OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

Objective:To study the effect of preoperative pancreatic duct stent placement in enucleation (EN) of pancreatic tumor adjacent to the main pancreatic duct (MPD).Methods:Clinical data of 56 patients with benign or borderline pancreatic tumor adjacent to the MPD undergoing EN in the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from January 2022 to September 2024 were retrospectively analyzed, including 25 males and 31 females, aged (32.0±5.5) years. Among the patients, 35 (62.5%) were solid pseudopapillary neoplasm, 15 (26.8%) were neuroendocrine tumor, and 6 (10.7%) were serous cystic tumor. According to whether the pancreatic duct stent was placed through encoscopic retrograde cholangiopancreatography preoperatively, patients were divided into the stent group ( n=20, observation group) and no-stent group ( n=36, control group). The operation time, intraoperative pancreatic duct injury, tumor enucleation time and blood loss, grade B/C pancreatic fistula and postoperative hospital stay were compared between the two groups. Results:All patients underwent EN successfully. The operation time in the observation group was shorter than that in the control group [150.0 (143.5, 159.0) vs 158.0 (150.0, 180.0) min, Z=-2.08, P=0.031], and the rate of intraoperative MPD injury in the observation group was lower than that in the control group [10.0% (2/20) vs 38.9% (14/36), χ2=5.26, P=0.022]. The tumor enucleation time and blood loss were comparable between the two groups (both P>0.05). The rate of postoperative grade B/C pancreatic fistula in the observation group was lower than that in the control group [15.0% (3/20) vs 41.7% (15/36), χ2=4.19, P=0.041], and the postoperative hospital stay was also shorter in the observation group [(7.9±1.6) vs (9.3±2.1) d, t=-2.57, P=0.014]. Conclusion:Under the premise of matured endoscopic operation, preoperative pancreatic duct stent placement through ERCP in the EN of pancreatic tumor adjacent to the MPD can protect the MPD during operation, reduce the occurrence of postoperative grade B/C pancreatic fistula, and shorten the postoperative hospital stay.

Objective:To investigate the clinical efficacy of haploidentical high-dose in vitro non-T-cell-depleted peripheral blood hematopoietic stem cell transplantation (haplo-HDPSCT) in treating adult patients with Ph + acute lymphoblastic leukemia (Ph + ALL) . Method:This retrospective analysis was conducted on the clinical efficacy of 25 adult patients with Ph + ALL who underwent haplo-HDPSCT from July 2011 to June 2022 at our hospital. Results:This study included 25 patients with a median age of 27 (16-61) years, consisting of 12 males and 13 females. CR1 and ≥CR2 before transplantation were found in 23 and 2 cases, positive and negative minimal residual lesions were observed in 8 and 17 cases, and myeloablative conditioning and reduced-intensity conditioning were reported in 21 and 4 cases, respectively. Hematopoietic function was restored in all 25 patients after stem cell infusion. Of the 25 patients who underwent transplantation, 16 developed acute graft-versus-host disease (aGVHD). The cumulative incidence rates of Ⅱ-Ⅳ and Ⅲ-Ⅳ aGVHD were (40.4±11.3) % and (4.8±4.6) %, respectively. Four patients experienced relapse after transplantation, the cumulative relapse rates at 1 and 2 years after transplantation were (4.0±3.9) % and (14.5±7.9) %, respectively. The 2-year overall survival rate after transplantation was (81.3±8.5) % and the disease-free survival rate was (77.1±9.1) %.Conclusion:This study reveals that the unique haplo-HDPSCT protocol achieves good clinical efficacy in Ph + ALL treatment.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

Objective:To study the association between subtypes of hypertension and risk for all-cause mortality and cardio-cerebrovascular mortalities in the elderly in communities of Beijing.Methods:The data were collected from the Beijing Healthy Aging Cohort Study. The elderly in 5 urban areas (former Xicheng, former Xuanwu, Fangshan, Haidian and Tongzhou) and 4 rural areas (Yanqing, Miyun, Huairou and Daxing) in Beijing were selected as the study subjects by multi-stage stratified cluster random sampling. The baseline survey was conducted from July 2009 to September 2015. The follow-up was conducted until March 31, 2021, and a total of 6 326 participants were enrolled. Cox proportional hazard regression model was used to analyze the association of SBP, DBP, normal blood pressure, high normal blood pressure, simple systolic hypertension, simple diastolic hypertension and systolic diastolic hypertension with all-cause mortality and cardio-cerebrovascular mortality.Results:By March 31, 2021, the median follow-up time was 6.30 years, the all-cause mortality density was 201.67/10 000 person-years, and the cardio-cerebrovascular mortality density was 90.20/10 000 person-years. Multivariate Cox proportional hazard regression model analysis showed that the risk for all-cause mortality increased by 5.6% ( HR=1.056, 95% CI: 1.020-1.092), and the risk for cardio-cerebrovasculvar mortality increased by 12.5% ( HR=1.125, 95% CI: 1.071-1.182) for every 10 mmHg increase in SBP. The risk for all-cause mortality increased by 8.6% ( HR=1.086, 95% CI: 1.023-1.152), and the risk for cardio-cerebrovascular mortality increased by 19.9% ( HR=1.199, 95% CI: 1.101-1.306) for every 10 mmHg increase in DBP. Compared with the normal blood pressure group, the risk for all-cause mortality increased by 64.8% ( HR=1.648, 95% CI: 1.049-2.591) and the risk for cardio- cerebrovascular mortality increased by 112.8% ( HR=2.128, 95% CI: 1.069-4.233) in the simple diastolic hypertension group. The risk for all-cause mortality increased by 34.4% ( HR=1.344, 95% CI: 1.023-1.467) and the risk for cardio-cerebrovascular mortality increased by 111.3% ( HR=2.113, 95% CI: 1.384-3.225) in the systolic-diastolic hypertension group. Conclusions:In the elderly in communities of Beijing, beside systolic-diastolic hypertension. It is necessary to pay close attention to the simple diastolic hypertension, which has lower prevalence, and give targeted prevention and treatment.

Objective:To investigate the association of urinary albumin-to-creatinine ratio (UACR) in normal range and cardiovascular health (CVH) score with cardio-cerebroascular and all-cause mortality in urban elderly residents in Beijing.Methods:Based on Beijing Healthy Aging Cohort Study, data from 1 817 elderly participants with normal UACR were analyzed, and UACR was used as both continuous and categorical variable. "Life's Essential 8" was used to develop a CVH score. Statistical analysis was performed by using software SPSS 26.0 and R 4.2.1, including two independent samples t-test, χ2 test and non-parametric test. Multivariable Cox proportional hazard regression models stratified by CVH score and the restricted cubic spline were used to analyse the association of UACR with the risk for cardio-cerebrovascular and all-cause mortality. Results:By March 31, 2021, the median follow-up time M ( Q1, Q3) was 11.28 (10.84, 11.36) years, a total of 308 deaths were recorded during follow-up, and the mortality density was 163.87/10 000 person-years. The age of the participants was (71.4±6.6) years, and 1 070 participants were women. The results showed that the risk for both cardio-cerebrovascular disease and all-cause mortality decreased with the decrease of UACR in the low CVH score group ( HR=0.500, 95% CI: 0.341-0.734; HR=0.793, 95% CI: 0.647-0.971), and in the high CVH score group, there was a decreasing trend in the risk for cardio-cerebrovascular mortality with the decrease of UACR ( HR=0.665, 95% CI: 0.447-0.990). Compared with the participants with low CVH score and higher UACR, the risk for cardio-cerebrovascular and all-cause mortality decreased by 68.9% and 45.6%, respectively, in the participants with high CVH score and lower UACR ( HR=0.311, 95% CI: 0.131-0.739; HR=0.544, 95% CI: 0.360-0.822), and the risk for all-cause mortality decreased by 26.7% in the participants with high CVH score and higher UACR ( HR=0.733, 95% CI: 0.542-0.993). Conclusions:In urban elderly residents in Beijing, higher UACR were associated with a significantly increased risk for cardio-cerebrovascular and all-cause mortality, and in the low-CVH score group, decreased UACR was protective factor against cardio-cerebrovascular and all-cause mortality. The combined effect of cardiovascular health status and normal UACR had a greater protection against the risk for cardio-cerebrovascular and all-cause mortality.

Objective:To describe and analyze the distribution characteristics of a body shape index (ABSI) and its association with all-cause mortality in the elderly in communities of Beijing.Methods:The baseline and follow-up data of 10 423 subjects in Beijing Healthy Aging Cohort Study were used. The endpoint outcome was all-cause mortality in follow-up. The associations of ABSI, BMI and waist circumference with all-cause mortality were analyzed with a Cox proportional hazard regression model.Results:The mean follow-up time in this cohort was 6.36 years and the all-cause mortality was 15.27%. The restricted cubic spline results showed that ABSI showed a "U" association with all-cause mortality in the total population. After adjustment for confounding factors, compared with the normal ABSI group, the risk for all-cause mortality was higher in the low ABSI group ( HR=1.69, 95% CI: 1.32-2.17) and high ABSI group ( HR=1.75, 95% CI: 1.40-2.18). Compared with the normal BMI group, low BMI was associated with an increased risk for all-cause mortality ( HR=1.70, 95% CI: 1.40-2.08). Compared with the normal waist circumference group, central obesity was associated with a decreased risk for all-cause mortality ( HR=0.89, 95% CI: 0.80-0.99). The results of gender specific analysis on ABSI association with all-cause mortality were similar to that in total population, but the strength of association varied among different age groups. Cross-grouping results showed that older people with normal BMI and waist circumference and abnormal ABSI had an increased risk of all-cause mortality ( HR=1.91, 95% CI: 1.22-2.99). Conclusions:In Beijing, ABSI is correlated with the risk for all-cause mortality in the elderly population, which is more sensitive and specific than the traditional indicators (BMI and waist circumference). They can be used as one of the physical measurement indicators for all-cause mortality risk prediction in the health risk assessment and management in the elderly.

Objective:To explore the association between physical activity (PA) level and all-cause mortality in the elderly with different obesity status in Beijing.Methods:The study subjects were from the Cardiovascular and Cognitive Healthy Study in Middle-Aged and Elderly Residents of Beijing, a total of 3 746 individuals aged ≥60 years in the baseline survey between 2013 and 2015 were included in the study. Questionnaire survey and physical examination were conducted to collect the basic information of the individuals. The metabolic equivalent of the elderly was used to calculate the PA level, and an international PA questionnaire was used to determine the PA intensity. BMI, waist-to-height ratio (WHtR) and a body shape index (ABSI) were used to evaluate individuals' obesity status. The distribution of different PA levels under different obesity states was described by using bar chart and cumulative percentage bar chart. Cox proportional hazard regression model was used to analyze the correlation between the level of PA and all-cause mortality risk in different types of obesity status.Results:By December 31, 2019, the median follow-up time was 5.46 years, and the mortality density was 244.55/10 000 person-years. Compared with the individuals in high-PA intensity group, the all-cause mortality risk increased by 41% ( HR=1.41, 95% CI: 1.14-1.76) and 122% ( HR=2.22, 95% CI: 1.76-2.81), respectively, in moderate and low PA intensity groups. Compared with the individuals in high-PA intensity-high-obesity group, based on the BMI, the all-cause mortality risk increased by 85% ( HR=1.85, 95% CI: 1.08-3.16) and 250% ( HR=3.50, 95% CI: 2.01-6.10) in those in moderate-PA intensity-high-obesity group and in low-intensity-high-obesity group. Based on the WHtR, the all-cause mortality risk increased by 53% ( HR=1.53, 95% CI: 1.02-2.29) and 218% ( HR=3.18, 95% CI: 2.09-4.86), respectively, in those with moderate-PA intensity-high-obesity and those with low-PA intensity-high-obesity. According to the ABSI, the all-cause mortality risk increased by 120% in those in low-PA intensity-high-obesity group ( HR=2.20, 95% CI: 1.53-3.18). Based on any one of the indicators BMI, WHtR, or ABSI, there was no significant difference in all-cause mortality risk between high-intensity-moderate-obesity group and high-intensity-low-obesity group (all P>0.05). Conclusions:PA level is closely associated with the all-cause mortality risk in the elderly in communities of Beijing. Increasing PA level can not only reduce the all-cause mortality risk but also reduce even eliminate the excess all-cause mortality risk associated with obesity.

Objective To investigate the mechanism of glycogen synthase kinase-3β（GSK-3β） participating in stroke-induced inflammatory brain injury through endoplasmic reticulum-mitochondria coupling， and to provide a theoretical reference and potential targets for precise treatment. Methods A rat model of middle cerebral artery occlusion was established， and the rats were divided into sham-operation group， model group， and GSK-3β inhibitor（TDZD-8） intervention group. Neurological function score was used to evaluate the degree of brain injury； TTC staining was used to evaluate cerebral infarct area； electron microscopy was used to observe mitochondrial ultrastructure； mitochondrial calcium concentration was measured； ELISA was used to measure the levels of inflammatory factors[tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）]， and Western blot was used to measure the expression levels of related proteins. Results Compared with the sham-operation group， the model group had significant neurological function impairment， an increase in cerebral infarct area， and significant increases in the expression levels of inflammatory factors and GSK-3β，with enhanced endoplasmic reticulum-mitochondria coupling and mitochondrial calcium overload. TDZD-8 significantly improved the above indicators and reduced the levels of inflammatory factors and cerebral infarct area. Conclusion Abnormal activation of GSK-3β damages brain tissue by regulating endoplasmic reticulum-mitochondria coupling and promotes mitochondrial calcium overload and inflammatory response. Inhibiting GSK-3β activity can effectively improve stroke-induced inflammatory brain injury， which provides a new pathway and a molecular target for developing precise treatment strategies.
Stroke

Objective:To construct a nomogram model for predicting the risk factors of gastrointestinal bleeding following laparoscopic pancreaticoduodenectomy (LPD) based on relevant risk factors and evaluate its predictive value.Methods:A retrospective analysis was conducted on 466 patients with periampullary space occupying lesion who underwent LPD at the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University, from January 2021 to December 2024. Among them, there were 284 males and 182 females, aged (59.9±10.7) years. Patients were randomly divided into a training cohort ( n=326) and a validation cohort ( n=140) using a random number table (7: 3 ratio). Based on whether patients suffered gastrointestinal bleeding, the training cohort was further stratified into a gastrointestinal bleeding group ( n=23) and control group ( n=303). Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for gastrointestinal bleeding. A nomogram was constructed based on multivariate results, and its predictive performance was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results:Compared to the control group, the gastrointestinal bleeding group exhibited significantly higher age, higher rates of postoperative pancreatic fistula (POPF) and intra-abdominal infection, along with lower body mass index, and lower levels of fibrinogen and albumin (all P<0.05). Multivariate analysis identified age ( OR=1.065, 95% CI: 1.002-1.132), fibrinogen ( OR=0.486, 95% CI: 0.243-0.969), albumin ( OR=0.840, 95% CI: 0.741-0.953), POPF ( OR=4.299, 95% CI: 1.348-13.716), and postoperative intra-abdominal infection ( OR=6.352, 95% CI: 1.476-27.341) as independent predictors of gastrointestinal bleeding (all P<0.05). The nomogram demonstrated robust discrimination, with an AUC of 0.861 (95% CI: 0.784-0.939), sensitivity of 82.6%, and specificity of 82.2% in the training cohort. In the validation cohort, the AUC was 0.824 (95% CI: 0.675-0.973), with sensitivity and specificity of 80.0% and 83.8%, respectively. Calibration curves indicated excellent agreement between predicted and observed outcomes. DCA revealed superior net clinical benefit of the nomogram over " treat-all" or " treat-none" strategies within threshold probabilities of 0-0.9 (training) and 0-0.75 (validation). Conclusion:The nomogram based on age, fibrinogen, albumin, POPF, and intra-abdominal infection provides accurate prediction of gastrointestinal bleeding after LPD and demonstrates high clinical utility for risk stratification and decision-making in periampullary space occupying lesion patients.