ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

Objective To explore the influence of different hardness surfaces on gait coordination in patients with functional ankle instability(FAI). Methods Qualisys Infrared Optical Motion Capture System was used to test the coordination and variability of 15 FAI patients on the right side at Nanjing Normal University from May to July,2023.The gait cycle data were collect-ed and intercepted,and coupling angle(CA)and standard deviation of coupling angle(SDCA)were calculated by Matlab to compare the differences on different hardness surfaces. Results On coronal plane,CA of hip-ankle joint was higher on the hard surface than on the soft surface during middle stage of support and early stage of swing,and lower on its rest stages and the gait stages of hip-knee joint and knee-ankle joint than on the soft surface(P<0.01).On sagittal plane,CA of hip-ankle joint and knee-ankle joint was smaller on the hard surface than on the soft surface during middle and late stages of support,and larger than on the soft surface during their rest stages,and the gait stages of hip-knee joint(P<0.01).On horizontal plane,CA of hip-knee joint was lower on the hard surface than on the soft surface during the late stage of support,and higher than on the soft surface during its early stage of swing and bearing stage of hip-ankle joint(P<0.01).Compared with the hard surface,SDCA was smaller on the soft surface than on the hard surface only in the hip-ankle on the sagittal plane and during bearing stage of hip-knee joint,and was greater than on the hard surface for the rest(P<0.01). Conclusion FAI patients showed more distal dominance on soft surface than on hard surface during most gait cycle on 3D plane,i.e.,advantage of ankle varus and plantar flexion increased,and advantage of hip joint decreased;the coordination variability was generally higher on soft surface than on hard surface.These findings suggested that FAI patients may increase the risk of recurrent lateral ankle sprain walking on soft surface.

During the process of dairy farming,various factors such as physical injury and bacterial infection act upon body tissues or organs,leading to the disruption of skin or mucous tissue integ-rity and subsequent tissue injury and trauma.The healing of these injuries is a complex process that necessitates the coordinated efforts of different cells and involvement of diverse cytokines.A-mong them,the interaction between macrophages and myofibroblasts is indispensable for efficient tissue repair.Nod-like receptor protein 3(NLRP3),a pattern recognition receptor in the innate im-mune system,may play a regulatory role in modulating this intricate process.In this study,cow myofibroblasts and M1 type bone marrow-derived macrophages were cultured in vitro,followed by collection of cell culture supernatant for co-culture analysis.Both cytokine secretion levels in M1 type bone marrow-derived macrophages as well as expression patterns levels of myofibroblast growth factor protein and mRNA were detected.The regulatory mechanism underlying NLRP3 in-volvement in mediating interactions between these two cell types was investigated using NLRP3 inhibitor MCC950.The results showed that an effective method for culturing cow muscle fibroblasts in vitro was successfully established and myofibroblast conditioned medium(MFbCM)could regulate M1 macrophage secretion profiles.Moreover,M1 macrophage conditioned medium(M1?CM)was found to influence myofibroblast growth factor expression levels.Our findings sug-gest that NLRP3 plays a significant regulatory role during crosstalk between myofibroblasts and M1-type pro-inflammatory macrophages.

Objective:To explore the pathogenesis of primary hemophagocytic syndrome with UNC13D and MYO5A gene mutations.Methods:A case of adult hemophagocytic syndrome with gene mutation of UNC13D and MYO5A admitted to The 940th Hospital of the Joint Logistic Support Force of the PLA on January 28, 2022 was retrospectively analyzed in terms of laboratory examination, gene atlas of its close relatives and prognosis, and related literature was reviewed.Results:The patient was finally diagnosed with primary hemophagocytic syndrome, and chemotherapy was performed twice with hemophagocytic lymphohistiocytosis(HLH)-2004 regimen. The HLA matching of his cytoplasm was semi-compatible. Considering that his cytoplasm carried blood-macrophage related genes, it was not suitable to be selected as a donor, and there were no other suitable relatives. He was transferred to another hospital for allogeneic hematopoietic stem cell transplantation, but failed to receive allogeneic hematopoietic stem cell transplantation during telephone follow-up, and died.Conclusion:The gene mutation of primary hemophagocytic syndrome is the gold standard for the diagnosis of primary HLH. There may be dual gene inheritance pattern in primary HLH, and the combination of immune disorder caused by viral infection and genetic factors may lead to the pathogenesis of primary HLH.

Postoperative radiotherapy increase the overall survival rate offor breast cancer improves overall survivalpatients, but. Nevertheless, the heart is at risk of radioactive heart damageradiation-induced cardiac injury due to its anatomical location, which is inevitably exposed to radiation during radiotherapy. The heart is considered a "high-risk organ" sensitive to radiation, and its radiation dose should be as low as possible. Previous studies have evaluated the effect of overall heart radiation dose on long-term cardiovascular events, but the. However, new study has found that the average heart dose does not accurately reflect the degree of heart radiation exposure. In recent years, more and morewidespread attention has been paid to subclinical cardiac injury after radiotherapy, aiming at early identification of latent cardiac injury. In addition, the relationship between specific cardiac substructural doses and arrhythmias is unclear. This paper focuses onIn this article, the limitations of average cardiac dose in predicting radioactive heart injuryradiation- induced cardiac injury, the indicators of early identification of the indicators for cardiac injury and the influencing factors of radiation-induced cardiac injury in breast cancer radioactive heart injurywere illustrated, and focuses on the relationship between radiation damage of different cardiac substructures and arrhythmia was evaluated, so asaiming to achieve fine cardiac risk management in breast cancer patients and reduce the non-cancer mortality in breast cancer patients.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

Objective:This study comprehensively analyzed the genomic characterizations of human parainfluenza virus type 3 (HPIV3) strains circulating in six provinces and cities of China (Beijing, Henan, Jilin, Anhui, Gansu, and Shandong) during the period of 2019-2020. The aim was to elucidate the intricate genetic variations and molecular evolutionary trends within the HPIV3 genome.Methods:Based on genotypic differentiation, genetic divergence, and spatial and temporal distribution, 12 representative HPIV3 strains (including 7 of C3a subtype, 2 of C3b subtype and 3 of C3f subtype) were selected from the aforementioned provinces, and the complete genome sequence was successfully obtained by overlapping amplification of fragments using nested RT-PCR. Subsequently, a complete genome database of global representative HPIV3 strains was constructed and analyzed using bioinformatics tools.Results:The length of complete genome of the 12 HPIV3 strains in the present study varied between 15 227 bp and 15 370 bp, the G+ C content ranged from 35.1% to 35.3% and the nucleotide identity intermediated from 97.6% to 99.6%. Compared with the prototype strain (GenBank accession number: NC_001796.2), the nucleotide identity of 12 HPIV3 strains ranged from 94.2% to 94.5%. Analysis of the complete genome of HPIV3 available in China and globally showed that the genomic variation of HPIV3 was mainly shaped by substitution mutations, and no base deletions or gene recombination were observed.Only a six-base insertion (ATTAAA) was found in the F gene’s 3′UTR region of a representative strain originating from Jilin province (CHN/Jilin036/2019/C3b) in this study, and its potential pathogenic significance needs to be further investigated. Amino acid analysis of the encoded proteins revealed that the C3a lineage of HPIV3, widely prevalent both in China and worldwide, exhibits lineage-specific mutation sites in the N, P and L proteins. Furthermore, within the Chinese prevalent C3a strains, a distinctive mutation site (N216S) in L protein was also identified. Notably, specific variant sites have not been found in Chinese C3b and C3f branch strains. Based on the complete genome, the comprehensive evolutionary analysis showed that the time to the most recent common ancestor (tMRCA) of global HPIV3 strains was estimated to 1927 (95% HPD: 1901-1945), with an average molecular evolutionary rate of 5.29 × 10 -4 substitutions/site/year, while the average molecular evolutionary rate of HPIV3 strains in China is 5.24 × 10 -4 substitutions/site/year. In addition, each gene of HPIV3 was subjected to negative selection pressure, with the P, HN and F genes showing the most significant nucleotide variation and higher rates of molecular evolution than the other genes. Conclusions:This study reveals that the complete genome of HPIV3 strains circulating in six provinces and cities of China tend to evolve conservatively. Moreover, substitution emerge as the main driving force for molecular evolution of HPIV3.

Objective: To investigate whether a deep learning-based model using unenhanced computed tomography (CT) at baseline could predict the malignancy of pulmonary nodules. Methods: A deep learning model was trained and applied for the discrimination of pulmonary nodule in Dr. Wise Lung Analyzer. This study retrospectively recruited 130 consecutive participants with pulmonary nodules detected on CT who undergoing biopsy or surgery from May 2009 to June 2017 in Jinling hospital. A total of 136 pulmonary nodules were included in this study, including 86 malignant nodules and 50 benign ones. All patients underwent CT scans 2 times at least, the first scan was defined as baseline and the last scan before the pathological results was defined as final scan. The ROC curve of deep learning model was plotted and the AUCs were calculated. Delong test was used to examine the difference of AUCs baseline and final scan. The nodules were further divided into subsolid nodule group (pure ground-glass nodule and part solid nodule) (n=87) and solid nodule group (n=49). The difference of AUCs at baseline and final scans was evaluated intra two groups. Results: The AUCs of the deep learning model at final and baseline scans were 0.876 and 0.819, respectively. There was no significant difference between them (P=0.075). The result indicated that the model could predict the consequences of pulmonary nodules well at baseline. In small nodules (longest diameter ≤10mm), the AUC at final scan (0.847) was better than it at baseline scan (0.734), but there was no significant difference between them (P=0.058). In solid nodule group, The AUC at final scan (0.932) was better than it at baseline scan (0.835), but there was no significant difference between them (P=0.066). In subsolid nodule group, the deep learning model exhibited consistent performance at final scan (AUC, 0.759) with the baseline scan (AUC, 0.728, P=0.580). Conclusions The deep learning model could predict the malignancy of pulmonary nodules including small ones at baseline, and the model exhibited consistent performance between baseline and final scans in subsolid nodules.

Objective: To investigate the relationship of plasma albumin and hypersensitive C-reactive protein (Hs-CRP) with 5-year all-cause mortality among Chinese older adults aged 65 and older. Method: Data was collected in 8 longevity areas of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) study conducted by Chinese Center for Disease Control and Prevention and Peking University at baseline survey in 2012 and 2014, the participants enrolled in 2012 was followed-up in 2014 and 2017, the participants enrolled in 2014 was followed-up in 2017 only. Finally, 3 118 older adults aged 65 and older with complete information on albumin, Hs-CRP and body mass index (BMI) were included in this study. Plasma samples of older adults were collected for the detection of albumin and Hs-CRP at baseline survey. Survival status and follow-up time was recorded for all participants. All older adults were divided into 4 groups according to the levels of plasma albumin and Hs-CRP, and Cox proportional hazard models were constructed to assess their influence on the risk of all-cause mortality. Results: Among 3 118 older adults included, the prevalence of hypoalbuminemia was 10.1% (316/3 118), and was 22.8% (711/3 118) for elevated Hs-CRP. During 10 132 person-years of follow-up, 1 212 participants died. Participants with hypoalbuminemia had increased risk of all-cause mortality, with an hazard ratio (HR) and 95% confidential interval (CI) of 1.18 (1.01-1.38), compared to participants with normal plasma albuminemia; participants with elevated Hs-CRP had increased risk of all-cause mortality, with an HR (95%CI) of 1.18 (1.04-1.35), compared to participants with normal plasma Hs-CRP. Participants with normal plasma albumin and elevated Hs-CRP, with hypoalbuminemia and normal Hs-CRP, with hypoalbuminemia and elevated Hs-CRP also had increased risk of all-cause mortality when compared to those with normal plasma albumin and normal Hs-CRP, the HR (95%CI) were 1.16 (1.01-1.34), 1.11 (0.91-1.37) and 1.43 (1.11-1.83), respectively. Conclusion Hypoalbuminemia and elevated Hs-CRP were responsible for increased risk of 5-year all-cause mortality among Chinese older adults from 8 longevity areas.

Objective To investigate the relationship of plasma albumin and hypersensitive C?reactive protein (Hs?CRP) with 5?year all?cause mortality among Chinese older adults aged 65 and older. Method Data was collected in 8 longevity areas of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) study conducted by Chinese Center for Disease Control and Prevention and Peking University at baseline survey in 2012 and 2014, the participants enrolled in 2012 was followed?up in 2014 and 2017, the participants enrolled in 2014 was followed?up in 2017 only. Finally, 3 118 older adults aged 65 and older with complete information on albumin, Hs?CRP and body mass index (BMI) were included in this study. Plasma samples of older adults were collected for the detection of albumin and Hs?CRP at baseline survey. Survival status and follow?up time was recorded for all participants. All older adults were divided into 4 groups according to the levels of plasma albumin and Hs?CRP, and Cox proportional hazard models were constructed to assess their influence on the risk of all?cause mortality. Results Among 3 118 older adults included, the prevalence of hypoalbuminemia was 10.1% (316/3 118), and was 22.8% (711/3 118) for elevated Hs?CRP. During 10 132 person?years of follow?up, 1 212 participants died. Participants with hypoalbuminemia had increased risk of all?cause mortality, with an hazard ratio (HR) and 95% confidential interval (CI) of 1.18 (1.01-1.38), compared to participants with normal plasma albuminemia; participants with elevated Hs?CRP had increased risk of all?cause mortality, with an HR (95%CI) of 1.18 (1.04-1.35), compared to participants with normal plasma Hs?CRP. Participants with normal plasma albumin and elevated Hs?CRP, with hypoalbuminemia and normal Hs?CRP, with hypoalbuminemia and elevated Hs?CRP also had increased risk of all?cause mortality when compared to those with normal plasma albumin and normal Hs?CRP, the HR (95%CI) were 1.16 (1.01-1.34), 1.11 (0.91-1.37) and 1.43 (1.11-1.83), respectively. Conclusion Hypoalbuminemia and elevated Hs?CRP were responsible for increased risk of 5?year all?cause mortality among Chinese older adults from 8 longevity areas.