The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Life satisfaction components and all-cause and cause-specific mortality: A large prospective cohort study.

BACKGROUND: Which life satisfaction components could be a target of positive psychological interventions for longevity is largely unknown. We aimed to investigate association of the composite measure of life satisfaction and its individual components with mortality. METHODS: This cohort study included UK Biobank participants who responded to questions concerning five components of life satisfaction at baseline. We generated a composite score representing overall life satisfaction, ranging from 0 (lowest) to 5 (highest). The outcomes were all-cause and cause-specific mortality. We used multivariable Cox regression to estimate hazard ratios (HR) for the associations of interest. RESULTS: Among 165,842 eligible participants, 12,261 all-cause deaths were observed over a median of 12.9-year follow-up. Overall life satisfaction was inversely associated with all-cause mortality (adjusted HR 0.94 [95% CI: 0.93-0.95] per 1 score increment). Health satisfaction showed the strongest association with all-cause mortality, with a fully adjusted HR of 0.52 (95% CI: 0.49-0.55) for high/extreme satisfaction and 0.63 (95% CI: 0.59-0.66) for moderate satisfaction, compared with unsatisfaction (P-trend<0.001), independent of other satisfaction components, regardless of physical health and sociodemographics. The association for family, friendship, work and financial satisfaction was attenuated when adjusted for other life satisfaction components. Similar findings were observed for cause-specific mortality. LIMITATIONS: Observational study with single baseline measurement of life satisfaction precludes the ability to establish causal relationship. CONCLUSIONS: Higher overall life satisfaction was associated with lower mortality. As the major contributor to lower mortality regardless of physical health and sociodemographics, health satisfaction could be an important target of positive psychological interventions for longevity.

Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort.

BACKGROUND: Previous studies indicated that glucosamine supplements may have a general anticancer effect. This study aimed to assess whether the potential effect differs across different types of cancers in a large prospective cohort study. METHODS: All participants from the UK Biobank who were free of cancers and had complete information on glucosamine use at baseline were included and followed up from 2006 until 2021. Cox proportional hazards models were used to assess the associations between regular glucosamine use and different site-specific cancers. Subgroup analyses were performed to explore potential interactions. Several sensitivity analyses were conducted to assess the robustness of the main findings. RESULTS: A total of 450,207 eligible participants (mean age: 56.2 years; females: 53.3%) were included, of whom 84,895 (18.9%) reported regular glucosamine use at baseline. During a median of 12.5 years follow-up, glucosamine use was significantly associated with an increased risk of overall cancer [HR, 1.04; 95% confidence interval (CI), 1.01-1.06], skin cancer (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.07; 95% CI, 1.01-1.13), and with a reduced risk of lung cancer (HR, 0.88; 95% CI, 0.79-0.97) after adjusting for potential confounders. Statistical interaction was observed for gender, age, and education for the association of glucosamine use with overall cancer risk (all Pinteraction < 0.027). These results remained unchanged in the sensitivity analyses. CONCLUSIONS: Regular glucosamine use was associated with lower risk of lung cancer but higher risk of skin cancer, prostate cancer, and overall cancer. IMPACT: The roles of glucosamine use potentially differ in the development of different site-specific cancers.

Optimization of the Process for Preparing Bivalent Polysaccharide Conjugates to Develop Multivalent Conjugate Vaccines against Streptococcus pneumoniae or Neisseria meningitidis and Comparison with the Corresponding Licensed Vaccines in Animal Models.

OBJECTIVE: This study aimed to describe, optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides (CPs) with tetanus toxoid (TT) as bivalent conjugates. METHODS: Different molecular weights (MWs) of polysaccharides, activating agents and capsular polysaccharide/protein (CP/Pro) ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk. Using the described method and optimized parameters, a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models. RESULTS: The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC, while higher MWs were superior for Pn4-TT-Pn14, Pn6A-TT-Pn6B, Pn7F-TT-Pn23F and Pn8-TT-Pn11A. For activating polysaccharides, 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) was superior to cyanogen bromide (CNBr), but for Pn1, Pn3 and MenC, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC) was the most suitable option. For Pn6A-TT-Pn6B and Pn8-TT-Pn11A, rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses, while for Pn4-TT-Pn14, higher CP/Pro ratio was better. Instead of interfering with the respective immunological activity, our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts. CONCLUSION: The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines, laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials.

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.

Translation and validation of the Chinese version of the MD Anderson symptom inventory for measuring perioperative symptom burden in patients with gynecologic cancer.

BACKGROUND: Gynecologic cancers are among the most prevalent malignancies in China. Cervical and uterine cancer respectively account for the sixth and eighth highest incidence of cancer among Chinese women. Abdominal surgery is one of the important treatment methods for gynecological tumors. However, the tumor- and surgery-related symptom burden are not well studied owing to a lack of a standardized and validated assessment tool in the Chinese population. The study aimed to translate and validate the MD Anderson Symptom Inventory for measuring perioperative symptom burden in gynecologic cancer patients (MDASI-PeriOp-GYN) and examine the utility of the Chinese version of MDASI-PeriOp-GYN. METHODS: The MDASI-PeriOp-GYN was translated in a stepwise manner. First, two native speakers independently translated the 9 PeriOp-GYN symptom items. Then the nine items were translated back into English by two different bilingual translators. After discussion and revision, the four translators reached an agreement. Finally, the finalized Chinese version was administered to women with three common gynecologic cancer types (cervical, ovarian, and endometrial cancers) recruited from the gynecological oncology department of Sichuan Cancer Hospital & Institute between July and October 2019. The reliability and validity of the translated version were assessed. RESULTS: Overall, 324 women with gynecologic cancers were enrolled. Cronbach's α values were 0.826 and 0.735 for the symptom severity and interference scales, respectively. Test-retest reliability values were 0.885, 0.873, and 0.914 for symptom severity, PeriOp-GYN, and interference scales. Significant correlations were found between the MDASI-PeriOp-GYN-C and EORTC QLQ-C30 along with the QLQ-OV28 module (- 0.608-0.871, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by time intervals, surgery type, and functional status (all P < 0.01). CONCLUSIONS: The MDASI-PeriOp-GYN-C is a valid and reliable tool for measuring symptoms in Chinese patients undergoing surgery for gynecologic cancers. The tool could be used in clinical practice and clinical trials to instantly gather patients' health and quality of life data.

Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis.

OBJECTIVE: To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. METHODS: Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. RESULTS: A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( CI): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% CI: -1.60, -1.09), -1.10 kg/m 2 (95% CI: -1.42, -0.78), and -1.28 cm (95% CI: -1.69, -0.86), respectively. CONCLUSION: GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

The potential neuritogenic activity of aqueous extracts from Morchella importuna in rat pheochromocytoma cells.

The aim of this study was to explore the neuritogenic effects of aqueous extracts from the fruiting bodies of Morchella importuna (MEA). 3-(4, 5-dimethythiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was carried out to assess the cytotoxicity of MEA. Neurite outgrowth stimulation assay was used to evaluate the potentiation of neuritogenic activity induced by MEA. The specific inhibitors for TrkA, MEK/ERK and PI3K signaling pathway were served to clarify the mechanism of MEA's neuritogenic effects. It was shown that MEA could mimic neuritogenic activity of NGF, a kind of representative neurotrophic factors with no significant cytotoxicity, and stimulate neurite outgrowth in a dose-dependent manner of PC12 cells. The neuritogenic activity induced by MEA required activity of PI3K/Akt and MEK/ERK1/2 signaling pathways, as well as parts of TrkA receptor. Accordingly, MEA could be used as a promising neuritogenic-stimulation compound for nervous diseases treatment.

Antifungal Activity of Eucalyptus Oil against Rice Blast Fungi and the Possible Mechanism of Gene Expression Pattern.

Eucalyptus oil possesses a wide spectrum of biological activity, including anti-microbial, fungicidal, herbicidal, acaricidal and nematicidal properties. We studied anti-fungal activities of the leaf oil extracted from Eucalyptus. grandis × E. urophylla. Eleven plant pathogenic fungi were tested based on the mycelium growth rates with negative control. The results showed that Eucalyptus oil has broad-spectrum inhibitory effects toward these fungi. Remarkable morphological and structural alterations of hypha have been observed for Magnaporthe grisea after the treatment. The mRNA genome array of M. grisea was used to detect genes that were differentially expressed in the test strains treated by the Eucalyptus oil than the normal strains. The results showed 1919 genes were significantly affected, among which 1109 were down-regulated and 810 were up-regulated (p < 0.05, absolute fold change >2). According to gene ontology annotation analysis, these differentially expressed genes may cause abnormal structures and physiological function disorders, which may reduce the fungus growth. These results show the oil has potential for use in the biological control of plant disease as a green biopesticide.

Risk factors for methicillin-resistant Staphylococcus aureus carriage among residents in 7 nursing homes in Shanghai, China.

BACKGROUND: Nursing home residents are a population at risk for methicillin-resistant Staphylococcus aureus (MRSA) carriage, but few data about MRSA in this setting in Shanghai are available. The aim of this study is to determine the prevalence and risk factors for MRSA carriage in nursing home residents in Shanghai, China. METHODS: Four hundred forty-three residents from 7 nursing homes in Shanghai, China, participated in this study; nasal and axillary swabs were obtained from these residents. Laboratory identification for S aureus and antimicrobial susceptibility testing were performed when isolated. Data, including individual resident characteristics and nursing home characteristics, were collected and analyzed. RESULTS: Of the 443 participating residents, 99 (22.3%) and 45 (10.2%) residents were colonized by S aureus and MRSA, respectively. Previous hospitalization (odds ratio [OR], 2.564; 95% confidence interval [CI], 1.214-5.415; P = .014), presence of an invasive device (OR, 3.455; 95% CI, 1.678-7.113; P = .001), chloramphenicol therapy (OR, 7.672; 95% CI, 1.807-32.580; P = .006), and macrolides therapy (OR, 2.796; 95% CI, 1.056-7.403; P = .038) were independent risk factors for MRSA colonization. Low expenditure per month and less good sanitary condition also increased the risk for MRSA colonization. CONCLUSIONS: Our study suggests that nursing homes are significant reservoirs for MRSA. Implementation of infection control strategies must be given high priority in nursing homes to fight the high prevalence of MRSA, and increased convenience and feasibility should also be realized with these control strategies for MRSA colonization.

[Effects of forest regeneration patterns on the quantity and chemical structure of soil solution dissolved organic matter in a subtropical forest.] / 更新方式对亚热带森林土壤溶液可溶性有机质数量及化学结构的影响.

Using the negative pressure sampling method, the concentrations and spectral characte-ristics of dissolved organic matter (DOM) of soil solution were studied at 0-15, 15-30, 30-60 cm layers in Castanopsis carlesii forest (BF), human-assisted naturally regenerated C. carlesii forest (RF), C. carlesii plantation (CP) in evergreen broad-leaved forests in Sanming City, Fujian Pro-vince. The results showed that the overall trend of dissolved organic carbon (DOC) concentrations in soil solution was RF>CP>BF, and the concentration of dissolved organic nitrogen (DON) was highest in C. carlesii plantation. The concentrations of DOC and DON in surface soil (0-15 cm) were all significantly higher than in the subsurface (30-60 cm). The aromatic index (AI) was in the order of RF>CP>BF, and as a whole, the highest AI was observed in the surface soil. Higher fluorescence intensity and a short wave absorption peak (320 nm) were observed in C. carlesii plantation, suggesting the surface soil of C. carlesii plantation was rich in decomposed substance content, while the degree of humification was lower. A medium wave absorption peak (380 nm) was observed in human-assisted naturally regenerated C. carlesii forest, indicating the degree of humification was higher which would contribute to the storage of soil fertility. In addition, DOM characte-ristics in 30-60 cm soil solution were almost unaffected by forest regeneration patterns.

Kallistatin inhibits TGF-ß-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression.

Kallistatin, an endogenous protein, consists of two structural elements: active site and heparin-binding domain. Kallistatin exerts beneficial effects on fibrosis by suppressing transforming growth factor (TGF)-ß synthesis in animal models. TGF-ß is the most potent inducer of endothelial-mesenchymal transition (EndMT), which contributes to fibrosis and cancer. MicroRNA (miR)-21 is an important player in organ fibrosis and tumor invasion. Here we investigated the potential role of kallistatin in EndMT via modulation of miR-21 in endothelial cells. Human kallistatin treatment blocked TGF-ß-induced EndMT, as evidenced by morphological changes as well as increased endothelial and reduced mesenchymal marker expression. Kallistatin also inhibited TGF-ß-mediated reactive oxygen species (ROS) formation and NADPH oxidase expression and activity. Moreover, kallistatin antagonized TGF-ß-induced miR-21 and Snail1 synthesis, Akt phosphorylation, NF-κB activation, and matrix metalloproteinase 2 (MMP2) synthesis and activation. Kallistatin via its heparin-binding site blocked TGF-ß-induced miR-21, Snail1 expression, and ROS formation, as wild-type kallistatin, but not heparin-binding site mutant kallistatin, exerted the effect. Conversely, kallistatin through its active site stimulated the synthesis of endothelial nitric oxide synthase (eNOS), sirtuin 1 (Sirt1) and forkhead box O1 (FoxO1); however, these effects were blocked by genistein, a tyrosine kinase inhibitor. This is the first study to demonstrate that kallistatin's heparin-binding site is crucial for preventing TGF-ß-induced miR-21 and oxidative stress, while its active site is key for stimulating the expression of antioxidant genes via interaction with an endothelial surface tyrosine kinase. These findings reveal novel mechanisms of kallistatin in protection against fibrosis and cancer by suppressing EndMT.

[Comparison of simple pooling and bivariate model used in meta-analyses of diagnostic test accuracy published in Chinese journals].

OBJECTIVE: To investigate the use of simple pooling and bivariate model in meta-analyses of diagnostic test accuracy (DTA) published in Chinese journals (January to November, 2014), compare the differences of results from these two models, and explore the impact of between-study variability of sensitivity and specificity on the differences. METHODS: DTA meta-analyses were searched through Chinese Biomedical Literature Database (January to November, 2014). Details in models and data for fourfold table were extracted. Descriptive analysis was conducted to investigate the prevalence of the use of simple pooling method and bivariate model in the included literature. Data were re-analyzed with the two models respectively. Differences in the results were examined by Wilcoxon signed rank test. How the results differences were affected by between-study variability of sensitivity and specificity, expressed by I2, was explored. RESULTS: The 55 systematic reviews, containing 58 DTA meta-analyses, were included and 25 DTA meta-analyses were eligible for re-analysis. Simple pooling was used in 50 (90.9%) systematic reviews and bivariate model in 1 (1.8%). The remaining 4 (7.3%) articles used other models pooling sensitivity and specificity or pooled neither of them. Of the reviews simply pooling sensitivity and specificity, 41(82.0%) were at the risk of wrongly using Meta-disc software. The differences in medians of sensitivity and specificity between two models were both 0.011 (P<0.001, P=0.031 respectively). Greater differences could be found as I2 of sensitivity or specificity became larger, especially when I2>75%. CONCLUSION: Most DTA meta-analyses published in Chinese journals(January to November, 2014) combine the sensitivity and specificity by simple pooling. Meta-disc software can pool the sensitivity and specificity only through fixed-effect model, but a high proportion of authors think it can implement random-effect model. Simple pooling tends to underestimate the results compared with bivariate model. The greater the between-study variance is, the more likely the simple pooling has larger deviation. It is necessary to increase the knowledge level of statistical methods and software for meta-analyses of DTA data.

Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis.

INTRODUCTION: Kallistatin levels in the circulation are reduced in patients with sepsis and liver disease. Transgenic mice expressing kallistatin are resistant to lipopolysaccharide (LPS)-induced mortality. Here, we investigated the effect of kallistatin on survival and organ damage in mouse models of established sepsis. METHODS: Mice were rendered septic by cecal ligation and puncture (CLP), or endotoxemic by LPS injection. Recombinant human kallistatin was administered intravenously six hours after CLP, or intraperitoneally four hours after LPS challenge. The effect of kallistatin treatment on organ damage was examined one day after sepsis initiation, and mouse survival was monitored for four to six days. RESULTS: Human kallistatin was detected in mouse serum of kallistatin-treated mice. Kallistatin significantly reduced CLP-induced renal injury as well as blood urea nitrogen, serum creatinine, interleukin-6 (IL-6), and high mobility group box-1 (HMGB1) levels. In the lung, kallistatin decreased malondialdehyde levels and HMGB1 and toll-like receptor-4 (TLR4) synthesis, but increased suppressor of cytokine signaling-3 (SOCS3) expression. Moreover, kallistatin attenuated liver injury, serum alanine transaminase (ALT) levels and hepatic tumor necrosis factor-α (TNF-α) synthesis. Furthermore, delayed kallistatin administration improved survival in CLP mice by 38%, and LPS-treated mice by 42%. In LPS-induced endotoxemic mice, kallistatin attenuated kidney damage in association with reduced serum creatinine, IL-6 and HMGB1 levels, and increased renal SOCS3 expression. Kallistatin also decreased liver injury in conjunction with diminished serum ALT levels and hepatic TNF-α and TLR4 expression. In cultured macrophages, kallistatin through its active site increased SOCS3 expression, but this effect was blocked by inhibitors of tyrosine kinase, protein kinase C and extracellular signal-regulated kinase (ERK), indicating that kallistatin stimulates a tyrosine-kinase-protein kinase C-ERK signaling pathway. CONCLUSIONS: This is the first study to demonstrate that delayed human kallistatin administration is effective in attenuating multi-organ injury, inflammation and mortality in mouse models of polymicrobial infection and endotoxemia. Thus, kallistatin therapy may provide a promising approach for the treatment of sepsis in humans.

The association of TGFB1 genetic polymorphisms with high myopia: a systematic review and meta-analysis.

OBJECTIVE: The TGFB1 gene is among the most studied genes in high myopia due to its role in scleral remodeling. But reported findings of association on TGFB1 and high myopia are inconsistent. This present study is to evaluate the association of TGFB1 polymorphisms and high myopia. METHODS: A comprehensive literature search was conducted on studies published up to April 5, 2015. Summary odds ratios (ORs) and 95% confidence intervals were analyzed. Heterogeneity across studies was evaluated by Cochran Q statistic test and the I(2) index. Sensitivity analyses were conducted by the approach of one-study remove to assess the influence of single study on the combined effect. RESULTS: Eight studies were included in this study for meta-analysis. Rs1982073 was associated with high myopia in dominant model (OR=1.64; 95% CI=1.04~2.58; P<0.05), heterozygous model (OR=1.54; 95% CI=1.02~2.33; P<0.05), homozygous model (OR=1.90; 95% CI=1.01~3.55; P=0.05) and allelic model (OR=1.36; 95% CI=1.01~1.84; P=0.05). However, there was no statistical significance when Bonferroni correction was considered. Rs4803455 was associated with high myopia in recessive model (OR=0.40; 95% CI=0.25~0.64; P<0.01) and homozygous model (OR=0.42; 95% CI=0.26~0.68; P<0.01). Rs1800469 was associated with high myopia in allelic model (OR=0.78; 95% CI=0.64~0.96; P<0.05). And the associations can withstand Bonferroni correction in models mentioned above when referring to rs4803455 (P<0.01) and rs1800469 (P<0.05). CONCLUSIONS: Meta-analysis of existing data revealed a suggestive association of TGFB1 rs1982073 and rs4803455 with high myopia.

Meta-analysis of randomized controlled trials comparing latanoprost with timolol in the treatment of Asian populations with chronic angle-closure glaucoma.

BACKGROUND: To evaluate the efficacy and safety of latanoprost compared with timolol in the treatment of Asian patients with chronic angle-closure glaucoma (CACG). METHODS: Relevant trials were identified through systematic searches of Medline, EMBASE, PubMed, Cochrane Library, Google Scholar and several Chinese databases. The main outcome measures included absolute and relative reduction of intraocular pressure (IOP) at mean, peak and trough from baseline, ocular adverse effects and systemic adverse events. RESULTS: Seven randomized controlled trials with 685 patients were included. In comparison with timolol, latanoprost reduced absolute IOP in CACG patients by more than 2.3 mmHg (95%CI, 1.8∼2.9, P<0.01), 2.4 mmHg (95%CI, 1.9∼2.9, P<0.01) and 2.5 mmHg (95%CI, 1.6∼3.3, P<0.01) at mean, peak and trough, respectively. As for relative IOP, there is 9.0% (95%CI, 6.6∼11.4, P<0.01), 9.7% (95%CI, 7.6∼11.8, P<0.01), and 10.8% (95%CI, 7.4∼14.3, P<0.01) greater reduction among latanoprost users than among timolol users. The differences were statistically significant at all time points (1, 2, 4, 8, 12, and 24 weeks). More ocular adverse effects (OR = 1.49, 95% CI, 1.05∼2.10, P = 0.02) and less systemic adverse events (OR = 0.46, 95% CI, 0.25∼0.84, P = 0.01) were observed in latanoprost group in comparison with timolol group. CONCLUSION: Compared with timolol, latanoprost was significantly more effective in lowering IOP of Asian patients with CACG, with higher risk of ocular adverse effects but lower risk of systemic adverse events, and might be a good substitute for CACG patients.

Human kallistatin administration reduces organ injury and improves survival in a mouse model of polymicrobial sepsis.

Kallistatin, a plasma protein, has been shown to exert multi-factorial functions including inhibition of inflammation, oxidative stress and apoptosis in animal models and cultured cells. Kallistatin levels are reduced in patients with sepsis and in lipopolysaccharide (LPS)-induced septic mice. Moreover, transgenic mice expressing kallistatin are more resistant to LPS-induced mortality. Here, we investigated the effects of human kallistatin on organ injury and survival in a mouse model of polymicrobial sepsis. In this study, mice were injected intravenously with recombinant kallistatin (KS3, 3 mg/kg; or KS10, 10 mg/kg body weight) and then rendered septic by caecal ligation and puncture 30 min later. Kallistatin administration resulted in a > 10-fold reduction of peritoneal bacterial counts, and significantly decreased serum tumour necrosis factor-α, interleukin-6 and high mobility group box-1 (HMGB1) levels. Kallistatin also inhibited HMGB1 and toll-like receptor-4 gene expression in the lung and kidney. Administration of kallistatin attenuated renal damage and decreased blood urea nitrogen and serum creatinine levels, but increased endothelial nitric oxide synthase and nitric oxide levels in the kidney. In cultured endothelial cells, human kallistatin via its heparin-binding site inhibited HMGB1-induced nuclear factor-κB activation and inflammatory gene expression. Moreover, kallistatin significantly reduced apoptosis and caspase-3 activity in the spleen. Furthermore, kallistatin treatment markedly improved the survival of septic mice by 23% (KS3) and 41% (KS10). These results indicate that kallistatin is a unique protecting agent in sepsis-induced organ damage and mortality by inhibiting inflammation and apoptosis, as well as enhancing bacterial clearance in a mouse model of polymicrobial sepsis.

[Community structure and diversity of entophytic bacteria in Tricholoma matsutake in Sichuan Province, Southwest China].

In order to understand the diversity and community structure of endophytic bacteria in Tricholoma matsutake, 14 Tricholoma matsutake samples were collected from 7 main production counties of Xiaojin, Yajiang, Muli, Yanyuan, Yanbian, Huidong and Mianning. The entophytic bacterial community structure and diversity were investigated by PCR denaturing gradient gel electrophoresis (PCR-DGGE). The results showed that the diversity and community structure of endophytic bacteria in T. matsutake varied significantly, while those from the environments alike had high similarity. In addition, each T. matsutake sample contained more than 15 species of endophytes, with that from Yanyuan having the highest endophytes diversity index and abundance, while those from Xiaojin were the lowest. Phylogenetic tree showed that endophytic bacterial species in T. matsutake were abundant. Dominant bacterial population in T. matsutake collected from different places varied, and Pseudomonas, Ewingella and Bacillus were distributed in all samples and retained a certain advantage. Alcaligenes and Sphingobacterium distributed in most samples, while Duganella and Lysinibacillus only in certain ones. This study demonstrated that the endophytic bacteria in T. matsutake were abundant and diversified, which could be in favor of searching the dominant bacteria promoting the growth of T. matsutake.

[Diffuse large B-cell lymphoma of testis: a clinicopathologic and immunophenotypic study of 58 cases].

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype, diagnosis and differential diagnosis, and prognostic factors of testicular diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical and pathologic profiles of 58 cases of testicular DLBCL were investigated.Immunohistochemical stainings and EBER1/2 in situ hybridization were performed on formalin fixed tissues. RESULTS: The average age of the patients was 62.1 years, and the median age was 65 years. The course of disease was short in most of the cases. Clinical stages at diagnosis were mainly stage I or II (87.9%, 51/58). Forty eight patients (82.8%) had unilateral testis involvement. Inguinal lymphadenopathy was observed in 12 (20.7%) patients and the other organs were seldom involved. Morphologically, centroblast-like neoplastic cells infiltrated interstitial tissue of testis diffusely and invaded into seminiferous tubules. Tunica albuginea and vessels were involved in 14 (24.1%) and 10 (17.2%) patients, respectively. Immunophenotype analysis showed predominant non-GCB type of DLBCL (48/58, 82.8%) by Hans classification. No EBV infection was detected. Follow-up data were available in 48 (82.8%) patients. Twenty eight patients (58.3%) died of the disease. One-year, 3-year, and 5-year overall survivals were 55.7%, 31.6% and 27.6%, respectively. Age (older than 60 years), B-symptoms, high serum level of LDH, advanced Ann Arbor stage as well as lack of combination of therapy were associated with a poor prognosis. CONCLUSIONS: This large series of testicular DLBCL mainly present with local disease at diagnosis. Most cases show non-GCB immunophenotype. Despite early clinical stage at presentation, the prognosis is poor. Combined chemotherapy postoperation may prolong survival of the patients.