Advances in Helicobacter pylori vaccine research: From candidate antigens to adjuvants-A review.

BACKGROUND: Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric-related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection. METHODS: PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms-H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed. RESULTS: Most of the candidate antigens used as H. pylori vaccines in these literatures are whole-cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible. CONCLUSIONS: This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers.

Survival results of surgical resection versus CT-guided percutaneous ablation for stage Ⅰnon-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To evaluate the survival results of surgical resection (SR) and CT-guided percutaneous ablation (PA) for stageⅠnon-small cell lung cancer (NSCLC). Methods    The PubMed, Web of Science, EMbase, The Cochrane Library, CNKI, VIP, Wanfang databases from inception to June 2021 were searched to collect comparative studies on the survival results between SR and CT-guided PA treatment for stageⅠNSCLC. RevMan 5.3 software was used for statistical analysis of data. Results    A total of 3 114 patients were included in 11 studies. The results of meta-analysis showed that compared with the PA group, the SR group had a higher 2-year postoperative overall survival (OS) rate (OR=1.44, 95%CI 1.00-2.06, P=0.05), 3-year postoperative OS rate (OR=2.37, 95%CI 1.47-3.81, P<0.001), 5-year OS rate (OR=1.64, 95%CI 1.19-2.28, P<0.01), 5-year progression-free survival rate after operation (OR=2.43, 95%CI 1.54-3.82, P<0.001) and lower local recurrence rate (OR=0.26, 95%CI 0.13-0.54, P<0.001). There were no statistical differences between the two groups in terms of 1-year postoperative OS rate, 1-year, 2-year, and 3-year tumor-related survival rates, 1-year, 2-year tumor-free survival rates, or distant postoperative recurrence rate (P>0.05). Conclusion    For patients with stageⅠNSCLC with optimal basic conditions, surgery is a more appropriate treatment. For patients who cannot withstand surgical injuries or refuse surgery, CT-guided PA is also a potential alternative treatment. However, this conclusion needs  to be verified by prospective controlled trials with larger sample sizes and a more rigorous design.

Guild-level microbiome signature associated with COVID-19 severity and prognosis

COVID-19 severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples collected from 300 in-hospital COVID-19 patients at time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), Redundancy Analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Random Forest model based on these 33 HQMAGs classified patients from different severity groups (average AUC = 0.79). Co-abundance network analysis found that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Random Forest regression showed that these 33 HQMAGs at admission had the capacity to predict 8 clinical parameters, which are predictors for COVID-19 prognosis, at Day 7 in hospital. Moreover, the dominance of Guild 1 over Guild 2 at admission predicted the death/discharge outcome of the critical patients (AUC = 0.92). Random Forest models based on these 33 HQMAGs classified patients with different COVID-19 symptom severity, and differentiated COVID-19 patients from healthy subjects, non-COVID-19, and pneumonia controls in three independent datasets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission.

Predictive value of preoperative blood parameters on the efficacy of microscopic varicocele ligation for infertility patients with varicocele / 中国医师杂志

Objective:To investigate the predictive value of preoperative blood parameters on the efficacy of microscopic varicocele ligation in the treatment of infertility patients with varicocele.Methods:The clinical data of 110 patients with varicocele admitted to Xi′an People′s Hospital and Tangdu Hospital of Air Force Military Medical University from June 2016 to January 2021 were analyzed retrospectively. Successful operation was defined as the restoration of all semen parameters (sperm concentration, forward motility, morphology, etc.) to normal values 6 months after operation. The patients were divided into effective treatment group (group A, 78 cases) and ineffective treatment group (group B, 32 cases). The blood parameters of the two groups were compared before operation. Spearman correlation analysis was used to determine the relationship between blood parameters [neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV)] and the success of microscopic varicocele ligation. The predictive value of blood parameters (NLR and MPV) to the success of microscopic varicocele ligation was analyzed by receiver operating characteristic (ROC) curve.Results:There was no significant difference in clinical characteristics, and sex hormone levels between the two groups before operation (all P>0.05); There were statistically significant differences in NLR and MPV in blood parameters between the two groups (both P<0.05), and there was no significant differences in other blood parameters (both P>0.05). There was no significant difference in semen parameters between the two groups before operation (all P>0.05). After operation, the semen volume, semen concentration, forward movement and sperm morphology of patients in group A were significantly improved compared with those before operation (all P<0.05), while the parameters of patients in group B had no significant difference compared with those before operation (all P>0.05). There was a negative correlation between preoperative NLR and the success rate of spermatic vein ligation ( r=-0.719, P<0.01), and a positive correlation between MPV and the success rate of spermatic vein ligation ( r=0.522, P<0.01). The ROC curve was used to analyze the threshold of predictive variables for the success of spermatic vein ligation. The optimal critical value of NLR was 2.01 ( P<0.01), and the optimal critical value of MPV was 11.45 ( P<0.01). Conclusions:Low NLR (<2.01) and high MPV (>11.45) may be useful preoperative predictive tools for identifying the group of infertile varicocele patients who would benefit most from microscopic spermatic vein ligation.

Thirty-six critical cases of emergency helicopter transferring between hospitals / 中华危重病急救医学

Objective:To summarize critical cases of emergency helicopter transferring between hospitals and improve the quality and safety of critical care.Methods:The task records of Guangxi Aviation Medical Rescue Training Base from September 2017 to September 2020 were retrieved. The mission acceptance, implementation results, disease spectrum composition, pre-transfer preparation and medical intervention on board were summarized.Results:① General information: a total of 168 patients of helicopter transfer requests were registered, of which 36 patients were transferred, 35 patients were successful, 1 patient had cardiac arrest during the landing phase, and died several hours after continuous resuscitation. Of the 36 patients 30 were males and 6 were females, with median age of 50.5 (29.8, 66.0) years old, the average transfer time was (54.95±17.89) minutes, and the average transfer distance was (205.74±74.68) km. ② Disease spectrum included 11 cases of stroke (30.55%), 7 cases of trauma (19.45%), 5 cases of severe pneumonia (13.89%), 5 cases of heart and macro-vascular diseases (13.89%), 5 cases of abdominal emergency (13.89%), and 3 other conditions (8.33%).③ Severity: 31 patients (86.11%) were severe (≥15) according to acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score; 19 patients (52.78%) were high-risk emergency transport (≥6) according to Hamilton early warning score (HEWS); 6 patients (85.71% of trauma patients) were severe trauma (≥16) according to injury severity score (ISS). ④ Preparation before transfer: remote consultation was carried out to evaluate the latest state of the patient's condition, especially the respiratory and circulatory conditions. Relevant items were reviewed and emergency treatments were implemented when necessary. Targeted preparation was made for accidents that might occur during transfer, such as electrocardiogram (94.44%), blood gas analysis (94.44%), brain CT (36.11%) and other auxiliary examinations, endotracheal intubation or tracheotomy (72.22%), deep vein catheterization (91.67%), placement of gastric tube (86.11%) and urinary tube (88.89%), adjustment of sedative (38.89%), vasoactive drugs (58.33%) and drugs for dehydration and lowering intracranial pressure (33.33%), and fixation of fracture (11.11%), etc. ⑤ On-board medical intervention: cardiac monitoring, blood pressure, respiration and blood oxygen monitoring were carried out in all patients. The parameters of patients using ventilator were adjusted in time (66.67%). The dosage of patients using micropump was adjusted in time (91.67%). Other aspects included the use of sedative and analgesics (38.89%), sputum suction nursing (75.00%), all kinds of catheter nursing (endotracheal intubation/incision nursing of 72.22%, indwelling catheter nursing of 88.89%), and cardiopulmonary resuscitation for patient with cardiac arrest (2.78%).Conclusion:As the patients transferred by helicopter are mainly those of critically ill at this stage, the requirements for airborne medical equipment and rescue technology are high, and there is an urgent need to establish technical specifications and personnel training standards.

Analysis of the prognostic factors of renal function after nephron sparing surgery / 中华泌尿外科杂志

Objective:To investigate the prognostic factors of renal function after nephron sparing surgery (NSS) in renal tumor patients.Methods:The data of 115 patients who underwent NSS in our hospital from December 2016 to December 2018 were retrospectively analyzed. There were 75 males and 40 females, aged (49.50±12.94) years. The body mass index was (24.59±3.59) kg/m 2. The maximum diameter of the tumor was (3.66±1.32) cm. The R. E.N.A.L. score was (6.43±1.60). Laparoscopic partial nephrectomy was performed in 61 cases and robot-assisted laparoscopic partial nephrectomy was performed in 54 cases, and all of which were successfully completed. Operative time, WIT and postoperative pathological results were recorded. Blood creatinine value, GFR of affected kidney, GFR of healthy kidney, total GFR, GFR preserving rate (the ratio of postoperative GFR to preoperative GFR), functioning parenchymal volume (FPV) of the affected kidneys, and FPV preserving rate of the affected kidneys (the ratio of postoperative FPV and preoperative FPV) were recorded 6 months after surgery. FPV was measured by the ellipsoid approximation on CT images before and after surgery. Paired sample t test was used to compare GFR and FPV before and after surgery. Spearman rank correlation analysis was used to evaluate the correlation between the study factors and GFR preserving rate of the affected kidneys. Multivariate linear regression models were used to analyze independent predictors of renal function of the affected kidneys. Independent sample t test was used for comparison between group of WIT≤25 min and group of WIT>25 min. Results:All of the 115 patients in this study underwent successfully operations, with the median operation time of 135(75-245) min, and WIT(24.57±5.51) min. Postoperative GFR of the affected kidneys(35.50±7.81)ml/(min·1.73 m 2) was significantly different from preoperative GFR( P<0.001). The FPV preserving rate of the affected kidneys was (84.28±4.37)%, which was significantly lower than that preoperative FPV of the affected kidneys ( P<0.001). Spearman rank correlation analysis showed that there was a strong positive correlation between the FPV preserving rate of the affected kidneys and the GFR preserving rate of the affected kidneys ( r=0.802), WIT was negatively correlated with the GFR preserving rate of the affected kidneys ( r=-0.503). Multiple linear regression analysis showed that preoperative GFR of the affected kidneys ( b=-0.150, P=0.008), WIT ( b=-0.443, P<0.001) and the FPV preserving rate of the affected kidneys ( b=1.638, P<0.001) were independent predictors of the GFR preserving rate of the affected kidneys. WIT>25 min group had a significantly lower GFR preserving rate of the affected kidneys than WIT≤25 min group [(68.77±10.88)% vs.(79.34±8.88)%, P<0.001]. Conclusions:In the case of short WIT (<30 min), the reservation of normal renal tissue is the most important variable prognostic factor of renal function after NSS, and short WIT plays a secondary role. Under the premise of complete tumor resection, normal renal tissue should be reserved as much as possible and WIT should be controlled within 25 min.

Option of minimally invasive technique for living donor nephrectomy / 中华泌尿外科杂志

Objective To discuss the optimal operation mode and operation path in minimally invasive technique for living donor nephrectomy.Methods From September 2013 to August 2015, 68 living donor nephrectomy was retrospectively reviewed. Thirty-one patients were performed with robotic-assisted laparoscopic living donor nephrectomy(robotic group), twenty-nine patients underwent totally retroperitoneal laparoscopic living donor nephrectomy(non hand assisted group),and eight patients were performed with hand assisted retroperitoneal laparoscopic living donor nephrectomy(hand assisted group). Operation time, warm ischemia time, intraoperative hemorrhage volume, hospitalization time, complications and preoperative and postoperative serum creatinine value of the recipients between the two groups were compared.Results The operations of three groups were all performed successfully. Intraoperative hemorrhage volume in the three groups were(39±15)ml,(62±37)ml and(53±19)ml, and there were significant differences between these groups(P<0.05). But hospitalization time ,operation time, warm ischemia time and complications occurred rate in the three groups had no significant difference(P>0.05). In robotic group,2 donors occurred with splenic injury during operation and 1 donor was detected with hemorrhage after operation. In non-hand assisted group, 1 donor occurred with urinary tract infection, 1 donor occurred with external iliac vein thrombosis. In hand assisted group 1 donor was detected with wound fat liquefaction after operation. All the donors were followed up for more than 9 months, no hypertension, proteinuria and renal dysfunction complications were detected. The blood creatinine in three groups of recipients after operation of 5th day and 28th day were(118±26)μmol/L, (130±33)μmol/L,(128±41)μmol/L and(114±17)μmol/L,(116±34)μmol/L,(115±29)μmol/L, respectively, and there was no statistical difference(P>0.05).Conclusions Minimally invasive technique for living donor nephrectomy is beneficial to patients' recovery. Surgery doctors should combine personal experience and the hospital's hardware conditions and other factors. The principle is to ensure the donor's safety and to balance the interests of the donor and the recipient, to choose their own most skilled way of surgery.

Clinical Observation of Alteplase Intravenous Thrombolysis in the Treatment of Acute Cerebral Infarction / 中国药房

OBJECTIVE:To observe the bleeding,therapeutic efficacy and ADR of patients with acute cerebral infarction (ACI) treated by alteplase intravenous thrombolysis. METHODS:140 ACI patients were randomly divided into group A and B with 70 cases in each group. Group A was give alteplase 0.6 mg/kg for intravenous thrombolytic therapy,and group B was given al-teplase 0.9 mg/kg for intravenous thrombolytic therapy. The bleeding after thrombolysis,bleeding time,therapeutic efficacy and ADR were compared between 2 groups. RESULTS:The incidence of Subcutaneous ecchymosis,gingival bleeding,bleeding of di-gestive tract and intracranial hemorrhage of group A were 4.29%,2.86%,2.86% and 2.86%;those of group B were 14.29%, 12.86%,11.43% and 11.43%;the bleeding time of those symptomsin 2 groups were(6.04±0.75)and(7.22±0.56)h、(24.63± 10.24)and(35.22±9.87)min、(3.04±0.11)and(4.08±0.25)h、(3.12±0.48)和(4.53±0.66)h respectirely,with statistical signifi-cance(P0.05). CONCLUSIONS:The bleeding should be monitored strictly when ACI patients receive alteplase intravenous thrombolysis,and low-dose alteplase thrombolysis can ultimately reduce the incidence of bleeding.

Preliminary evaluation of sunitinib as first line therapy in treating patients with metastatic renal cell carcinoma / 中华泌尿外科杂志

[Abstact] Objective To investigate the efficacy and safety of sunitinib as first line therapy in treating those patients with metastatic renal cell carcinoma ( mRCC ) .Methods A total of 66 patients , including 42 male and 24 female cases ,with metastatic renal cell carcinoma were enrolled from January 2009 to June 2014.The median age was 52 years (range 26-75 years).According to American Joint Committee On Cancer (AJCC) staging,there were 35 cases of T3 stage,31 cases of T4 stage.All patients had distant metastasis ,including single organ metastasis in 52 patients and multiple organ metastasis in 14 cases.Sixty-one patients received prior radical nephrectomy ,5 patients received biopsy .Sixty-two patients were diagnosed as renal clear cell carcinoma and 4 patients were diagnosed as renal papillary cell carcinoma .Sunitinib was administered in standard 4/2 regimens.Briefly, patient takes 50 mg once a day orally for 4 weeks.Then the sunitinib will be stopped for 2 weeks.Six weeks was defined as 1 cycle.It should be continued until disease progression or occurrence of intolerable adverse reactions .The efficacy of sunitinib should be evaluated within 2 cycles.Results The duration of following-up ranged from 5 to 66 months.The efficacy could be evaluated in 63 patients.Two patients ( 3.2%) achieved complete remission .Twelve patients ( 19.0%) achieved partial remission.Forty-five patients (71.4%) demonstrated stable disease and 4 patients (6.3%) developed progressive disease .The disease control rate was 93.7%(59/63) and the objective response rate was 22.2%(14/63).2 (3.2%) patients died due to the progression of disease .The most commonⅠ-Ⅱadverse events included fatigue in 36 cases ( 57.1%) , thrombocytopenia in 36 cases ( 57.1%) , hand-foot syndrome in 32 cases (50.8%),hypertension in 27 cases (42.9%),neutropenia in 15 cases (23.8%), hypothyroidism in 12 cases (19.0%), diarrhea in 6 cases (9.5%) and alopecia in 4 cases (6.3%).Ⅲ-Ⅳ adverse events were hand-foot syndrome in 4 cases ( 6.3%) , hypertension in 2 cases ( 3.2%) , neutropenia in 5 cases (7.9%) and thrombocytopenia in 5 cases (7.9%).Most mild adverse reactions after symptomatic treatment could be alleviated ,did not affect the medication .When the adverse events returned to the Ⅰ-Ⅱdegree, the 37.5 mg sunitinib was resumed once daily by orally.NoⅢ-Ⅳadverse events were reported again.Conclusions Sunitinib was efficacious in the treatment of advanced renal cell carcinoma.Most mild adverse events were tolerable ,and severe adverse events need medical treatment .

Safety and feasibility of retroperitoneal laparoscopic adrenalectomy for different diameter adrenal tumor / 中国医师进修杂志

Objective To evaluate the safety and feasibility of retroperitoneal laparoscopic adrenalectomy for different diameter adrenal tumor.Methods The clinical dam of 61 patients who underwent retroperitoneal laparoscopic adrenalectomy from January 2009 to June 2013 were retrospectively analyzed,the patients were divided into A group (the diameter of adrenal tumor ＞ 6 cm,24 cases) and B group (the diameter of adrenal tumor 3-6 cm,37 cases) according to the diameter of adrenal tumor.The therapeutic effect was compared between 2 groups.Results All procedures were performed successfully.There were statistical differences in operative time and estimated blood loss between A group and B group [(138 ± 66) min vs.(106 ± 45) min and (324 ± 168) ml vs.(165 ± 50) ml] (P ＜ 0.05).There were no statistical differences in the rate of complication and blood transfusion between 2 groups (P ＞ 0.05).There was no statistical difference in hospital stay after operation between 2 groups [(6.7 ± 1.2) d vs.(5.4 ± 0.6)d] (P ＞ 0.05).A group was followed up for (22 ± 10) months,during which time no local recurrence was noted in 19 cases by B-mode ultrasonography,3 cases were missed,and 2 cases were alive with hydronephrosis or pancreatic cyst.B group was followed up for (24 ± 11) months,during which time no local recurrence was noted in 32 cases by B-mode ultrasonography,4 cases were missed,and 1 case was found with renal dysfunction.The pathology of most tumors in A group included medullary lipoma,pheochromocytoma and ganglioneuroma,in B group included adenoma,pheochromocytoma and medullary lipoma.Conclusion Minimally invasive and safe procedure for skillful surgeons in the treatment of tumor diameter larger than 6 cm.

Molecular epidemiological characteristics of clinically isolated carbapenem-resistant Acinetobacter baumannii in Changsha / 中南大学学报(医学版)

OBJECTIVE@#To survey antibiotic resistance of clinical isolates of Acinetobacter baumannii in Changsha and to investigate molecular epidemiological characteristics of carbapenem-resistant Acinetobacter baumannii.@*METHODS@#A total of 205 non-duplicated, clinical isolates of Acinetabacter baumannii from 10 general hospitals in Changsha were collected from March 2010 to December 2010. The K-B disk diffusion method was applied for the drug-susceptibility test; a modified, double-disk synergy test was used to detect metallo-β-lactamase (MBL), and a modified Hodge test was used for the screening of carbapenemase. PCR was used to amplify carbapenemase genes (including OXA-23, OXA-24, OXA-51, IMP-1, and VIM-2) and the positive products were sequenced. Enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) was used for DNA typing and test of homology.@*RESULTS@#Of the 18 antibiotics tested, 14 had a high rate of resistance (>50% of the isolates tested), with piperacillin the highest (80.5% of strains), and cefoperazone/sulbactam the lowest (2.5%). In total, 115 carbapenem-resistant Acinetobacter baumannii strains were confirmed, but their MBL phenotype and genes were all negative. Seventy-one positive strains were detected by the modified Hodge test, among which 64 strains were OXA-23-positive. All the 115 strains were positive for the amplification of the OXA-51 gene, and no strain was found which carried OXA-24 or OXA-58 gene. Seven genomic types were included in the 115 Acinetobacter baumannii. The major prevalence types were Type B ( 72 strains) and Type A (19 strains).@*CONCLUSION@#Multiple drug resistance of clinically isolated Acinetobacter baumannii is a serious problem in Changsha. Production of OXA-23 and OXA-51 carbapenemases is an important mechanism of resistance to carbapenem antibiotics, and there is prevalence of the same clones in these carbapenem-resistant strains.

Effect of siRNA Interference of HRG-1 on bladder cancer T24 cells in vitro / 中国医师杂志

Objective To observe the expression change of HRG-1 gene between urinary bladder carcinoma and normal tissues,and to investigate the effect of HRG-1-siRNA on the proliferation and apoptosis of human bladder carcinoma cells.Methods Immunohistochemisty was used to detect the expression of HRG-1 in 85 cases of bladder carcinomas and 20 normal bladder tissues.The siRNA of HRG-1 was designed,synthesized,and transfected into bladder cancer cell line T24.Results The HRG-1 gene expression had significant differences between bladder carcinoma and normal bladder tissues (P ＜ 0.05).The positive expression of HRG-1 gene had significant differences between the pathological grades and clinical stages of bladder carcinomas (P ＜0.05).After treated with siRNA,the expression levels of HRG-1 protein and mRNA in T24 cells decreased obviously (P ＜ 0.05).The apoptosis rate of T24 cells transfected with HRG-1-siRNA was significantly different from control-siRNA group and blank group (P ＜ 0.01).Conclusions The high expression of HRG-1 gene may play an important role in bladder carcinoma,and siRNA targeting HRG-1 can suppress HRG-1 protein expression markedly and enhance apoptosis of T24 cells.

Chromosome genetic changes in hepatocellular carcinoma with double exposure to hepatitis B virus/aflatoxin B1 : A preliminary study from Guangxi / 中华肝胆外科杂志

ObjectiveTo study the chromosome genetic changes in hepatocellular carcinoma (HCC) with double exposure to hepatitis B virus/aflatoxin B1 (HBV/AFB1) in Guangxi.Method Differences in genomic alterations in 32 patients with HCC were analyzed using comparative genomic hybridization(CGH).Results(1) The majority of chromosome copy number in the 32 HCC samples had varying degrees of change.The amplification of chromosome regions were 1q,7q,8q,with the high frequency regions being 1q,8q.The deletion of chromosome regions were 1p,4q,8p,9p,13q,14q,16p,16q,17p,18q,19p,Y,with the high frequency regions being 1p,4q,8p,16q,17p,19p;(2) There were also some high copy number amplification or deletion of small regions,such as 2p25.1-p25.2,3q22.3-q23,7p14.1-p14.3,and 9p13.2-9p21; (3) Hierarchical clustering analysis showed that the rate of deletion of chromosome 13q decreased progressively in the following 4 groups:-HBsAg(+)/AFB1 (+),HBsAg(+)/AFB1 (-),HBsAg( - )/AFB1 ( + ),and HBsAg( - )/AFB1 (-) (x2=6.452,P＜0.05).4p was found mainly to be amplified in the HBsAg(+)/AFB1(-)group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg( - )/AFB1(-) groups.19q was found mainly to be amplified in the HBsAg(+)/AFB1(+) group,but it was mainly deleted in the HBsAg(-)/AFB1(+),and HBsAg(-)/AFB1(-) groups.ConclusionThe chromosome genetic changes of HCC in Guangxi showed multiplicity.The deletion of chromosome 19p,2p25.1-25.2,3q22.3-q23,7p14.1-p14.3 and amplification of chromosome 9p13.2-9p21 are probably unique genetic characteristics of HCC in this region.The combined effects of Hepatitis B virus and aflatoxin B1 may contribute to deletion of chromosome 13q of HCC in Guangxi.

The inhibitory effects of N-myc down-stream regulated gene-2 on proliferation of bladder carcinoma cell line T24 in vitro / 中国医师杂志

Objective To explore the expression of a new candidate tumor suppressor N-myc downstream regulated gene 2 (NDRG2) in bladder cancer tissues and to investigate its clinical and pathological significance.Methods Formalin-fixed,paraffin-embedded tissue sections from 62 cases of bladder carcinomas and 10 cases of normal bladder tissues were analyzed retrospectively with immunohistochemistry (S-P method).Results The NDRG2 gene was highly expressed in normal bladder tissues,but low expressed in bladder carcinoma tissues.Positive expression of NDRG2 was detected in 8 of the 10 (80.0％) normal tissues and 40.3％ in bladder carcinoma ones (x2 =3.98,P ＜0.05).Furthermore,with the degree of malignancy increased,the positive expression of NDRG2 in bladder carcinoma samples was decreased.The expression of NDRG2 in bladder carcinoma was negatively correlated(r =-0.288,P ＜0.05) with C-myc(r =-0.436,P ＜0.01) and positively correlated with p53 in bladder carcinoma tissues(r =0.717,P ＜0.01).Conclusions The level of NDRG2 expression was lower in bladder carcinomas than in normal tissues.NDRG2 may play an important role in bladder carcinogenesis and in the progress of bladder cancers.

The synergistic effects of docetaxel and adenovirus-mediated NDRG2 gene on prostate cancer cell line DU145 / 中国医师杂志

Objective To investigate the antitumor activities of adenovirus-mediated NDRG2 gene (Ad-NDRG2) and docetaxel on human prostate cancer DU145 cells.Methods The protein expressions of cyclin D1,cycliu E,and NDRG2 in the cells were determined by Western blot.MTT and flow cytometry were used to observe the effects of docetaxel (10-6 mol/L,10-7 mol/L,and 10-s mol/L) and Ad-NDRG2 on prostate cancer cell line DU145 in single or synergistic administration ways for 24 and 48 hours in vitro.Male BALB/C-nu mice with DU145 prostate cancer cell lines were treated by docetaxel and Ad-NDRG2 singly or synergistically in vivo.Results After infected by adenovirus,the protein expression of NDRG2 increased,but cyclin D1 and cyclin E decreased in DU145 cells.Ad-NDRG2 inhibited the cell growth (inhibition ratio =41.8％,t =4.18,P ＜0.01),promoted apoptosis (apoptosis ratio =32.4％,x2 =11.66,P ＜0.05),changed the ratio of G2/M phase from 50.2％ to 23.6％,and reversed partially the G2/M arrest,of DU145 cells induced by 10-7 mol/L docetaxel.In vivo experiment showed that docetaxel,Ad-NDRG2,and combination of docetaxel and Ad-NDRG2 inhibited tumor growth with a inhibition rate of 30.7％,28.2％,and 55.8％,respectively.The coefficient of drug interaction (CDI) of docetaxel and Ad-NDRG2 was 0.89.Conclusions Ad-NDRG2 can enhance the growth suppression and apoptosis induced by docetaxel in synergistic way in vitro and in vivo.It demonstrated the great potential of Ad-NDRG2 in the treatment of androgen-independent prostate carcinoma.

Laparoscopic retroperitoneal lymph node dissection (report of 7 cases) / 中华泌尿外科杂志

Objective To study the clinical efficacy of laparoscopic retroperitoneal lymph node dissection (LRPLND) for stage Ⅱ nonseminomatous testicular cancer. Methods Seven patients (mean ages 28 years, 4 had the tumors on the left side and 3 on the right) underwent LRPLND during 1 to 4 weeks after orchiectomy for clinical stage Ⅱ nonseminomatous testicular cancer. The dissection-al boundaries included the ipsilateral ureter laterally, the renal vessels superiorly, abdominal aorta and the bifurcation of the iliac artery inferiorly. The operative time, intraoperative blood loss, intra-or postoperative complications, tumor markers and ejaculation were observed. Results LRPLND was completed in all patients. Operative time ranged from 140 to 220 min (mean 180 min). Intraoperative blood loss ranged from 80 to 127 ml (mean 95 ml) and no transfusions were required. No intra- or postoperative complications occurred because of the procedure. At 2 weeks after operation, serum al-pha fetoprotein decreased from (15 to 1247 μg/L) to (2 to 8 μg/L), and beta human chorionic gona-dotropin decreased from (5 to 59 μg/L) to (0.5 to 2.5 μg/L). All patients recovered ejaculation dur-ing 10 to 12 weeks after operation. After a mean follow-up period of 21 months (range 12 to 26), no disease recurrence or metastasis was observed. Conclusion LRPLND is a safe, effective, minimally invasive procedure in the management of stage Ⅱ nonseminomatous testicular cancer patients.

A novel vaccine targeting gastrin-releasing peptide: efficient inhibition of breast cancer growth in vivo.

Gastrin-releasing peptide (GRP), a bombesin-like peptide, is an autocrine growth factor that can stimulate the growth of various cancer cells. We developed a novel protein vaccine HSP65-(GRP-10)(6) (HG6) that consists of six copies of a 10-amino acid residue epitope of GRP C-terminal fragment carried by mycobacterial 65 kDa HSP65 and then immunized mice via subcutaneous injection. Strong humoral and cell-mediated immune responses were induced. High titer of anti-GRP antibodies was detected in immunized mice sera by ELISA and verified by Western blot analysis. Activity of CD4+T lymphocytes, especially high levels of interferon (INF)-gamma, were developed in mice immunized with HG6 when compared with HSP65 or PBS. We found that immunogene tumor therapy with a vaccine based on GRP was effective at both protective and therapeutic antitumor immunity in breast tumor models in mice. The purified GRP monoclonal antibody (McAb) was proved to be potential in inhibiting EMT-6 tumor cell proliferation in vitro. The attenuation induced by active immune responses on tumor-induced angiogenesis was observed with an intradermal tumor model in mice. Taken together, we demonstrate for the first time that immune responses that are elicited by a novel chimeric protein vaccine targeting GRP can suppress the proliferation of breast tumor cell EMT-6 in mice, and it may be of importance in the further exploration of the applications of other autocrine growth factor identified in human and other animal in cancer therapy.

Fluid replacement monitoring during perioperative period of renal transplantation / 中国组织工程研究

BACKGROUND: The nutritional support, as well as the water and electrolyte balance during the perioperative period in the renal transplantation recipients at diuresis stage are important to the functional restoration of transplanted kidneys.OBJECTIVE: To explore the method and opportunity of the nutritional support and the handling of the water and electrolyte balance in perioperative period of renal transplantation.DESIGN, TIME AND SETTING: A retrospective clinical analysis was performed in the Department of Urology, Xijing Hospital from June 2003 to June 2007.PARTICIPANTS: Ninety-six patients of chronic renal failure underwent allograft renal transplantation. They comprised 59 males and 37 females, aged 17-67 years, with a mean of 35.7 years.METHODS: The perioperative physiological features of the renal transplantation recipients were summarized retrospectively. The recipients' condition during the perioperative period was divided into two stages at the opening point of allograft blood current. The vital signs of the patients maintained at a stable level before operation. All patients received blood transfusion since the operation began, and were supplemented with albumin before opening the vessels. Urinary production exceeding 100 mL per hour indicated the beginning of fluid replacement, which was a simplified transfusion for the patients at diuresis stage following renal transplantation.MAIN OUTCOME MEASURES: Blood inosine, urea nitrogen, electrolyte, blood sugar and urine of the patients were detected at one day postoperatively.RESULTS: During 12-16 hours postoperatively, the urinary production was 260-1 200 mL, average 520 mL per hour. Blood routine test showed 8 cases developed mild hyponatremia, accounting for 8.3%, 3 cases occurred high potassium and healed after renal functional recovery, 1 case presented low potassium and healed with supplement therapy. There were no abnormal changes of blood chlorine. The blood glucose among 21 cases (21.9%) was higher than the normal level, and recovered following hormone maneuver. The electrolytes and blood glucose were detected to be normal in other patients, without any case with low calcium or magnesium. The urine specific gravity arranged during 1.010-1.015.CONCLUSION: The colloid such as erythrocytes, blood plasma and albumin should be mainly infused before the opening of allograft blood current. And the water and electrolytes is recommended to administrate promptly and regularly during the diuresis stage. The healing of the stoma benefits from the adequate nutritional support. The metabolic acidosis still should be prevented when the urinary production returns normal.

IGF-Ⅱ inhibits adriamycin-induced apoptosis of HepG2 / 中华普通外科杂志

Objective To investigate the effects of IGF-Ⅱ on adriamycin-induced apoptosis of hepatocellular carcinoma cell line(HepG2).Methods Cultured HepG2 cells were divided into:①group A:control group;②group B:ADM group(200 ng/ml);③group C:2 ng/ml IGF-Ⅱ+200 ns/ml ADM group;④group D:20 ng/ml IGF-Ⅱ+200 ng/ml ADM group;⑤group E:200 ng/ml IGF-Ⅱ+200 ng/ml ADM group. After HepG2 were treated for 48 h,MTT colorimetry was performed to determine the cell viability,Flow cytometry was used to detect the cell apoptosis rate,and Weastern-blot was performed to evaluate the expression of survivin. Results The cell viability of group A、B、C、D、E was respectively 0.568±0.025、0.201±0.020、0.232±0.027、0.268±0.013 and 0.304±0.019;The cell apoptosis rate of group A、B、C、D;E was respectively 6.9％±1.3％、35.4％±2.1％、31.2％±2.2％、26.4％±1.7％and 21.7％±1.9％;Survivinβ-actin of group A、B、C、D、E was respectively 0.527±0.039、0.147±0.081、0.311±0.069、0.421±0.033 and 0.469±0.031.The cell viability in IGF-Ⅱ+ADM group was better than ADM group(P＜0.01),the cell apoptosis rate in IGF-Ⅱ+ADM group was significantly lower than ADM group(P＜0.01),the expression level of survivin in IGF-Ⅱ +ADM group was significantly higher than ADM group(P＜0.01). Conclusions IGF-Ⅱ inhibits ADM-induced apoptosis of HepG2 cells,probably by up-regulating cell's survivin expression.

Study on Immunotolerance of Kidney Graft Induced by Tolerant Dendritic Cells / 医学研究杂志

Objective To study the immune tolerance effect after renal transplantation,an animal model of tolerant dentritic cell adaptive transfer renal transplantation was constructed.Methods Tolerant Dentritic cells from SD rats were separated and purification in vitro,after a series of procedures,the Dentritic cells were administrated in the portal vein of Wistar rats,then conduct the operation of renal transplantation for Wistar rats.Renal tissue pathology and splenic lymphocyte reaction were test in 3、5、7、9、11、和13d after renal transplantation.Results After the renal transplantation,time of acute rejection happened in control group and experimental group is 4.69?1.26d and 10.69?1.63d,respectively.The mean survive time between two group has significant difference.Conclusion Renal transplantation immune tolerance could be induced by the tolerant dentritic cell of donor,by the mean of administrating the cell into host portal vein.The immune tolerance has specificity.