AIM: To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice. METHODS: Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice. After acteoside administration in DBA/2J mice, anterior segment observation, intraocular pressure (IOP) monitoring, electrophysiology examination, and hematoxylin and eosin staining were used to analyze any potential effects. Immunohistochemistry (IHC) assays were used to verify the proteomics results. Furthermore, retinal ganglion cell 5 (RGC5) cell proliferation was assessed with cell counting kit-8 (CCK-8) assays. Serta domain-containing protein 4 (Sertad4) mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis, respectively. RESULTS: Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein. Compared with the saline group, the acteoside treatment group showed decreased IOP, improved N1-P1 wave amplitudes, thicker retina, and larger numbers of cells in the ganglion cell layer (GCL). The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group. Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury. CONCLUSION: Sertad4 is differentially expressed in DBA/2J mice. Acteoside can protect RGCs from damage, possibly through the downregulation of Sertad4, and has a potential use in glaucoma treatment.

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Objective: To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system. Methods: This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis. Results: The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×109/L, 1.41×109/L, and 355×109/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS (P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival (P<0.05), but not progression-free survival (P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%-75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion: This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Short-course radiotherapy (SCRT) based Total Neoadjuvant Therapy (TNT) has been used for the treatment of locally advanced rectal cancer (LARC). However, studies show that the pCR rate of patients still hovers around 20%. It has been found that radiation therapy possess synergistic anticancer effects with immune checkpoint inhibitor therapy by altering the tumor immune microenvironment (TIME). Therefore, this phase II clinical trial (ClinicalTrials.gov identifier: NCT05086627) we aimed to evaluate the efficacy and safety of SCRT based TNT combined with tislelizumab in LARC patients. This is a prospective, open-label, single-center, phase II randomized controlled trial. Patients initially diagnosed with rectal cancer cT1-2N+M0 or cT3-4NanyM0 were recruited and underwent total mesorectal excision (TME) surgery after completing neoadjuvant therapy. Control group patients received SCRT (25Gy/5f) followed by four cycles of CapeOX. And trial group patients received an additional intravenous infusion of 200mg tislelizumab on the first day of each cycle of CapeOX. Mismatch repair (MMR) and microsatellite instability (MSI) tests were performed in all cases. Adverse events (AEs) were recorded and follow-up was performed for 36 months. The pathological complete response (pCR) rate was set as the primary endpoint, and the major pathologic response (MPR, TRG0+TRG1), 3-year PFS, 3-year OS and treatment safety were set as the secondary endpoints. A total of 63 patients were recruited, of which 49 completed the study protocol, including 23 in the control group and 26 in the trial group. All patients had pMMR/MSS status except for 1 patient with pMMR/MSI-H. In the control group, 22 patients received surgical treatment, and 6 patients achieved pCR (26.09%). In the trial group, 25 patients received surgical treatment, and 16 patients achieved pCR (61.54%). SCRT based TNT combined with tislelizumab followed by TME surgery exhibited a favorable pCR in LARC. A multicenter, double-blind, randomized controlled trial is warranted.

Glaucoma is the primary cause of irreversible blindness worldwide. The current treatments are primarily based on drug usage or surgical operation to reduce intraocular pressure (IOP). However, it is expensive and requires patients to insist on taking the medicine for a long time. The suprachoroidal space (SCS) is the space between the choroid and the sclera, which forms part of the uveovortex pathway in the circulation of aqueous humor. So far, it is still challenging to realize the injection of hydrogels into the SCS with long-term duration. In this work, an in situ-forming polyzwitterionic polycarboxybetaine hydrogel is designed and injected to expand SCS to increase the drainage of aqueous humor from the eye via the uveovortex pathway, thus reducing IOP for at least 6 weeks, while commercial hyaluronic acid hydrogel can only last for about 4 weeks. The clinical ophthalmological safety assessment examination shows that the treatment of polyzwitterion hydrogel is well-tolerated that leads to minimal inflammatory reaction, and histopathology assessment demonstrates that the SCS is expanded after injection of the hydrogel. Further analysis of ultrasound biomicroscopy reveals that there is a strong correlation between IOP reduction and SCS expansion. In short, the polyzwitterion hydrogel developed in this work can prolong the period of IOP reduction by expanding SCS, thus treating ocular hypertension and glaucoma without resorting to drugs or regular surgery.

Background Primary angle closure glaucoma (PACG) is the most common type of glaucoma in China. Laser peripheral iridotomy (LPI) is the primary choice to treat PAC: We aim to evaluate the changes of biometric parameters of anterior segment and to find possible biometric predictors of the effect of laser peripheral iridotomy (LPI) in primary angle closure (PAC) eyes using swept-source optical coherent tomography (OCT). Methods LPI was performed in 52 PAC eyes of 28 participants. The change of intraocular pressure and anterior segment parameters, including angle opening distance (AOD500), AOD500 area, trabecular iris space area (TISA500), TISA500 volume, trabecular iris angle (TIA500), iridotrabecular contact (ITC) index, ITC area, anterior chamber volume (ACV), anterior chamber depth (ACD), lens vault (LV) and lens thickness (LT) before and 1 week after LPI were measured by Tomey CASIA2 anterior segment OCT. We also estimate and analyze potential associated factors possibly affecting the change of anterior chamber parameters. Results No post-laser complications were found. The ACD, LV and LT did not change significantly 1 week after LPI. AOD500, AOD500 area, TISA500, TISA500 volume, TIA500, ACV increased significantly after LPI. There was significant decrease in ITC index and ITC area. LT was positively correlated to the change of ITC index (β = 0.239, *p = 0.045). Conclusions The anterior segment architecture significantly changed after LPI in PAC spectrum eyes. Crystalline lens measurements remained unchanged before and after LPI. AS-OCT can be used to follow anterior chamber parameter changes in PAC spectrum eyes. LT may play a role in the therapeutic effect of LPI.

Background Lung function is a heritable complex phenotype with obesity being one of its important risk factors. However, knowledge of their shared genetic basis is limited. Most genome-wide association studies (GWASs) for lung function have been based on European populations, limiting the generalisability across populations. Large-scale lung function GWASs in other populations are lacking. Methods We included 100 285 subjects from the China Kadoorie Biobank (CKB). To identify novel loci for lung function, single-trait GWAS analyses were performed on forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC in the CKB. We then performed genome-wide cross-trait analysis between lung function and obesity traits (body mass index (BMI), BMI-adjusted waist-to-hip ratio and BMI-adjusted waist circumference) to investigate the shared genetic effects in the CKB. Finally, polygenic risk scores (PRSs) of lung function were developed in the CKB and their interaction with BMI's association on lung function were examined. We also conducted cross-trait analysis in parallel with the CKB using up to 457 756 subjects from the UK Biobank (UKB) for replication and investigation of ancestry-specific effects. Results We identified nine genome-wide significant novel loci for FEV 1 , six for FVC and three for FEV 1 /FVC in the CKB. FEV 1 and FVC showed significant negative genetic correlation with obesity traits in both the CKB and UKB. Genetic loci shared between lung function and obesity traits highlighted important biological pathways, including cell proliferation, embryo, skeletal and tissue development, and regulation of gene expression. Mendelian randomisation analysis suggested significant negative causal effects of BMI on FEV 1 and on FVC in both the CKB and UKB. Lung function PRSs significantly modified the effect of change in BMI on change in lung function during an average follow-up of 8 years. Conclusion This large-scale GWAS of lung function identified novel loci and shared genetic aetiology between lung function and obesity. Change in BMI might affect change in lung function differently according to a subject's polygenic background. These findings may open new avenues for the development of molecular-targeted therapies for obesity and lung function improvement.

Early diagnosis and precise monitoring of the development of proliferative diabetic retinopathy (PDR) can significantly improve therapeutic strategies and help decrease blindness caused by it. Extracellular vesicles (EVs) were recently found to be involved in intercellular communications and are a potential source for the discovery of novel biomarkers. The current study aims to investigate the effectiveness of microRNAs (miRNAs) encapsulated in small EVs (sEVs) as minimally invasive biomarkers for PDR. SEVs were extracted from plasma of healthy subjects, diabetic patients, nonPDR patients and PDR patients. Then, we performed microarray analysis to determine the miRNA expression profile. MiR-431-5p expression doubled in the PDR patients compared with the healthy controls and the diabetic patients. We further found that miR-431-5p expression was 2.3 times higher in 4-hydroxynonenal treated human retinal capillary endothelial cells (HRCECs) than the control. After transfection with miR-431-5p mimics, proliferation of HRCECs was promoted, while transfection with miR-431-5p inhibitor demonstrated the opposite effect. The present findings indicate that circulating sEVs showed a differential miRNA profile in PDR patients. MiR-431-5p was involved in the pathogenesis of PDR development and may function as a novel biomarker for PDR.

Purpose: To determine the relationship between pubertal development and postpubertal gonadal function in childhood cancer survivors. Methods: Childhood cancer survivors (>= 10 years of age) who received follow-up care in a pediatric oncology group in an academic medical center during the period from January 1, 1985, to July 1, 2010 were included in this case series. Their pubertal development and gonadal function were evaluated. Results: The cohort consists of 39 males (age 10-21 years) and 35 females (age 10-29 years) with a variety of cancer diagnosis and treatments. The average age at diagnosis was similar to 7.5 years. The average age at the time of the study was 16 and 16.7 years in males and females, respectively, representing a mean follow-up interval of similar to 9 years. Despite the fact that 60% of survivors received cyclophosphamide equivalents and 16.2% received cranial radiation or brain tumor resection, the majority of survivors (68%) presented with both normal puberty and normal gonadal functions at the time of follow-up. In 27% of survivors, puberty development did not predict gonadal function in early adulthood: 20% of survivors had normal puberty, but abnormal gonadal function; 7% of survivors had abnormal puberty, but gonadal function remained normal as young adults. Conclusions: Most childhood cancer survivors had normal puberty and gonadal function despite a variety of cancer treatment modalities. However, normal puberty did not predict normal gonadal function later in life in many survivors. Therefore, close follow-up with gonadal function in adolescent and early adulthood years is essential.

Objective To comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age. Methods This study included 92 284 participants aged 39–51 years from China Kadoorie Biobank born around the famine period and without major chronic diseases at baseline. We categorised participants into non-famine births (born between 1 October 1956 and 30 September 1958, and 1 October 1962 and 30 September 1964) and famine births (born between 1 October 1959 and 30 September 1961). The outcomes were incident cardiovascular disease, cancer and respiratory system disease. Cox regression was used to estimate adjusted HR and 95% CI for famine exposure. Subgroup analyses were performed according to baseline characteristics. Results During a median 10.1 years of follow-up, we identified 4626 incident ischaemic heart disease (IHD) cases, 7332 cerebrovascular disease cases, 3111 cancer cases and 16 081 respiratory system disease cases. In the whole population, prenatal famine exposure was not statistically associated with the risks of developing any chronic diseases in adulthood. However, for urban participants, compared with non-famine births, famine births had a higher risk of cerebrovascular disease (HR 1.18; 95% CI 1.09 to 1.28); such association was not shown for rural participants (p for interaction <0.001). Also, we observed the associations of prenatal famine exposure with IHD (HR 1.15; 95% CI 1.05 to 1.26) and cerebrovascular disease (HR 1.13; 95% CI 1.05 to 1.21) in participants with lower physical activity level, but not in those with higher ones (all p for interaction=0.003). Conclusion Our findings indicate that prenatal exposure to the Chinese famine might be associated with an increased cardiovascular risk and such risk may be modified by adult lifestyle.

Spinal cord injury causes central nervous system damage. Rho inhibits axonal regeneration. This study is intended to analyze the effect of inhibition of Rho expression on axonal repair. The oligodendrocytes were isolated and divided into NC group and shRNA-RhoA group followed by analysis of the average length of axon growth and average microtubule fluorescence density by immunofluorescence, Nogo, MAG and RhoA expression were by Real time PCR. Wistar rats were separated into control group; SCI group and shRNA-RhoA group followed by analysis of the BBB scores and the Reuter score of sensory function, RhoA expression by Real time PCR and Western blot, Caspase3 activity as well as Nogo and MAG expression by Real time PCR. Compared with NC group, shRNA-RhoA group showed significantly increased average length of axon growth and average microtubule fluorescence density at the distal axon and reduced expression of RhoA, Nogo and MAG (P < 0.05). In comparison to control group, SCI group presented significantly increased RhoA expression, decreased BBB score, increased Reuter score and Caspase3 activity as well as elevated Nogo and MAG expression (P < 0.05). The shRNA-RhoA group significantly decreased RhoA expression, increased BBB score, decreased Reuter score and Caspase3 activity, and reduced Nogo and MAG expression compared with SCI group (P < 0.05). Inhibiting RhoA expression can promote axon extension and regenerative repair. Targeting RhoA reduces axon growth inhibitory factor expression, inhibits apoptosis and effectively alleviates SCI.

OBJECTIVES To explore whether lower outdoor temperature increases cardio-cerebrovascular disease risk through regulating blood pressure and whether indoor heating in winter is beneficial to prevent cardio-cerebrovascular disease in cold areas. METHODS We analyzed the data of 38 589 participants in Harbin from the China Kadoorie Biobank (CKB) during 2004-2008, with an average of 7.14-year follow-up. Linear regression analysis was performed to estimate the relationship between outdoor temperature and blood pressure. Cox regression analysis and logistic regression analysis were used to analyze the association of blood pressure with cardio-cerebrovascular event risk. Mediation analysis was performed to explore the role of blood pressure in the association between outdoor temperature and cardio-cerebrovascular events risk. RESULTS There was an increase of 6.7 mmHg in SBP and 2.1 mmHg in DBP for each 10 °C decrease in outdoor temperature when outdoor temperature was higher than 5 °C. There was an inverse association between outdoor temperature and cardio-cerebrovascular event morbidity. The increases in blood pressure and cardio-cerebrovascular event morbidity were attenuated in months when central heating was fully provided. Participants with hypertension have higher risks of cardio-cerebrovascular disease (hazard ratio 1.347; 95% CI 1.281--1.415), CVD (hazard ratio 1.347; 95% CI 1.282--1.416), MACE (hazard ratio 1.670; 95% CI 1.560--1.788) and stroke (hazard ratio 1.683; 95% CI 1.571--1.803). Mediation analysis demonstrated that the association between outdoor temperature and cardio-cerebrovascular events risk was potentially mediated by blood pressure. CONCLUSION Temperature-driven blood pressure potentially mediates the association between outdoor temperature and cardio-cerebrovascular events risk. Indoor heating in winter is probably beneficial to cardio-cerebrovascular disease prevention by inhibition of blood pressure increase.

Mesenchymal stem cells (MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles (EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique anti-inflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings.

OBJECTIVE:To explore the relationship between spicy food intake and overweight or obesity in the population, and provide theoretical basis for dietary prevention of obesity. METHODS:The data of this study was collected from the cross-sectional population of China Kadoorie Biobank(CKB) in Harbin from 2004 to 2008. A cluster random sampling method was used to select 57 555 subjects aged 30-79(23 254 males and 34 301 females). Demographic information and habits information such as smoking and drinking were obtained by face-to-face questionnaires. Food frequency questionnaires were used to obtain information on various foods including spicy food intake. Physical examination was used to obtain indicators of height and weight. Logistic regression method was used to analyze the influence of spicy food intake and its interaction with predilection for meat/vegetarian diet on the risk of overweight and obesity. RESULTS:Compared with people who intake spicy foods with low frequency, the risk of overweight and obesity in people with a high frequency of intake spicy foods increased by 29%(OR=1.285, 95%CI 1.251-1.319, P<0.001) in males and 33%(OR=1.329, 95%CI 1.294-1.364, P<0.001) in females. Compared with the people who intake spicy food with a slightly intensity, the risk of overweight and obesity in males and females with a extremely intensity of intake spicy foods increased by 20%(OR=1.198, 95%CI 1.137-1.259, P=0.011) and 19%(OR=1.194, 95%CI 1.141-1.247, P=0.003), respectively. In the male population, the risk of overweight and obesity was the highest among those who preferred meat and had high frequency and degree of spicy food intake. There was an interaction between meat/vegetarian preference and spicy food intake(P<0.001). CONCLUSION:Intake spicy food can increase the risk of overweight and obesity, while reducing the intake of spicy foods and meats can be more effective in prevent overweight and obesity.

Background Active commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population. Methods and Results A total of 104 170 urban commuters without major chronic diseases at baseline were included from China Kadoorie Biobank. Self‐reported commuting mode was defined as nonactive commuting, work at home or near home, walking, and cycling. Multivariable Cox regression was used to examine associations between commuting mode and cardiovascular disease. Overall, 47.2% of the participants reported nonactive commuting, 13.4% reported work at home or work near home, 20.1% reported walking, and 19.4% reported cycling. During a median follow‐up of 10 years, we identified 5374 incidents of ischemic heart disease, 664 events of hemorrhagic stroke, and 4834 events of ischemic stroke. After adjusting for sex, socioeconomic status, lifestyle factors, sedentary time, body mass index, comorbidities, household air pollution, passive smoking, and other domain physical activity, walking (hazard ratio, 0.90; 95% CI, 0.84–0.96) and cycling (hazard ratio, 0.81; 95% CI, 0.74–0.88) were associated with a lower risk of ischemic heart disease than nonactive commuting. Cycling was associated with a lower risk of ischemic stroke (hazard ratio, 0.92; 95% CI, 0.84–1.00). No significant association was found of walking or cycling with hemorrhagic stroke. The associations of commuting mode with major cardiovascular disease were consistent among men and women and across different levels of other domain physical activity. Conclusions In urban China, cycling was associated with a lower risk of ischemic heart disease and ischemic stroke. Walking was associated with a lower risk of ischemic heart disease.

Objective Aim to examine the independent and joint associations of physical activity (PA) and sedentary leisure-time (SLT) with risk of diabetes and assess the extent to which these associations were mediated by adiposity. Research design and methods The prospective China Kadoorie Biobank recruited ~512 000 adults from 10 diverse areas across China. Self-reported PA was estimated based on type, frequency and duration of specific types of PA, covering four domains (occupation, leisure, household and commuting). SLT was defined as hours per day spent watching television, reading or playing card games. Stratified Cox proportional hazards models were used to estimate adjusted HRs (aHRs) for PA and SLT associated with incident diabetes. Analyses were stratified by age-at-risk (5-year intervals), sex and region and adjusted for household income, education, alcohol consumption, smoking, fresh fruit intake, self-reported general health status, family history of diabetes and body mass index (BMI) status. Analyses of total PA, occupational and non-occupational PA and SLT were mutually adjusted for each other, as appropriate. Results After ~9 years of follow-up, there were 14 940 incident diabetes cases among 460 736 participants without prior diabetes or cardiovascular diseases at baseline. The mean (SD) age at baseline was 51 (10.6) years, 59% were women and 43% resided in urban areas. Overall, the mean BMI was 23.5 (3.3) kg/m 2 , which differed by ~0.5 kg/m 2 among individuals in the highest compared with the lowest PA and SLT groups. PA was inversely associated the risk of diabetes 16% (aHR: 0.84, 95% CI 0.81 to 0.88) lower in top than bottom fifth. After further adjustment for BMI this was attenuated to 0.99 (95% CI 0.98 to 1.00). SLT was positively associated with diabetes and each 1 hour per day higher usual level was associated with aHR of 1.13 (95% CI 1.09 to 1.17) for diabetes, attenuated to 1.05 (95% CI 1.01 to 1.09) after further adjustment for BMI. Conclusions Among Chinese adults, higher levels of PA and lower levels of SLT were associated with lower risks of diabetes with no evidence of effect modification by each other. These associations appeared to arise mainly through adiposity.

Key Points Question Is chronic hepatitis B virus infection associated with a higher risk of any cancer type when compared with individuals without hepatitis B virus? Findings This population-based cohort study of 496 732 Chinese individuals found that hepatitis B surface antigen seropositivity was associated with the risk of hepatocellular carcinoma, stomach cancer, colorectal cancer, oral cancer, pancreatic cancer, and lymphoma. The associations were validated in an independent population and tissue-based studies. Meaning Chronic hepatitis B virus infection was associated with nonliver cancer, especially digestive system cancers.

Background Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). Methods The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology-ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. Findings 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week-ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1.58, 95% CI 1.36-1.84, p<0.0001) than for ischaemic stroke (1.27, 1.13-1.43, p=0.0001). For myocardial infarction, however, genotype-predicted mean alcohol intake was not significantly associated with risk (RR per 280 g per week 0.96, 95% CI 0.78-1.18, p=0.69). Usual alcohol intake in current drinkers and genotype-predicted alcohol intake in all men had similarly strong positive associations with systolic blood pressure (each p<0.0001). Among women, few drank and the studied genotypes did not predict high mean alcohol intake and were not positively associated with blood pressure, stroke, or myocardial infarction. Interpretation Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Objective: To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC). Methods: 71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery. Moreover, the difference between two groups in short-term effects were evaluated. Results: The daily energy supply of control group was 30.1%-43.74% higher than that of the experimental group (P<0.05). The resting energy expenditure (REE) of the research group after surgery was lower than that before operation. The levels of prealbumin, albumin and lymphocyte count were higher in research group than the controls at the 7th day after surgery whereas the opposite was true for the creatinine, urea nitrogen, C-reactive protein and procalcitonin (P<0.05). Similarly, the rate of malnutrition and nutritional risk became lower in the research group (P<0.05). The gastrointestinal function recovery of patients in the research group was comparable to that of the control group (P>0.05). Moreover, the complication rate and hospitalization costs of in research group were significantly lower than that of in control group (P<0.05). For patients with or without nutritional risks before surgery, the nutritional index and inflammatory index in the research group were better than those in the control group. Conclusion: Postoperative precision nutrition therapy may improve the postoperative nutritional status and short-term effects of patients with AGC after NC.

To assess the efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) to promote the healing of large and refractory macular holes (MHs).