Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Ferroptosis,a programmed cell death induced by iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species,is a key pathological mechanism of neuronal death during the progression of Alzheimer's disease(AD),contributing to the formation of"Ferroptosis Hypothesis"for AD pathogenesis.In recent years,there has been extensive research on therapeutic strategies for AD based on the pathogenic mechanism of ferroptosis,focusing primarily on the dysregulation of brain iron metabolism and redox regulation in microenvironment.However,presence of blood-brain barrier and intricate pathological environment within brain impose limitations on intracranial drug transportation,distribution and therapeutic efficacy,thereby necessitating advancements in drug delivery technology.Based on description of ferroptosis process and its regulatory mechanisms,this review explores the association between iron overload and redox imbalance with neuronal loss and AD development,and additionally,summarizes the advancements in nano drug delivery systems targeting iron overload and redox imbalance for potential anti-AD treatments,so as to offer some novel perspectives for AD treatment and drug development.

Objective To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus(iNPH)using two-sample bidirectional Mendelian randomization.Methods The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog,FinnGenR10 and MRCIEU GWAS.The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10.We used the inverse-variance weighted(IVW)method to perform the principal analyses.Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger-intercept test performed to evaluate the pleiotropy for sensitivity analyses.Results IVW result showed that frequent daytime nap was associated with higher odds of iNPH(OR=3.3393,95 CI%:1.0646-10.4742,P=0.0270).Cochrane Q-statistics test and MR Egger-intercept test showed that the MR analysis had no pleiotropy or heterogeneity(P>0.05).The external validation reproduced this result(OR=2.5660,95 CI%:1.1680-5.6373,P=0.0189;OR=4.0424,95 CI%:1.5709-10.4024,P=0.0038).Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype.Conclusion The frequency of daytime naps is causally associated with iNPH,and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Objective:To investigate pediatric colonoscopy procedures and the associated changes in the disease spectrum.Methods:The clinical data of 1 087 children who underwent pediatric colonoscopy at the Second Affiliated Hospital of Nanjing Medical University and Yili Prefecture Friendship Hospital Affiliated to Nanjing Medical University from January 2012 to December 2022 were retrospectively collected. Patients were divided into 0-3 ( n=165), 4-6 ( n=307), 7-10 ( n=275) and 11-14 ( n=340) years groups according to their age, and also divided into two time periods according to the examination time point, 2012-2017 ( n=302) and 2018-2022 ( n=785) groups. Indicators that were observed and analyzed included the primary reasons for colonoscopy, types and proportions of abnormalities, distribution of cases and symptoms by period and age group, and disease diagnosis and treatment before and after colonoscopy. Results:A total of 1 238 colonoscopies were completed in 1 087 children. Blood in the stool was the most common cause (337/1 087, 31.00%). The most abnormalities were found in intestinal polyps (190/1 087, 17.48%) and inflammatory bowel disease (IBD) (181/1 087, 16.65%), as well as in 95 cases (95/1 087, 8.74%) who were confirmed autism and requested colonoscopy placement for fecal microbiota transplantation (FMT). There were differences in case distribution and symptoms among different age groups: polyps were most common in the 0-3 years group (75/165, 45.45%), and IBD was most common in the 11-14 years group (97/340, 28.53%). Compared with 2012-2017, during 2018-2022, the proportion of colonoscopies for polyps in children decreased [from 49.67% (150/302) to 5.10% (40/785), P<0.001], while the proportion for IBD increased [from 12.25% (37/302) to 18.34% (144/785), P=0.016], and autism requiring colonoscopic duct placement for FMT increased [from 2.32% (7/302) to 11.21% (88/785), P<0.001]. Conclusion:Pediatric colonoscopy plays an important role in the diagnosis and treatment of pediatric diseases. With the increasing clinical application demands, diversified procedures such as pre-FMT colonoscopic duct placement are becoming important directions for the future development of pediatric colonoscopy.

Objective:To investigate the risk factors for organoid culture failure in colorectal cancer.Methods:This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples.Results:The median (range) duration of organoid culture was 7 (3–12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant ( P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ 2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ 2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335–0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285–0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154–63.131, P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112–61.882, P=0.039) were identified as independent protective factors. Conclusions:The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

Objective:To investigate the risk factors for organoid culture failure in colorectal cancer.Methods:This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples.Results:The median (range) duration of organoid culture was 7 (3–12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant ( P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ 2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ 2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335–0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285–0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154–63.131, P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112–61.882, P=0.039) were identified as independent protective factors. Conclusions:The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

Background and Objectives: The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN. Methods: and Results: Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its con-trol lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H2O2 to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H2O2 -induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H2O2 -induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H2O2 -induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H2O2 -induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN. Conclusions MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKTpathway through PTEN.

Objective:To explore the efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy combined with total laparoscopic D2 radical gastrectomy in the treatment of gastric cancer.Methods:The clinical data of 127 patients with gastric cancer who were admitted to the Central Hospital of Hanzhong in Shaanxi Province from August 2017 to July 2019 were retrospectively analyzed. All patients underwent total laparoscopic D2 radical gastrectomy, of which 58 patients underwent total laparoscopic D2 radical gastrectomy combined with intraoperative hyperthermic intraperitoneal chemotherapy (observation group), and 69 patients underwent total laparoscopic D2 radical gastrectomy (control group). Observation indicators included surgical and postoperative recovery situations and postoperative tumor-related indicators. Follow-up was performed by using outpatient examination and telephone interview, and the content of follow-up included patient's adjuvant chemotherapy, tumor recurrence and metastasis, and surgery-related complications.Results:In the observation group, the intraoperative blood loss was (199±48) ml, the number of lymph node dissection was 35±8, the total hospitalization cost was (53 261±4 316) yuan, alanine aminotransferase was (30±10) U/L, and creatinine was (124±26) μmol/L; in the control group, the intraoperative blood loss was (184±46) ml, the number of lymph node dissection was 34±13, the total hospitalization cost was (52 146±4 817) yuan, alanine aminotransferase was (31±10) U/L, and creatinine was (128±33) μmol/L; there were no significant differences between the two groups ( t values were 1.833, 0.618, 1.363, 0.721, and 0.856, all P > 0.05). In the observation group, the operating time was (352±44) min, carcinoembryonic antigen (CEA) at 1 month after operation was (3.9±2.1) ng/ml,CEA at 6 months after operation was (12.7±7.2) ng/ml, tumor abnormal protein (TAP) at 1 month after operation was (75±36) μm 2,TAP at 6 months after operation was (131±33) μm 2; in the control group, the operating time was (308±58) min,CEA at 1 month after operation was (8.3±4.5) ng/ml, CEA at 6 months after operation was (15.8±4.2) ng/ml, TAP at 1 month after the surgery was (88±24) μm 2, TAP at 6 months after operation was (149±37) μm 2; there were significant differences between the two groups ( t values were 4.792, 7.185, 2.832, 2.284, and 2.984, all P<0.05). One hundred and twenty seven patients were followed up for 12-24 months. Fifty-one and 58 patients in the observation group and control group received postoperative adjuvant chemotherapy, and there was no significant difference between the two groups ( χ2 = 0.389, P = 0.533). Tumor recurrence was respectively detected in 0 and 6 patients in the observation group and control group at 6 months after operation; tumor recurrence was respectively detected in 2 and 11 patients in the observation group and control group at 1 year after operation; the differences in the recurrence rates between the two groups were statistically significant (both P < 0.05). Conclusion:Intraoperative hyperthermic intraperitoneal chemotherapy combined with total laparoscopic surgery for gastric cancer does not increase the patient's perioperative risk and the incidence of postoperative complications, and it can reduce the risk of postoperative recurrence and improve the short-term efficacy.

Objective: To investigate the value of enhanced recovery after surgery (ERAS) in D2 radical resection of distal gastric cancer under total laparoscopy and its effect on inflammatory factors. Methods: The clinical data of 50 patients with distal gastric cancer at Hanzhong Central Hospital from March 2016 to October 2017 were retrospectively analyzed. The patients were divided into the observation group (25 cases) and the control group (25 cases). The observation group received totally laparoscopic radical D2 gastrectomy for distal gastric cancer under the guideline of ERAS; the control group received totally laparoscopic radical D2 gastrectomy for distal gastric cancer under the guideline of the traditional method. The changes of perioperative related indexes, postoperative recovery and postoperative inflammatory indexes were compared between the two groups. Results: All 50 patients successfully completed the operation. The operation time was (287.2±52.3) min and (296.8±57.9) min, respectively of the observation group and the control group; the number of lymph node dissection was (34.0±11.0) and (34.6±14.3), respectively of the observation group and the control group. There were no significant differences in the above indexes between the two groups (all P > 0.05). The hospitalization time, the hospitalization cost, the postoperative time of getting out of bed of the observation group was (22.0±2.8) d, (61 044.4±4 692.7) yuan, (12.8±1.8) h. The hospitalization time, the hospitalization cost, the postoperative time of getting out of bed of the control group was (23.9±1.9) d, (63 875.81±4 392.6) yuan, (23.7±8.2) h. And there were statistically significant differences between the two groups (all P < 0.05). The pain score on the 1st day was (5.0±0.8) score and (6.4±1.0) score, and on the 4th day was (2.7±0.9) score and (3.9±0.9) score, respectively of the observation group and the control group, and there was a statistical difference (all P < 0.05). There was no statistical difference in the 7th day pain score between the two groups (P > 0.05). There were no statistically significant differences in the tumor necrosis factor α, interleukin-6 (IL-6), C-reactive protein and procalcitonin on the day before the operation of both groups (all P > 0.05); the levels of above four factors in the observation group were lower than those in the control group on the 1st, 4th and 7th day after the operation, and the differences were statistically significant (all P < 0.05). Conclusion The application of ERAS in totally laparoscopic radical resection of gastric cancer can improve the postoperative condition, significantly reduce the inflammatory reaction of patients, which has a certain value of improving the quality of life of patients.

Objective To investigate the expression levels of peripheral blood and clinical signifi-cance of High mobility group protein B1 (HMGB1) and toll-like receptor 4 (TLR-4) in children with systemic lupus erythematosus (SLE). Methods Enzyme-linked immuno sorbent assay (ELISA) was used to deter-mine the HMGB1 levels in the serum of peripheral venous blood samples from 33 SLE patients and 10 healthy children. RT-polymerase chain reaction (PCR) technique was used to detect the HMGB1-mRNA expression in the mononuclear cells of peripheral blood. Flow cytometry was adopted to detect the CD14/TLR-4 on the surface of mononuclear cell membrane in the peripheral blood of active SLE patients. One-way analysis of variance (ANOVA) was used to compare HMGB1 levels between the two groups. Pearson correlation and Logistic regression were used for correlation analysis. Results ① The levels of HMGB1 and HMGB1 mRNA in the peripheral blood of SLE active patients [(25.8 ±3.9) ng/ml and (0.80 ±0.16) respectively] were signifi-cantly higher than the stable group [(9.3 ±2.7) ng/ml and (0.46 ±0.18) respectively, F=7.0, 2.8, P<0.05] and healthy children [(9.1 ±0.9) ng/ml and (0.34 ±0.10) respectively, F=50.2, 7.5, P<0.05]. ② The CD14/TLR-4 expressions on the surface of mononuclear cell membrane in the peripheral blood of SLE active patients (91.2±1.3) were significantly higher than the stable group [(87.6±2.8), F=0.8, P<0.05] and the healthy children [(87.0±2.2), F=0.9, P<0.05].③There was significant positive correlation (r=0.48, P<0.05) between the levels of HMGB1 and CD14/TLR-4 in different SLE patients. In addition, the levels of HMGB1 were also positively correlated (r=0.48, P<0.01) with the detected concentrations of urinary protein in SLE patients. However, in the stable and healthy groups, there was no correlation between HMGB1 and CD14/TLR-4 and urinary protein. These indicate that HMGB1 outside the cell membrane were involved in SLE morbidity in children through TLR-4. Conclusion The mononuclear cells in peripheral blood of children with SLE can secrete HMGB1, which could lead to the increase of HMGB1 level in the serum of peripheral blood, and possibly participate in kidney damage of SLE through CD14/TLR-4.