Objective To screen specific antibodies to Helicobacter pylori(H.pylori)in serum,and establish antibody panels and discrimination models for different infection status,which are non-invasive and suitable for gastric cancer screening in Chinese population.Methods A total of 300 subjects with different H.pylori statuses were enrolled depending on an endoscopy screening cohort in a high-risk area of gastric cancer,including current,past,and negative infections.The recomLine Helicobacter IgG 2.0 immunoblotting assay was used to analyze and screen 10 H.pylori specific antibodies in serum samples.Results A total of nine antibody reactivity against CagA,VacA,GroEL,FliD,HpaA,gGT,HtrA,NapA,and CtkA showed significant differences among different H.pylori infection status groups(all P＜0.05).A panel comprising the nine antibodies distinguished exposure subjects to H.pylori(current and past infections)from negatives,with an area under the curve(AUC)of 0.935(95%CI:0.907-0.963).The combination of four antibodies(CagA,GroEL,FliD,and gGT)may help to discriminate current and past infection subjects,with an AUC of 0.927(95%CI:0.891-0.964).Conclusion The antibody panels and discriminant models for H.pylori infection status established in the present study may provide a potential and non-invasive screening method for the development of precise gastric cancer prevention strategies.

Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

Objective To screen specific antibodies to Helicobacter pylori(H.pylori)in serum,and establish antibody panels and discrimination models for different infection status,which are non-invasive and suitable for gastric cancer screening in Chinese population.Methods A total of 300 subjects with different H.pylori statuses were enrolled depending on an endoscopy screening cohort in a high-risk area of gastric cancer,including current,past,and negative infections.The recomLine Helicobacter IgG 2.0 immunoblotting assay was used to analyze and screen 10 H.pylori specific antibodies in serum samples.Results A total of nine antibody reactivity against CagA,VacA,GroEL,FliD,HpaA,gGT,HtrA,NapA,and CtkA showed significant differences among different H.pylori infection status groups(all P＜0.05).A panel comprising the nine antibodies distinguished exposure subjects to H.pylori(current and past infections)from negatives,with an area under the curve(AUC)of 0.935(95%CI:0.907-0.963).The combination of four antibodies(CagA,GroEL,FliD,and gGT)may help to discriminate current and past infection subjects,with an AUC of 0.927(95%CI:0.891-0.964).Conclusion The antibody panels and discriminant models for H.pylori infection status established in the present study may provide a potential and non-invasive screening method for the development of precise gastric cancer prevention strategies.

Objective:To compare the effects of Feishu(BL13)combined with Tianshu(ST25)and Feishu(BL13)alone on pulmonary function and tissue inflammation in asthma model rats. Methods:Forty-eight Sprague-Dawley rats were randomly divided into a normal group,a model group,a lung treatment group,and a lung-intestine treatment group according to the random number table method,with 12 rats in each group.Except for the normal group,rats in the other three groups were sensitized by ovalbumin followed by atomization stimulation to establish the asthma model.After the model was made successfully,rats in the lung treatment group were treated with acupuncture at bilateral Feishu(BL13)for 30 min;rats in the lung-intestine treatment group were treated with acupuncture at bilateral Feishu(BL13)and Tianshu(ST25)for 15 min,respectively,for 30 min in total.Acupuncture was performed once a day for 14 d.Rats in the other two groups did not receive any intervention.After intervention,the pulmonary function of each group of rats was measured by a pulmonary function tester.The histopathological changes stained by hematoxylin-eosin staining and the collagen deposition degree stained by Masson in lung tissue,as well as the inflammatory cells in the bronchoalveolar lavage fluid(BALF)stained by Wright's-Giemsa staining were observed under a light microscope;the levels of interleukin(IL)-4,IL-5,IL-13,IL-17,IL-25,IL-33,leukotrienes(LT),thymic stromal lymphopoietin(TSLP),and prostaglandin D2(PGD2)were detected by enzyme-linked immunosorbent assay. Results:Compared with the normal group,the peak expiratory flow(PEF),the dynamic lung compliance(Cdyn),the forced expiratory flow 25%(FEF25%),the forced expiratory volume in the first second/forced vital capacity(FEV1/FVC),and the maximum mid-expiratory flow(MMEF)in the model group were significantly decreased(P<0.01 or P<0.05);the lung resistance(RL),the collagen deposition,the IL-4,IL-5,IL-13,IL-17,IL-33,LT,TSLP,and PGD2 levels,and the neutrophil proportion in the BALF were increased significantly(P<0.01 or P<0.05).Compared with the model group,the FEF25%and FEV1/FVC in the pulmonary function were significantly increased(P<0.01,P<0.05),while the collagen fiber deposition and the levels of IL-4,IL-5,IL-13,IL-17,LT,TSLP,and PGD2 were significantly decreased(P<0.01 or P<0.05)in the lung treatment group;the PEF,FEF25%,and FEV1/FVC in pulmonary function were significantly increased(P<0.01 or P<0.05),while the RL and the collagen fiber deposition,as well as the neutrophil proportion and the levels of IL-4,IL-5,IL-13,IL-17,IL-33,LT,TSLP,and PGD2 in the BALF were significantly decreased(P<0.01 or P<0.05)in the lung-intestine treatment group.Compared with the lung treatment group,the IL-5 level in the rat lung tissue of the lung-intestine treatment group was decreased(P<0.05). Conclusion:Acupuncture in the lung treatment and the lung-intestine treatment groups improved pulmonary function,lung inflammation,and inflammatory cells in the BALF in asthma model rats;the lung-intestine treatment was better than lung treatment in improving the IL-5 level.The combination of Feishu(BL13)and Tianshu(ST25)was superior to Feishu(BL13)alone in the treatment of asthma in trend.

Objective: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). Methods: A propensity score matching algorithm was performed between the BEP and PC groups. The χ2 test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. Results: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8–44 years), and the median follow-up period was 63 months (range, 2–191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. Conclusion The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.

Objective:To provide evidence for optimizing the screening strategy for gastric cancer (GC), we evaluated the risk of incident GC for individuals with different precancerous gastric lesions in a prospective cohort study.Methods:Based on the National Upper Gastrointestinal Cancer Early Detection Program launched in Linqu, Shandong, a high-risk area of gastric cancer in China, we included a total of 14 087 subjects diagnosed with different gastric lesions stages by endoscopic screening from 2012 to 2018. Study subjects were prospectively followed up until December 31, 2019. The incidence of GC during the follow-up was ascertained by repeated endoscopic examinations, cancer, death registry reports, and active follow-up of study subjects and was confirmed by reviewing medical records extracted from the hospital information management system. The Poisson regression model was applied to calculate the relative risk ( RR) and 95% CI for GC occurrence among subjects with different gastric lesions. Results:Among 14 087 subjects with different gastric lesions as determined by their first endoscopic examination in 2012-2018, 7 608 (54.00%) had a global diagnosis of superficial gastritis (SG), 2 848 (20.22%) had chronic atrophic gastritis (CAG), 3 103 (22.03%) had intestinal metaplasia (IM), and 520 (3.69%) had low-grade intestinal neoplasia (LGIN). During the follow-up, 109 subjects were diagnosed with GC, including 63 with high-grade intestinal neoplasia (HGIN) and 46 with invasive GC. Compared to subjects having normal gastric mucosa or SG, those with CAG ( RR=3.85, 95% CI: 2.04-7.28), IM ( RR=5.18, 95% CI: 2.79-9.60), and LGIN ( RR=19.08, 95% CI: 9.97-36.53) had significantly increased risk of progression to GC. Individuals with these gastric lesions had an elevated risk of developing HGIN and invasive GC. For subjects with LGIN, the RR was 22.96 (95% CI: 9.71-54.27) for developing HGIN and 14.64 (95% CI: 5.37-39.93) for developing invasive GC. Subgroup analyses found that all age group subjects with LGIN diagnosed during the initial endoscopic examination had a significantly increased risk of developing the GC. Conclusions:Our large-scale prospective study on a high-risk area of GC showed that most residents aged 40-69 years had gastric lesions of different stages. Subjects with more advanced gastric lesions had a significantly increased risk of progression to GC.

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group ( P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.

The liquid chromatography tandem mass spectrometry was used to detect the urinary proteomics of 223 residents aged 40-69 years old who participated in the National Upper Gastrointestinal Cancer Early Detection Program in Linqu County, Shandong Province from November 22 to December 7, 2018, and analyze the alcohol consumption related proteomic profiles and individual urinary protein. There were significant differences in urinary protein profiles between alcohol consumption group and non-alcohol consumption group. The expression of 26 urinary proteins was up-regulated and 20 urinary proteins were down-regulated in alcohol consumption group ( P<0.05). The differentially expressed proteins had enzyme inhibitor activity and phospholipid binding function, and mainly enriched in pathways involving proximal tubule bicarbonate regeneration, complement and coagulation cascade, and cholesterol metabolism. The protein expressions of complement factor I (CFI), angiotensin converting enzyme 2 (ACE2) and protein C inhibitor (SERPINA5) were positively correlated with daily alcohol consumption.

Objective:To explore the value of prenatal MRI in the diagnosis of isolated mild and moderate bilateral ventriculomegaly and neural development of the fetuses after birth.Methods:This is a retrospective study involving 244 singleton fetuses with isolated mild or moderate lateral ventriculomegaly diagnosed by both prenatal ultrasound and MRI in Huzhou Maternity & Child Health Care from May 2013 to June 2017, consisting of 82 cases with bilateral ventriculomegaly (BVM) and 162 with unilateral ventriculomegaly (UVM). The two groups were further divided into two subgroups: mild (lateral ventricle width: 10.0-12.0 mm, bilateral 56 cases, unilateral 120 cases) and moderate group (lateral ventricle width: >12.0-<15.0 mm, bilateral 26 cases, unilateral 42 cases). In addition, 50 singleton fetuses without any abnormality in the nervous system in prenatal check were included in the control group during the same period. All neonates were reexamined by ultrasound within one week after birth, and followed up regularly at the age of 3, 6, 12 and 18 months. Gesell Development Schedules (GDS) were used to evaluate the central nervous system's function, and postnatal changes in lateral ventriculomegaly were observed. Statistical analysis was performed by t, F, Chi-square tests (or Fisher's exact test). Results:(1) There was no difference among intervals between MRI scan and delivery in the BVM, UVM, and the control groups. The disappearance rate of lateral ventriculomegaly after birth was 80.4% (45/56) in the mild BVM group, 42.3% (11/26) in the moderate BVM group, 88.3% (106/120) in the mild UVM group, and 57.1% (24/42) in the moderate UVM group ( χ2=35.183, P<0.001). (2) The GDS evaluation results in the BVM group at 6, 12, and 18 months after birth were worse than those in the UVM group (all P<0.0167). The GDS evaluation results in the BVM group were worse than those in the control group at 3 and 6 months after birth [3 months: normal: 58.5% (48/82) vs 86.0% (43/50), borderline: 22.0% (18/82) vs 10.0% (5/50), delay: 19.5% (16/82) vs 4.0% (2/50), χ2=11.425; 6 months: normal: 63.4% (52/82) vs 88.0% (44/50), borderline: 19.5% (16/82) vs 8.0% (4/50), delay: 17.1% (14/82) vs 4.0% (2/50), χ2=9.678; all P<0.0167]. (3) The GDS evaluation results in the moderate BVM group at 6, 12, and 18 months after birth were worse than those in the moderate UVM group [6 months: normal: 30.8% (8/26) vs 69.0% (29/42), borderline: 30.8% (8/26) vs 21.4% (9/42), delay: 38.5% (10/26) vs 9.5% (4/42), χ2=11.417; 12 months: normal: 53.8% (14/26) vs 88.1% (37/42), borderline: 23.1% (6/26) vs 9.5% (4/42), delay: 23.1% (6/26) vs 2.4% (1/42), χ2=11.199; 18 months: normal: 65.4% (17/26) vs 95.2% (40/42), borderline: 15.4% (4/26) vs 2.4% (1/42), delay: 19.2% (5/26) vs 2.4% (1/42), χ2=10.568; all P<0.0167]. The GDS evaluation results of the moderate BVM group at 3, 6, 12, and 18 months after birth were worse than the control group. (4) In the BVM group, the GDS scores at 18 months of age were better than those at three months of age ( χ2=8.224, P=0.016). Conclusions:(1) Most mild BVM would disappear spontaneously after birth, while more in mild UVM cases. (2) The postnatal GDS evaluation results of the BVM group is significantly worse than that of the UBM group at months of age; (3) Fetuses with less severe isolated BVM are more likely to have improved GDS score after birth.