OBJECTIVE To investigate the protective effect and mechanism of vincamine derivative Vin24 on the pathological symptoms of diabetic peripheral neuropathy(DPN)in mice.METHODS Forty 8-week-old male C57BL/6N mice were randomly di-vided into control group(Control),model group(STZ),vincamine group(STZ+Vin)and Vin24 group(STZ+Vin24).Except the con-trol group,the rest three groups of mice were intraperitoneally injected with streptozocin(STZ,150 mg·kg-1)to induce type 1 diabe-tes and administration was started six weeks later.Thirty 18-week-old male db/db mice were randomly divided into model group(db/db),vincamine group(db/db+Vin)and Vin24 group(db/db+Vin24).Ten age-matched wild-type mice were used as a control group(db/m).The vincamine group were gavaged 30 mg·kg-1 of vincamine daily.The Vin24 group was gavaged 46.8 mg·kg-1 of Vin24,while the control and model group were given the same amount of saline daily,for four weeks.Sensory functions of the mice were as-sessed by assays against tactile and thermal allodynia threshold.A Laser Speckle Imaging System was used to detect the peripheral blood flow.The epidermal tissues of foot pads were collected for PGP9.5 immunofluorescence to measure the intraepidermal nerve fiber(IENF)density.Primary dorsal root ganglia(DRG)neurons were isolated for β-tubulin Ⅲ immunofluorescence to evaluate neurite outgrowth.Additionally,DRG tissues were extracted for ATF3 immunofluorescence for the evaluation of DRG neuronal apoptosis,and Western blot analysis was used to measure the protein levels of Bcl-2,Bax,Cleaved-Caspase3 and Caspase3.RESULTS The tact-ile and thermal allodynia thresholds were decreased(P<0.01,P<0.001),and peripheral blood flow was increased(P<0.001)in Vin24-treated DPN mice.The IENF density was increased(P<0.05,P<0.01)and DRG neurite outgrowth was improved(P<0.001)in Vin24 group compared with that in the model group.Immunofluorescence assay results indicated that the number of ATF3(a marker of neuronal apoptosis)-positive neurons was obviously decreased(P<0.01,P<0.001)in DRG tissues of Vin24-treated DPN mice.Western blot results demonstrated that the protein level of anti-apoptotic protein Bcl-2 was significantly increased(P<0.05),and the protein levels of pro-apoptotic proteins Bax and Cleaved-Caspase3 were significantly decreased(P<0.05)in DRG tissues of Vin24-treated DPN mice.CONCLUSION Vincamine derivative Vin24 inhibits the activation of Cleaved-Caspase3 and reduces the neuronal apoptosis levels by regulating Bcl-2/Bax/Caspase3 pathway,and eventually alleviates DRG neuronal damage and improves peripheral neuropathy in diabetic mice.

Objective:To discuss the relationship between 18F-FDG PET/CT metabolic parameters and clinical pathological indicators and prognosis in cutaneous malignant melanoma (CMM). Methods:A total of 100 CMM patients (62 males, 38 females, age (56.5±2.5) years) who underwent 18F-FDG PET/CT scans at the Second Xiangya Hospital of Central South University from August 2013 to November 2022 were retrospectively enrolled. Clinical pathological indicators (such as primary site, TNM staging, sentinel lymph node (SLN) status) and metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), whole-body MTV (wb-MTV), and whole-body TLG (wb-TLG)) were collected. ROC curve analyses were used to determine the PET parameters thresholds for progression-free survival (PFS) and melanoma-specific survival (MSS). Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards regression models were used to analyze the prognosis of patients′ PFS and MSS, and a nomogram survival prediction model was constructed. Results:Results of ROC curve analyses showed that the thresholds of SUV max of primary tumor (p-SUV max), MTV of primary tumor (p-MTV), TLG of primary tumor (p-TLG), wb-MTV and wb-TLG for predicting PFS and MSS were 7.13, 2.24 cm 3, 6.98 g, 2.57 cm 3, 8.04 g and 9.09, 2.34 cm 3, 7.44 g, 2.24 cm 3, 9.17 g, respectively. Results of univariate analysis indicated that several clinical pathological indicators and metabolic parameters were prognostic risk factors for PFS and MSS. Results of multivariate analysis indicated that metastases of SLN (hazard ratio( HR)=2.54, 95% CI: 1.09-5.90; P=0.030) and wb-TLG>8.04 g( HR=2.58, 95% CI: 1.17-5.72; P=0.019) were independent prognostic risk factors for PFS, while metastases of SLN ( HR=4.53, 95% CI: 1.54-13.35; P=0.006) and wb-TLG>9.17 g ( HR=2.48, 95% CI: 1.26-4.89; P=0.009) were independent risk prognostic factors for MSS. A nomogram survival prediction model based on PET metabolic parameter (wb-TLG) and clinical pathological indicator (SLN status) can effectively predict the prognosis of CMM patients. Conclusions:Clinical pathological parameters and PET parameters are associated with the prognosis of CMM patients. SLN status is critical for prognosis.

Objective To explore method of establishing and evaluating an asthma rat model with phlegm and blood stasis syndrome.Methods 60 SD male rats were randomly divided into 5 groups,a normal group,asthma group,combination of disease and syndrome(combination)group,DM group,and KCLW group,with 12 rats in each group.Asthma models were established using ovalbumin(OVA).A syndrome model of phlegm and blood stasis was established using a high-fat diet combined with the ice water bath method.We evaluated the asthma model through animal behavior observation,pathological section observation,inflammation index detection,and airway reactivity measurements.The phlegm and blood stasis syndrome model was evaluated via measurements of rat body mass,blood glucose,blood lipids,coagulation function,and hemorheological indexes and by observing symptoms and syndrome determination by Kechuan Liuwei mixture.Results(1)After OVA induction,the rats in the asthma model group and combination group showed symptoms such as shortness of breath,open mouth breathing,abdominal movement,restlessness,and irritability.HE staining showed the disordered arrangement of the bronchial mucosa in lung tissue,local detachment,thickening of the basement membrane and the bronchial tube wall,narrowing of the lumen,extensive infiltration of inflammatory cells,and congestion of capillaries.Compared with the normal group,the asthma model group and combination group(P＜0.05)had increased serum IL-4,IL-6,and TGF-β1.Penh values were increased after stimulation with various concentrations of Mch(P＜0.05).(2)Rats in the combination group showed symptoms such as chills,curling up with minimal movement,purple and dark claws,purple and black bruises on the tail,loose stools,and unclean perianal area.Compared with the rats in the asthma model group,rats in the combination group had increased body mass(P＜0.05)and blood glucose,triglyceride,and total cholesterol levels(P＜0.05),a shortened thrombin time(P＜0.05),increased fibrinogen content(P＜0.05),and significantly increased whole-blood viscosity at low,medium,and high shear rates(P＜0.05).The indexes were significantly improved after Kechuan Liuwei mixture administration.Conclusions The asthma rat model with phlegm and blood stasis syndrome can be established through OVA induction and high-fat diet combined with ice water bath.The model can be evaluated through behavioral observation,index measurements,and syndrome determination via formulas.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective To observe the glymphatic system functional changes of bilateral cerebral hemispheres in early-stage Parkinson disease(PD)patients complicated with unilateral limb motor symptoms.Methods A total of 52 early-stage PD patients complicated with unilateral limb motor symptoms were prospectively enrolled,including 21 cases of left-onset PD(LPD group),31 cases of right-onset PD(RPD group).Meanwhile,28 healthy individuals were recruited as healthy controls(HC group).Clinical data and indices of diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)were compared among 3 groups and between each 2 groups.The correlations of DTI-ALPS indices and clinical scales were analyzed.Results Significant difference of Hamilton depression scale(HAMD)score was found among 3 groups(P＜0.05).HAMD score of LPD group and RPD group were higher than that of HC group(both P＜0.017).There were significant differences of left and right cerebral hemispheres DTI-ALPS(DTI-ALPS_L,DTI-ALPS_R)indices among 3 groups(both P＜0.05).DTI_ALPS_R in LPD group was lower than that in HC group(P＜0.017),and DTI_ALPS_L in RPD group was lower than that in HC group(P＜0.017).No obvious correlation of bilateral cerebral hemisphere DTI-ALPS indices with clinical scales was detected in PD patients(all P＞0.05).Conclusion Like that of motor symptoms,glymphatic system dysfunction of PD patients had characteristics of laterality,manifested as DTI_ALPS_R decreased in LPD patients while DTI_ALPS_L decreased in RPD patients.

Objective:To investigate the effect of 18F-FDG combined with 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT on TNM staging and clinical treatment decision of patients with prostate cancer. Methods:Clinical data and PET/CT images of 31 patients (age (69.9±9.2) years) with prostate cancer who underwent PET/CT imaging with 18F-FDG and 18F-PSMA-1007 (dual-tracer imaging) in the Second Xiangya Hospital of Central South University from June 2020 to March 2022 were retrospectively analyzed. Paired χ2 test was used to compare the diagnostic efficacy of 18F-FDG, 18F-PSMA-1007 and combined imaging for diagnosing primary prostate cancer, regional lymph node metastases and distant metastases, and to analyze the influence of combined imaging on clinical treatment decision. Results:There were 282 metastatic sites in 31 patients, including 46 regional lymph node metastases in 13 patients and 236 distant metastases in 15 patients. The detection rates of 18F-PSMA-1007 PET/CT and combined imaging for primary lesions were higher than the detection rate of 18F-FDG PET/CT (100%(31/31), 100%(31/31) vs 64.5%(20/31); χ2=13.37, P<0.001). Based on analysis of patients, the detection rates of 18F-PSMA-1007 PET/CT and combined imaging for regional lymph node metastases were higher than the detection rate of 18F-FDG PET/CT (12/13, 12/13 vs 6/13; χ2=4.51, P=0.034), and the 3 detection rates for distant metastases were also significantly different (15/15, 15/15 vs 10/15; χ2=6.00, P=0.042). Based on analysis of lesions, the detection rates of 18F-PSMA-1007 PET/CT and combined imaging for regional lymph node metastases were higher than the detection rate of 18F-FDG PET/CT (95.7%(44/46), 97.8%(45/46) and 45.7%(21/46); χ2 values: 25.37-49.56, all P<0.001). The detection rate of combined imaging for distant metastases was higher than that of 18F-FDG or 18F-PSMA-1007 PET/CT alone (96.2%(227/236) vs 68.6%(162/236), 58.9%(139/236)); and the detection rate of 18F-FDG PET/CT was higher than that of 18F-PSMA-1007 PET/CT ( χ2 values: 4.85-94.22, all P<0.05). Clinical treatment decisions in 10 patients (32.3%, 10/31) were changed based on the results of combined imaging. Conclusion:For prostate cancer with suspected distant metastases, 18F-FDG and 18F-PSMA-1007 dual-tracer PET/CT imaging can improve staging and guide clinical treatment decisions.

Background The incidence of Legionnaires' disease is increasing globally and artificial water environment is becoming a common source of outbreaks. Molecular typing techniques can help prevent and control Legionella. Objective To understand the molecular epidemiological characteristics of Legionella pneumophila in artificial water environment of Shanghai hospitals, and provide a scientific basis for the prevention and control of Legionnaires' disease. Methods Water samples were collected from artificial water environment in 14 hospitals from May to October each year from 2019 to 2020 in Shanghai. A total of 984 water samples were collected from 8 Grade-A tertiary hospitals and 6 non-Grade-A tertiary hospitals, including 312 samples of cooling water, 72 samples of chilled water, and 600 samples of tap water. The water samples were isolated and serotyped for Legionella pneumophila and preserved, and the positive rate of Legionella pneumophila in the samples was used as an indicator of contamination. The preserved strains were resuscitated and 81 surviving strains were obtained for pulsed field gel electrophoresis (PFGE) typing analysis. Results A total of 124 Legionella pneumophila positive water samples were detected, with a positive rate of 12.60%. The positive rate was higher in the Grade-A tertiary hospitals (16.54%, 87/526) than in the non-Grade-A tertiary hospitals (8.08%, 37/458) (χ²=15.91, P<0.001). The positive rate of cooling water (23.40%) was the highest among different types of water samples, and the difference was statistically significant (χ²=61.19, P<0.001). The difference in positive rate of tap water was statistically significant among different hospital departments (χ²=11.37, P<0.05). The positive rate in 2019 (15.06%) was higher than that in 2020 (9.84%) (χ²=6.23, P<0.05). From May to October, August had the highest annual average positive rate (16.46%) and October had the lowest (8.54%), but the difference in positive rates among months was not statistically significant (χ²=5.39, P=0.37). The difference in positive rate among districts was statistically significant (χ²=24.88, P<0.001). A total of 131 strains of Legionella pneumophila were isolated, with serotype 1 (80.15%, 105/131) predominating. Among the 81 surviving strains of Legionella pneumophila subjected to PFGE typing, the band-based similarity coefficients ranged from 41.30% to 100%. Among the 29 PFGE band types (S1-S29) recorded, each band type included 1-10 strains, and S28 was the dominant band type. Four clusters (I-IV) of PFGE band types were identified, accounting for 66.67% (54/81) of all strains and containing 13 band types. Conclusion Legionella pneumophila contamination is present in the artificial water environment of hospitals in Shanghai from 2019 to 2020, and the contamination in tap water deserves attention. The detected serotype of Legionella pneumophila is predominantly type 1, and PFGE typing reveals the presence of genetic polymorphism. Therefore, the monitoring and control of Legionella pneumophila in hospital artificial water environment should be strengthened.

Objective:To retrieve and obtain relevant evidence of intra-abdominal pressure-oriented enteral nutrition assessment and management in patients with intra-abdominal hypertension, in order to provide evidence-based evidence for clinical medical staff to make enteral nutrition-related clinical decisions for patients with intra-abdominal hypertension.Methods:Systematic retrieval of Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature, UpToDate, PubMed, Cochrane Library, BMJ Best Practice and other English data, as well as domestic and foreign guidelines such as American Society for Parenteral and Enteral Nutrition, Scottish Intercollegiate Guidelines Network, etc. All evidence available on the Internet in both Chinese and English on intra-abdominal pressure-guided enteral nutrition strategies in adults with intra-abdominal hypertension, study types including clinical decision-making, systematic reviews/meta-analyses, evidence summaries, expert consensus, guidelines or related to the subject of this study closely related high-quality original research. The retrieval time was from the establishment of the database to November 2021. The literature evaluation tool was selected according to the research type. Two researchers trained in the evidence-based system independently evaluate the quality of the included literature, fully considering the clinical situation and expert opinions, and completed the evidence. Extracted and summarized.Results:Totally 13 articles were finally included, including 5 guidelines, 3 expert consensuses, 1 evidence summary and 4 original studies, and 29 evidence-based practice evidence of enteral nutrition in patients with intra-abdominal hypertension were collected, including the monitoring timing of enteral pressure, the pressure of enteral high pressure and the way of enteral nutrition, the pressure measurement of the abdominal cavity, the setting of abdominal pressure, the temperature conditions for early start of enteral nutrition, the selection of enteral pressure, the temperature setting of enteral nutrition nine aspects such as speed and regulation of internal nutrition and abdominal compartment syndrome prevention.Conclusions:This study summarizes the best evidence of intra-abdominal pressure management and enteral nutrition therapy in patients with intra-abdominal hypertension, and provides evidence-based basis for risk management, standardizing clinical practice, and ensuring treatment safety. In the stage of evidence transformation, clinical medical staff need to comprehensively weigh the benefits and risks of early enteral nutrition, and integrate evidence in combination with clinical practical application scenarios, so as to form a standardized early enteral nutrition management plan suitable for patients with intra-abdominal hypertension.

To explore prognostic factors in intermediate-risk acute myeloid leukemia (AML) patients with minimal residual disease (MRD) negativity (MRD<0.1%,MRD-)receiving autologous hematopoietic stem cell transplantation (auto-HSCT).A total of 59 intermediate-risk AML patients with MRD-were treated with auto-HSCT from January 2015 to September 2021 at Affiliated People′s Hospital of Ningbo University. The clinical data and laboratory results were collected retrospectively. Efficacy, clinical outcome and prognostic factors were analyzed. Univariate analysis was conducted by using log-rank test, the multivariate analysis by Cox proportional risk model.Among 59 patients, there were 27 males and 32 females with median age of 55 (31-69) years old.The median follow-up was 761(317-1 861)days. The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 76.1%±11.4% and 73.4%±11.6% respectively.The univariate analysis showed that age older than 50 years, TET2 gene mutation (TET2 +), achieving MRD negativity over 30 days (MRD 30+) were unfavorable factors of OS ( χ2=6.20, 33.20, 7.18; P=0.013,<0.001, 0.007). TET 2+, WT1 gene mutation (WT1 +), CD34 +cells<2×10 6/kg, MRD 30+were negative factors of EFS ( χ2=17.29, 4.47, 3.94, 9.393; P<0.001, 0.035, 0.047, 0.002).Multivariate analysis showed that MRD 30+, TET2 + were independent prognostic factors of OS and EFS (OS: HR=9.251, 25.839, P=0.036, 0.001;EFS: HR=5.851, 9.199, P=0.043, 0.002). Intermediate-risk AML patients with MRD 30+or TET2 + have very poor prognosis after auto-HSCT. Alternative regimens should be investigated.

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People