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 study the association between 24 h activities and Fundamental Motor Skills (FMS) among children with autism spectrum disorder (ASD) using compositional data analysis, and the expected changes in FMS after isochronous substitution of each activity, in order to provide reference basis for improving FMS levels in children with ASD. Methods: From October 2023 to April 2024, a total of 301 children with ASD aged 6-10 from 7 special education schools in Jinan, were investigated by cluster random sampling, and 24 h movement behaviors were calculated based on accelerator data. Test of Gross Motor Development- 2 was used to assess FMS. R software was used to perform the descriptive statistical, multiple linear regression and isochronous substitution analyses. Results: The proportion of moderatevigorous physical activity (MVPA) in children with ASD was positively related with FMS scores, locomotor, and object control skills ( β=12.42, 6.32, 6.10, P <0.01). Reallocating 15 min from sleep (SLP) to MVPA resulted in respective increases of 3.66, 1.91, and 1.75 points in FMS scores, locomotor skills, and object control skills ( P <0.05). Reallocating 15 min from sedentary behavior (SB) to MVPA resulted in respective increases of 3.72, 1.88 , and 1.83 points in FMS scores, locomotor skills, and object control skills ( P <0.05). Reallocating 15 min from light physical activity (LPA) to MVPA resulted in respective increases of 3.32, 1.57, and 1.74 points in FMS scores, locomotor skills, and object control skills ( P <0.05). Moreover, reallocating 15 min from SB to LPA resulted in an increase of 0.28 points in locomotor skills ( P <0.05). Dose response analysis revealed that substitution of MVPA for SLP, SB, and LPA in children with ASD enhanced their FMS levels, and their substitution was asymmetrical; and substitution of LPA for SB enhanced locomotor skills level. Conclusions Among the 24 h movement behaviors, increasing the time spent on MVPA and LPA have positive impacts on the FMS of children with ASD. Schools and families should optimize the allocation of 24 h activity time in children with ASD, so as to promote the improvement of FMS levels of children with ASD.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective To explore the effect of sling exercise with Tuina therapy on kinesiophobia in old patients with lumbar disc herniation,and analyze the mechanism based on brain-bone axis. Methods A total of 56 old patients with chronic lumbar disc herniation and kinesiophobia were selected from the Reha-bilitation Hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from September,2022 to December,2023;and randomly divided into control group(n=28)and experimental group(n=28).The control group accepted conventional exercise therapy,while the experimental group accepted sling exercise with Tuina therapy,for four weeks.They were assessed with simplified Chinese version of Tampa Scale of Kinesiophobia(TSK),Japanese Orthopaedic Association score(JOA)and Visual Analogue Scale for pain(VAS)before and after treatment,while the bone mineral density(BMD)was tested,the levels of osteoprote-gerin(OPG),norepinephrine(NE)and corticosteroids(Cor)in serum were measured,and the median frequency(MF)of weak-link erector spinae was detected with surface electromyography. Results Two cases dropped off in the control group,and one in the experimental group.The scores of all the assessment improved in both groups after treatment(|t|>14.168,P<0.001),as well as the serum levels of OPG,NE and Cor(|t|>2.103,P<0.05),BMD(|t|>2.726,P<0.05),and MF of erector spinae(|t|>14.736,P<0.001);all of them were better in the experimental group than in the control group(|t|>2.154,P<0.05). Conclusion Sling exercise with Tuina therapy can improve the pain and kinesiophobia of lumbar disc herniation in the old adults,which may promote the recovery of physical and mental function through regulating the levels of hor-mones and neurotransmitters related to the brain-bone axis.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective: To investigate the incidence and rank of chronic obstructive pulmonary disease and pneumoconiosis to the workers in different occupational positions in Jinchang Cohort. Methods: In January 2014, a cohort of follow-up population in jinchang city was taken as the research object, 17843 individuals among follow-up populations in Jinchang Cohort Study, removed the individuals with chronic obstructive pulmonary disease and pneumoconiosis before 2013, and counted the new incidence individuals diagnosed by the A-Class hospital in Grade III in Jinchang City, Gansu Province, as the investigation objects to investigate the incidence rate & rank of chronic obstructive pulmonary disease and pneumoconiosis. The statistical significance was tested by chi-square test. Results: The 2-year incidence rate of Chronic Obstructive Pulmonary Disease and Pneumoconiosis in the population of Jinchang Cohort Study were 11.60‰, 13.51‰ for male and 8.46‰ for female. the ranks of 2-year incidence rates of chronic bronchitis, emphysema, pneumoconiosis and other phenotypes of chronic obstructive pulmonary disease were 7.06‰、3.42‰、0.84‰、0.34‰, respectively. Incidence rate of chronic bronchitis among administrators and executive staffs were 10.45‰; incidence rate of chronic bronchitis among service staffs were 10.45‰; incidence rate of pneumoconiosis among mining staffs were 3.44‰. Conclusion The first incidence rank of chronic obstructive pulmonary disease and pneumoconiosis in Jinchang cohort is chronic bronchitis, and the risk factors are smoking and occupational exposure.

Objective To investigate the dynamic characteristic changes of gastrointestinal mucosa and its relationship with disease progression in rats with acute cerebral infarction. Methods Fifty-six male Wistar rats were selected as the study subjects, and they were divided into three groups: normal control, sham operation and cerebral infarction model groups by random number table method. The middle cerebral artery occlusion (MCAO) model was prepared by the modified Longa thread embolic method. The levels of gastrin (GAS) were monitored in each group after modeling for 24 hours, 4 days and 7 days; after the rats were killed, the sections of gastric antrum and small intestine were taken and stained with hematoxylin-eosin (HE) staining method, the histopathological changes of gastric and small intestinal mucosa were observed under light microscope, in the mean time the gastric and small intestinal mucosal pathological scores were also performed, and the differences of pathological scores among the three groups were compared. Results There were no statistical significant differences in GAS, gastrointestinal mucosa and small intestinal mucosal pathological scores between the normal control group and sham operation group at each time point (all P > 0.05); the GAS level in cerebral infarction model group was decreased gradually with time prolongation, reaching the lowest level 7 days after modeling, but the GAS level in cerebral infarction model group was significantly higher than that in normal group and shamoperation group (ng/L: 205.02±7.68 vs. 130.51±8.03, 145.29±7.68, both P < 0.05). The pathological scores of gastrointestinal mucosa and small intestinal mucosa in the cerebral infarction model group were increased first and then decreased with time prolongation, peaked on 4th day and decreased significantly on 7th day, the pathological scores of gastrointestinal mucosa and small intestinal mucosa in the cerebral infarction model group at each time point were significantly higher than those in the normal control group and sham-operated group (gastric mucosal pathological score: 82.50±2.95 vs. 21.38±1.57, 36.10±3.41; small intestinal mucosal pathological score: 62.00±2.78 vs. 18.25±1.39, 25.55±1.75, all P < 0.05). Under light microscopy, the normal control group showed complete normal morphological appearance, normal structure, orderly arrangement of villi and no infiltration of inflammatory cells; in shamoperation group, inflammatory cells infiltrated the lamina propria at each time point, and there were villi slightly uneven, enlarged stroma, congestion, edema occasionally seen and no obvious ulcer; in cerebral infarction model group, the various layers of gastrointestinal mucosal were not very clear, the glands were arranged irregularly and the capillaries dilated, and in part of tissues, congestion, hemorrhage, edema and inflammatory cell infiltration were seen obviously. Conclusion The injury of gastrointestinal mucosa in acute stage of cerebral infarction should be related to the stress stimulation and disease progress of cerebral infarction itself, not due to the abnormal secretion of GAS.

Proton pump inhibitors are H+ /K+-ATPase inhibitors, which can efficiently inhibit gastric acid secretion for a long time. As the latest inhibitory gastric acid drugs, proton pump inhibitors are the best choices for acid-related diseases such as gastroe-sophageal reflux disease, peptic ulcer and gastrointestinal lesions caused by nonsteroidal anti-inflammatory drugs. Proton pump inhibi-tors have significant inhibition to basal gastric acid, night gastric acid and gastric acid secretion caused by gastrin and food stimulation. This article reviewed the pharmacokinetic characteristics of five proton pump inhibitors in domestic market.

Objective To assess the prospect of integrated biphasic silk fibroin scaffold made by annulus fibrosus-nu?cleus pulposus tissue engineering in application as integrated intervertebral disc(IVD). Methods An integrated annulus fi brosus-nucleus pulposus(AF-NP)biphasic scaffold was made by silk fi broin using two different uncomplicated methods which were paraffin spheres-leaching method(outer AF phase)and phase separation method(inner NP phase). The scaf?fold was investigated by general observation, stereomicroscope and scanning electron microscopy(SEM). Its pore size, poros?ity, and compressive elastic modulus were determined. AF and NP cells were isolated from rabbit IVD and seeded into the corresponding phase of the scaffold respectively. The cell-scaffold complex was cultured for 48 hours. The biocompatibility of the scaffold was evaluated by SEM, live/dead staining while CCK-8 assay was used to assess cell proliferation. Results Stereomicroscope and SEM showed that AF phase and NP phase integrated perfectly without cross-linking. Both phases pos?sessed highly interconnected porous structure [pore size of AF and NP phase were(220.0±23.1)μm and(90.0±17.8)μm, re?spectively] and highly porosity(AF and NP phase were respectively 91%and 93%). In addition, this silk biphasic scaffold had impressive mechanical properties(150.7 ± 6.8)kPa. SEM revealed that disc cells attached to regions of pore walls, dis?tributed uniformly and secreted extracellular matrix. Live/Dead staining and cell count kit-8(CCK-8)analysis showed that the silk composite scaffold was non-cytotoxic to disc cells. Conclusion This silk biphasic AF-NP scaffold has satisfied pore size, porosity, biomechanical properties and biocompatibility, so it is ideal candidate for IVD tissue engineering.