Efficacy and safety of HER2-targeted therapy in patients with colorectal cancer: What should we expect from a meta-analysis?

Background and objectiveHuman epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and stomach cancers. However, the application of HER2-targeted therapy in colorectal cancer (CRC) remains controversial. We sought to assess the efficacy and safety of HER2-targeted therapy in CRC by performing a meta-analysis of relevant studies.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, and the ClinicalTrials.gov database to retrieve relevant studies. STATA 16 was used for the statistical analysis. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and incidence of treatment?related adverse events (TRAEs) were used as the outcome indicators analyzed by random- or fixed-effects models.ResultsA total of 267 patients from nine studies were included in this meta-analysis. The overall ORR and DCR were 27.5% (95% CI 16.8% to 39.6%) and 68.9% (95% CI 55.4% to 81.0%), respectively. No significant heterogeneity was found in PFS among these studies and the overall median PFS was 4.35 months (95% CI 3.70 to 4.99). The overall incidence of all-grade and grade 3 or higher adverse events were 93.5% (95% CI 88.4% to 97.4%) and 16.8% (95% CI 4.8% to 33.3%).ConclusionsHER2-targeted therapy was confirmed as a promising treatment for colorectal cancer, warranting further high-quality clinical randomized controlled trials to verify.     

The efficacy of Da Chaihu decoction combined with metformin tablets for type 2 diabetes mellitus: A systematic review and meta-analysis

ObjectiveTo assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone.MethodsThis systematic review and meta‐analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3.ResultsSix randomized controlled trials comprising 516 participants were included.The meta‐analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (−0.66 mmol/L; 95 % CI (confidence intervals) [− 1.28, − 0.04]), plasma glucose 2 h after meal (2-h PG) (−1.18 mmol/L; 95 % CI [−1.94, −0.42]) in six RCTs, body mass index (BMI) (−3.07 mmol/L; 95 % CI [−6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (−0.36 mmol/L; 95 % CI [−1.04, 0.31]) in three RCTs, and triglycerides (TG) (−0.76 mmol/L; 95 % CI [−1.37, −0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (−0.97 mmol/L; 95 % CI [−1.18, −0.76]).ConclusionsVery low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.     

血清淀粉样蛋白A对成人脓毒症诊断价值的Meta分析

目的系统评价血清淀粉样蛋白A(serum amyloid A,SAA)对成人脓毒症诊断的准确性。方法通过计算机检索知网、维普、万方、Sinomed、PubMed、Embase、Cochrane图书馆等公开发表的有关文献,通过QUADAS量表对纳入文献进行质量评估。采用Metadisc1.4和Stata12.0进行异质性分析,根据异质性结果选择效应模型进行定量合成;为减小异质性和阈值的影响,综合灵敏度和特异度的信息,以受试者工作特征曲线(SROC)、曲线下面积(AUC)及Q*指数进行综合评价。结果最终有13篇文献纳入Meta分析,结果显示,SAA对成人脓毒症诊断敏感度为0.72(95%CI 0.70~0.75)和特异度为0.69(95%CI 0.66~0.71),SROC的AUC为0.78,Q*指数为0.72。结论SAA对成人脓毒症诊断的敏感度和特异度较高,可为诊断成人脓毒症提供依据。     

Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice

The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50 mg/kg was administered by gavage once daily for 2 consecutive days, 6 h after CCl₄ intoxication. CCl₄ intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl₄ administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl₄-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.     

A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice

Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctadecylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400 nm and zeta potential of 40 mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell-mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41 ± 0.38 log₁₀ CFU) than traditional vaccine Bacillus Calmette–Guerin (BCG) (6.01 ± 0.33 log₁₀ CFU) and PBS control (6.53 ± 0.26 log₁₀ CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine.     

Boundary extension as a tool for detection of cognitive change among individuals with mild cognitive impairment: A preliminary study

ObjectivesRecent neuropathological research suggests that recognition memory supported by familiarity rather than recollection may be the earliest cognitive change in course of Alzheimer's disease (AD). Nonetheless, the findings on the issue of familiarity capacity in the prodromal AD remain inconsistent. Boundary extension (BE), in which the view recollected by the subject covers a wider angle than was actually observed, is a form of false memory. Given that BE occurs implicitly and automatically, it may be a candidate for assessing familiarity functioning in cases of AD. This was the issue explored in the current study.Methods: One-hundred and six participants comprising a younger adult group (YA, n = 40), a healthy older adult group (OA, n = 40), and a group of patients with mild cognitive impairment (MCI, n = 26) underwent testing for BE and neuropsychological functions. Parts of OA and MCI underwent analysis for plasma tau levels. Receiver-operating characteristic analysis was used to assess memory associated with familiarity and recollection among participants.Results: The OA and MCI groups could be differentiated by the degree of familiarity associated with BE, wherein the latter group displayed minimal familiarity. Among OAs, familiarity was positively associated with education level. We observed a correlation between plasma tau levels and various neuropsychological functions. Most of the associations between plasma tau levels and neuropsychological functions were mediated by education level.Conclusions: Our findings indicate that BE could detect early decline in familiarity and assess preserved cognitive functions in aging     

短链脂肪酸在肿瘤免疫治疗中的作用及机制研究进展

免疫治疗的临床应用显著提高了肿瘤患者的生存率,其机制除了其本身具有增强免疫细胞介导的抗肿瘤反应外,肠道微生物及其代谢产物的变化也发挥着重要作用。短链脂肪酸是结肠中细菌发酵未被小肠吸收的碳水化合物的主要产物,有研究表明短链脂肪酸具有免疫调节功能,可以影响肿瘤对免疫检查点抑制剂的应答。本文就近年来短链脂肪酸在肿瘤的免疫治疗过程中发挥作用的研究进展进行综述。     

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study

Objective The relationship between serum uric acid(SUA)levels and glycemic indices,including plasma glucose(FPG),2-hour postload glucose(2 h-PG),and glycated hemoglobin(HbA1 c),remains inconclusive.We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.Methods The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study.A total of 105,922 community-dwelling adults aged≥40 years underwent the oral glucose tolerance test and uric acid assessment.The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.Results A total of 30,941 men and 62,361 women were eligible for the current analysis.Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels,but with different inflection points in men and women.The thresholds for FPG,2 h-PG,and HbA1 c for men and women were 6.5/8.0 mmol/L,11.0/14.0 mmol/L,and 6.1/6.5,respectively(SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes,while the inflection points were reached earlier in men than in women.     

Secondary Heterotypic Versus Homotypic Infection by Coxsackie B Group Viruses: Impact on Early and Late Histopathological Lesions and Virus Genome Prominence

The impact of prior exposure to a different or identical strain of Coxsackievirus B (CVB) on murine CVB myocarditis was studied using a susceptible murine host (A/J[H-2 ^a]) and myocarditic CVB3 or avirulent CVB2 as primary or secondary infectants. The effects of secondary heterotypic infection (CVB2 followed by CVB3) and homotypic infection (CVB3 followed by CVB3) 28 days after primary inoculation, versus CVB2 or CVB3 alone, on injury and viral genomic replication, both early (day 7) and late (days 28 and 56), were evaluated. After the primary infection by CVB2, trivial viral RNA was present in the heart and other organs, and a substantial positivity was observed with CVB3 infection. Seven days after secondary heterotypic (CVB2-CVB3) infection, the quantity of CVB genome in heart, pancreas, liver, and spleen was increased compared with the virus genome in the CVB3-CVB3 group and in the group with primary CVB3 infection alone. This phenomenon was seen in the heart and spleen up to day 28 postsecondary infection. Tissue inflammation and necrosis in heart and pancreas were prominent 7 days postsecondary infection with CVB2-CVB3 and correlated well with an increased quantity of CVB genome. Virus genome was present in heart and spleen 28 days after CVB3 infection alone. Serum CVB3 neutralization titer was increased to 1:128 in CVB2-CVB3 group at days 7 and 28 postsecondary infection, and serum completely neutralized cytopathological effects of CVB3 in the CVB3-CVB3 group at day 7 and 28 postsecondary infection. Our results indicate that secondary heterotypic infection by CVB causes increased injury, inflammation, and CVB replication in target organs such as the heart and pancreas, as well as in immune compartments like the spleen. Compared with CVB3 alone, the intense inflammatory infiltrate in the CVB2-CVB3 group is as not due solely to postviral sensitization of the immune system, but rather to the inability of the host to eradicate the virus.     

不可逆电穿孔术联合新辅助化疗治疗局部进展期胰腺癌安全性和有效性的Meta分析

目的 评估不可逆电穿孔术（IRE）联合新辅助化疗治疗局部进展期胰腺癌患者的安全性和有效性。方法 检索PubMed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库、知网、万方和维普等数据库从建库至2022年3月发表的相关文献。采用RevMan5.4软件进行Meta分析。结果 最终纳入8项研究,其中随机对照试验1项、回顾性研究4项和前瞻性研究3项。共3 970例局部进展期胰腺癌患者,其中联合组344例,单纯化疗组3 626例。Meta分析显示联合组患者的总生存期明显高于单纯化疗组（OR=4.52, 95%CI: 2.63~7.77, P<0.00001）。但是联合组和单纯化疗组患者的疾病控制率差异无统计学意义（OR=0.58, 95%CI: 0.02~18.74, P=0.76）,疾病进展两组差异无统计学意义（OR=0.49, 95%CI: 0.23~1.02, P=0.06）。新辅助化疗联合IRE对患者治疗期间胃肠道反应（OR=0.37, 95%CI: 0.10~1.34, P=0.13）和骨髓抑制（OR=0.61, 95%CI: 0.26~1.40, P=0.24）等不良反应的发生率并无明显影响。结论 不可逆电穿孔术联合新辅助化疗可以显著改善局部进展期胰腺癌患者的预后,明显提高患者的总生存时间。