3.56 (1.28, 9.94)], Wuling Capsule [ OR (95% CI)=3.58 (1.13, 11.34)], Guanxinjing Capsule [ OR (95% CI)=5.69 (1.68, 19.32)] or Shugan Jieyu Capsule [ OR (95% CI)=9.29 (2.79, 30.96)]. Compared with Shugan Jieyu Capsule, Xinkeshu Tablets had better clinical efficacy [ OR (95% CI)=2.61 (1.16, 5.87)]. The SUCRA order of the effective rate of clinical efficacy was as follows conventional western medicine treatment combined with Zhenyuan Capsule (SUCRA=99.6)>with Xinkeshu Tablets (SUCRA=67.5) > with Wuling Capsule (SUCRA=65.0) > with Guanxinjing Capsule (SUCRA=41.6) > with Shugan Jieyu Capsule (SUCRA=25.8)>conventional western medicine treatment (SUCRA=0.5). Combined Xinkeshu Tablets [ MD (95% CI)=-8.85 (-14.16, -3.62)] was superior to conventional western medicine in reducing HAMD score. In terms of reducing HAMA score, compared with conventional western medicine therapy, the combination of Wuling Capsule [ MD (95% CI)=-7.61 (-14.82, -0.40)] and Xinkeshu Tablets [ MD=-6.18, 95% CI (-9.78, -2.58)] has better curative effect. The SUCRA of Chinese patent medicine in reducing HAMA of coronary heart disease complicated with anxiety and depression was combined with Wuling Capsule (SUCRA=82.8) > with Xinkeshu Tablets (SUCRA=78.2). In terms of adverse reactions, the safety of combined five Chinese patent medicines was better than that of conventional western medicine. Conclusions:The clinical efficacy and safety of conventional western medicine combined with five kinds of Chinese patent medicines in the treatment of coronary heart disease complicated with anxiety and depression were better than those of conventional western medicine alone. Among them, the combination of Zhenyuan Capsule was the most likely to be the best treatment. The combination of Xinkeshu Tablets was better in reducing HAMD scores, and the combination of Xinkeshu Tablets and Wuling Capsule is better in reducing HAMA scores. More high-quality RCT studies are needed to verify the conclusions.

Association between cognitive impairment and main metals among oldest old aged 80 years and over in China / 中华预防医学杂志

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

Association of hs-CRP with frailty and its components among the elderly over 65 years old in 9 longevity areas of China / 中华预防医学杂志

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.

Endoscopic retrograde cholangiopancreatography combined with SpyGlass in the diagnosis of intraductal papillary mucinous neoplasms of the bile duct / 中华消化内镜杂志

To evaluate the value of endoscopic retrograde cholangiopancreatography(ERCP)and SpyGlass in the diagnosis of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). Data of patients who underwent ERCP and SpyGlass in Hangzhou First People′s Hospital from January 2016 to December 2019 were analyzed. ERCP and SpyGlass features, complications, clinicopathologic characteristics and prognosis were retrospectively analyzed.A total of 9 patients (5 benign lesions and 4 malignant lesions) were included.ERCP was successfully performed in 9 cases, while SpyGlass was technically successful in 8 cases. Endoscopy showed mucus outflow from the papilla in 5 cases, and the mucus was removed by the balloon of ERCP in 8 cases.ERCP showed bile duct diffuse dilatation and filling defects in all patients. SpyGlass found the mucus in the bile duct in all patients. SpyGlass showed lesion mucosa were fish-egg like without vascular images (Ⅱtype, 3 cases), fish-egg like with vascular images (Ⅲ type, 1 case), villous (Ⅳtype, 4 cases). SpyGlass defined extent of the lesion in 8 cases. SpyGlass found that the lesion involved the intra and extrahepatic bile ducts in one case. Therefore, liver transplantation was recommended to avoid surgical exploration. One type Ⅲ lesion underwent a direct biopsy. The pathology showed moderate dysplasia, which was consistent with the postoperative pathology. No complication occurred. ERCP combined with SpyGlass could clarify the scope of IPMN-B and provide basis for surgical options, which is safe and effective in IPMN-B diagnosis.

Effect of Suanzaoren Tang on Learning Memory and TLR4/NF-κB Signaling Pathway in Rats with Chronic Sleep Deprivation / 中国实验方剂学杂志

Objective::To explore the mechanism of Suanzaoren Tang in improving learning and memory impairment induced by sleep deprivation based on Toll-like receptor (TLR4)/nuclear transcription factor-κB (NF-κB) signaling pathway. Method::The experimental rats were randomly divided into blank group, model group, melatonin group (2.5×10-4 g·kg-1·d-1) and Suanzaoren Tang group (12.96 g·kg-1·d-1). Except the blank group, the chronic sleep deprivation model was established in other groups. After 28 days of continuous administration, the learning and memory of the rats were assessed by Morris water maze. The expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of TLR4, NF-κB p65 and nuclear transcription factor inhibitory protein α (IκBα) in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and the protein expressions of TLR4, IκBα, p-IκBα and NF-κB p65 in the hippocampus of rats were detected by immunohistochemistry (IHC). Result::Compared with the blank group, the platform latency, total swimming distance and the first landing time of the model group increased significantly (P<0.01), while the number of crossing platforms and target quadrant time decreased significantly (P<0.01). Compared with the model group, the platform latency, total swimming distance and the first platform time were reduced in the melatonin group and the Suanzaoren group (P<0.05, P<0.01), while the number of crossing platforms and target quadrants time were increased(P<0.05, P<0.01). Compared with the blank group, the expression levels of TNF-α, IL-1β and IL-6 in the model group were significantly increased (P<0.01). Compared with the model group, the levels of TNF-α, IL-1β and IL-6 in the serum of melatonin group and Suanzaoren Tang group decreased (P<0.05, P<0.01). Compared with the blank group, mRNA and protein expression levels of TLR4 and NF-κB p65 in the hippocampus of the model group were increased (P<0.01), while mRNA and protein expression levels of IκBα were decreased (P<0.01). Compared with the model group, the mRNA and protein expressions of TLR4 and NF-κB p65 in the hippocampus of melatonin group and Suanzaoren Tang group decreased (P<0.05, P<0.01), while the mRNA and protein expression levels of IκBα increased (P<0.05, P<0.01). Compared with the blank group, the protein expression level of p-IκBα in the hippocampus of the model group was significantly increased (P<0.01). Compared with the model group, the protein expression level of IκBα in the hippocampus of melatonin group and Suanzaoren Tang group was increased (P<0.05, P<0.01). Conclusion::Suanzaoren Tang can improve learning and memory impairment induced by sleep deprivation in rats, and its mechanism may be related to its inhibition of TLR4/NF-κB signaling pathway in hippocampus.

Predictive value of four score systems on the bleeding risk in atrial fibrillation patients treated with dabigatran / 中华心血管病杂志

Objective: To compare the predictive value of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores on the bleeding risk in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran. Methods: Data of 942 NVAF patients participating a non-interventional prospective study of anticoagulant therapy with dabigatran, which was conducted in 12 centers from February 2015 to December 2017 in China, were analyzed. Complete HAS-BLED HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores data and follow-up data were available in the enrolled patients. The endpoint of the study was bleeding events occurred during a 6 months follow-up. Cox proportional hazards models were constructed to analyze the associations between HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores and risk of bleeding, and the area under the curve (AUC) of receiver operating characteristics curves (ROC) of each score was used to set the predictive value for bleeding risk. Results: Among the 942 patients, the mean age was (65.3±11.2) years old, 542 (57.5%) were males. A total of 93 (9.9%) bleeding events occurred during follow up, 89 (9.4%) events were minor bleeding, and 4 (0.4%) events were major bleeding. Patients with a high-risk HAS-BLED score had a 1.87-fold increased risk of bleeding compared with low-risk patients (HR = 2.87, 95% CI:1.26-6.51, P = 0.012). There was no statistically significant difference between low-medium-high-risk grading in other scoring systems and bleeding risk (all P>0.05). The AUC (95%CI) of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores were 0.558 (0.525-0.590), 0.520 (0.487-0.553), 0.513(0.480-0.545), 0.523(0.490-0.555), respectively. The AUC of all bleeding score systems were of ≤ 0.700. Conclusion: Among the NVAF patients taking dabigatran in China, the HAS-BLED bleeding risk score is superior to other 3 bleeding risk score on predicting the bleeding risk in these patients, but its predictive value is still relatively low.

Construction of a stable 4.1R gene knockout cell model in RAW264.7 cells using CRISPR/Cas9 technique / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a cell model of 4.1R gene knockout in murine macrophage cell line RAW264.7 using CRISPR/Cas9 technique.</p><p><b>METHODS</b>Three high?grade small?guide RNAs (sgRNAs) that could specifically identify 4.1R gene were synthesized and inserted into lentiCRISPRv2 plasmid. RAW264.7 cells were infected with sgRNA?Cas9 lentivirus from 293T cells transfected with the recombinant sgRNA?lentiCRISPRv2 plasmid, and the positive cells were screened using puromycin and the monoclonal cells were obtained. The expression of 4.1R protein in the monoclonal cells was measured by Western blotting, and the mutation site was confirmed by sequence analysis. Result A 4.1R gene knockout RAW264.7 cell line was obtained, which showed a 19?bp deletion mutation in the 4.1R gene sequence and obviously enhanced proliferation.</p><p><b>CONCLUSION</b>We successfully constructed a 4.1R gene knockout macrophage cell line using CRISPR/Cas9 technique, which may facilitate further investigation of the function of 4.1R in macrophages.</p>

Expression of protein 4.1 family in melanoma cell lines and its effect on cell proliferation / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the expression of protein 4.1 family members in mouse melanoma cell lines and evaluate their effect on cell proliferation.</p><p><b>METHODS</b>PCR and Western blot were used to detected to the expression of protein 4.1 family members (4.1R, 4.1B, 4.1G, and 4.1N) at the mRNA and protein levels in B16 and B16-F10 cell lines. The expression plasmid vector pEGFP-N1-EPB41L3 carrying 4.1B gene sequence amplified from genomic RNA of mouse embryo fibroblasts was constructed and transiently transfected into mouse melanoma cells. The change in cell proliferation was assessed using MTT assay.</p><p><b>RESULTS</b>The mRNA and protein expressions of all the protein 4.1 family members, with the exception of 4.1B, were detected in both B16 and B16-F10 cells. Transfection of cells with the eukaryotic expression vector pEGFP-N1-EPB41L3 markedly inhibited cell proliferation as compared with the non-transfected cells.</p><p><b>CONCLUSION</b>The eukaryotic expression vector carrying EPB41L3 sequence is capable of inhibiting the proliferation of mouse melanoma B16 and B16-F10 cells.</p>

A meta-analysis of bone morphogenetic protein for the treatment of open tibial fractures / 中国骨伤

<p><b>OBJECTIVE</b>To systematically assess the clinical efficacy of bone morphogenetic proteins in the treatment of open tibial fractures.</p><p><b>METHODS</b>Based on the principles and methods of Cochrane systematic reviews, the Cochrane Library, PubMed, EMBASE, Chinese Bio-medicine Database, China Journal Full-text Database, VIP database were searched from their establishment to April 2012 in whatever language. Related journals were handsearched as well. Randomized controlled trials (RCTs) of bone morphogenetic protein for the treatment of open tibial fractures were included. The quality of the included trials according to the Cochrane Handbook for Systematic Reviews of Interventions Version was assessed. The Cochrane Collaboration's software RevMan 5.1 was used for meta-analysis.</p><p><b>RESULTS</b>Three RCTs totaling 851 patients were included. The results showed that bone morphogenetic protein had no significant differences in fracture healing [RR = 1.16, 95% CI (0.95,1.41), P = 0.15], but lower secondary interventions incidence rate [RR = 0.72, 95% CI (0.58, 0.89), P = 0.003]. There were no significant differences between the two groups in the incidence of adverse events of infection [RR = 1.31, 95% CI (0.94, 1.81), P = 0.11] and pain [RR = 0.92, 95% CI (0.79, 1.08), P = 0.30].</p><p><b>CONCLUSION</b>Bone morphogenetic protein has certain advantages in treating open tibial fractures. It needs more high-quality articles to assess the long-term effect of different courses of treatments. The above conclusion still needs more high-quality randomized controlled trails to be verified owing to the limitations of the number and quality of systematic review included studies.</p>