1.Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy.
Ze MI ; Qing YAO ; Yan QI ; Jinhai ZHENG ; Jiahao LIU ; Zhenguo LIU ; Hongpei TAN ; Xiaoqian MA ; Wenhu ZHOU ; Pengfei RONG
Acta Pharmaceutica Sinica B 2023;13(2):819-833
Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.
2.Surveillance and genetic characteristics of imported cases of measles virus of D8 genotype in Hebei province
Hui DU ; Wei WANG ; Yanli CONG ; Jingpo ZHANG ; Yu GUO ; Zhenguo ZHANG ; Qi LI
Chinese Journal of Epidemiology 2021;42(6):1012-1017
Objective:To understand the epidemiological and genotypic characteristics of imported cases of measles virus of D8 genotype in Hebei province.Methods:Epidemiological investigation of measles cases in surveillance was carried out. The throat swabs of the measles cases in acute phase were collected for real time RT-PCR identification, measles virus culture and genotype identification.Results:A total of 36 imported measles cases of genotype D8 were detected. The cases were mainly distributed in 8 counties of Handan city. Number of confirmed measles cases in Cheng'an county was the highest, accounting for 58.33% (21/36) of all the reported cases. All patients had fever and rash, and 55.55% (20/36) of the cases were under 2 years old and 86.11% (31/36) of the cases had no immunization history. The children with pneumonia accounted for 44.12% (15/34) of the total children with D8 genotype measles virus infection. The nucleotide and amino acid homologies between the imported measles virus genotype D8 and the WHO reference strain of D8 genotype (D8-Manchester.UNK/30.94) were 98.4%-98.6% and 97.3%, respectively. Compared with the strains of H1 genotype in China, the nucleotide and amino acid homologies were 92.8%-93.1% and 93.3%, respectively.Conclusions:The imported cases of measles virus of D8 genotype might have caused local transmission in Hebei province. Molecular epidemiological surveillance for measles virus needs to be further strengthened. It is necessary to detect and control the epidemic early and improve the coverage rate and timely rate of measles vaccination. It is also important to prevent cross infection in hospitals.
3.The impact of a magnetic field on the dose distribution using the Bebig 60Co HDR sources
Zhenguo CUI ; Jiayi CHEN ; Weikang YUN ; Qi LIU ; Yanling BAI
Chinese Journal of Radiation Oncology 2020;29(3):193-196
Objective To evaluate the impact of an external magnetic field on the dose distribution and electronic disequilibrium region around a Bebig type 60Co HDR brachytherapy source and to judge the feasibility of applying MRI scanner during brachytherapy.Methods The source model was established based on the Monte Carlo package Geant4 software.The simulated geometries consisted of the 60Co source inside a water phantom of 10.0cm× 10.0cm× 10.0cm in size.The magnetic field strength of the 0T,1.5T and 3.0T was considered,respectively.The voxels with a size of 0.2 mm,0.5 mm and 0.5 mm were established along the x-,y-and z-axis.The influence of the magnetic field on the Kerma (kinetic energy released to matter) distribution and dose distribution within the 10.0mm region from the source center was evaluated.Furthermore,the ratio of the Kerma to dose as a function of the distance to the center source was acquired.Results The 1.5T magnetic field exerted no effect on the dose distribution adjacent to 60Co HDR brachytherapy source,whereas3.0T magnetic field caused significant increase in the dose distribution within r<6 mm from the source center.The dose distribution was increased by 40% at r=5.4 mm from the source center.The ratio of Kerma to dose was less than 1 within the region of 1.2 mm<r<6.0 mm,suggesting that 3.0T magnetic field can lead to electronic disequilibrium within a larger region from the source center.Conclusions For Bebig 60Co HDR brachytherapy source,it is safe and reliable to apply1.5T external magnetic field.Nevertheless,3.0T magnetic field can cause high dose risk.Consequently,safety assessment and verification should be delivered prior to clinical application.
4.Histomorphometryof the vertebra and its correlations with MRI signal intensity in rabbits with fluoride treatment
Haifeng XU ; Jin QI ; Jinshen WANG ; Xiangyang XU ; Qi ZHOU ; Zhenguo ZHAO ; Yong LU ; Kemin CHEN ; Yongli ZHANG ; Lianfu DENG
Chinese Journal of Orthopaedics 2018;38(19):1195-1203
Objective To analyze histomorphometrical characteristics of the bone and bone marrow tissues of the lumbar vertebrae in rabbits with fluoride treatment,and its correlation with signal intensity of MRI.Methods Forty New Zealand albino rabbits aged three months old were randomly divided into fluoride exposure of 30 cases and control of 10 cases,male and female,half each.One hundred milligrams of sodium fluoride were added to the municipal water each liter (fluoride content 100 mg/L) as drinking waterto fluorine for 180 days.Twenty-four of 30 cases with fluoride exposure had complete data (male10 casesand female14 cases).The same municipal water was used as control drinking water (fluoride content < 0.9 mg/L).Eight of 10 cases with control had complete data (male andfemale in half).Twenty-four cases with fluoride treatment and complete data were classified into sensitive and resistant type according to the MRI signal intensity of the lumbar vertebra.Histomorphometrics of the vertebra and its correlation with the MRI signal intensity,and sensitivity in early diagnosis of osteofluorosis and feasibility of susceptibility to osteofluorosis detected with MRI were analyzed.Results Theratios of trabecular bone volume (BV),hematopoietic cell volume (HV) and fluid volume (FV) in bone marrow tissue to total cavernous tissue volume (TT) in group with fluoride treatment were 18.3%±2.6%,45.2%±6.0% and 10.4%±5.7% respectively.These were 14.5%±2.8%,36.3%±7.3% and 6.2%±2.1% in control group respectively.These parameters in fluoride group were significantly increased compared to control group.The ratio 26.0%± 8.0% of adipocyte volume (AV) to TV in fluoride group was significantly lower than that 43.3%±5.6% in control group.Two of 24 cases with fluoride exposure (8.3%,2/24) were sensitive and the remaining 22 (91.7%,22/24) were in resistance.The valuesof BV/TT,HV/TV and FV/TV were considered to be sensitive,resistant and control from large to small,while AV/TV value were opposite.A comparison resuhs of signal intensity in MRI showed that vertebra T1WI contrast to noise ratio (CNR) in the sensitive was the minimum (3.0±0.8),followed by resistance (21.3±3.8) andmaximum in the control (28.3±3.1),but CNR of FsT2WIwas opposite.There were positive associations between T1WI and AV/TV,FV/TV and BV/TV,and between FsT2WI and FV/TV and BV/ TV.There were inverse associationsbetween FsT2WI and AV/TV.Theoptimal threshold value of the vertebra T1WI CNR was 23.2 or lessin early diagnosis of skeletal fluorosis,with sensitivity of 83.3% and specificity of 100%.FsT2WI was 5.7 or more,with sensitivity of 45.8% and specificity of 100%.Conclusion The pathogenesis of osteofluorosis is relative to changes in bone marrow microenvironment and cells number in bone marrow tissue,and is correlated to MRI signal intensity.
5.Early versus traditional postoperative oral feeding in patients undergoing elective colorectal surgery: a meta-analysis of safety and efficacy.
Kun ZHANG ; Sirong CHENG ; Qi ZHU ; Zhenguo HAN
Chinese Journal of Gastrointestinal Surgery 2017;20(9):1060-1066
OBJECTIVETo compare the outcomes of early oral feeding (EOF) and the traditional oral feeding (TOF) in postoperative patients with colorectal cancer using Meta-analysis.
METHODSThe databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP and Wanfang Data were searched to collect randomized controlled trial (RCT) about EOF versus TOF in patients undergoing elective colorectal surgery. The retrieval time span was from inception to June 1, 2016. The studies were screened according to the inclusion and exclusion criteria. The data were extracted and the quality was evaluated by 2 reviewers independently. The Meta-analysis was conducted using RevMan 5.2 software.
RESULTSA total of 14 studies with 1 807 patients (906 cases in EOF group and 901 cases in TOF group) were included. The time to first passage of flatus (MD=-16.11 h, 95%CI:-18.27 to -13.94 h, P=0.00), postoperative hospital stay (MD=-1.92 d, 95%CI:-2.83 to -1.01 d, P=0.00), hospitalization cost (ten thousand yuan) (MD=-0.58, 95%CI:-0.71 to -0.46, P=0.00) were less in EOF group compared to TOF group. EOF patients had lower total complication rate (OR=0.68, 95%CI:0.48 to 0.95, P=0.03), in which the pulmonary infection (OR=0.27, 95%CI:0.13 to 0.53, P=0.00), pharyngolaryngitis (OR=0.06, 95%CI:0.04 to 0.11, P=0.00) were lower than those in TOF group, while the tube reinsertion (OR=2.34, 95%CI:1.08 to 5.07, P=0.03) was higher. The incidence of anastomotic leakage, nausea, vomiting, abdominal distension, diarrhea, and wound infection between two groups was not significantly different(all P>0.05). There was no significant difference between two groups in IgM (P>0.05), while the IgA (MD=0.3, 95%CI:0.12 to 0.48, P=0.00), IgG (MD=2.13 ,95%CI:0.82 to 3.44, P=0.001), CD4+ (MD=3.80, 95%CI:2.55 to 5.04, P=0.00), CD4+/CD8+ (MD=0.22, 95%CI:0.04 to 0.41, P=0.02) in EOF group were higher than those in TOF group. Postoperative CRP decreased rapidly in EOF group (MD=-30.10, 95%CI:-48.07 to -12.13, P=0.00), and IL-6 was not significantly different (P>0.05). EOF patients had higher serum albumin level 5 days after operation (MD=3.27, 95%CI: 2.48 to 4.07, P=0.00).
CONCLUSIONSEOF can promote gas passage and defecation, reduce postoperative hospital stay and treatment costs. Also, it can decrease the incidence of complications and postoperative inflammation, and maintain immune function.
6.Clinical efficacy of laparoscopic surgery for pelvic radiation induced enteritis
Jian WANG ; Zhenguo ZHAO ; Xiaodong NI ; Qi MAO ; Danhua YAO ; Yousheng LI ; Jieshou LI
Chinese Journal of Digestive Surgery 2017;16(7):720-724
Objective To investigate the clinical efficacy of laparoscopic surgery for pelvic radiation induced enteritis (PRIE).Methods The retrospective cross-sectional study was conducted The clinical data of 66 patients with PRIE who were admitted to the Nanjing General Hospital of Nanjing Military Command from January 2012 to December 2015 were collected.Laparoscopic surgery will be applied to patients based on patients' clinical manifestations after completing relative examinations.Observation indicators:(1) surgical situations:surgical method,conversion to open surgery,reoperation,surgical incision length,grade of abdominal adhesions,surgical time,volume of intraoperative blood loss,duration of postoperative hospital stay;(2) occurrence of surgical complications;(3) follow-up situations.Follow-up using telephone interview was performed to detect patients' survival and recurrence of PRIE up to April 2016.Measurement data with normal distribution were represented as x±s.Results (1) Surgical situations:① of 59 patients with small intestinal obstruction,11underwent laparoscopic small intestinal resection or enterostomy,including 2 with conversion to open surgery due to dense adhesions,1 due to uncertainty of tumor recurrence and 1 due to intestinal canal dilatation affected vision;48 underwent laparoscopic resection of ileocecum,including 1 1 with conversion to open surgery due to dense adhesions,2 due to iliac vessels injury and 4 due to injuries of sigmoid colon,rectum and bladder.Four patients with colonic obstruction and proctitis underwent laparoscopic colostomy,without conversion to open surgery.One patient received conversional open surgery and underwent intestinal resection of internal fistula + exclusion of rectal stump due to intestine-rectum fistula induced dense adhesions.One patient with anal atresia underwent laparoscope-assisted resection of pelvic tissues and rectal stump.One patient with localized peritonitis underwent laparoscope-assisted ileostomy.② Among 66 patients,4 received reoperations,including 2 with cervical cancer and 2 with rectal cancer,reoperations of 4 patients were respectively caused by intestine-rectum fistula,rectovaginal fistula,anastomotic fistula and ostomy + stoma reversion.Of 4 patients with reoperations,1 received conversion to open surgery due to dense adhesions and then underwent intestinal resection of internal fistula+exclusion of rectal stump,1 with rectovaginal fistula underwent laparoscopic colostomy,1 with anastomotic fistula underwent resection and anastomosis of small intestine due to dense adhesions and 1 underwent laparoscopic ileostomy and stoma reversion.③ Sixty-six patients received 70 operations,including 46 laparoscopic surgeries and 24 conversion to open surgeries.Surgical incision length and average length were respectively 3.0-6.0 cm,4.0 cm in 46 laparoscopic surgeries and 8.0-25.0 cm,15.5 cm in 24 conversion to open surgeries.Grade 0,1,2 and 3 of abdominal adhesions were detected respectively in 7,13,13,13 laparoscopic surgeries and in 1,1,12,10 conversion to open surgeries.Operation time,volume of intraoperative blood loss and duration of postoperative hospital stay were respectively (128±50) minutes,(108±56) mL,(30± 15)days in 46 laparoscopic surgeries and (173±44) minutes,(222± 105) mL,(38± 19) days in 24 conversion to open surgeries.(2) Occurrence of surgical complications:1 patient was complicated with bladder injury in 46 laparoscopic surgeries,and 2,4 and 2 patients in 24 conversion to open surgeries were respectively complicated with bladder injury,colorectal injury and injury of right iliac vessels,they received intraoperative symptomatic treatment.Two,3,3,6 and 1 patients were respectively complicated with pleural effusion,wound infection or dehiscence,venous catheter infection,anastomotic fistula and cholestatic cholecystitis after 46 laparoscopic surgeries.One,5,1,4,2 and 1 were respectively complicated with pleural effusion,wound infection or dehiscence,venous catheter infection,anastomotic fistula,cholestatic cholecystitis and abdominal wall hemorrhage after 24 conversion to open surgeries.They were improved by symptomatic treatment.(3) Follow-up situations:all the 66 patients were followed up for 4-50 months,with a median time of 26 months.During the follow-up,3 patients died of intraperitoneal infection,short bowel syndrome and pulmonary infection,and 3 patients had PRIE.Conclusion The appropriate surgical method is selected based on clinical manifestations of patients,and laparoscopic surgery is safe and feasible for PRIE.
7.Expression and Clinical Significance of Serum Levels of IL-12, IFN-γ,EPO and Ferritin in Patients with Acute Leukemia
Luzhuang ZHANG ; Xiaojie SONG ; Xicai CUI ; Zhenguo QI ; Lan YU
Progress in Modern Biomedicine 2017;17(22):4311-4313,4329
Objective:To study the expressions of serum levels of intedeukin-12 (IL-12),interferon-γ (IFN-γ),erythropoietin (EPO) and ferritin in patients with acute leukemia and its clinical significance.Methods:76 patients with acute leukemia who were treated in our hospital from July 2015 to July 2016 were selected as the observation group,including 31 cases of newly diagnosed group,25 cases of remission group and 20 cases of relapse group.And another 76 cases who had taken the physical examination in our hospital were selected as the control group.Then the levels of serum IL-12,IFN-γ,EPO and ferritin in patients were observed and compared between the two groups.Results:The levels of IL-12 and IFN-γ in the observation group were significantly lower than those of the control group,and the levels of EPO and ferritin were significantly higher than those of the control group (P <0.05).The levels of serum IL-12 and IFN-γ in the untreated group and the relapse group were significantly lower than those of the remission group [(84.21± 5.43)pg/mL,(98.7± 7.98)pg/mL VS(112.43± 10.21) pg/mL,(38.54± 3.56)pg/mL,(49.87± 4.02)pg/mL VS(108.32± 8.43)pg/mL](P <0.05),and the levels of EPO and ferritin were significantly higher than those of the remission group [(402.32± 42.31) mIU/mL (321.58± 30.21)mIU/mL VS (98.21 ± 9.45) mIU/mLM (653.21 ± 54.24) ng/mLM (512.87 ± 43.45)ng/mL VS (342.15 ± 25.12)ng/mL] (P<0.05).Conclusion:The serum levels of IL-12 and IFN-γ in patients with acute leukemia were lower,and the expression of EPO and ferritin was higher,and the disease and prognosis could be evaluated by monitoring the changes of these indexes.
8.Clinical significance analysis of lymph node metastasis on the middle and lower segment of 186 cases of Ⅱ and Ⅲ stage of esophageal squamous cell carcinoma patients
Xuezhi WANG ; Zhipan HONG ; Feng GUO ; Wenqiang YAN ; Zhenguo QI ; Shijun LI ; Zhen LIU
Journal of Chinese Physician 2015;17(1):74-77
Objective To investigate lymph node metastasis on the middle and lower segment of lⅡ and Ⅲ stage of esophageal squamous cell carcinomas,understand the factors influencing the lymph node metastasis,and provide the basis for the key areas of lymph node cleaning.Methods A retrospective study was made on the specimens of 186 patients who were middle and lower segment of Ⅱ and Ⅲ stage of esophageal squamous cell carcinomas,who had underwent radical operation through left thoracic,thoraco abdominal two field lymph node cleaning.All the cases were patients from April 2010 to December 2013 at the Inner Mongolia Medical University Clinical Medical College of Chifeng.Results A percentage (67.9%) of patients (126/186) was found with lymph node metastasis.A total of 4259 lymph node was dissected,with an averaged cleaning of (22.9 ± 8.1) lymph nodes for each case.A total of 622 lymph nodes (14.6% =622/4 259) existed metastasis.The rate of mediastinum metastasis for middle and lower segment of esophageal cancer was 56.1% and 16.5%,respectively.The rate of metastasis to the lower mediastinal lymph nodes was 34.6% and 54.4%,respectively.The rate of metastasis to the celiac lymph nodes was 23.4% and 46.8%,respectively.A significant difference was found in the metastasis locations of middle and lower segment of esophageal carcinomas (P < 0.05).The top three locations of lymph node metastasis in the middle segment of esophageal squamous cell carcinomas were the lymph nodes of left artery paraesophageal,carina,and gastric bypass.The top three locations of lymph node metastasis in the lower segment of esophageal squamous cell carcinomas were paraesophageal,cardia,and gastric lymph nodes.The depths of tumor invasion,differentiation,intravascular cancer embolus were statistically significant effect on lymph node metastasis rate (P < 0.05).Tumor location,and lesion length had no significant effect on the lymph node metastasis rate (P > 0.05).Conclusions The lower segment of Ⅱ,Ⅲ stage esophageal squamous cell carcinoma with lymph node metastasis occurs in the lower mediastinal and abdominal lymph nodes.The middle segment Ⅱ,Ⅲ stage esophageal squamous cell carcinoma with lymph node metastasis occurs in the thoracic and abdominal lymph nodes with Jump transfer characteristics.The lymph node cleaning of the mid-dle segment includes the left artery near the stomach,paraesophageal,and carina lymph node.The lymph node cleaning of the lower segment includes paraesophageal,cardia,and gastric lymph nodes.The metastasis rate of vascular tumor thrombus is related to the depth of tumor invasion and differentiation degree.
9.Clinical characteristics of human infection with a novel avian-origin influenza A(H10N8) virus.
Wei ZHANG ; Jianguo WAN ; Kejian QIAN ; Xiaoqing LIU ; Zuke XIAO ; Jian SUN ; Zhenguo ZENG ; Qi WANG ; Jinxiang ZHANG ; Guanghui JIANG ; Cheng NIE ; Rong JIANG ; Chengzhi DING ; Ran LI ; Peter HORBY ; Zhancheng GAO
Chinese Medical Journal 2014;127(18):3238-3242
BACKGROUNDNovel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A (H10N8) virus which can infect humans and cause severe diseases.
METHODSCollecting clinical data of three cases of human infection with a novel reassortment avian influenza A (H10N8) virus in Nanchang, Jiangxi Province, China.
RESULTSThree cases of human infection with a new reassortment avian influenza A(H10N8) virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome (ARDS) and intractable respiratory failure.
CONCLUSIONThis novel reassortment avian influenza A (H10N8) virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.
Aged ; Antiviral Agents ; therapeutic use ; Female ; Fluoroquinolones ; therapeutic use ; Humans ; Imipenem ; therapeutic use ; Influenza A Virus, H10N8 Subtype ; drug effects ; pathogenicity ; Influenza, Human ; complications ; diagnosis ; drug therapy ; Male ; Middle Aged ; Oseltamivir ; therapeutic use
10.Current situation of the clinical competence training for clinical medicine postgraduates with professional degree and its countermeasures
Jinkui LIANG ; Wen QI ; Jianping JIANG ; Zhenguo ZHONG ; Meichun YANG ; Jing LENG
Chinese Journal of Medical Education Research 2012;11(4):341-344
Extensive attention was paid on how to ensure the cultivation quality for postgraduates with professional degree under the background of the enrollment expansion.The problems in the cultivation of postgraduates with professional degree including declined quality among enrolled students,inefficient training program,unsound management system and little clinical operation chance were analyzed combined with the practice and explore in the clinical competence training for postgraduates with professional degree in Guangxi university of Traditional Chinese Medicine.Some countermeasures were put forward in improving clinical competence for postgraduates with professional degree,for instance the improvement of the management system,tutor team,quality supervision system,clinical skill training and the construction of training bases.

Result Analysis
Print
Save
E-mail