Flexocatalytic Reduction of Tumor Interstitial Fluid/Solid Pressure for Efficient Nanodrug Penetration.

The practical efficacy of nanomedicines for treating solid tumors is frequently low, predominantly due to the elevated interstitial pressure within such tumors that obstructs the penetration of nanomedicines. This increased interstitial pressure originates from both liquid and solid stresses related to an undeveloped vascular network and excessive fibroblast proliferation. To specifically resolve the penetration issues of nanomedicines for tumor treatment, this study introduces a holistic "dual-faceted" approach. A treatment platform predicated on the WS2/Pt Schottky heterojunction was adopted, and flexocatalysis technology was used to disintegrate tumor interstitial fluids, thus producing oxygen and reactive oxygen species and effectively mitigating the interstitial fluid pressure. The chemotherapeutic agent curcumin was incorporated to further suppress the activity of cancer-associated fibroblasts, minimize collagen deposition in the extracellular matrix, and alleviate solid stress. Nanomedicines achieve homologous targeting by enveloping the tumor cell membrane. It was found that this multidimensional strategy not only alleviated the high-pressure milieu of the tumor interstitium─which enhanced the efficiency of nanomedicine delivery─but also triggered tumor cell apoptosis via the generated reactive oxygen species and modulated the tumor microenvironment. This, in turn, amplified immune responses, substantially optimizing the therapeutic impacts of nanomedicines.

Multivariable non-singular terminal composite sliding mode control of gas-water-coal mixture lifting system.

In order to ensure the stability of flow rate and valve pressure difference during gas-water-coal mixture lifting, a multivariable non-singular terminal composite sliding mode (MNTCSM) controller based on accurate feedback linearization is proposed. The multi-input multi-output nonlinear system with time delay and coupling is transformed into a multi-input multi-output uncoupled linear system by using an improved Smith predictor and accurate feedback linearization. At the same time, the MNTCSM controller is designed to make the flow and pressure tracking errors of the decoupling system converge to zero in a finite time. Finally, simulations and experiments are designed for different control methods to verify the feasibility and effectiveness of the proposed scheme.

RNA-seq revealed the anti-pyroptotic effect of suramin by suppressing NLRP3/caspase-1/GSDMD pathway in LPS-induced MH-S alveolar macrophages.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), acting as one common sepsis-associated organ injury, induces uncontrolled and self-amplifies pulmonary inflammation. Given the lack of clinically effective approaches, the mortality rate of it still remains high. Suramin(SUR), as an antiparasitic drug initially, was found to ameliorate sepsis associated ALI in our previous work. However, the underlying mechanism of its protective effects has not been clarified. Pyroptosis, categorized as an inflammatory form of programmed cell death, could aggravate lung inflammatory responses via inducing alveolar macrophages (AM) pyroptosis. METHODS: MH-S AM cell line was stimulated with or without lipopolysaccharide (LPS) or suramin, and the differential expression genes (DEGs) were excavated using RNA sequencing (RNA-seq). To identify the regulatory roles of these genes, pyroptosis-related genes (PRGs), GO/KEGG and GSEA analysis were conducted. We also performed WB, qRTPCR and ELISA to validate the RNA-seq results and further expound the protective effect of suramin. RESULTS: 624 DEGs were identified between control (CON) and lipopolysaccharide (LPS) groups, and enrichment analysis of these genes revealed significantly enriched pathways that related to immune system and signal transduction. Meanwhile, 500 DEGs were identified in LPS/SUR+LPS group. In addition to the pathways mentioned above, IL-17 pathway and C-type lectin receptor signaling pathway were also enriched. All 6 pathways were connected with pyroptosis. Concurrently, the "DESeq2" R package was used to identify differentially expressed PRGs. Nod1, Nod2, interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF), NLRP3 were upregulated under LPS stimulation. Then, in SUR+LPS group, Nod2, IL-6, IL-1b, NLRP3 were downregulated. The validation results of WB, qRT-PCR, and ELISA showed: the protein and mRNA expression levels of NLRP3, caspase-1, GSDMD and the concentrations of IL-1b, IL-18 were decreased when treated with suramin and LPS. CONCLUSION: Suramin could inhibit NLRP3/caspase-1/GSDMD canonical pyroptosis pathway in LPS-induced MH-S alveolar macrophages.

Liver-Inspired Polyetherketoneketone Scaffolds Simulate Regenerative Signals and Mobilize Anti-Inflammatory Reserves to Reprogram Macrophage Metabolism for Boosted Osteoporotic Osseointegration.

Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti-inflammatory reserve (arginase-2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase-2 in the anti-inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti-inflammatory reserves in bone regeneration.

Finite element analysis of screw fixation durability under multiple boundary and loading conditions for a custom pelvic implant.

Despite showing promising functional outcomes for pelvic reconstruction after sarcoma resection, custom-made pelvic implants continue to exhibit high complication rates due to fixation failures. Patient-specific finite element models have been utilized by researchers to evaluate implant durability. However, the effect of assumed boundary and loading conditions on failure analysis results of fixation screws remains unknown. In this study, the postoperative stress distributions in the fixation screws of a state-of-the-art custom-made pelvic implant were simulated, and the risk of failure was estimated under various combinations of two bone-implant interaction models (tied vs. frictional contact) and four load cases from level-ground walking and stair activities. The study found that the average weighted peak von Mises stress could increase by 22-fold when the bone-implant interactions were modeled with a frictional contact model instead of a tied model, and the likelihood of fatigue and pullout failure for each screw could change dramatically when different combinations of boundary and loading conditions were used. The inclusion of additional boundary and loading conditions led to a more reliable analysis of fixation durability. These findings demonstrated the importance of simulating multiple boundary conditions and load cases for comprehensive implant design evaluation using finite element analysis.

A Single Aptamer-Dependent Sandwich-Type Biosensor for the Colorimetric Detection of Cancer Cells via Direct Coordinately Binding of Bare Bimetallic Metal-Organic Framework-Based Nanozymes.

A typical colorimetric sandwich-type sensor relies on dual antibodies/aptamers to specifically visualize the targets. The requirement of dual antibodies/aptamers and low signal intensity inevitably increases the design difficulty and compromises the sensing sensitivity. In this work, a novel sandwich-type aptasensor was developed using single aptamer-functionalized magnetic nanoparticles as a specific recognition unit to target cancer cells and a bimetallic metal-organic frameworks (MOFs)-based nanozymes as a colorimetric signal amplification unit. The well-defined crystalline structure of UIO-66 MOFs enabled the introduction of Fe/Zr bimetal nodes, which possessed integrated properties of the peroxidase-like nanozyme activity and direct coordinately binding to the cell surface. Such a novel construction strategy of sandwich-type aptasensors achieved simple, sensitive, and specific detection of the target cancer cells, which will inspire the development of biosensors.

Changes in psoas muscle size and ambulatory function after internal hemipelvectomy without reconstruction.

Internal hemipelvectomy without reconstruction of the pelvis is a viable treatment for pelvic sarcoma; however, the time it takes to return to excellent function is quite variable. Some patients require greater time and rehabilitation than others. To determine if psoas muscle recovery is associated with changes in ambulatory function, we retrospectively evaluated psoas muscle size and limb-length discrepancy (LLD) before and after treatment and their correlation with objective functional outcomes. T1-weighted MR images were evaluated at three intervals for 12 pelvic sarcoma patients following interval hemipelvectomy without reconstruction. Correlations between the measured changes and improvements in Timed Up and Go test (TUG) and gait speed outcomes were assessed both independently and using a stepwise multivariate regression model. Increased ipsilesional psoas muscle size from three months postoperatively to latest follow-up was positively correlated with gait speed improvement (r = 0.66). LLD at three months postoperatively was negatively correlated with both TUG (r = -0.71) and gait speed (r = -0.61). This study suggests that psoas muscle strengthening and minimizing initial LLD will achieve the greatest improvements in ambulatory function. LLD and change in hip musculature remain substantial prognostic factors for achieving the best clinical outcomes after internal hemipelvectomy. Changes in psoas size were correlated with the amount of functional improvement. Several patients in this study did not return to their preoperative ipsilateral psoas size, indicating that monitoring changes in psoas size could be a beneficial rehabilitation strategy.

A dual-responsive "Yin-Yang" photothermal delivery system to accelerate Parthenolide anti-tumor efficacy.

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.

Icaritin-elevated circ_0000190 suppresses the malignant progression of multiple myeloma by targeting miR-301a.

Icaritin has potential anticancer effects on various cancers, including multiple myeloma (MM). Recent studies claim that Icaritin can regulate the expression of noncoding RNAs (ncRNAs) in cancer development. This study aimed to investigate the role of circular RNA_0000190 (circ_0000190) and functional mechanism in Icaritin-treated MM. The expression of circ_0000190 and miR-301a was detected by quantitative real-time polymerase chain reaction. Cell cycle, apoptosis, migration, and invasion were investigated using flow cytometry assay, and transwell assay, respectively. The expression of BAX, BCL2, MMP2, and CCND1 was detected by western blot. The predicted target relationship between circ_0000190 and miR-301a was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The activation of JAK1/STAT3 pathway was examined using western blot. Circ_0000190 was strikingly downregulated in MM specimens and cell lines, and Icaritin promoted the expression of circ_0000190. In function, circ_0000190 overexpression promoted MM cell cycle arrest and apoptosis but restrained the ability of migration and invasion. Icaritin blocked the development of MM by increasing circ_0000190 expression. MiR-301a was identified as a target of circ_0000190, and miR-301a reintroduction largely abolished the effects of circ_0000190 overexpression. The activation of JAK1/STAT3 pathway was promoted by miR-301a restoration. Icaritin played anticancer effects in MM partly by enhancing the expression of circ_0000190 and regulating the circ_0000190/miR-301a pathway. This study enhanced the understanding of the mechanism of Icaritin associated with circRNAs in MM.

MRI characteristics and correlation with pathology of an unusual inflammatory myofibroblastic tumor of the bladder.

We report a case of inflammatory myofibroblastic tumor of the bladder (IMTB) that arises from left posterior bladder wall. The IMTB usually demonstrates slight hypointensity on T1WI, heterogeneous bright hyperintensity on T2WI, hyperintensity on DWI, and no restricted diffusion on ADC map. IMTB exhibits irregular ring enhancement and scatters stripe-like enhancement in central area with progressive and persistent enhancement pattern on CE-MRI. High-contrast multisequence MRI may be a potential technique to distinguish IMTB from other bladder tumors.

Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats.

This study was designed to evaluate the gastroprotective activity of cirsilineol in hydrochloric acid (HCl)/ethanol-induced gastric ulcer model. Cirsilineol was administered at the doses of 20 and 40 mg/kg in HCl/ethanol-induced rats. The gastroprotective ability was verified by determining the ulcer score, total acidity, hemoglobin, inflammatory cytokines, lipid peroxides, and enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) in gastric tissue and serum biochemical analysis. The results showed a favorable increase in the hemoglobin level, antioxidant enzymes (SOD and CAT), restored electrochemical balance (carbon dioxide & anion gap) while a noticeable decrease in ulcer index, total acidity, lipid peroxides, inflammatory cytokines (interleukin-1 beta [IL-1ß], IL-6, and tumor necrosis factor alpha) in rats treated with the cirsilineol. The serum biochemical analysis on liver markers (alkaline phosphatases, alanine aminotransferase, and aspartate aminotransferase), kidney markers (urea, creatinine, albumin, globulin, total protein), and lipid profile (triglyceride, high-density lipoprotein, total cholesterol) were attenuated by cirsilineol treatment in rats. Histopathology showed enhanced gastric protection and preserved the integrity of gastric mucosa upon cirsilineol administration. These results ultimately suggest that cirsilineol has gastroprotective effects that prevent the development of gastric ulcer.

Index-based dietary patterns and stomach cancer in a Chinese population.

OBJECTIVES: Dietary factors are of importance in the development of stomach cancer. This study aims to examine index-based dietary patterns associated with stomach cancer in a Chinese population. METHODS: Using data from a population-based case-control study conducted in Jiangsu Province, China, we included a total of 8432 participants (1900 stomach cancer cases and 6532 controls). Dietary data collected by food frequency questionnaire was evaluated by modified Chinese Healthy Eating Index-2016 (mCHEI-2016) and the US Healthy Eating Index-2015 (HEI-2015). Multiple logistic regression analyses were applied to examine the association of mCHEI-2016 and HEI-2015 with stomach cancer while adjusting for potential confounders. The possible interactions between mCHEI-2016 or HEI-2015 and established risk factors were explored. RESULTS: Among nonproxy interviews, after adjusting for potential confounding factors, a higher score of sodium, reflecting lower intake per day, was inversely associated with stomach cancer [odds ratio (OR), 0.95; 95% CI, 0.91-0.99 for mCHEI-2016; OR, 0.97; 95% CI, 0.94-0.99 for HEI-2015]. No clear associations with stomach cancer were identified for total scores of HEI-2015 (OR, 0.98; 95% CI, 0.87-1.10 with a 10-point increase, P trend = 0.98) and mCHEI-2016 (OR, 1.05; 95% CI, 0.94-1.17 with a 10-point increase, P trend = 0.22). However, the relation between stomach cancer and the mCHEI-2016 was modified by BMI, with a possible inverse association in normal-weight subjects. CONCLUSIONS: Our findings highlight that reduced intake of dietary sodium would prevent the development of stomach cancer. The data indicate a heterogeneity between normal weight and overweight's dietary factors in relation to stomach cancer.

Dietary Intake of Fatty Acids, Total Cholesterol, and Stomach Cancer in a Chinese Population.

To investigate the associations between dietary fatty acids and cholesterol consumption and stomach cancer (SC), we analyzed data from a population-based case-control study with a total of 1900 SC cases and 6532 controls. Dietary data and other risk or protective factors were collected by face-to-face interviews in Jiangsu Province, China, from 2003 to 2010. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple unconditional logistic regression models and an energy-adjusted method. The joint associations between dietary factors and known risk factors on SC were examined. We observed positive associations between dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and total cholesterol and the development of SC, comparing the highest versus lowest quarters. Increased intakes of dietary SFAs (p-trend = 0.005; aOR, 1.11; 95% CI, 1.01-1.22 with a 7 g/day increase as a continuous variable) and total cholesterol (p-trend < 0.001; aOR, 1.13; 95% CI, 1.06-1.22 with a 250 mg/day increase as a continuous variable) were monotonically associated with elevated odds of developing SC. Our results indicate that dietary SFAs, MUFAs, and total cholesterol are associated with stomach cancer, which might provide a potential dietary intervention for stomach cancer prevention.

Relationships between marijuana use, severity of marijuana-related problems, and health-related quality of life.

Studies on the relationships between marijuana use and quality of life have reported mixed findings. Based on a survey of 123 marijuana users conducted in Los Angeles during 2017-2018, we investigated the relationships between marijuana use frequency, severity of marijuana-related problems, and health-related quality of life (HRQoL). Results indicated that (1) marijuana use frequency was positively related to severity of marijuana-related problems; (2) severity of marijuana-related problems was negatively related to mental domain of HRQoL but was not significantly related to physical domain of HRQoL; and (3) marijuana use frequency was positively associated with mental health symptoms and physical health conditions, and both in turn were negatively linked to mental and physical domains of HRQoL, respectively. Reduction of marijuana-related problems and mitigation of mental and physical health problems may improve HRQoL among marijuana users. The study findings may contribute to developing treatment interventions for marijuana use that simultaneously address marijuana-related problems and associated mental and physical issues.

Escalating Opioid Dose Is Associated With Mortality: A Comparison of Patients With and Without Opioid Use Disorder.

OBJECTIVE: Prescription Drug Monitoring Programs (PDMPs) are intended to help reduce prescription drug misuse and opioid overdose, yet little is known about the longitudinal patterns of opioid prescribing that may be associated with mortality. This study investigated longitudinal opioid prescribing patterns among patients with opioid use disorder (OUD) and without OUD in relation to mortality using PDMP data. METHODS: Growth modeling was used to examine opioid prescription data from the California PDMP for a 4-year period before death or a comparable period ending in 2014 for those remaining from a sample of 7728 patients (2576 with OUD, and 5152 matched non-OUD controls) treated in a large healthcare system. RESULTS: Compared to controls, individuals with OUD (alive and deceased) had received significantly more opioid prescriptions, greater number of days' supply, and steeper increases of opioid dosages over time. For morphine equivalents (ME, in grams), the interaction of OUD and mortality was significant at both intercept (ß = 10.4, SE = 4.4, P < 0.05) and slope (ß = 6.0, SE = 1.1, P < 0.001); deceased OUD patients demonstrated the sharpest increase (ie, an average yearly increment of 7.84 grams over alive patients without OUD) and ended with the highest level of opioids prescribed before they died (ie, 20.2 grams higher). Older age, public health insurance, cancer, and chronic pain were associated with higher number and dose of opioid prescriptions. CONCLUSIONS: Besides the amount of prescriptions, clinicians must be alert to patterns of opioid prescription such as escalating dosage as critical warning signals for heightened mortality risks, particularly among patients with OUD.

Reduction in Cannabis Use and Functional Status in Physical Health, Mental Health, and Cognition.

Treatment for substance use disorders has traditionally been abstinence-oriented, but evaluating the merits of low-level cannabis use as potential treatment endpoint may identify benefits that are clinically relevant for treatment-seeking individuals who do not attain abstinence. This study explores if reduction in cannabis use to a lower level of use is related to improved physical health, mental health, and perceived cognitive functions. Study participants with a history of problematic cannabis use (n = 111) completed assessments. Regression models were used to explore the relationship between past 30-day cannabis use levels (abstinent [57%], low use [22%] defined as less than or equal to 3 days per week, and heavy use [22%] defined as 4 or more days of use per week) and functional status in physical health, mental health, and cognition. Compared to heavy users, both abstinent and low-use individuals were similarly associated with better global health, appetite, and depression outcomes. Abstinent users also reported improved sleep, anxiety, and self-reported cognitive functioning relative to heavy users. Thus, reduction in cannabis use to lower levels is associated with beneficial outcomes important to health and other areas of functioning in individuals with problematic cannabis use.

Reductions in cannabis use are associated with improvements in anxiety, depression, and sleep quality, but not quality of life.

AIMS: This study examined the longitudinal association between reductions in cannabis use and changes in anxiety, depression, sleep quality, and quality of life. METHODS: Secondary analyses were conducted based on data from a cannabis use disorder medication trial in 302 adults (ages 18-50). Changes in symptoms of anxiety and depression, sleep quality, and quality of life were assessed in relation to changes in cannabis use during the 12-week trial of treatment. RESULTS: Based on the slope of individual cannabis use trajectory, the sample was classified into two groups (Cannabis Use Reduction, n=152 vs. Cannabis Use Increase, n=150) which was included as a binary covariate in subsequent modeling. Controlling for demographics (age, gender, race/ethnicity), treatment condition, and time-varying tobacco and alcohol use, separate latent growth curve models showed a significant association between the Cannabis Use Reduction group and improvement (i.e., lower values in slope) in anxiety (ß=-0.09, SE=0.04; p<0.05), depression (ß=-0.11, SE=0.04; p<0.01), and sleep quality (ß=-0.07, SE=0.03; p<0.05) over the observation period, but not in quality of life. CONCLUSIONS: These results indicate a longitudinal relationship between reductions in cannabis use and improvements in anxiety, depression, and sleep quality. Clinicians treating patients with co-occurring cannabis use and problems with anxiety, depression, or sleep quality should attend to cannabis use reduction as a component of treatment.

High Mortality Among Patients With Opioid Use Disorder in a Large Healthcare System.

OBJECTIVES: Elevated mortality has been observed among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system. METHODS: Mortality data were linked with electronic health records of 2576 OUD patients cared for in a large university health system from 2006 to 2014. RESULTS: There were 465 deaths confirmed (18.1% of the study participants), corresponding to a crude mortality rate of 48.6 per 1000 person-years and standardized mortality ratio of 10.3 (95% confidence interval [CI] 9.4-11.3). Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer (16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV]) were the leading causes of death. HCV (hazard ratio [HR] 1.99, 95% CI 1.62-2.46) and alcohol use disorder (HR 1.27, 95% CI 1.05-1.55) were 2 clinically important indicators of overall mortality risk. Tobacco use disorder (adjusted HR [AHR] 2.58, 95% CI 1.60-4.17) was associated with increased risk of cardiovascular death, HCV infection (AHR 2.55, 95% CI 1.52-4.26) with cancer mortality risk, and HCV (AHR 1.92, 95% CI 1.03-3.60) and alcohol use disorder (AHR 5.44, 95% CI 2.95-10.05) with liver-related mortality risk. CONCLUSIONS: Patients with OUD in a general healthcare system demonstrated alarmingly high morbidity and mortality, which challenges healthcare systems to find innovative ways to identify and treat patients with substance use disorder.

Reproductive factors are associated with oesophageal cancer risk: results from a meta-analysis of observational studies.

To further evaluate the association between reproductive events and the development of oesophageal cancer, we searched relevant studies using electronic databases (PubMed, ISI Web of Science). Study-specific relative risks with corresponding 95% confidence intervals (CI) in all analyses were used and multiple summary relative risk (SRR) estimates were calculated. We carried out subgroup analyses and used meta-regression techniques to explore potential sources of heterogeneity. Sensitivity analysis was carried out to identify whether pooled results were influenced by individual studies and publication bias was assessed by Begg's funnel plots and the Egger regression asymmetry test. Fourteen studies were eligible for inclusion in the meta-analysis, summarizing a total of 3816 oesophageal cancer cases. We found that age at menopause (SRR=0.70; 95% CI: 0.51-0.95) and hormone replacement therapy (SRR=0.67; 95% CI: 0.56-0.81) had an association with a decreased risk of oesophageal cancer. A similar result was obtained for parity (SRR=0.79; 95% CI: 0.71-0.89) and ever breastfeeding (SRR=0.65; 95% CI: 0.43-0.97). In contrast, postmenopausal status was associated with increased risk (SRR=1.65; 95% CI: 1.28-2.14). No statistically significant link was found with other exposures. Our meta-analysis supports the substantial influence of reproductive factors, which could be causally linked to oesophageal cancer.