Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy.

Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression in high-grade serous ovarian cancer and triple-negative breast cancers promotes DNA double-strand break resection, homologous recombination (HR), and subsequent therapeutic resistance. Our investigations reveal that Syk is activated by ATM following DNA damage and is recruited to DNA double-strand breaks by NBS1. Once localized to the break site, Syk phosphorylates CtIP, a pivotal mediator of resection and HR, at Thr-847 to promote repair activity, particularly in Syk-expressing cancer cells. Inhibition of Syk or its genetic deletion impedes CtIP Thr-847 phosphorylation and overcomes the resistant phenotype. Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.

Higher-Than-Expected Burden of Alcohol-Related Liver Diseases During COVID-19 Pandemic in the USA, with a Tapering Trend.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to an increase in alcohol-related liver disease (ALD). The aim of this study was to evaluate the magnitude of ALD hospitalization surge during the pandemic in the USA. MAIN MEASURES: A retrospective trend analysis of adult hospitalizations for ALD at acute care hospitals across the USA in 2016-2020 was conducted. Hospitalizations were identified using the International Classification of Diseases 10 codes for ALD and non-alcoholic-related liver disease. Outcomes measured included the predicted monthly volume of hospitalizations for ALD and inpatient mortality rates. KEY RESULTS: During the 2020 pandemic, monthly ALD hospitalizations reached 10,247 representing a 20.7% increase compared to pre-pandemic monthly average of 8490. Additional 4163 ALD hospitalizations occurred during the pandemic, in addition to a pre-pandemic uptrend. The peak of excess ALD hospitalizations was from May to October (monthly excess of 1138) decreasing to monthly excess of 280 in November and December. The excess increase in ALD hospitalizations was primarily observed in young adults, totaling 5256 cases affecting both male (2101 excess cases) and females (2041 excess cases). The age-standardized monthly mortality rate during the pandemic was notably higher than expected at 0.9% (95% CI 0.4 to 1.4%). CONCLUSIONS: The COVID-19 pandemic led to a significant increase in ALD hospitalizations, above and beyond the pre-existing upward trend, which tapered towards the end of 2020, suggesting a possible decline in the pandemic's impact. The excess increase in ALD hospitalizations was observed primarily in young adults and affected both males and females. These findings highlight the need for further attention to the long-term consequences of the pandemic.

Triangular Triazine-Triphenylamine Functionalized Hybrid Fluorescent Porous Polymers for Detection and Photodegradation of Tetracycline Hydrochloride.

First, an organic semiconductor fluorescent molecule of 4',4″,4"'-(2,4,6-triphenyl-1,3,5-triazine)-4-(N,N-diphenyl-(1,1'-biphenyl)-4-amine (TPTz) is successfully synthesized by the Suzuki-Miyaura coupling reaction of 2,4,6-tris(4-bromophenyl)-1,3,5-triazine with 4-(diphenylamino)phenylboronic acid. TPTz offers as high as 85% fluorescence quantum yield and a strong solvent effect, with fluorescent colors across the visible spectrum in different solvents. Then, an organic-inorganic hybrid fluorescent porous polymer of PCS-TPTz with a surface area of 714 m2 g-1 and pore volume of 0.660 cm3 g-1 is prepared by the Friedel-Crafts reaction of TPTz and octavinylsilsesquioxane; PCS-TPTz showed a high fluorescence quantum yield of 17% with a large Stokes shift of up to 280 nm. The excellent fluorescence properties and insolubility of PCS-TPTz make it to act as a heterophase sensor for tetracycline hydrochloride (TH) with a KSV of 2.39 × 104 M-1. In addition, PCS-TPTz exhibits an excellent photodegradation activity for antibiotic TH without the requirement for additional oxidants or pH adjustments. ESR spectra and free radical trapping experiment indicate that superoxide radical (•O2-) is the active radical for achieving the photodegradation. The simultaneous detection and degradation of TH are achieved by PCS-TPTz.

FUS-Mediated CircFGFR1 Accelerates the Development of Papillary Thyroid Carcinoma by Stabilizing FGFR1 Protein.

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.

Effect of physical activity on incidence and mortality in patients with gastric cancer: evidence from real-world studies.

PURPOSE: Physical activity (PA) has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between PA and the risk of developing gastric cancer (GC). The purpose of this study was to evaluate the impact of PA on the incidence and mortality risk of GC through a meta-analysis, as well as investigate potential dose-response relationships. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of PA on the risk of GC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results showed that PA correlated with lower incidence of GC (RR: 0.83, 95% CI: 0.77-0.90), decreased risk of GC mortality (RR: 0.76, 95% CI: 0.66-0.89). The results of the subgroup analysis showed that PA was associated with reduced incidence of GC across gender, different regions, study designs, different sites of GC and different types of PA. A linear relationship was found for frequency of PA. CONCLUSIONS: This meta-analysis found that PA was associated with a reduced risk of GC incidence and mortality. The correlation between PA and GC occurrence was in a dose-response relationship.

Incidence and outcomes of thromboembolic and bleeding events in patients with liver cirrhosis in the USA.

BACKGROUND & AIMS: Understanding the epidemiology of bleeding and thromboembolism (clotting) in liver cirrhosis provides important data for future studies and policymaking; however, head-to-head comparisons of bleeding and clotting remain limited. METHODS: This is a populational retrospective cohort study using the US National Readmission Database of 2018 to compare the incidence and outcomes of bleeding and clotting events in patients with liver cirrhosis. The primary outcomes were the 11-month incidence proportion of bleeding and clotting events. RESULTS: Of 1 304 815 participants, 26 569 had liver cirrhosis (45.0% women, mean age 57.2 [SD, 12.7] years). During the 11-month follow-up, in patients with cirrhosis, for bleeding and clotting events, the incidence proportions was 15.3% and 6.6%; the risk-standardized all-cause mortality rates were 2.4% and 1.0%; the rates of intensive care intervention were 4.1% and 1.9%; the rates of rehabilitation transfer were .2% and .2%; the cumulative length of stays were 45 100 and 23 566 days; total hospital costs were 147 and 84 million US dollars; total hospital charges were 620 and 365 million US dollars. Compared to non-cirrhosis, liver cirrhosis was associated with higher rates of bleeding (adjusted hazard ratio, 3.02 [95% CI, 2.85-3.20]) and portal vein thrombosis (PVT) (18.46 [14.86-22.92]), and slightly lower risks of other non-PVT venous thromboembolic events (.82 [.75-.89]). CONCLUSIONS: Bleeding is more common than thromboembolism in patients with liver cirrhosis, causes higher morbidity, mortality and resource utilization. Liver cirrhosis is an independent risk factor for bleeding and PVT, but not non-PVT thromboembolism including venous thromboembolism, acute myocardial infarction and ischemic stroke.

Highly Electroactive Tissue Engineering Scaffolds Based on Nanocellulose/Sulfonated Carbon Nanotube Composite Hydrogels for Myocardial Tissue Repair.

Myocardial infarction (MI) has been a serious threat to the health of modern people for a long time. The introduction of tissue engineering (TE) therapy into the treatment of MI is one of the most promising therapeutic schedules. Considering the intrinsic electrophysiological activity of cardiac tissue, we utilized 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-oxidized cellulose nanofibrils (TOCNs) with excellent biocompatibility as the substrate, and sulfonated carbon nanotubes (SCNTs) with remarkable conductivity and water dispersibility as the electrically active material, to prepare TOCN-SCNT composite hydrogels. By adjusting the content of SCNTs from 0 to 5 wt %, TOCN-SCNT hydrogels exhibited conductivity ranging from 5.2 × 10-6 to 6.2 × 10-2 S cm-1. Just with 1 wt % incorporation of SCNTs, the hydrogel played a role in promoting the adhesive growth and proliferation of cells. The hydrogel expressed higher Connexin 43 (Cx-43) and cardiac troponin-T proteins compared with controls, demonstrating great potential in constructing a myocardial TE scaffold.

Inflammation and nutritional status indicators as prognostic indicators for patients with locally advanced gastrointestinal stromal tumors treated with neoadjuvant imatinib.

BACKGROUND: Previous studies have confirmed that preoperative nutritional-inflammatory indicators can predict prognosis in various malignancies. However, to the best of our knowledge, no study has investigated the assessment of systemic inflammatory immunity index (SII) combined with prognostic nutritional index (PNI) scores to predict prognosis after neoadjuvant treatment with imatinib in locally advanced gastrointestinal stromal tumours (LA-GIST). The aim of this study was to evaluate the predictive value of pretreatment SII-PNI scores in predicting recurrence after neoadjuvant therapy with imatinib in patients with LA-GIST. METHODS: We retrospectively analyzed 57 patients with LA-GIST who received imatinib neoadjuvant from January 2013 to March 2019. Patients were divided into recurrence and non-recurrence groups according to their follow-up status, and SII and PNI cut-offs were calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 544.6) and low PNI (≤ 47.2); score of 1, either high SII (≥ 544.6) or low PNI (≤ 47.2); score of 0, no high SII (≥ 544.6) nor low PNI (≤ 47.2). RESULTS: All patients received imatinib neoadjuvant therapy for a median treatment period of 8.5 months (ranging from 3.2 to 12.6 months), with 8 patients (14.04%) and 49 patients (85.96%) developing recurrence and non-recurrence, respectively. Patients with a high SII-PNI score had a significantly worse recurrence-free survival time than those with a low SII-PNI score (P = 0.022, 0.046), and had a poorer pathological response (P = 0.014). Multivariate analysis demonstrated that the SII-PNI score was an independent prognostic factor for prediction of recurrence-free survival (P = 0.002). CONCLUSION: The pre-treatment SII-PNI score can be used to predict the efficacy after neoadjuvant treatment with imatinib in patients with LA-GIST, which may be a promising predictor of recurrence-free survival time for patients.

Gastrointestinal hospitalization during COVID-19 pandemic in the United States: Analysis of a nationwide inpatient sample.

BACKGROUND AND AIM: We aim to systematically investigate gastrointestinal (GI) hospitalizations in the United States during the early phase of the COVID-19 pandemic on a national level and the consequence that may inform practice and policies. METHODS: A retrospective cross-sectional analysis of adult hospitalizations with GI-related diagnoses or procedures in the United States in 2020 was used, with hospitalizations from 2016 to 2019 used for contextual information. RESULTS: Hospitalizations with principal and secondary GI diagnoses decreased by 13.3% and 8.2% from 2019 to 2020, respectively. Most GI diagnoses decreased in 2020, with a few exceptions including alcoholic liver disease (increased by 7.8% as a principal diagnosis) and acute liver failure (increased by 11.6% as a secondary diagnosis). The mortality rate of hospitalizations with GI disease increased in 2020 compared with 2019 (for principal diagnosis: adjusted odds ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001; for secondary diagnosis: adjusted odds ratio 1.10, 95% confidence interval 1.07-1.13, P < 0.001). Most GI procedures decreased except for a notable 8.3% increase in gastrostomy. The per-GI-hospitalization rate of procedures increased for hospitalizations with a principal GI diagnosis (56.4% vs 55.6%, P = 0.003) or unchanged for hospitalizations with secondary GI diagnoses (18.3% vs 18.2%, P = 0.512). CONCLUSION: The COVID-19 pandemic resulted in a decrease in the volume of GI hospitalizations and procedures in 2020, but there was an increase in the mortality rate and some specific diagnoses including alcoholic liver disease and acute liver failure. These findings will likely enlighten future research and healthcare resource allocation for GI diseases.

Effect of aspirin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from randomized controlled trials and real-world studies.

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The across studies results show that aspirin use associated with lower incidence of PCa (RR: 0.96, 95% CI: 0.95-0.98), and reduced mortality (RR: 0.88, 95% CI: 0.82-0.95). The results of the subgroup analysis indicated that both cohort and population studies in the Americas showed a reduction in PCa incidence and mortality with aspirin use. A linear correlation was observed between dosage/duration of aspirin use and its protective effect. Additionally, post-diagnosis aspirin use was associated with decreased risk of PCa mortality. CONCLUSIONS: This meta-analysis revealed an independent correlation between the use of aspirin and reductions in both the incidence and mortality rates of PCa. However, randomized controlled trials did not find any association between aspirin use and PCa. Furthermore, the impact of aspirin on PCa occurrence was found to be dependent on both dosage and duration.

Does aspirin reduce the incidence, recurrence, and mortality of hepatocellular carcinoma? A GRADE-assessed systematic review and dose-response meta-analysis.

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71-0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65-0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60-0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02-1.20). CONCLUSIONS: This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.

Short-term exposure to ambient ozone and cardiovascular mortality in China: a systematic review and meta-analysis.

Air pollution is a major public health concern in China. Notwithstanding this, there is limited evidence regarding the impact of short-term exposure to ambient ozone on cardiovascular mortality in the Chinese population. Therefore, we conducted this meta-analysis to address this important question. The random-effects model was applied to pool the results from individual studies. Finally, 32 effect estimates extracted from 19 studies were pooled in this meta-analysis. The pooled relative risk for cardiovascular mortality for each 10 µg/m3 increment in ozone concentration was 1.0068 (95% CI: 1.0049, 1.0086). Ths significant positive association between ozone exposure and cardiovascular mortality was also observed in different two-pollutant models. This meta-analysis revealed that exposure to ozone was associated with an increased risk of cardiovascular mortality in China, and more efforts on controlling the population from ozone are needed to improve cardiovascular health of Chinese population.

Mycorrhizal symbiosis promotes the nutrient content accumulation and affects the root exudates in maize.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are a group of important symbiotic microorganisms found in ecosystems. Maize is the second most produced food crop globally. To investigate the mechanisms by which mycorrhizal symbiosis improves maize yields, the effects of mycorrhizal symbiosis on root vigor, nutrient accumulation in various tissues, and root exudates were investigated. We propose the following hypothesis: The secretion of organic acids in root exudates has antagonistic or synergistic effects, which are related to the rhizosphere environment. AMF symbiosis will enhance this effect. RESULT: Rhizophagus aggreatus, Claroideoglomus etunicatum, and Funneliformis mosseae were used to inoculate maize plants separately; meanwhile, maize was inoculated with the above three fungi together for another processing. The plant tissues were sampled at five growth stages: V12 (twelve-leaf), VT (Tassel), R1 (Silking), R2 (Blister), and R4 (Dough stage). The root vigor, and nutrient content in different maize organs and organic acids in root exudates were determined in these stages. The results show that mycorrhizal symbiosis significantly improved the root vigor of maize, especially for plants inoculated with F. mosseae. AMF symbiosis significantly increased N, P, and K accumulation. Mixed inoculation with arbuscular mycorrhizal fungi significantly promoted the accumulation of N and K in maize. P accumulation was significantly promoted by C. etunicatum inoculation. Mycorrhizal symbiosis reduced the levels of protocatechuic, vanillic, citric, and ferulic acid in maize root exudates and increased the levels of p-hydroxybenzoic and caffeic acid. Except for syringic, chlorogenic and succinic acid, the levels of other organic acids in root exudates were higher in plants inoculated with F. mosseae than in other treatments. CONCLUSION: This study demonstrates that mycorrhizal symbiosis improves root vigor and promotes nutrient accumulation at various sites; in addition, mycorrhizal symbiosis affects the content of organic acids in root exudates.

Prevalence and prognosis of increased pancreatic enzymes in patients with COVID-19: A systematic review and meta-analysis.

INTRODUCTION: The prevalence of increased pancreatic enzymes (elevated serum amylase and/or lipase) and its relationship to clinical outcomes in patients with coronavirus disease 2019 (COVID-19) infection is not known. METHODS: A systematic review and meta-analysis of relevant studies reporting prevalence and impact of increased pancreatic enzymes (defined as an elevation in amylase and/or lipase levels above the upper limit of normal [ULN] value) in COVID-19 was undertaken. RESULTS: A total of 36,496 patients from 21 studies were included for this meta-analysis. The overall prevalence and mortality for increased pancreatic enzymes (>ULN) in COVID-19 were 25.4% (95% CI, 15.8%-36.2%) and 34.6% (95% CI, 25.5%-44.4%), respectively. The overall prevalence and mortality for increased pancreatic enzymes (>3 × ULN) were 6.1% (95% CI, 3.6%-9.2%) and 39.2% (95% CI, 18.7%-61.6%), respectively. Patients with increased pancreatic enzymes, including elevated serum lipase or amylase of either type, had worse clinical outcomes, including need for ICU admission, mechanical ventilation and mortality. DISCUSSION: Increased pancreatic enzymes is frequent and may exacerbate the consequences of COVID-19 infection.

Subjective Changes of Taste and Smell in Conjunction With Anxiety and Depression Are Associated With Symptoms in Globus Patients Without Evidence of Pathologic Acid Reflux.

BACKGROUND/AIM: Patients suffering from globus often report decreased enjoyment when eating as well as a psychological abnormality. Some patients exhibit taste and smell changes (TSCs) when compared with the period before the diagnosis. The main aim of this study was to explore if TSCs and psychological abnormality are present in patients with globus, whether they are associated with the severity of throat symptoms, and the potential risk factors for globus. PATIENTS AND METHODS: A total of 116 included patients who met the Rome IV diagnostic criteria for globus had been performed 24-hour pH monitoring, and the results shown no evidence of pathologic acid reflux. Meanwhile, 125 healthy controls were enrolled in this prospective study. All subjects completed several questionnaires including the Taste and Smell Survey, the Glasgow Edinburgh Throat Scale, the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD). Multiple logistic regression was performed to explore the potential risk factors for globus. The study protocol was registered on the Chinese Clinical Trial Registry (No. ChiCTR-2100044972). RESULTS: First, globus patients without evidence of pathologic acid reflux exhibited a 58.62% and 31.03% change in taste and smell, respectively, while their levels of anxiety and depression were 51.72% and 44.83%, respectively. Second, there was a significant difference in the taste score (Z=-4.954, P<0.001) and smell score (Z=-4.552, P<0.001) between globus group patients and healthy controls. Similarly, globus group patients had a higher HAMA score (9.52±2.437 vs. 3.12±1.059, t=6.867, P<0.001) and HAMD score (9.79±2.931 vs. 3.16±1.650, t=6.416, P<0.001) when compared with the healthy controls. Third, in globus group patients, the Glasgow Edinburgh Throat Scale was significantly correlated with the taste score (Spearman ρ=0.782; P<0.001), smell score (Spearman ρ=0.582; P=0.001), HAMA (Spearman ρ=0.676; P<0.001), and HAMD (Spearman ρ=0.672; P<0.001). In addition, the taste score was significantly correlated with HAMA (Spearman ρ=0.532; P=0.004) and HAMD (Spearman ρ=0.681; P<0.001), while the smell score was significantly correlated with HAMD (Spearman ρ=0.392; P=0.035). Finally, multivariate logistic regression revealed that TSCs, anxiety, and depression were significant independent risk factors for globus, with depression exhibiting the highest degree of association (odds ratio: 3.244). CONCLUSIONS: TSCs and psychological comorbidities are prominent in globus patients without evidence of pathologic acid reflux. The obtained results indicated that there is a strong relationship between TSCs, psychological comorbidities, and globus. Therefore, awareness of this high prevalence of TSCs and psychological disorder may help to better understand the severity of throat symptoms.

Placebo Response Rates in Acupuncture Therapy Trials for Functional Dyspepsia: A Systematic Review and Meta-Analysis.

BACKGROUND: Functional dyspepsia (FD) is a functional digestive disease with limited management selection. Previous studies revealed that acupuncture therapy is effective for FD. However, because sham controls were not implemented in most clinical trials following acupuncture therapy, it is difficult to differentiate overall treatment responses from placebo. This study aims to quantify placebo responses in clinical trials in which FD patients received sham manual acupuncture (MA) and sham electroacupuncture (EA). MATERIALS AND METHODS: Randomized controlled trials of MA and EA for FD patients were searched in PubMed, Web of Science, Cochrane Library, and Embase databases, as well as 4 Chinese language databases from inception to January 2021. RevMan 5.20 software was used for pooled analysis of symptom scores and quality of life. The symptom scores were combined using standard mean difference (SMD) or weighted mean difference (WMD) with a 95% confidence interval (CI). The quality of included studies was tested using modified Jadad scale and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. Egger's test, Begg's test, and sensitivity analyses were conducted using Stata 11.0 statistical software. The protocol of this study is registered in PROSPERO as CRD42021233858. RESULTS: After screening, the current systematic review included 13 randomized controlled trials, of which 8 studies were used in the meta-analysis. Regarding subjective outcomes, the combined effect of sham MA on FD symptoms was [SMD=-0.42, 95% CI (-0.72, -0.12); P=0.005], whereas sham EA treatment was [SMD=-0.54, 95% CI (-0.81, -0.27); P<0.001]. The combined effect on FD quality of life of post-sham MA group was [SMD=-0.32, 95% CI (-0.52, -0.12); P=0.002]. With regard to objective outcomes, the combined effect of sham EA on dominant frequency was [WMD=-0.11, 95% CI (-0.30, -0.08); P=0.24], while the combined effect of sham EA on dominant power was [WMD=-3.35, 95% CI (-8.04, 1.35); P=0.16]. CONCLUSIONS: Sham MA and sham EA remarkably improve symptoms and quality of life scores of FD without influencing objective outcomes, highlighting the significance of sham controls in acupuncture therapy clinical trials.

Combined systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) predicts chemotherapy response and prognosis in locally advanced gastric cancer patients receiving neoadjuvant chemotherapy with PD-1 antibody sintilimab and XELOX: a prospective study.

BACKGROUND: Previous studies have confirmed that systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) can predict the prognosis and chemotherapy efficacy of various malignant tumors. However, to the best of our knowledge, no study investigated the SII combined with PNI score to predict the efficacy of anti-programmed death 1 (anti-PD-1) antibody sintilimab and XELOX regimen (capecitabine plus oxaliplatin) in the treatment of locally advanced gastric cancer. This study aims to evaluate the predictive value of pre-treatment SII-PNI score on the sensitivity of sintilimab immunotherapy combined with XELOX chemotherapy in patients with locally advanced gastric cancer. METHODS: We registered a prospective clinical study involving 30 locally advanced gastric cancer patients from March 2020 to July 2021. The pre-treatment SII and PNI were calculated from peripheral blood samples, and the cut-off value was calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 568.5) and low PNI (≤ 52.7); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI. RESULTS: All patients were evaluated by RECIST1.1 criteria after four cycles of sintilimab immunotherapy combined with XELOX chemotherapy, including 5 patients with TRG 3 and 25 patients with non-TRG 3. The SII-PNI score of non-TRG 3 patients was significantly lower than that of TRG 3 patients (P = 0.017). The medial progression free survival of patients with low SII-PNI score was significantly better than that of patients with high SII-PNI score (P < 0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting progression-free survival (P = 0.003). CONCLUSION: The pre-treatment SII-PNI score is a significant indicator for predicting chemosensitivity of locally advanced patients after sintilimab immunotherapy combined with XELOX chemotherapy, which can help to identify high-risk groups and predict prognosis. TRIAL REGISTRATION: The registered name of the trial is "Prospective clinical study of sintilimab combined with chemotherapy for neoadjuvant therapy in locally advanced gastric cancer". Its Current Controlled Trials number is ChiCTR2000030414. Its date of registration is 01/03/2020.

Effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced GIST.

BACKGROUND: Currently, the effect of skeletal muscle loss during neoadjuvant imatinib therapy on clinical outcomes in patients with locally advanced gastrointestinal stromal tumors (LA-GIST) remains unclear. This study aims to investigate the relationship between changes in skeletal muscle and postoperative complications, survival and tumor response in patients with LA-GIST during neoadjuvant therapy with imatinib. METHODS: We retrospectively analyzed pre- and post-treatment computed tomography images of 57 GIST patients who underwent radical surgery after neoadjuvant therapy with imatinib from January 2013 to March 2019. Skeletal muscle index (SMI) was measured at the L3 vertebral level in all patients. A cut-off value (SMI < 52.3 cm2/m2 and < 38.6 cm2/m2 for men and women, respectively) published in a previous study was used to define sarcopenia. Based on gender, we defined ΔSMI (%)/250 days above 9.69% for men and ΔSMI (%)/250 days above 7.63% for women as significant muscle loss (SML). Factors associated with postoperative complications and tumor response were analyzed using logistic regression, and predictors affecting patient prognosis were analyzed using Cox regression. RESULTS: Of the 57 patients, sarcopenia was present before and after neoadjuvant therapy in 20 (35.09%) and 28 (49.12%) patients, respectively. It was not associated with immediate or long-term clinical outcomes. However, patients with SML during neoadjuvant therapy had a higher incidence of postoperative complications (60.00% vs. 25.00%, p = 0.008), worse pathological regression (44.00% vs. 75.00%, p = 0.017) and worse 3-year survival (Male, 68.75% vs. 95.45%, p = 0.027; Female, 66.67% vs. 100.00%, p = 0.046) than patients without SML. CONCLUSION: The development of SML during neoadjuvant therapy in LA-GIST patients, rather than pre- and post-treatment sarcopenia, is a major prognostic factor for the long-term prognosis and is also associated with recent postoperative complication rates and pathological regression.

Does aspirin have an effect on risk of death in patients with COVID-19? A meta-analysis.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has shown unprecedented impact world-wide since the eruption in late 2019. Importantly, emerging reports suggest an increased risk of thromboembolism development in patients with COVID-19. Meanwhile, it is found that aspirin reduced mortality in critically ill patients with non-COVID-19 acute respiratory distress syndrome. Therefore, a meta-analysis was performed to investigate the effects of aspirin on COVID-19 mortality. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. Random effects models were used to calculate pooled relative risks (RRs) with 95% confidence intervals (Cis) to estimate the effect of aspirin on COVID-19 mortality. Relevant subgroup analyses and sensitivity analyses were also performed. RESULTS: The results showed that aspirin use was associated with a reduction in COVID-19 mortality (adjusted RR 0.69; 95% CI 0.50-0.95; P < 0.001). Subgroup analysis found that the low-dose group was associated with a reduced COVID-19 mortality (adjusted RR 0.64; 95% CI 0.48-0.85; P < 0.01). Aspirin use was associated with reduced COVID-19 mortality in Europe and America (crude RR 0.71; 95% CI 0.52-0.98; P = 0.04), and results from cohort studies suggested that aspirin use was a protective factor for COVID-19 mortality (adjusted RR 0.73; 95% CI 0.52-0.99; P = 0.04). Meanwhile, aspirin use was not associated with bleeding risk (crude RR 1.22; 95% CI 0.80-1.87; P = 0.96). CONCLUSIONS: This meta-analysis found that aspirin use was associated with a reduction in mortality in patients with COVID-19 and not with an increased risk of bleeding.

Combined exposure to multiple metals on cardiovascular disease in NHANES under five statistical models.

BACKGROUND: It is well-documented that heavy metals are associated with cardiovascular disease (CVD). However, there is few studies exploring effect of metal mixture on CVD. Therefore, the primary objective of present study was to investigate the joint effect of heavy metals on CVD and to identify the most influential metals in the mixture. METHODS: Original data for study subjects were obtained from the National Health and Nutrition Examination Survey. In this study, adults with complete data on 12 kinds of urinary metals (antimony, arsenic, barium, cadmium, cobalt, cesium, molybdenum, mercury, lead, thallium, tungsten, and uranium), cardiovascular disease, and core covariates were enrolled. We applied five different statistical strategies to examine the CVD risk with metal exposure, including multivariate logistic regression, adaptive elastic net combined with Environmental Risk Score, Quantile g-computation, Weighted Quantile Sum regression, and Bayesian kernel machine regression. RESULTS: Higher levels of cadmium, tungsten, cobalt, and antimony were significantly associated with Increased risk of CVD when covariates were adjusted for multivariate logistic regression. The results from multi-pollutant strategies all indicated that metal mixture was positively associated with the risk of CVD. Based on the results of multiple statistical strategies, it was determined that cadmium, tungsten, cobalt, and antimony exhibited the strongest positive correlations, whereas barium, lead, molybdenum, and thallium were most associated with negative correlations. CONCLUSION: Overall, our study demonstrates that exposure to heavy metal mixture is linked to a higher risk of CVD. Meanwhile, this association may be driven primarily by cadmium, tungsten, cobalt, and antimony. Further prospective studies are warranted to validate or refute our primary findings as well as to identify other important heavy metals linked with CVD.