OBJECTIVES: To investigate the role of the calcium/calmodulin (CaM)-mediated activation of calcineurin (CN)-nuclear factor of activated T cells (NFAT) signaling pathway in mediating the regulatory effect of hyperforin (HY) on stress-induced depression-like disorder (DP) in mice. METHODS: C57BL/6J mice were randomly divided into control group, DP model group, and hyperforin treatment group (n=15). Behavioral changes of the mice were assessed using open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), light/dark box test (LDB), and novel object suppression test (NSFT). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the CA1 region of the hippocampus, and serum serotonin (5-HT) and norepinephrine (NA) levels were detected with ELISA. Western blotting was used to analyze the expressions of TNF-α, IL-1β, IL-2, and CN-NFAT pathway proteins. In cultured BV-2 microglial cells with lipopolysaccharide (LPS) stimulation, the effects of hyperforin and CN inhibitor (CNIS) on expressions of ionized calcium-binding adapter molecule 1 (IBA-1), 5-HT, NA, inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay, ELISA or Western blotting. RESULTS: Compared with the control mice, the mice in DP group showed significantly reduced activity in OFT, decreased sucrose consumption in SPT, reduced shuttle crossing in LDB, and lowered food intake in NSFT with significantly increased immobility in TST. The mice with DP showed significantly decreased TH-positive neurons, lowered 5-HT and NA levels, and increased expressions of TNF-α, IL-1β, IL-2 and CaM-CN-NFAT pathway proteins. In cultured BV-2 cells, LPS stimulation strongly increased cellular IBA-1 expression, decreased the levels of neurotransmitters (5-HT and NA), and increased the levels of inflammatory cytokines and CN-NFAT signaling, and these changes were effectively reversed by treatment with hyperforin or CNIS. CONCLUSIONS Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.
Animals ; Mice, Inbred C57BL ; Mice ; Microglia/drug effects* ; Depression/etiology* ; Perylene/pharmacology* ; Calcineurin/metabolism* ; NFATC Transcription Factors/metabolism* ; Calcium Signaling/drug effects* ; Stress, Psychological ; Phloroglucinol/pharmacology* ; Signal Transduction ; Male ; Behavior, Animal/drug effects* ; Terpenes

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective:To investigate the application value of laparoscopic natural orifice specimen extraction surgery (NOSES) based on purse-string suture for sigmoid colon and upper rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 14 patients undergoing laparoscopic NOSES based on purse-string suture for sigmoid colon and upper rectal cancer in The First Affiliated Hospital of Sun Yat-sen University from October 2022 to June 2023 were collected. There were 8 males and 6 females, aged (56±10)years. Observation indicators: (1) surgical conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. All patients underwent laparoscopic NOSES based on purse-string suture for sigmoid colon and upper rectal cancer successfully, without conversion to open surgery. The operation time of 14 patients was (162±32)minutes, and the volume of intraoperative blood loss was (22±12)mL. (2) Postoperative conditions. Time to postoperative first out-of-bed activity, time to postoperative first flatus, time to postoperative first drinking, time to postoperative initial liquid food intake, duration of postoperative hospital stay of 14 patients were (1.6±0.7)days, (2.1±0.6)days, (2.4±0.6)days, (3.8±1.0)days, (6.0±0.9)days, respectively. None of patient had perioperative complications such as postoperative anastomotic leakage and bleeding. (3) Follow-up. All 14 patients were followed up for (9.7±1.9)months. There was no postoperative recurrence, metastasis or death in 14 pati-ents.Conclusion:The laparoscopic NOSES based on purse-string suture can be used for sigmoid colon and upper rectal cancer, which is safe and feasible.

Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations. The results showed that amputation caused pathological changes in the cardiovascular system of animals, including endothelial injury, inflammation, and angiosclerosis. The degree of cardiovascular injury was higher in the AKA group than in the BKA group. This study sheds light on the internal mechanisms of amputation's impact on the cardiovascular system. Based on the amputation level of patients, the findings recommend more comprehensive and targeted monitoring after surgery and necessary interventions to prevent cardiovascular diseases.
Animals ; Animal Experimentation ; Cardiovascular System ; Cardiovascular Diseases ; Hypertension ; Amputation, Surgical

【Objective】 To investigate the clinical characteristics and prognostic factors of small cell carcinoma of bladder (SCCB), and to explore the efficacy of neoadjuvant therapy. 【Methods】 Clinical information of 47 SCCB patients were retrospectively collected, and the clinical and pathological features were compared with those of urothelial carcinoma (UBC). The prognostic factors and efficacy of neoadjuvant therapy were also investigated. 【Results】 SCCB had higher baseline tumor staging, and was more likely to invade the muscle (100%) and metastasize distantly (21.3%). The overall survival was poor (median: 13.1 months, 1-year survival rate: 53.7%, 5-year overall survival rate: 15.4%). Tumor T staging was a risk factor for SCCB, while neoadjuvant therapy was an independent protective factor that significantly reduced the risk of recurrence and metastasis (HR: 0.189, 95%CI: 0.051-0.697, P=0.012) and death (HR: 0.177, 95%CI: 0.045-0.698, P=0.013), and significantly improved disease-free survival and overall survival. In addition, compared with neoadjuvant chemotherapy alone, neoadjuvant chemotherapy combined with immunotherapy could improve the pathological complete response rate. 【Conclusion】 SCCB is highly malignant and prone to metastasis, and has a poor prognosis. Neoadjuvant therapy combined with radical cystectomy is recommended as the first-line treatment.

OBJECTIVE: To investigate the incidence and influencing factors of hypertension among civil aviation pilots. METHODS: A total of 1 169 civil aviation pilots in Northern China were selected into the study by the method of convenient sampling. Physical examination, laboratory test and questionnaire survey were conducted. RESULTS: The prevalence of hypertension in Northern China was 4.7%(55/1 169). Multivariate regression analysis showed that the relative risk factors ranking from high to low were, age over 30 years [odds ratio(OR)=6.81, 95% confidence interval(95%CI) 3.57-12.98)], total flight hours over 1 000 hours(OR=4.24, 95%CI 2.14-8.41), flight hours over 500 hours in the past year(OR=2.91, 95%CI 1.57-5.40), obesity(OR=2.50, 95%CI 1.08-5.81), fasting blood glucose(OR=2.24, 95%CI 1.21-4.13), and frequent long-distance flight(OR=2.38, 95%CI 1.24-4.58). These factors were the risk factors of hypertension in civil aviation pilots(P<0.05). CONCLUSION: Age, total flight hours, flight hours in the past year, obesity, fasting blood glucose, frequent long-distance flight are related to the prevalence of hypertension in civil aviation pilots.

Objective: To observe the perioperative changes of serum thrombomodulin in patients with and without cardiogenic shock undergoing off-pump coronary artery bypass grafting surgery. Methods: A total of 66 patients with coronary artery disease who underwent off-pump coronary artery bypass grafting surgery between June and December 2015 in our hospital were included in this study.The patients were divided into non-cardiogenic shock group (n=51) and shock group (n=15) according to the absence or presence of cardiogenic shock.The clinical data of the two groups were analyzed.Arterial blood samples were collected immediately after anesthesia, and at 4, 8, 16, 24, 48 and 72 hours after surgery.The levels of serum thrombomodulin were tested with enzyme-linked immunosorbent assay. Results: (1)The prevalence of diabetes was significantly higher (64.7%(33/51) vs. 20.0%(3/15), P<0.01), while prevalence of myocardial infarction was significantly lower (41.2%(21/51)vs. 100%(15/15), P<0.01) in non-cardiogenic shock group than in cardiogenic shock group.(2)The peak plasma creatinine level, troponin I level and creatine kinase MB level were significantly lower in the non-cardiogenic shock group than in the cardiogenic shock group ((88.5±36.7) μmol/L vs. (122.6±71.1) μmol/L, 1.3(0.2, 2.7) μg/L vs. 16.4(5.8, 23.4) μg/L and (18.8±4.7) μg/L vs.(49.3±15.9) μg/L, respectively, all P<0.05). (3)Mechanical ventilation time was significantly longer (11.5 (9.0, 18.0) hours vs. 20.0 (8.5, 82.5) hours, P=0.02), and frequency of intra-aortic balloon pump use (0 vs. 100%, P<0.01) was significantly higher in the cardiogenic shock group than in the non-cardiogenic shock group.(4) Prevalence of atrial fibrillation (5.9%(3/51) vs. 80.0%(12/15)) and myocardial infarction (19.6%(10/51)vs. 93.3%(14/15)) that occurred during and after surgery was significantly lower in the non-cardiogenic shock group than in the shock group(all P<0.01). (5)The serum thrombomodulin concentration was similar among various time point in the non-cardiogenic shock group: 3.30(2.68, 7.44), 4.09(2.95, 7.18), 4.35(2.68, 8.22), 3.50(2.95, 8.00), 3.41(2.60, 5.97), 3.30(2.65, 5.42)and 3.94(2.82, 5.60) μg/L, taken immediately after anesthesia, and at 4, 8, 16, 24, 48 and 72 hours after surgery respectively, and was 2.44(1.97, 2.67), 2.21(1.93, 2.83), 2.64(2.29, 2.67), 2.84(2.26, 2.94), 3.35(2.43, 4.05), 2.76(2.73, 2.97) and 3.81(2.96, 5.96)μg/L respectively, in the cardiac shock group (all P>0.05). The serum thrombomodulin levels at 4 and 8 hours after surgery were higher in the non-cardiogenic shock group than cardiogenic shock group(all P<0.05). Conclusion Compared with the non-cardiogenic shock group, the peak serum thrombomodulin level appears later and recovers slower in cardiogenic shock patients who underwent off-pump coronary artery bypass grafting surgery.

Objective To explore the efficacy of multiple target therapy in treatment of patients with chronic moderate and severe IgA nephropathy with hyperuricemia.Methods Seventy-six patients with chronic progressive moderate and severe IgA nephropathy with hyperuricemia were enrolled the current study and randomly divided into observation group and control group.Patients in control group were treated with allopurinol,prednisone,benner pury and valsartan,while those in observation group were treated with urokinase,mycophenolate mofetil besides the basis of control group for 6 months.The blood uric acid (UA),24 h urine protein,mean arterial pressure (MAP) and creatinine clearance rate (Ccr) were determined and analyzed.Results The levels of UA,24 h urinary protein,MAP and Ccr in observation group and control group were same before treatment (P ＞ 0.05).After 6 months treatment,the levels of UA,24 h urine protein,MAP and Ccr in observation group were (413.7 ± 90.7) μmol/L,(1.15 ± 0.57) g/L,(87.7 ± 10.6) mmHg and (81.9 ± 3.7) ml/min respectively,significantly different from those of the control group ((369.6 ± 67.2) μ mol/L,(0.77 ±0.51) g/L,(81.6 ±12.3) mmHg and (86.4 ±6.8) ml/min;t =2.219,2.802,2.132,3.230;P ＜0.05).The rate of adverse reactions in two groups was not significantly differnent(9.7％ (3/31) vs 9.1％ (3/33) ; x2 =0.006,P =0.936).Conclusion Multiply target therapy is effective and safe in terms of treating chronic progressive moderate and severe IgA nephropathy with hyperuricemia.