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 investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective To observe the clinical efficacy of shugan yishen recipe in the treatment of postmenopausal estrogen receptor-positive breast cancer patients during endocrine therapy.Methods A total of 110 postmenopausal breast cancer patients undergoing aro-matase inhibitor endocrine therapy at Shanghai Municipal Hospital of Traditional Chinese Medicine from July 2021 to September 2023 were divided into observation group and control group by random number table method,with 55 patients in each group..Both groups received standard treatment;the observation group also took shugan yishen recipe,while the control group also took shugan yishen recipe placebo,treatment for 12 weeks.The clinical efficacy,traditional Chinese medicine syndrome scores,bone metabolism,tumor markers,T-cell subsets(CD4+,CD8+,CD4+/CD8+)of the two groups were observed,and the safety was evaluated.Results A total of 106 patients completed the experiment,with 53 patients in each group.After treatment,the total clinical effective rate was 75.5％in the observation group,and 58.5％in the control group,the clinical effect of the observation group was better than that of the control group(P＜0.01).Compared with before treatment,TCM syndrome scores in both groups were decreased(P＜0.01).After treatment,β-c-terminal te-lopeptide of type-Ⅰ collagen(β-CTX),carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and CD8+were all decreased compared with those before treatment(P＜0.05);N-mid osteocalcin(N-MID),CD4+,CD4+/CD8+were higher than those before treatment(P＜0.01).After treatment,β-CTX,N-MID,CA153,CD8+and CD4+/CD8+in the observation group were significantly better than those in the control group(P＜0.01).Conclusion Shugan yishen recipe can improve bone metabolism abnor-malities caused by endocrine treatment in postmenopausal patients with estrogen receptor-positive breast cancer,reduce serum tumor marker levels,enhance immune function of patients,and is safe and effective.

Objective To evaluate the efficacy of one stage laparoscopic choledocholithotomy and cholecystectomy vs.ERCP cholecystolithiasis and cholecystectomy (staged) for cholecystolithiasis complicated with choledocholithiasis.Methods From Jan 2015 to Jun 2017,100 consecutive patients underwent randomized one-stage (TCLCBDE + LC) or two-stage (ERCP + subsequent LC) treatment for common bile duct (CBD) stones.Data evaluated were hospital costs,success rate of one-stage versus two-stage management,postoperative morbidity and GIQLI.Results 47 patients underwent ERCP plus LC two-stage treatment while 46 patients underwent one-stage treatment.Overall success rate of primary intervention for CBD stone clearance was 95.7％ and 97.8％ (P =1.0).Postoperative morbidity was 10.6％ vs.6.5％ (P =0.735),and postoperative hospital stay was (16 ± 5) days vs.(11.9 ± 2.9) days (P ＜ 0.01).One-stage laparoscopic transcystic management was the least costly option compared to two-stage management (19 415 ±2 167)yuan vs.(26 767 ±4 387)yuan (P ＜0.01).GIQLI improved faster in one-stage management group.Conclusion Transcystic one-stage management for gall stones with choledocholithiasis results in shorter hospital stay,lower costs and faster recovery than the two-stage management.

Endoscopic ultrasonography (EUS)is routinely performed before endoscopic submucosal dissection (ESD)for treatment of upper gastrointestinal stromal tumors.However,when a miniprobe sonography (12,15 and 20 MHz)was used,the size of tumor revealed by EUS was often inconsistent with what it actually was,which might increase the difficulty of ESD and the risk of perforation and massive bleeding.Aims:To investigate the value of standard probe (5 and 7.5 MHz)EUS in detecting the size of upper gastrointestinal stromal tumors before ESD.Methods:Clinical data of patients who were suspicious of esophageal and gastric stromal tumors by gastroscopy and EUS from Jan.2012 to Oct.2014 at the Renmin Hospital of Wuhan University were collected.Of them,195 cases treated by ESD were retrospectively analyzed.Results:Of 195 cases treated by ESD,37 cases diagnosed by standard probe EUS and 108 cases diagnosed by miniprobe EUS were confirmed as stromal tumors by pathology.Fourteen cases were failure for ESD and then transferred to surgical treatment,one was due to misjudgement of the origin of tumor by standard probe EUS and 9 were due to misjudgement of the size of tumor by miniprobe EUS.The misjudgement rate of standard probe EUS was lower than that of miniprobe EUS with an insignificant difference (2.7%vs.8.3%,P>0.05).In 9 cases misjudged by miniprobe EUS, the size of tumor presented by miniprobe EUS was significantly smaller than its real size [(1.22 ±0.51)cm vs.(3.97 ±1.06)cm,P<0.01].ESD was avoided or terminated in 3 cases because of the accurate estimation of tumor origin, structure and blood flow by standard probe EUS.Conclusions:For patients who are going to receive ESD for suspected upper gastrointestinal stromal tumors,it would be best to select standard probe EUS to detect the size,origin and blood flow of the tumor before ESD.It will decrease the risk and improve the success rate of ESD.

Objective To analyze risk factors and complication characteristics of healthcare-associated infection (HAI)in patients with lung cancer,and provide evidence for the formulation of HAI management strategy. Methods HAI-related articles were retrieved from China Biology Medicine (CBM),China National Knowledge Infrastructure (CNKI),Wanfang database,Vip database,PubMed,and Embase,all data were conducted Meta-analysis.Results A total of 19 articles involving 8 069 hospitalized patients with lung cancer (1 280 had HAI)were included.Meta-analysis on combined values of medical factors for HAI were as follows:OR(95%CI )of anti-tumor therapy(radiotherapy and chemotherapy),number of chemotherapy (≥ 2 times ),antimicrobial prophylaxis, immunosuppressant therapy,and invasive operation were 3.13 (1 .82,5.39),9.20 (3.04,27.87),3.23 (1 .77, 5.91),2.00(1 .56,2.57),and 2.28(1 .81 ,2.88),respectively;Meta-analysis on combined values of complication factors for HAI were as follows:OR (95% CI )of pulmonary diseases,chronic obstructive pulmonary disease (COPD),diabetes,renal dysfunction,malnutrition,hypoalbuminemia,neutropenia,and leukopenia were 2.65 (1 .74,4.02),2.40 (1 .76,3.27),2.25 (1 .85,2.73 ),2.56 (1 .18,5.52),5.51 (1 .70,17.89),2.05 (1 .56, 2.70),3.38(1 .40,8.18),and 2.10 (1 .22,3.62),respectively.Conclusion HAI-related factors of medical treat-ment and complications in patients with lung cancer are diversity,risk factors for HAI in patients with lung cancer are anti-tumor therapy,immunosuppressant therapy,antimicrobial prophylaxis,invasive operation,pulmonary dis-eases,COPD,diabetes,renal dysfunction,malnutrition,hypoalbuminemia,neutropenia,and leucopenia.

Objective To provide the evidences for the management strategies of ventilator-associated pneumonia (VAP) in neonates,we systematically reviewed all related studies and analyzed the high-risk primary disease and medical factors of VAP in neonates.Methods We retrieved all related studies in CNKI,Wanfang,VIP,CBM,Pubmed and Embase and evaluated their quality by Newcastle-Ottawa Scale and analyzed all data by qualitative and Meta-analysis.Results There were 12 case-control studies with higher methodological quality and involving 1 994 neonates and with 708 VAP patients.Six studies involving 872 neonates were included,the odds ratio of respiratory distress syndrome(OR=2.81) and malnutrition(OR=5.18) had significant differences between VAP and non-VAP group.Seven studies involving 1 110 neonates were included and the odds ratio of patients with corticosteroids (OR=3.12),central inhibitors (OR=2.31),antacids (OR=4.35) and Gamma globulin with large doses (OR=2.35) had significant differences between VAP group and non VAP.Four studies involving 554 neonates were included and the odds ratio of patients with closed chest drainage (OR=1.81)and umbilical vein catheterization (OR=9.19) had significant differences between VAP group and non VAP.Six studies involving 1 139 neonates were included and the odds ratio of patients with parenteral nutrition (OR=1.82)and blood transfusions (OR=2.49) had significant differences between VAP group and non VAP.Conclusions Our study confirms that the respiratory distress syndrome and malnutrition corticosteroids,central inhibitors,antacids,Gamma globulin with large doses,closed chest drainage,umbilical vein catheterization,parenteral nutrition and blood transfusions are important risk and early-warning factors.

Background:Gastrointestinal carcinoids are prone to be neglected in clinical practice because of the poor specific symptoms in early stage. Aims:To analyze the clinicopathological characteristics,treatment modalities and prognosis of a series of cases of gastrointestinal carcinoids for strengthening the understanding of the disease. Methods:A total of 116 patients diagnosed as gastrointestinal carcinoids by pathology from Jan. 1997 to Jan. 2010 in 8 hospitals at Wuhan were enrolled in this retrospective study. Data on sex,age,major symptoms,diagnostic approaches,treatment modalities, pathological features and prognosis, etc. were collected and analyzed. Results:The most common sites of the gastrointestinal carcinoids were rectum(59. 5%)and stomach(19. 8%);the most common symptoms were abdominal pain,abdominal distention and hematochezia. The positivity rates of immunohistochemical marker NSE,Syn and CgA were 92. 7%,87. 5% and 62. 5%,respectively. The proportion of stomach carcinoids with diameter larger than 2 cm was 73. 9%, and that of rectal carcinoids was only 13. 0%(P <0. 001). Most of the gastric carcinoids(81. 8%)infiltrated into or breakthrough the serosa;the rate of lymph node involvement in gastric carcinoids was significantly higher than that in rectal carcinoids(72. 7% vs. 17. 1%,P<0. 001),while typical carcinoids were less common in stomach than in rectum(60. 9%vs. 95. 7%,P<0. 001). Only one(4. 3%)gastric carcinoid patient underwent endoscopic therapy,while that for rectal carcinoids was 24 cases(34. 8%,P=0. 003). Surgical operation was the main therapeutic method for both gastric and rectal carcinoids. The 3-and 5-year survival rates for rectal carcinoids were 92. 8% and 62. 3%,respectively,and those for gastric carcinoids were 62. 6% and 49. 2%,respectively;there were no significant differences between the two groups(P>0. 05). Conclusions:Gastrointestinal carcinoids enrolled in this study distributed mainly in rectum and stomach. As compared with rectal carcinoids,gastric carcinoids were more advanced in disease stage with poorer prognosis. Regular health checks, strengthening the understanding of the disease,and grasping the specificities of carcinoids distributed at different sites might be helpful for the early diagnosis and treatment of gastrointestinal carcinoids,thus improving the survival rate.

OBJECTIVETo investigate the role ofCD4+CD25+ T regulatory (Treg) cells, T helper (Th)17cells and interleukin (IL)-6 in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and determine their value as prognostic markers.

METHODSThe Chinese National Knowledge Infrastructure (CNKI), WanFang, Chinese Scientific Journals (VIP), PubMed, Embase and Web of Science databases were searched for English language case-control studies on the relationship between regulatory T lymphocytes and ACLF.The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis was designed according to the PICOS approach recommended by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. RevMan software, version 5.1, was used to perform the meta-analysis.

RESULTSNine case-cohort studies were selected for inclusion in the metaanalysis.The results of the meta-analyses showed that the level of CD4+CD25+ Treg cells was not significantly different between patients with HBV-related ACLF and patients with chronic hepatitis B (CHB) (mean difference (MD)=0.59, 95% confidence interval (CI)-1.68, 2.85, P=0.61) nor between patients with HBVrelated ACLF and healthy controls (MD=1.12, 95% CI:-1.42, 3.66, P=0.39). Thus, it appears that ACLF patients do not have a higher level of CD4+CD25+ Treg cells than CHB patients or healthy controls. However, the ACLF patients did appear to have a significantly higher level of Th17 cells than both the CHB patients (MD=1.73, 95% CI:0.21, 3.26, P=0.03) and the healthy controls (MD=1.62, 95% CI:(0.52, 2.72, P=0.004). In addition, the ACLF patients also had significantly higher level than both the CHB patients (MD=11.69, 95%CI:1.98, 21.40, P=0.02) and the healthy controls (MD=13.17, 95% CI:1.38, 24.95, P=0.03).

CONCLUSIONCD4+CD25+ Treg cells may be an important protective factor in the progression and prognosis of HBV-related ACLF, while Thl7 cells and IL-6 may be risk factors for further progression and worsened prognosis.

Acute-On-Chronic Liver Failure ; diagnosis ; immunology ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Disease Progression ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Interleukin-6 ; immunology ; Prognosis ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology