Objective:To investigate the effect of microgravity-mediated Notch1 signaling on macrophage polarization on bone homeostasis.Methods:The animal model was constructed by tail-limb suspension(HLS)to simulate the microgravity environment.The animals were grouped into Control group,HLS group,HLS+NC group,HLS+si group,HLS+rhNF-κB group.ELISA was used to detect the content of TNF-α and IL-1β in serum of rats.TUNEL staining was used to detect the apoptosis of bone tissue.Immunofluo-rescence was used to detect the polarization of macrophages in bone tissue.The rat osteoblast CP-R091 microgravity model was con-structed by simulating the microgravity environment with a rotating wall bioreactor.The cell experiments were divided into Control group,HLS group,HLS+NC group,HLS+si group,HLS+rhNF-κB group.CCK-8 test was used to detect the proliferation activity of cells in each group,and AO test was used to test the apoptosis rate of cells in each group.PCR was used to detect the expression of os-teogenesis-related genes in bone tissues and cells.Western blot was used to detect the expression of Notch1,hair division-related en-hancer-1(HES-1),and Notch pathway ligand 1(Jagged1)in bone tissues and cells of each group.Results:Compared with control group,the contents of TNF-α and IL-1β in the serum of the rats in the HLS group,the apoptosis rate,and the proportion of M1 macro-phages were significantly increased.Compared with HLS group,the HLS+si group could obviously partially reverse the change trend of the above parameters,while HLS+rhNF-κB group significantly changed the above parameter values.Compared with control group,the proliferation activity of the cells in the HLS group was significantly reduced,and the apoptosis rate was significantly increased.Com-pared with HLS group,the HLS+si group could obviously partially reverse the change trend of the above parameters,while the HLS+rhNF-κB group made the above parameter values worse.The expressions of the osteogenesis-related genes collagen type Ⅰ(COL1),osteocalcin(OCN)and Runt-related transcription factor 2(RUNX2)in bone tissues and cells in the microgravity environment were significantly decreased,while the expressions of Notch-1,Hes-1 and Jagged1 were significantly increased,and the differences were statistically significant(all P<0.05).Conclusion:Microgravity-mediated Notch1 signaling regulates M1/M2 polarization of macro-phages,participates in cell proliferation and apoptosis in bone tissue,and affects the progress of bone homeostasis.

Objective:To analyze the epidemiological and etiological characteristics of a death case of meningococcal meningitis in Hengyang city, Hunan Province in 2024.Methods:Epidemiological investigation of the death case was performed, and samples from the patient and close contacts were collected. Following cultivation and isolation, Neisseria meningitidis ( Nm) strains were analyzed by antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE), and whole-genome sequencing for analyzing epidemiological and etiological characteristics. Phylogenetic analysis was carried out using core genomic multilocus sequence typing (cgMLST). Results:The case was a 16-year-old high school boarding student with fulminant meningococcal meningitis. He had shock symptoms, and died within 24 h of the onset of symptoms. Six Nm strains were isolated from the patient and his roommates, belonging to two distinct clades. Isolate 144569 from the patient was highly homologous to isolate 144572 from a close contact, both belonging to the highly pathogenic sublineage L44.1 of CC4821. The typical molecular features was C: P1.7-2, 14: F5-101: ST4821 (CC4821). The two strains carried the antimicrobial resistance genes of gyrA-71 and penA-552, indicating reduced susceptibility to quinolone and penicillin, which was with their resistance phenotype. The isolates from four close contacts clustered within the same clade, characterized by the molecular features of B: P1.18-25, 9-18: ST5829 (UA). Conclusions:The death case is caused by Nm serogroup C from highly pathogenic sublineage L44.1 of CC4821. The spread of this isolate has the potential risk of outbreaks of invasive meningococcal disease. It is necessary to enhanced the molecular epidemiological surveillance, particularly focusing on the transmission of multiple serogroups of Nm among adolescents and the increasing exposure risk.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbio-sis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione(GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating in-flammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

Objective: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient’s resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects Methods: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. Results: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). Conclusion msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.

Objective:To investigate the biological mechanisms underlying the effect of the Chinese herbal medicine Oxalis cor-niculata on human prostate cancer PC-3 cells.Methods:Through in vitro experiment,we treated human prostate cancer PC-3 cells with different concentrations of Oxalis corniculata,assessed the viability of the cells by MTT assay,examined their apoptosis by flow cytometry,evaluated their migration and invasiveness by Transwell assay,and determined the expressions of the proteins p65,p-p65,IκBα and p-IκBα in the NF-κB pathway using protein imprinting technology.Results:Compared with the blank control,Oxalis cor-niculata significantly inhibited the proliferation and induced the apoptosis of the PC-3 cells(P＜0.05),suppressed their migration and invasiveness in a dose-dependent manner(P＜0.05),and upregulated the expression of IκBα and downregulated those of p-p65 and p-IKBα in the NF-κB pathway(P＜0.05).Conclusion:Oxalis corniculata can inhibit the proliferation,migration and inva-siveness and induce the apoptosis of human prostate cancer PC cells,which may be attributed to its abilities of inhibiting the expres-sions of p-p65 and p-IκBα and regulating the activity of the NF-κB pathway.

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ²=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female ; Humans ; Adult ; Medroxyprogesterone Acetate/adverse effects* ; Endometrial Hyperplasia/pathology* ; Dydrogesterone/adverse effects* ; Hyperplasia ; Prospective Studies

OBJECTIVES: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children. METHODS: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed. RESULTS: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure. CONCLUSIONS Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.
Child ; Humans ; Esophageal Stenosis/therapy* ; Constriction, Pathologic/complications* ; Dilatation/methods* ; Caustics ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R. METHODS: Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label. RESULTS: The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results. CONCLUSIONS SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome