BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

Objective To investigate the role of sphingosine kinase-1(SPHK1)in regulating migration and invasion of gastric cancer(GC)cells.Methods TIMER2.0,GEPIA and HPA databases were used to investigate SPHK1 expression in GC,and its association with prognosis of the patients was analyzed using Kaplan-Meier Plotter database.In 40 clinical GC and adjacent tissue samples,SPHK1 and MKI67 expressions were detected with immunohistochemistry,Western blotting,and RT-qPCR.Gene enrichment pathway analysis was conducted to explore the biological functions of SPHK1.In HGC-27 and MGC-803 cells,the effects of lentivirus-mediated SPHK1 knockdown or overexpression on cell migration and invasion and expressions of key proteins in the nuclear factor-κB(NF-κB)signaling were evaluated using cell scratch test,Transwell assays and Western blotting.The changes in tumorigenic capacity of the transfected GC cells were evaluated in nude mice.Results SPHK1 was highly expressed in GC tissues in negative correlation with overall survival,overall survival after progression,and relapse-free survival of the patients(all P<0.001).In clinical GC samples,SPHK1 and MKI67 expressions showed a positive correlation(P=0.00049)and were both significantly up-regulated(P<0.001).Gene enrichment pathway analysis suggested the involvement of SPHK1 in cell adhesion,migration,angiogenesis and the NF-κB pathway(P<0.05).In the cell experiment,SPHK1 knockdown significantly decreased while SPHK1 overexpression enhanced migration and invasion abilities of the GC cells.SPHK1 positively regulated the expressions of phosphorylated P65(P-P65),VEGFA and IL-17,and blocking the NF-κB pathway by PDTC significantly lowered migration and invasion ability of the cells.In nude mice,the GC cells with SPHK1 knockdown resulted in significantly reduced tumor size and mass,while the SPHK1-overexpressing cells showed enhanced tumorigenicity.Conclusion SPHK1 regulates migration and invasion of GC cells via the NF-κB signaling pathway and may serve as a potential diagnostic marker for GC progression.

Objective To investigate the role of sphingosine kinase-1(SPHK1)in regulating migration and invasion of gastric cancer(GC)cells.Methods TIMER2.0,GEPIA and HPA databases were used to investigate SPHK1 expression in GC,and its association with prognosis of the patients was analyzed using Kaplan-Meier Plotter database.In 40 clinical GC and adjacent tissue samples,SPHK1 and MKI67 expressions were detected with immunohistochemistry,Western blotting,and RT-qPCR.Gene enrichment pathway analysis was conducted to explore the biological functions of SPHK1.In HGC-27 and MGC-803 cells,the effects of lentivirus-mediated SPHK1 knockdown or overexpression on cell migration and invasion and expressions of key proteins in the nuclear factor-κB(NF-κB)signaling were evaluated using cell scratch test,Transwell assays and Western blotting.The changes in tumorigenic capacity of the transfected GC cells were evaluated in nude mice.Results SPHK1 was highly expressed in GC tissues in negative correlation with overall survival,overall survival after progression,and relapse-free survival of the patients(all P<0.001).In clinical GC samples,SPHK1 and MKI67 expressions showed a positive correlation(P=0.00049)and were both significantly up-regulated(P<0.001).Gene enrichment pathway analysis suggested the involvement of SPHK1 in cell adhesion,migration,angiogenesis and the NF-κB pathway(P<0.05).In the cell experiment,SPHK1 knockdown significantly decreased while SPHK1 overexpression enhanced migration and invasion abilities of the GC cells.SPHK1 positively regulated the expressions of phosphorylated P65(P-P65),VEGFA and IL-17,and blocking the NF-κB pathway by PDTC significantly lowered migration and invasion ability of the cells.In nude mice,the GC cells with SPHK1 knockdown resulted in significantly reduced tumor size and mass,while the SPHK1-overexpressing cells showed enhanced tumorigenicity.Conclusion SPHK1 regulates migration and invasion of GC cells via the NF-κB signaling pathway and may serve as a potential diagnostic marker for GC progression.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To adopt the systematical evaluation method to compare the efficacies between endoscopic retrograde appendicitis therapy (ERAT) versus laparoscopic appendectomy (LA) for treating feca-lith incarceration appendicitis.Methods The databases of PubMed,WANGFANG,CNKI,Cochrane Library and Embase were retrieved by computer.The retrieval time was 2016-2021.The EART related clinical trials were collected,the literatures conforming to the inclusion standard conducted the Jadad scoring,the basic situ-ation of each study and various observation indications (abdominal pain relief,time in bed,hospitalization du-ration,hospitalization expenses,postoperative CRP,postoperative complications) in the ERAT group and LA group were extracted respectively.The RevMan 5.3 software was used for conducting the statistical analysis. Results A total of 33 trials with a total of 2630 patients were included.There were 1294 cases in the ERAT group and 1336 cases in the LA group.The meta analysis results showed that the remission rate of abdominal pain at postoperative 12 h (RR=1.23,95％CI:1.06-1.43),time in bed (with d or h as the unit,WMD=-3.00,95％CI:-3.93 to-2.07;WMD=-9.51,95％CI:-16.12 to-2.90),hospitalization duration (WMD=-2.44,95％CI:-2.90 to-1.98),treatment costs (WMD=-3.00,95％CI:-5.34 to-0.67),postoperative CRP (WMD=-4.94,95％CI:-7.43 to-2.45) and postoperative complications incidence rate (RR=0.24,95％CI:0.18-0.32) had statistical difference between the two groups (P<0.05).Conclu-sion ERAT has more advantages than LA in treating fecalith incarceration appendicitis.

This article reviews the current situation, influencing factors, evaluation tools, and intervention measures of sleep disorders in family caregivers of Alzheimer disease (AD) patients, so as to provide reference for improving the sleep quality and quality of life of family caregivers in AD patients.

Objective:To investigate the features of the brain structural network in patients with postpartum depression (PPD).Methods:This cross-sectional study included PPD patients who visited the mental health counseling clinic after delivery at the Jiangsu University Affiliated Yixing Hospital from June 2013 to September 2022 (PPD group). Matched non-PPD postpartum women based on age, years of education, and body mass index who came for postpartum follow-up (non-PPD postpartum group), and non-pregnant women who visited the hospital or underwent physical examinations during the same period (non-pregnant group) were also included. Demographic data and diffusion tensor imaging (DTI) data were collected for all three groups. The brain was partitioned into 90 regions using an anatomical template to construct the brain structural network. Network-based statistics (NBS) were applied to further screen and construct subnetworks. The efficacy of the subnetworks in identifying PPD was evaluated through multivariable logistics regression models and receiver operating characteristic curves. A comparison of the connectivity strength of white matter tracts and topological attributes of brain structural network parameters was conducted using independent samples t-tests, and the results were corrected using the false discovery rate (FDR) method. Results:(1) A total of 116 subjects were included, with 40 in the non-pregnant group, 40 in the non-PPD postpartum group, and 36 in the PPD group. PPD group had higher Edinburgh Postnatal Depression Scale (EPDS) scores than the non-pregnant and non-PPD postpartum groups [(18.0±4.1) scores vs. (2.5±1.2) and (6.1±2.1) scores, F=340.40; t=24.65,10.60 and 16.16 in pairwise comparison; all P<0.001]. (2) Compared to the non-pregnant group, there was a decrease in the connectivity strength of nine white matter tracts within the brain structural network of the postpartum group (including left dorsolateral superior frontal gyrus-left anterior cingulate and paracingulate gyrus, left dorsolateral superior frontal gyrus-right amygdala, left dorsolateral superior frontal gyrus-left insula, left insula-left lentiform nucleus, left insula-left hippocampus, left hippocampus-right amygdala, left hippocampus-left precuneus, left anterior cingulate and paracingulate gyrus-right amygdala, and right amygdala-right hippocampus) (all P<0.05, FDR corrected). No increased connection strengths were observed. There were no significant differences in the connection strengths of these nine tracts between the non-PPD and PPD groups. (3) A characteristic subnetwork for the maternal group was successfully constructed based on the nine tracts, which exhibited typical small-world properties (σ>1). Compared to the non-PPD maternal group, the characteristic path length in the PPD group was increased [(3.904±0.328) vs. (4.130±0.433), t=－2.58], and global efficiency was decreased [(0.361±0.036) vs. (0.331±0.053), t=2.91] (both P<0.05). Local property comparisons showed that the node efficiency values for the left dorsolateral superior frontal gyrus, left insula, left anterior cingulate and paracingulate gyrus, left hippocampus, right hippocampus, right amygdala, left precuneus and left putamen in the PPD group were significantly reduced [(0.273±0.023) vs. (0.267±0.030), t=0.98; (0.299±0.035) vs. (0.276±0.041), t=2.64; (0.265±0.019) vs. (0.258±0.025), t=1.38; (0.318±0.028) vs. (0.305±0.031), t=1.92; (0.312±0.027) vs. (0.302±0.031), t=1.50; (0.322±0.030) vs. (0.298±0.026), t=3.71; (0.356±0.040) vs. (0.338±0.056), t=1.62; (0.346±0.028) vs. (0.331±0.036), t=1.74; all P<0.05]. However, only the differences in node efficiency values for the left insula and right amygdala remained significant after FDR correction (corrected P=0.041 and 0.003). (4) Global efficiency, as well as node efficiency for the left insula and right amygdala, demonstrated good value for identifying PPD [areas under the curve (AUC) and their 95% CI were 0.827 (0.732-0.922), 0.741 (0.628-0.854), and 0.761 (0.653-0.867), respectively], with even better performance when combined [0.897 (0.828-0.969)]. (5) In the PPD group, global efficiency ( r=－0.43, P=0.008), node efficiency for the left insula ( r=－0.39, P=0.019), and node efficiency for the right amygdala ( r=－0.42, P=0.011) were all negatively correlated with EPDS scores. Conclusion:Aberrations in global efficiency, node efficiency for the left insula, and node efficiency for the right amygdala may serve as characteristic neuroimaging biomarkers for PPD.

Objective To test the reliability and validity of the Chinese version of the Nine-Item Avoidant/Restrictive Food Intake Disorder Scale (NIAS) in patients with inflammatory bowel disease (IBD). Methods Based on convenience sampling method, 304 patients from the Treatment Center for Inflammatory Bowel Disease of two Grade Ⅲ Level hospitals A in Jiangsu Province were selected as the research objects, and they were investigated by a general information questionnaire, NIAS, and the Satisfaction with Food-Related Life (SWFL). Item analysis (discrimination analysis, correlation coefficient) and reliability analysis of the total scale and subscales (Cronbach's α coefficient) were performed. Exploratory factor analysis, confirmatory factor analysis, criterion-related validity, convergent validity, and discriminant validity were used to test the validity of the scale. Results The Chinese version of NIAS contained 9 items, including 3 subscales of picky eating, appetite and fear; the confirmatory factor analysis indicated a good construct validity in 3-factor model[χ²/df=2.340, root mean square error of approximation (RMSEA)=0.078, standardized root mean square residual (SRMR)=0.046, incremental fit index (IFI)=0.969, comparative fit index (CFI)=0.969, normed fit index (NFI)=0.948, goodness of fit index (GFI)=0.951, the Tucker-Lewis index (TLI)=0.951]; the correlation coefficient between the total score of the Chinese version of NIAS and the SWFL scale was -0.353, indicating a strong correlation; the aggregated validity CR values for each dimension of the scale were 0.821 to 0.855, and the AVE values were 0.606 for appetite, 0.621 for picky eating, and 0.664 for fear. The total Cronbach's α coefficient of the Chinese version of the NIAS scale was 0.82, and the Cronbach's α coefficients for dimensions of picky eating, appetite and fear were 0.87, 0.71 and 0.92 respectively, indicating the Chinese version of the NIAS scale had good internal consistency and stability. Conclusion The Chinese version of the NIAS scale has good reliability and validity, and can be used to evaluate avoidant and restrictive food intake disorder behaviors in IBD patients.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.