Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

ObjectiveTo investigate the patterns of chronic disease comorbidity among permanent elderly residents in Xuhui District of Shanghai, and to analyze the impact of different comorbidity patterns on the elderly’s ability to perform activities of daily living. MethodsBased on data from the 2015 and 2021 Surveys on Health Status and Health Service Utilization among Permanent Residents in Xuhui District of Shanghai, the study included permanent residents who fully participated in both surveys, were aged 60 years or older at the 2015 survey, self-reported having a chronic disease, and reported no significant changes in their chronic disease status between the two surveys. A prospective cohort study design was adopted, using the 2015 data as the baseline and the 2021 survey data as follow-up data. Physical examinations and questionnaire surveys were conducted by the Shanghai Xuhui District Center for Disease Control and Prevention in the subdistricts and towns within the jurisdiction from April to July in both 2015 and 2021. Latent class analysis (LCA) was used to classify comorbidity patterns across 11 types of chronic diseases. The smaller the values of the Akaike information criterion (AIC), the Bayesian information criterion (BIC), and the sample-corrected Bayesian information criterion (aBIC), the better the model fits. The Barthel index (BI) and the Lawton and Brody Instrumental Activities of Daily Living Scale (LB-IADL) were used to assess the participants’ activities of daily living (ADL) and instrumental activities of daily living (IADL). Multiple linear regression and multivariate logistic regression models were used to analyze the association between different comorbidity patterns and ADL and IADL. ResultsA total of 1 608 study participants were enrolled. Among them, 671 (41.73%) self-reported having no chronic diseases. The prevalence of 11 types of chronic diseases was as follows: hypertension in 743 participants (46.21%), heart disease in 148 participants (9.20%), cerebrovascular disease in 37 participants (2.30%), diabetes or abnormal blood glucose in 310 participants (19.28%), other endocrine system diseases (non-diabetic) in 39 participants (2.43%), malignant tumors in 37 participants (2.30%), chronic lung disease in 16 participants (1.00%), gout in 8 participants (0.50%), musculoskeletal disorders in 34 participants (2.11%), gastric or digestive system diseases in 27 participants (1.68%), and dyslipidemia in 15 participants (0.93%). LCA was used to classify comorbidity patterns of chronic diseases among older adults into 1 to 9 latent category combinations. Model 5 (i.e., 5 latent categories) had the lowest BIC (7 112.69) and aBIC (6 909.38), with a relatively low AIC (6 768.20), indicating the best model fit; thus, five latent categories represented the optimal combination in this study. The five latent categories (and their respective proportions of study participants) were the healthy control group (41.73%), the hypertension group (31.28%), the diabetes-hypertension group (19.28%), the severe illness group (5.29%), and the other metabolic diseases group (2.43%). According to multiple linear regression analyses, compared with the healthy control group, the diabetes-hypertension group had significantly lower BI-20 scores (b=-0.952, 95%CI: -1.317‒ -0.587, P<0.001) and lower IADL scores (b=-0.744, 95%CI: -0.999‒ -0.489, P<0.001); the severe illness group (b=-0.644, 95%CI: -1.072‒ -0.217, P=0.003) and the hypertension group (b=-0.344, 95%CI: -0.562‒ -0.125, P=0.002) had lower IADL scores. According to multivariate logistic regression analyses, compared with the healthy control group, older adults in the diabetes-hypertension group had a higher risk of disability (OR=2.835, 95%CI: 1.392‒5.774), impaired ADL function (OR=2.470, 95%CI: 1.637‒3.726), and impaired IADL function (OR=1.739, 95%CI: 1.264‒2.392); older adults in the severe illness group had a higher risk of impaired ADL function (OR=2.206, 95%CI: 1.171‒4.155). ConclusionAmong the elderly participating in the Survey on Health Status and Health Service Utilization of Permanent Residents in Xuhui District of Shanghai, diabetes-hypertension is one of the key chronic disease comorbidity combinations and has adverse effects on both ADL and IADL. Community health management should prioritize the elderly with diabetes-hypertension comorbidity, and strengthen early screening and comprehensive interventions to slow the decline in ADL and IADL.

Objective To explore the effects of sigma-1 receptor(Sig-1R)on brain function in rats after cardiopulmo-nary resuscitation and its protective role in brain injury.Methods Rats were randomly assigned to four groups with 20 in each:sham-operated control(sham group),6-hour post-resuscitation(PR 6 h group),12-hour post-resuscitation(PR 12 h group)and 24-hour post-resuscitation(PR 24 h group).In the latter three groups,cardiac arrest was induced by as-phyxiation,and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest.The rats were scored for neu-rological deficits at 6,12 and 24 hrs after resuscitation,respectively;after that,the rats were executed,and the expres-sion of Sig-1R protein,mitochondrial function index,and endoplasmic reticulum stress index apoptosis index were detec-ted by Western blot and immunohistochemistry.The correlation between Sig-1R and mitochondrial,endoplasmic reticulum stress and apoptosis indexes was evaluated.Results Compared with the sham-operated group,the rats in test group showed a gradual decrease in neurological deficit scores,Sig-1R protein expression,brain tissue adenosine triphos-phate(ATP)concentration and mitochondrial membrane potential(MMP)levels at 6,12,and 24 hrs of PR(P＜0.05);CHOP protein,activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated(P＜0.05).In addition,Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05)but positively correlated with mitochondrial membrane potential level(P＜0.05).Conclusions Sig-1R ex-pression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.

Objective:To explore the impact of female body mass index (BMI) on pregnancy outcomes in artificial insemination with donor sperm (AID).Methods:A retrospective cohort study was conducted on 4 484 couples with 9 852 AID treatment cycles treated at Reproductive Center of Guangdong Institute of Reproductive Science from January 2011 to September 2024. Participants were divided into four groups based on BMI: low BMI group (BMI<18.5 kg/m 2), normal BMI group (18.5 kg/m 2≤BMI<24.0 kg/m 2), overweight group (24.0 kg/m 2≤BMI<28.0 kg/m 2), and obese group (BMI≥28.0 kg/m 2). General characteristics and pregnancy outcomes were compared across groups. Kaplan-Meier survival analysis was used to calculate cumulative pregnancy rates from one to six cycles. Generalized estimating equations (GEE), univariate and multivariate logistic and Cox regression analysis were performed, adjusting for age, basal follicle-stimulating hormone, basal luteinizing hormone, endometrial thickness, clinical diagnosis, and treatment protocol, to explore correlations between female BMI and clinical pregnancy rate, spontaneous abortion rate, and cumulative pregnancy rate. Results:1) There were no statistically significant differences in clinical pregnancy rate and spontaneous abortion rate among the low BMI group, the normal BMI group, the overweight group, and the obesity group (all P>0.05). 2) Cumulative pregnancy rates for AID cycles 1-6 were 17.60%, 31.60%, 43.08%, 54.37%, 61.83% and 73.68%, respectively. 3) Multivariate GEE analysis revealed that female age ( OR=0.962, 95% CI: 0.950-0.974, P<0.001), endometrial thickness ( OR=1.040, 95% CI:1.011-1.069, P=0.006), and natural cycles ( OR=1.171, 95% CI: 1.060-1.294, P=0.002) influenced clinical pregnancy rates. Compared with the normal BMI group, there were no statistically significant differences in clinical pregnancy rates of low BMI group, overweight group, and obese group (all P>0.05). Multivariate logistic analysis showed that female age ( OR=1.051, 95% CI: 1.012-1.091, P=0.010), endometrial thickness ( OR=0.920 , 95% CI: 0.847-1.000, P=0.049) and polycystic ovary syndrome ( OR=1.927, 95% CI: 1.044-3.556, P=0.036) influenced spontaneous abortion rates. Compared with the normal BMI group, there were no statistically significant differences in spontaneous abortion rates of low BMI group, overweight group and obese group (all P>0.05). 4) Cox regression analysis indicated that female age ( HR=0.939, 95% CI: 0.928-0.950, P<0.001), endometrial thickness ( HR=1.039, 95% CI: 1.013-1.066, P=0.003) and natural cycles ( HR=1.957, 95% CI: 1.785-2.146, P<0.001) influenced cumulative pregnancy rates. Compared with the normal BMI group, there were no statistically significant differences in cumulative pregnancy rates of low BMI group, overweight group and obese group (all P>0.05). Conclusion:Female BMI does not significantly affect clinical pregnancy rates, spontaneous abortion rates and cumulative pregnancy rates in AID.

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

Objective:To explore the significance of genetic diagnosis, clinical characteristics and treatment of congenital renal diabetes insipidus with arginine vasopressin receptor 2 ( AVPR2). Methods:Clinical data of three patients diagnosed as diabetes insipidus were retrospectively analyzed.Results:The three cases were 3-month, 5-month and 6-month male infants, respectively. The main manifestations were repeated fever and growth retardation with hypernatremia. Polydipsia, polyuria and persistent hypogravity uria appeared during the course . In case 1, the AVPR2 exon c.613_c.614del resulted in amino acid change p.Y205Cfs*53. The proband mother was a mutation carrier of AVPR2 gene, and the child was hemizygous and the mother was heterozygous. In case 2, there was a hemizygotic mutation in AVPR2 gene: c.255C>A(p.SP85Glu), which appeared to be a missense mutation. The father had no mutation, the mother had a heterozygous mutation, the aunt had no mutation, and the eldest brother had a hemizygous mutation. There was one hemizygotic variation in the AVPR2 gene in patient 3: c.167G>A(P.LY56ASP), which was a missense mutation. The father had no mutation, the mother had a heterozygous mutation. The minimum allele frequencies of the gene variants in case 2 and case 3 were not recorded in the reference population gene frequency database. The urine volume of 3 children was significantly reduced after treatment with hydrochlorothiazide and amiloride.After genetic test, all three cases were diagnosed as congenital renal diabetes insipidus caused by AVPR2 gene mutation. Conclusion:Genetic testing benefits to the early diagnosis of congenital renal diabetes insipidus.

OBJECTIVE To preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

Autism spectrum disorder（ASD）is a multifactorial，pervasive neurodevelopmental disorder.As the morbidity rate of ASD in children increases year by year，feeding and eating behaviors，as an important and common clinical problem in children with ASD，are gaining more and more attention.Many children with ASD often have food selection issues，chewing problems，food allergy and related gastrointestinal symptoms，and even serious diseases such as eating disorders，which negatively impact on their growth and development.There are many factors affecting feeding and eating behavior problems in children with ASD，such as sensory processing，ritualistic eating behavior，gastrointestinal symptoms，age，and parenting pressure.There are also a variety of interventions that can help to improve feeding and eating behavior problems in children with ASD.Strengthening the understanding of these influencing factors and intervention treatment methods is beneficial for improving the quality of life in children with ASD.

Microsurgery is a surgical technique that applies fine instruments to perform precise operations on tiny tissues and organs under optical magnification devices. Digital and intelligent technologies, such as digital imaging, virtual reality (VR), augmented reality (AR), mixed reality (MR), 3D design and reconstruction, 3D printing, digital navigation, mixed perception of multi-source heterogeneous information, automatic control, digital twins, Internet of Things, cloud computing, machine learning, deep learning, large-scale AI models, generative artificial intelligence and so on, have been enabling the innovative development in microsurgery. It will make significant changes in disease diagnosis and monitoring, treatment decision-making and surgical planning, precise and individualised surgery, doctor-patient interaction and healthcare, team collaboration and professional education, and will drive the innovative development in microsurgery.

Objective:To explore the application value of problem-based learning (PBL) combined with mini-clinical evaluation exercise (Mini-CEX) in the development of post competency for interns in the Department of Neurology.Methods:A total of 56 interns rotating at the Department of Neurology of The First Affiliated Hospital of Chongqing Medical University from June 2023 to January 2024 were enrolled as the study subjects. They were randomly divided into a control group and an experiment group using the random number table method, with 28 interns in each group. The control group received traditional methods including small lectures and teaching rounds, while the experimental group received the PBL teaching method combined with Mini-CEX. The teaching effectiveness was evaluated through theoretical assessments, practical skill evaluations, teacher and student satisfaction surveys, and Mini-CEX scale assessments conducted at the beginning, middle, and end of the rotation for the experimental group. The data were analyzed using SPSS 23.0 software. For continuous data, the independent-samples t test or Mann-Whitney U test was used for comparison between groups. The chi-square test was used for categorical data and the Kruskal-Wallis H test for repeated-measurement data. Results:The theoretical scores [(45.36±2.67) vs. (42.00±4.29), P<0.01] and practical skill scores [(45.11±2.53) vs. (42.39±4.53), P<0.01] were significantly higher in the experimental group compared to the control group. The Mini-CEX score of the experimental group at the end of the rotation was notably higher than that at the beginning of rotation ( P<0.05), and their abilities improved continuously. The satisfaction rates of teachers and students in the experimental group were 71.43% (20/28) and 67.86% (19/28), respectively, which were significantly higher than those in the control group [39.29% (11/28) and 35.71% (10/28), P<0.05]. Conclusions:The teaching model integrating PBL and Mini-CEX can effectively enhance the post competency of interns in the Department of Neurology, thus offering a new perspective for clinical undergraduate teaching.