1.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
2.Isolated anterior cerebral artery territory infarction: etiology, clinical features, and outcome
Guangsheng WANG ; Junjie BAO ; Ting HU ; Yuanyuan TIAN ; Li HUANG
International Journal of Cerebrovascular Diseases 2024;32(6):414-420
Objective:To investigate the etiology, clinical features and outcome of isolated anterior cerebral artery (ACA) territory infarction.Methods:Patients with isolated ACA territory infarction admitted to the Affiliated Shuyang Hospital of Xuzhou Medical University from April 2019 to December 2023 were retrospectively included. The demographic and clinical data were collected. The etiology subtypes of stroke were divided into large artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), and stroke of undetermined etiology (SUE). At 90 days after onset, the modified Rankin Scale was used to evaluate the outcome. 0~2 points were defined as good outcome, and >2 points were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent risk factors for poor outcomes. Results:A total of 67 patients with isolated ACA territory infarction were enrolled, including 31 males (46.27%), aged 67.20±12.59 years. There were 26 patients (38.81%) of LAA type, 10 (14.93%) of CE type, 7 (10.45%) of SVO type, 12 (17.91%) of SOE type, and 12 (17.91%) of SUE type. Fifty-two patients (77.61%) had good outcome, while 15 (22.39%) had poor outcome. There were significant differences in gender, diabetes, atrial fibrillation, antithrombin-Ⅲ activity, urinary incontinence, cognitive impairment, and the baseline National Institutes of Health Stroke Scale (NIHSS) score among different etiological subtypes (all P<0.05). Multivariate logistic regression analysis showed that previous stroke history (odds ratio 17.995, 95% confidence interval 1.276-253.852; P=0.032) and high baseline NIHSS score (odds ratio 2.094, 95% confidence interval 1.333-3.292; P=0.001) were the independent risk factors for poor outcome. Conclusions:The most common etiology of isolated ACA territory infarction is LAA, and most patients have good outcome. Previous stroke history and high baseline NIHSS score are the independent risk factors for poor outcome.
3.Anterior choroidal artery territory infarction: infarct size and its related factors
Guangsheng WANG ; Ting HU ; Jinjian YANG ; Yuanyuan TIAN ; Li HUANG ; Longxiang ZHOU ; Yuanwei WANG ; Hanpei GU ; Ying WANG
International Journal of Cerebrovascular Diseases 2020;28(5):348-354
Objective:To investigate the infarct size and its related factors in patients with anterior choroidal artery (AchA) territory infarction.Methods:From April 2016 to April 2018, consecutive patients with acute AchA territory infarction hospitalized in the Department of Neurology, the Affiliated Shuyang Hospital of Xuzhou Medical University were enrolled retrospectively. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of the disease at baseline, and the Diffusion-Weighted Imaging (DWI) was used to determine the side, location, size, and morphology of the infarct lesions. The patients were divided into small infarction group (<20 mm) and large infarction group (≥20 mm). Multivariate logistic regression analysis was used to determine the independent risk factors for infarct size. Results:A total of 100 consecutive patients with acute AchA territory infarction were enrolled, including 86 (86.0%) in small infarction group, 14 (14.0%) in large infarction group. Based on the NIHSS score, there were 89 patients with mild stroke, 9 with moderate stroke, and 2 with severe stroke. According to DWI, 69 patients (69.0%) had long cord-like infarcts and 31 (31.0%) had other shapes of infarcts. The baseline NIHSS score (7.0 [2.0-10.5] vs. 3.0 [2.0-4.0]; Z=2.353, P=0.019) and the proportion of patients with severe stroke (14.3% vs. 0%; P=0.018), the infarcts in posterior part of periventricular area (85.7% vs. 57.0%; χ2=4.180, P=0.041) and medial globus pallidus (21.4% vs. 4.7%; χ2=5.206, P=0.023), and cord-like infarction (92.9% vs. 65.1%; χ2=4.332, P=0.037) in patients of the large infarction group were significantly higher than those of the small infarction group; leukocyte count (7.7±1.7×10 9/L vs. 6.6±1.8×10 9/L; t=2.214, P=0.036) and platelet count (234.5±39.5×10 9/L vs. 198.0±49.4×10 9/L; t=2.618, P=0.010) were significantly higher than those of the small infarction group; the proportion of patients with sensory impairment was significantly higher than that of the small infarction group (50.0% vs. 24.4%; χ2=3.908, P=0.048). Multivariate logistic regression analysis showed that platelet count (odds ratio 1.018, 95% confidence interval 1.000-1.621; P=0.044) and stroke severity (odds ratio 18.245, 95% confidence interval 1.534-217.052; P=0.022) were significantly and positively correlated with the infarct size. Conclusion:The related factors of the infarct size in patients with AchA territory infarction included sensory impairment, baseline NIHSS score, stroke severity, morphology and location of infarct lesions, and leukocyte and platelet counts, of which platelet count and stroke severity were independently positively correlated with the infarct size.
4.A comparison of different suturing methods to prevent or reduce complications of calcaneal fracture incision
Jiang YU ; Zhaoyang HU ; Guangsheng LI ; Min HU ; Chuancheng PU ; Xuejun RAN
The Journal of Practical Medicine 2018;34(1):93-95,99
Objective To explore variety of suture methods in the prevention or reduction of calcaneal fracture incision complications.Methods The data on 120 patients receiving open reduction and internal fixation of the calcaneus fractures in our hospital from January 2014 to December 2015 were collected.A lateral L-like incisionwas used.Allgower-Donati suture,interrupted vertical mattress suture,intradermal suture,and interrupted suture were applied to manage the incision.The incidence of tension blisters in the incision and its surrounding areas,skin flap necrosis,stitch-cutting edge in the skin,and plate exposure was statistically analyzed.The SPSS 18.0 was used for statistical analysis,and P < 0.05 was statistically significant.Results Postoperative complication rate was 6.7% for Allgower-Donati suture,13.3% for interrupted vertical mattress suture,26.7% for intradermal suture and 33.3% for interrupted suture (P < 0.05).Conclusions Allgower-Donati suture can prevent or reduce wound complications of calcaneal fractures effectively,and it is worthy of extensive clinical use.
5.Efficacy and safety of low-dose levonorgestrel-releasing intrauterine system in Chinese women: a multicenter, single-arm, open labeled interventional trial
Cuifeng QIAN ; Guangsheng FAN ; Qinping LIAO ; Shuying WU ; Duanduan LA ; Wen DI ; Baihua DONG ; Hongwei LIU ; Liangdan TANG ; Zheng'ai XIONG ; Hanwang ZHANG ; Yali HU ; Naiming YANG ; Mulan REN ; Hong SHI ; Gaopi DENG ; Zirong HUANG
Chinese Journal of Obstetrics and Gynecology 2018;53(6):409-413
Objective To evaluate the efficacy,bleeding profile and safety of low-dose levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women of childbearing age.Methods A multi-center,open-label,single-arm clinical trial conducted at 16 centres in China enrolled 773 healthy women of childbearing age (mean age 31.6 years old,range 18 to 40 years old),who demanded contraception,from April 2006 to June 2013.All women placed LNG-IUS 8 for 3 years and then been followed up at 3,6,9,12,18,24,30,36 months.The efficacy variables including pregnancy rate and expulsion rate were analyzed using life table,while observing adverse events (AE) to evaluate the safety.The bleeding profile happened during the study was assessed using 90-day reference intervals (World Health Organization criteria).Results Eight pregnancies occurred among 773 women,resulting in a overall Pearl index of 0.42 per 100 women years.The 3-year cumulative pregnancy rate was 0.37 per 100 women years and the 3-year cumulative expulsion rate was 1.99 per 100 women years.The number of women with bleeding/spotting reduced and the bleeding/spotting days declined over time.Totally 219 AE were reported related to LNG-IUS 8 placements.The most common AE were vaginal bleeding (8.2%,63/773)and the ovarian cyst (6.2%,52/773).LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage of women with dysmenorrhea as well as the days of dysmenorrhea decreased over time.The percentage of women satisfied or very satisfied with LNG-IUS 8 was 87.2% (622/713).Conclusion LNG-IUS 8 is highly effective and safe for Chinese healthy women of childbearing age.
6.Safety and efficacy of endoscopic self-expandable metal stent implantation for malignant colonic obstruction
Bin ZENG ; Liang CHEN ; Yong DAI ; Guangsheng HU ; Aijun LIAO
China Journal of Endoscopy 2016;22(3):88-91
Objective To evaluate the safety and efficacy of endoscopic implantation of self-expandable metallic stent (SEMs) for malignant colorectal obstruction. Methods A total of 108 patients who had undergone endoscopic SEMs implantation for malignant colonic obstruction from January 2011 to May 2014 were enrolled. The clinical suc-cess rates and the complications were reviewed. Results The clinical success rates were 92.59%(100/108). Abdomi-nal pain, perforation and bleeding were the most common post-procedure complications, the rates of which were 16.67% (18/108), 7.41% (8/108), 6.48% (7/108), respectively. The abdominal pain in most patients was self-reliev-ing except for 6 patients with perforation of colon. Patients with perforation were cured by emergency surgery. The 7 patients developing bleeding recovered themselves. Conclusion The success rate of endoscopic SEMs implantation is satisfactory in the study. As a bridge to surgery or a palliative care method, endoscopic SEMs implantation is effec-tive and safe for malignant colorectal obstruction.
7.Clinical efficacy and complications of transoral endoscopic peroral endoscopic myotomy for achalasia
Bin ZENG ; Guangsheng HU ; Weiwei ZHOU ; Liang CHEN ; Yong DAI ; Aijun LIAO
China Journal of Endoscopy 2016;22(7):26-30
Objective To explore the clinical efficacy and complications of transoral endoscopic peroral endo﹣scopic myotomy (POEM) for achalasia (AC). Methods 38 patients with AC received POEM treatment from January 2013 to January 2013 in our digestive endoscopy center. Procedure-related complications and gastroesophageal re﹣flux were observed, and ECKARDT score and the lower esophageal sphincter pressure changes were analysed. Results All patients underwent POEM successfully. No serious POEM-related complications were observed, bleed﹣ing, gas related complications were treated successfully by conservative treatment. Postoperative follow-up time was 10.4 months (range 9 to 12 months), the symptoms of all the patients were alleviated, ECKARDT score average from preoperative 8.7 points dropped to postoperative 1.2 points (P<0.01), esophageal sphincter pressure decreased sig﹣nificantly, mean pressure dropped from preoperative (33.40 ± 11.80) mmHg to postoperative (13.50 ± 4.30) mmHg (P< 0.01) and gas related complications occurred in 6 cases (15.78 %), esophageal reflux occurred rate total was 23.68%(9/38). Conclusion POEM is safe and effective for the treatment of AC, and has better long-term effect.
8.Optimum dose of Oxycodone for anesthesia induction in patients undergoing laparoscopic cholecystectomy
Huayan LYU ; Chonghui HU ; Na YANG ; Guangsheng DU ; Zhanhong WEI
China Journal of Endoscopy 2016;22(8):29-33
Objective To determine the optimum dose of Oxycodone for anesthesia induction in patients undergoing laparoscopic cholecystectomy. Methods Ninety patients, ASA Ⅰ or Ⅱ , scheduled for elective LC, were randomly divided into 3 groups using random number table (O 1~O 3 groups, n = 30 each). Anesthesia was induced with iv Propofol 1.00~2.00 mg/kg, Oxycodone 0.20 mg/kg, 0.3 mg/kg and 0.4 mg/kg (O 1~O 3 groups, respectively), and Vecuronium 0.10 mg/kg. Before anesthesia induction ( T0 ), 1 min after Laryngeal Mask intubating ( T1 ), the instant of pneumoperitoneum ( T2 ), separation of the gallbladder ( T3 ), wake up immediately ( T4 ), leaving the recovery room ( T5 ), the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. At T4, leaving the recovery room ( T5 ), 4 hours after the operation ( T6 ), 8 hours after operation (T7), the numeric pain rating scale (NRS) were recorded. The overall amount of remifentanil and Oxycodone were record. The wake up time, additional analgetic cases and the adverse reactions were recorded. Results The average HR, SBP and DBP fluctuations in the O 2 and O 3 groups were not more than 20.00% of the basal values. There was no significant difference in wake up time between the three groups. There were 22 cases of patients, the NRS> 4, in O1 group requires additional analgesics after they wake up, more than O 2 and O 3 group (7, 3 respectively, P < 0.05). The overall Oxycodone consumption of the three groups were O1: (18.93 ± 4.34) mg (0.90~2.60 mg),O2: (25.50 ± 4.49) mg (1.40~3.00 mg), O3: (26.10 ± 4.55) mg (1.80~3.40 mg) (F = 23.79, P = 0.000). There was no significant difference in adverse reactions between the three groups, but one patient had respiratory depression in O3 group. Conclusion The optimum dose of Oxycodone for anesthesia inducing in laparoscopic cholecystectomy were 0.30 mg/kg.
9.Content Determination of Astragaloside in Danggui Buxue Formula Granule by HPLC
Guangsheng LI ; Fang QIN ; Jiling YANG ; Wenwen HU ; Junli ZHANG ; Weixin ZHANG
China Pharmacy 2015;26(36):5131-5133
OBJECTIVE:To establish a method for content determination of astragaloside in Danggui buxue formula granule, and investigate the influence of different conditions of dissolution on the content. METHODS:HPLC was performed on the column of Aglient C18 with mobile phase of acetonitrile-water(28:72,V/V)at flow rate of 1.0 ml/min,column temperature was 25 ℃,and the injection volume was 10 μl. RESUITS:The linear range of astragaloside was 2.91-17.46 μg;RSDs of precision,stability were lower than 2%,and reproducibility tests was 3.63%,recovery was 95.76%-98.20%(RSD=1.03%,n=6). The optimized use method was mixing the two granules with 80 ℃ hot water and keeping heat preservation for 5 min successively before taken. CON-CLUSIONS:The method is simple and reproducible,and can be used for the content determination of astragaloside in Danggui bux-ue formula granule.
10.The characteristics of PET scan in the Alzheimer disease and vascular dementia
Shuwen XU ; Guangsheng GAO ; Shuyi LUO ; Shaotong XIANG ; Hao XIAO ; Fangfang HU ; Weiping CHEN ; Yuedong HUANG
Chinese Journal of Nervous and Mental Diseases 2014;(8):469-473
Objective To investigate early and differential diagnosis of Alzheimer disease and vascular dementia (VD)using FDG-PET scan. Methods Clinical data was collected from AD,VD and normal control(NC). 18F-2-fluo-ro-deoxy-D-glucose(18F-FDG)PET scan was conducted to detect the cerebral FDG metabolism. The average standard uptake value (SUV) of cerebral regions was expressed as semiquantitative index relative to ipsilateral cerebellum. Re-sults There were no differences in age and the mean total scores of the mini mental status examination (MMSE) between patients with VD and those with AD.The AD group showed that the SUV was significantly decreased in the right frontal, parietal,temporal lobe,hippocampus,temporo-parietal junction,and bilateral posterior cingulate cortex compared to the VD and in the bilateral posterior cingulate cortex,temporo-parietal junction,frontal and temporal lobe comparing to the NC(P≤0.01). SUV was significantly increased in the right parietal,posterior cingulate cortex and hippocampus whereas was significantly decreased in the left frontal lobe,temporo-parietal junction and thalamus in the VD compared with NC group(P≤0.01). Conclusion AD patients have typical features of 18F-FDG PET which may be helpful for the diagnosis of AD in the early stage.

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