Objective To investigate the protective effect and mechanism of nicorandil on lipopolysac-charide(LPS)-induced human microvascular endothelial cells(HPMVECs)injury based on BMP9/BMPR2/SMAD pathway and its mechanism.Methods The HPMVECs injury model induced by LPS(100 ng/mL)was established.The normal cultured HPMVECs were set as the NC group,and other model cells were set as the model group(LPS group),low,medium and high concentrations nicorandil groups(nicorandil 50,100,200μmol/L),si-NC+high nicorandil group,and si-BMP9+high nicorandil group.MTT assay was used to detect the cell proliferation activity;the apoptosis and intracellular ROS level were detected by flow cytometry;the levels of MDA,SOD and CAT in cells were detected by the micro assay;the levels of TNF-α,IL-6 and IL-1β in cells were detected by ELISA;the mRNA levels of BMP9,BMPR2 and SMAD1 were detected by RT-qPCR;and the expression of BMP9,BMPR2,SMAD1,Bcl-2,Bax proteins in cells was detected by Western blot.Re-sults Compared with the NC group,the proliferation activity of HPMVECs,SOD,CAT levels,Bcl-2 protein,BMP9,BMPR2,SMAD1 mRNA and protein expression levels in the LPS group were decreased(P＜0.05),the apoptosis rate and the Bax protein expression level,ROS,MDA,TNF-α,IL-6 and IL-1β levels were in-creased(P＜0.05).Compared with the LPS group,the proliferation activity of HPMVECs,SOD,CAT levels,Bcl-2 protein level,BMP9,BMPR2,SMAD1 mRNA and protein expression levels in the low,middle and high concentrations nicorandil groups were increased,the apoptosis rate and the Bax protein level,ROS,MDA,TNF-α,IL-6 and IL-1β levels were decreased obviously(P＜0.05);compared with the high concentration nic-orandil group,the si-BMP9+high nicorandil group and LPS group showed the same trend,si-BMP9 was able to reverse the protective effect of high nicorandil group on LPS induced HPMVECs injury to some extent.Conclusion Nicorandil could reduce the oxidative stress,inflammatory reaction and cell apoptosis induced by LPS in HPMVECs and inhibit LPS induced HPMVECs injury by up-regulating the expression of BMP9/BM-PR2/SMAD pathway.

ObjectiveTo analyze the HIV infection characteristics and influencing factors among the spouses of HIV/AIDS patients in Shanghai. MethodsA cross-sectional survey was conducted to collect demographic， behavioral， epidemiological and spousal HIV detection information of newly reported and married patients with HIV/AIDS in Shanghai from January 2018 to July 2022 in the comprehensive HIV prevention and control information system of Chinese Center for Disease Prevention and Control. Descriptive analysis was used to analyze the HIV positivity rate of the spouses of HIV patients and the influencing factors were analyzed by univariate and multivariate logistic regression models. ResultsA total of 1 233 subjects were investigated， and the first HIV-testing positivity rate of the spouses of HIV/AIDS patients was 29.3% （361/1 233）. There were statistically significant differences in the HIV-testing positivity rate among spouses of HIV/AIDS patients by different age， gender， education level， occupation， transmission route， quantity of non-marital sexual activities， quantity of homo-sexual activities， and baseline CD4 cell count level （P<0.05）. Spouses of the HIV/AIDS patients aged ≥65 years old， female， heterosexual transmission， less non-marital sex， and no history of homosexual sex had relatively high HIV positive rate. The HIV-positive detection rate of spouses in the ≥65 age group was 1.81 times higher than that in the <45 age group. The HIV-positive detection rate of spouses in the female group was 3.66 times higher than that in the male group， and the HIV-positive detection rate of spouses in the homosexual transmission group was 0.25 times higher than that of the heterosexual transmission group. ConclusionRisk awareness of HIV infection among married people with spouses should be improved. The key populations with the characteristics such as females as the first HIV-positive reporter， and heterosexual transmission should be paid special attention.Their spouses should be mobilized to conduct HIV-testing as early as possible

Objective:To investigate the efficacy and safety of a novel modified Blumgart pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD).Methods:Between May 2021 and January 2022, 13 successive cases from Lihuili Hospital Affiliated to Ningbo University who underwent LPD were enrolled in this retrospective study. The study retrospectively analyzed the demographic characteristics, perioperative outcomes, and pathological results of these cases.Results:Twenty patients underwent LPD success-fully and one required conversion to open surgery. The operative time was (308.6 ± 61.7) min. The duration for PJ was (26.7 ± 4.3) min. The estimated blood loss was (188.1 ± 94.2) ml. The postoperative hospital stay was (14.2 ± 3.5) d. There was one case of biochemical leakage and no case of grade B or grade C pancreatic fistula.Conclusions:The new method is safe, simple and feasible. The novel method could reduce the incidence of pancreatic fistula and other complications after LPD.

Objective To investigate the clinical pathologic features of a distinct variant of focal cortical dysplasia (FCD) characterized by neuronal loss of layer four.Methods Between 2005 and 2017,approximately 3 000 surgeries were performed for the treatment of intractable epilepsy at Xuanwu Hospital,Capital Medical University and Yuquan Hospital,Tsinghua University.Retrospective analysis of clinic-pathological data of patients with epilepsy surgery was made and histological manifestations of neuronal loss of cortical layer four were included in this study.Results In this cohort,25 patients (22 males and three females) were identified with early onset pharmaco-resistant epilepsy and regionally circumscribed neuronal loss of cortical layer four in surgical specimens from the occipital lobe.Histologically,except for neuronal loss in cortical layer four in all cases,glial scar lesions were found in some patients.Thus the histology of those cases can be subdivided into two groups:group A (13 cases):neuronal loss of cortical layer four without glial scar lesions;and group B (12 cases):neuronal loss of cortical layer four with glial scar lesions.Due to the prominent horizontal disorganization of cortical layering and lack of any other microscopically visible principle lesion,group A should be classified hitherto as FCD International League Against Epilepsy (ILAE) type Ⅰ b,however,group B with scar lesions and cortical dysplasia around the main leision,should be classified as FCD ILAE type Ⅲd.This retrospective analysis of clinical histories revealed a perinatal distress in 20 patients (80％),suggesting an acquired pathomechanism.Magnetic resonance imaging revealed abnormal signals in the occipital lobe in all patients,and signal changes suggestive of encephalomalacia were found in 18 patients.Surgical treatment achieved favorable seizure control (Engel class Ⅰ and Ⅱ) in 18 patients (75％ among 24 available follow up).Comparion of the two groups with age at epilepsy onset (group A:5.00±2.76,group B:5.01±3.78),the proportion of perinatal distress (group A:11/13,group B:9/12) and the follow-up results (favorable seizure control of the two groups was 9/13,9/11 respectively) showed that there was no statistically significant difference between the two groups.Conculsion Neuronal loss of cortical layer four in the occipital lobe should be classified as a distinct variant of FCD ILAE type Ⅲd.

Objective: To evaluate the safety and efficacy of foam sclerotherapy for bleeding internal hemorrhoids. Methods: Consecutive adult patients (aged 18-60 years) with bleeding hemorrhoids were prospectively enrolled between March 2017 and March 2018. All patients were randomly assigned to the foam sclerotherapy (FS) group and the liquid sclerotherapy (LS) group. The foam and liquid sclerotherapy of hemorrhoids nucleus was performed by cap-assisted colonic endoscopy. Results: A total of 108 patients were enrolled, including 62 males (57.4%) with mean age of 44.0±7.6 years. There was no significant difference in gender, age, or body mass index between the FS (n = 55) group and the LS (n =53) group. The total amount of lauromacrogol injection in the FS group was 3.7±0.9 mL, which was significantly lower than that in the LS group (8.0±2.2 mL, P<0.001). In the LS group, 8 patients (15.1%) developed bleeding after needle removal, which was significantly higher than that in the FS group [5.5%(3/53), P=0.022]. Significant pain was found in 2 patients (3.8%) in the LS group and 0 in the FS group (P= 0.025). The short-term cure rate and effective rate of the FS group were 87.3% (48/55) and 9.1% (5/55), while those were 69.8% (37/53) and 22.6% (12/53) in the LS group, respectively (P=0.046). Conclusion Foam sclerotherapy is safe and effective in the treatment of bleeding internal hemorrhoids.

Objective To understand the effectiveness of peroral endoscopic myotomy(POEM)for achalasia and secondary severe malnutrition in children and the effectiveness of nutrition support before and after POEM.Method Treatment of POEM,nutrition support(tube feeding by percutaneous endoscopic gastrostomy three months before operation)in one case were recorded and analyzed.Results POEM was successful without any complication such as perforation,bleeding,and pneumoderm.The child suffered from fever after surgery,which was dissolved after symptomatic treatment three days later.Chest pain was relieved after changing position.The diet was changed from liquid to semifluid,and then to normal diet.The child did not have dysphagia.During the 6-month follow-up,the patient had normal diets by oral route.The weight was 32 kg before achalasia and decreased to 18 kg after 9 months(at admission);it then increased to 29 kg after short-time(12 days)parenteral nutrition and long-time(3 months)enteral nutrition by percutaneous endoscopic gastrostomy,and then the patient received POEM.His weight was 30,31,31,29,and 31 kg 1,4,6,9,and 13 months,respectively,after POEM.Conclusion POEM can effectively cure achalasia in pediatric patients and improve the quality of life.Rational enteral nutrition can improve nutrition status and facilitate a successful POEM.

Background:Pancreatic cancer is obscure in onset and progresses rapidly with very poor prognosis. Photodynamic therapy( PDT)has been developed as a novel anti-tumor treatment modality since 1980s. At present,there are only limited researches on pancreatic cancer treated with PDT in vivo. Aims:To investigate the efficacy of quantum dots-RGD ( QDs-RGD)based PDT combined with gemcitabine for treatment of pancreatic cancer xenograft in nude mice. Methods:QDs-RGD probe was synthesized and nude mice bearing pancreatic cancer xenograft was established. Nude mice were imaged at 1,5,10 and 24 hours after injection of QDs-RGD and QDs by in vivo imaging system. Forty model nude mice were randomly divided into five groups:control group( without any treatment),simple illumination group( laser 630 nm, 120 J/cm2,20 min),PDT group(QDs-RGD 0. 5 nmol+laser irradiation),gemcitabine group(gemcitabine 50 mg/kg)and combination group(QDs-RGD 0. 5 nmol+laser irradiation+gemcitabine 50 mg/kg). All the nude mice were sacrificed 18 days later. Tumor weight and volume were measured and tumor inhibition rate was calculated. Results:Fluorescence of tumor was shown 1 hour after injection and became clearest at the 5th hour,then showing a decrescendo trend. Density of QDs surrounding tumor was significantly less than that of QDs-RGD and faded away at the 10th hour. Tumor weight and volume in PDT group,gemcitabine group and combination group were all significantly lower than those in control group and simple illumination group(P<0. 01),and those in combination group were significantly lower than those in PDT group and gemcitabine group(P <0. 05). No significant differences in tumor weight and volume were found between control group and simple illumination group(P >0. 05),as well as between PDT group and gemcitabine group(P >0. 05). Tumor inhibition rate in combination group,gemcitabine group and PDT group was 70. 5%,43. 5% and 37. 1%, respectively. Conclusions:QDs-RGD based PDT combined with gemcitabine can inhibit the growth of pancreatic cancer xenograft in nude mice,which introduces a new idea to the treatment of pancreatic cancer.

Objective To investigate the anti carcinoma role of integrin targeted photodynamic therapy (PDT) on pancreatic carcinoma cells in vitro.Methods Pancreatic carcinoma cells SW1990 were divided into four groups:cells without quantum dots (QDs) and light-treated as blank control group,pure light-treated group,photosensitizer group and PDT group.The targeting of QDs-arginine,glycine,aspartic acid (RGD) and integrin probe was confirmed by laser confocal microscopy.And as a photosensitizer for photodynamic therapy,after treated for 48 hours the morphology changes of pancreatic carcinoma cells of each group were observed.After 48 hours,the cell proliferation,apoptosis and cell cycle changes were detected by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry (FCM).The expressions of myeloid cell leukemia-1 (Mcl-1),protein kinase B(Akt) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) were detected by reverse transcriptase polymerase chain reaction(RT-PCR).The amount of reactive oxygen species (ROS) of each group were evaluated by fluorescence probe.One-way ANOVA was performed for comparison between groups to analyze the treatment effects of PDT group.Results The QDs RGD probe could effectively targeting pancreatic carcinoma cells.The MTT results indicated that the relative inhibition rate of pancreatic carcinoma cells proliferation of PDT group was statistically higher than that of the other groups at 24,48,72 h (F=73.00,85.10,126.58; all P＜0.01).The FCM results revealed that the cell apoptosis rate of PDT group (17.860％ ±1.230％) was higher than that of the other groups (F=130.617,P＜0.01) and cell cycle G0/G1 phase (69.14％±2.63％) and S phase (24.41％ ± 2.67 ％) retardance was also significant (all P＜0.05).The expression of proliferation and apoptosis related gene Mcl-1 and Akt at mRNA level was lower than that of the other groups however the expression of apoptosis-inducing ligand TRAIL at mRNA level was higher than that of the other groups (F=567.456,446.817,145.238; all P＜0.05).The ROS level of PDT group was higher than that of the other groups (F=3262.559,P＜0.01).Conclusion PDT with a QDs-RGD probe could significantly inhibit pancreatic carcinoma cell proliferation and promote cell apoptosis.

Objective To evaluate the sampling efficiency of rotary biopsy forceps in gastric precancerous lesions. Methods A total of 60 gastric lesions with suspected pre-cancerous characters under narrow band imaging were enrolled,and consecutive samples were taken from same lesion by one endoscopist with routine and rotary forceps,respectively. The most severe pathological diagnosis was regarded as the final diagnosis. Results There was a significant difference between rotary biopsy forceps and routine ones in regarding of sample quality and capability of minimize tissue damage (P＜0. 05). The concordance rate with final pathological diagnosis from sample taken by rotary biopsy forceps was higher than that from routine ones,but without significance (P＞0. 05). Conclusion The rotary biopsy forceps is superior to routine ones in sampling of gastric pre-cancerous lesions.

P-glycoprotein (P-gp) is an ATP-dependent multidrug efflux pump that acts as a major obstacle for oral drug delivery and cancer therapy. Recent reports have provided evidence that excipients often used in pharmaceutical formulations, such as Pluronic and TPGS, also have inhibitory effects on P-glycoprotein. Because inhibition of efflux transporters by polymeric inhibitors may dramatically increase the bioavailability of P-gp substrates with negligible side effects, identification of the mechanism and their structure activity relationship is therefore of significant importance for pharmaceutical development. Other than competitive inhibition for traditional inhibitors, polymeric inhibitors may modify P-gp function through alterations on membrane fluidity, inhibition of P-gp ATPase, depletion of intracellular ATP and down-regulating of P-gp expression. In the present review, the inhibition mechanism of potential polymeric inhibitors and their structure activity relationship will be discussed along with a brief introduction to the established methodologies.