Salmonella has demonstrated considerable potential as a vaccine vector,exhibiting robust immunogenicity,ease of oral administration,and cost-effective production.Live attenuated Salmo-nella carrying heterologous antigens can induce both localized mucosal immunity and systemic a-daptive immune responses in hosts after successfully reaching the intestinal tract via oral delivery.Recent advances such as permanent deletion of virulence genes,regulated-delayed attenuation and lysis systems,have initially achieved a balance between the safety and immunogenicity of these vaccine platforms.Nevertheless,practical applications of such vaccine vectors remain constrained by challenges related to gastrointestinal barrier obstruction,inefficient antigen delivery,and im-mune tolerance.With the rapid advancement of multidisciplinary technologies,these limitations are anticipated to be progressively addressed.This review presented a comprehensive summary and dis-cussion of the immune mechanisms,development strategies,current applications,advantages,and challenges associated with oral live attenuated Salmonella vaccine vectors.It also delineated the fu-ture direction of research and development,with a view to providing theoretical references for re-lated research.

Salmonella has demonstrated considerable potential as a vaccine vector,exhibiting robust immunogenicity,ease of oral administration,and cost-effective production.Live attenuated Salmo-nella carrying heterologous antigens can induce both localized mucosal immunity and systemic a-daptive immune responses in hosts after successfully reaching the intestinal tract via oral delivery.Recent advances such as permanent deletion of virulence genes,regulated-delayed attenuation and lysis systems,have initially achieved a balance between the safety and immunogenicity of these vaccine platforms.Nevertheless,practical applications of such vaccine vectors remain constrained by challenges related to gastrointestinal barrier obstruction,inefficient antigen delivery,and im-mune tolerance.With the rapid advancement of multidisciplinary technologies,these limitations are anticipated to be progressively addressed.This review presented a comprehensive summary and dis-cussion of the immune mechanisms,development strategies,current applications,advantages,and challenges associated with oral live attenuated Salmonella vaccine vectors.It also delineated the fu-ture direction of research and development,with a view to providing theoretical references for re-lated research.

OBJECTIVE: To observe the therapeutic effect of electroacupuncture at acupoints of liver meridian in patients with diminished ovarian reserve (DOR) of liver depression. METHODS: A total of 62 patients with DOR of liver depression were randomly divided into an electroacupuncture group (31 cases, 1 case discontinued) and a western medication group (31 cases, 1 case was eliminated). Electroacupuncture was applied at bilateral Taichong (LR 3), Ligou (LR 5), Ququan (LR 8), Jimai (LR 12) in the electroacupuncture group, with continuous wave, in frequency of 2 Hz and current of 0.5-1.0 mA, 30 min each time, once every other day, 3 times a week. Femoston was taken orally in the western medication group, oral estradiol tablets were taken for the first 14 days, followed by oral estradiol/progesterone complex tablets for the rest 14 days, 1 tablet a day. Both groups were treated for 3 consecutive menstrual cycles. Before and after treatment, the scores of TCM syndrome, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed, serum levels of follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were detected, and antral follicle count (AFC), peak systolic velocity (PSV) and resistance index (RI) of ovarian artery were measured by color Doppler ultrasound in the two groups, and the clinical efficacy was evaluated after treatment. RESULTS: After treatment, the scores of primary symptom and secondary symptom, as well as the total scores of TCM syndrome were decreased compared with those before treatment (P<0.01), the scores of SAS and SDS, as well as the serum FSH levels and RI of ovarian artery were decreased compared with those before treatment (P<0.01), while the serum AMH levels, AFC and PSV of ovarian artery were increased compared with those before treatment (P<0.05, P<0.01) in the two groups. After treatment, in the electroacupuncture group, the primary symptom score of TCM syndrome was higher than that in the western medication group (P<0.01), the secondary symptom score of TCM syndrome and the scores of SAS and SDS were lower than those in the western medication group (P<0.05, P<0.01). The total effective rate was 70.0% (21/30) in the electroacupuncture group and 73.3% (22/30) in the western medication group respectively, there was no significant difference in the total effective rate between the two groups (P>0.05). CONCLUSION Electroacupuncture at acupoints of liver meridian can effectively improve the clinical symptoms, anxiety and depression, regulate the serum sex hormone levels, increase AFC and improve ovarian blood supply in DOR patients of liver depression.
Humans ; Female ; Electroacupuncture ; Adult ; Acupuncture Points ; Meridians ; Ovarian Reserve ; Young Adult ; Liver Diseases/physiopathology* ; Liver/metabolism* ; Ovary/physiopathology* ; Treatment Outcome ; Depression/therapy*

Objective To systematically evaluate the efficacy and safety of magnesium isoglycyrrhizinate (MgIG) in the treatment of viral hepatitis based on clinical studies. Methods Searches were conducted in the databases of Cochrane, PubMed,Science Direct,CNKI,CMCI and Wanfang (until Dec.2016 since database setup) to identify randomized controlled tri-als (RCTs) evaluating clinical effects of MgIG vs Compound Glycyrrhizin(CG).Literatures according to inclusion and exclusion criteria were screened.All meta-analysises were conducted with RevMan version 5.3. Results A total of 3 790 patients enrolled in 32 studies were included in the meta-analysis.Firstly,the comparison of curative effect in two groups favors MgIG for the treat-ment of viral hepatitis[OR=2.87,95% CI=(2.29,3.61),P<0.000 01].Secondly,MgIG showed statistically significant benefit in reducing ALT [MD=-17.27,95%CI=(-28.87,-5.66),P=0.004],AST [MD=-14.18,95%CI=(-18.29,-10.08),P<0.000 01] and T-BiL[MD=-4.53,95%CI=(-6.38,-2.68),P<0.000 01].Lastly,comparative trials demonstrated a significant safety advantage of MgIG over CG [OR= 0.29,95%CI=(0.19,0.44),P<0.000 01]. Conclusion MgIG has a significant beneficial effect for the treatment of viral hepatitis by means of both decreasing transaminase and normalizing liver function.Fur-thermore,it is worth for the application in clinical use with less adverse drug reactions.

OBJECTIVETo compare the surgical effect of three-dimensional (3D) versus 2D laparoscopic surgery in ureter lithotomy.

METHODSFrom January 2014 to 2015 May, 45 patients with ureteral calculi were randomly allocated into 2 groups to undergo ureter lithotomy under 3D laparoscopy (25 cases) and 2D laparoscopy (20 cases). The time used for each surgical process (including the exposure, D-J tube discharge, suture and other surgical procedures) was recorded and compared between the two groups.

RESULTSThe operation was completed smoothly in all the 45 patients. In this cohort, the wound drainage tube was removed in a mean of 3.0mnplus;0.8 days after the operation, the catheter was removed after a week, and the double J tube was removed at 1 month. Follow-up intravenous pyelography at 3 months after the operation reveal ureteral stricture in none of the cases. Comparison of the surgical data showed that the time used in each surgical process was significantly shorter in the 3D group than in the 2D group (P<0.05). 3D laparoscopic surgery allowed more precise operation by providing a good sense of depth as in an open surgery to reduce the operation time.

CONCLUSIONSAs a minimally invasive surgical technique, 3D laparoscopic surgery facilitates more precise and easier operation compared with 2D laparoscopy in ureter lithotomy.

Humans ; Imaging, Three-Dimensional ; Kidney Pelvis ; Laparoscopy ; methods ; Operative Time ; Retroperitoneal Space ; Ureter ; Ureteral Calculi ; surgery

Objective To investigate the value of magnetic resonance imaging (MRI)-based intravenous thrombolysis in patients with wake-up ischemic strokes (WUIS).Methods Patients presenting within 12 hours of acute stroke symptom onset and those with WUIS confirmed by CT,excluding intracranial hemorrhage,were encouraged to perform an emergent brain MRI scan to confirm the diagnosis of hyperacute ischemic stroke (hyper-intense in DWI without hyper-intense change in T2WI or fluid attenuated inversion recovery (FLAIR)).These patients then received intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA).All patients were divided into either stroke presenting within 12 hours or WUIS.The clinical outcomes were assessed by the modified Rankin scale (mRS) and the Barthal index (BI) at baseline and at 90 days after the thrombolysis therapy.Results Two hundred and sixty-one patients (261/563,56.4％) had confirmed diagnosis of hyperacute ischemic stroke (WUIS,n =73,73/121 =60.3％ vs within 12 hours,n =188,188/342 =55.0％).Altogether,192 patients (139 in within 12 hours group,and 53 in WUIS group) received intravenous thrombolytic therapy with rt-PA.No significant differences were found between the 2 groups at the baseline characteristics and at 90 days outcomes after the thrombolysis therapy(x2 =1.296 and 1.473,P =0.538 and 0.489,respectively).Also no significant differences were found in the incidence rate of secondary hemorrhage (including both of asymptomatic and symptomatic) and mortality rate between the 2 groups.Conclusion MRI-based intravenous thrombolysis is safe and effective in the treatment of patients with hyperacute WUIS.

Objective To summarize the safety and efficacy of Sunitinib in the treatment of metastatic renal clear cell carcinoma. Methods Fifteen patients with clear cell metastatic RCC were treated with Sunitinib,with 11 males and 4 females,aged from 26 to 74 years with median age of 55 years.Thirteen cases of 15 were T3 to T4 stage,and 8 cases underwent radical nephrectomy,while 5 other cases underwent renal biopsy with the pathological diagnosis of renal cancer.The other two cases (one man and one woman)with the solitary kidney renal cell carcinoma ( stage T1a) and renal insufficiency,were diagnosed as metastatic renal cell carcinoma by biopsy.Sunitinib monotherapy was administered by the regimen of 6 weeks per cycle with daily oral Sunitinib 4 weeks,followed by 2 weeks off ( from 1 - 10 cycles).Response was evaluated by RECIST.Renal tumor was 9.52 ± 3.3 cm in diameter at baseline,and the assessment of metastases included retroperitoneal lymph nodes (6 cases),mediastinal lymph nodes (3 cases),brain (2 cases),lung (6 cases),bone (2 cases) and liver (2 cases).Karnofsky score,tumor changes,adverse events and the survival of each patient was assessed and recorded. Results The follow-up duration was from 1.5 - 15months,with median follow-up of 6 months,and tumor response was evaluated by RECIST.Seven of 15 patients (46.7％) treated with Sunitinib achieved partial responses (PR),7 patients (46.7％) demonstrated stable disease (SD),and 1 patient (6.7％) developed progressive disease (PD) during the follow-up.Objective Response Rate (ORR) was 46.7％,PR + SD was 93.3％,6 months PFS was 93.3％,and median PFS was 12 months,respectively.Renal tumor was 8.7 ± 4.0 cm in diameter after therapy.Two PR patients with the obvious effectiveness had experienced progressed hypertension,and one cases with hypertension that could be controlled below 140/90 mm Hg ( 1 mm Hg =0.133 kPa) by a single drug before treatment,showed increased blood pressure ( ＞ 160/105 mm Hg) following the second cycles treatment,who were administered increased dosage and combination therapy.The other case without history of hypertension,showed high blood pressure ( ＞ 150/100 mm Hg) in the third cycle,and could be controlled well by antihypertensive drugs.Fortunately,the tumor of these two cases reduced obviously by more than 50％. 1/2 adverse reactions of 12 cases:yellowing of the skin and yellow sweat ( 12 cases,80％ ),fatigue ( 12 cases,80％ ),4 cases of hypothyroidism (26.7％),bilirubin and triglyceride levels elevated in 7case (46.7％); Four cases showed 3/4 degree adverse events with the emergence of gastrointestinal bleeding in one case secondary to platelets reduction (6.7％).Three cases (20％) showed serious fatigue,nausea,vomiting and severe hand-foot skin reaction. Conclusions Sunitinib is recommended for the treatment of metastatic renal clear cell carcinoma with good efficacy and safety.

Objective To study the preventive effects of Nitroglycerin (NTG) on post-ERCP pancreatitis (PEP) and hyperamylasemia.Methods A total of 150 patients were enrolled and randomly divided into 2 groups to receive buccal NTG 0.5mg (NTG group) or buccal Vitamin C 0.1 g (control group).Incidence of PEP and hyperamylasemia and adverse reactions were observed.Results Three patients were excluded according to the exclusion criteria. The overall incidcnces of PEP and hyperamylascmia were 16.3％ (24/147) and 28.6％ (42/147),respectively.The incidence of hyperamylasemia in NTG group (15/74,20.3％) was significantly lower than that of control group (27/73,37.0％) (x2=5.032,P=0.025).Incidence of PEP in NTG group (12.2％) was lower than that of control group (20.5％) without significance (x2=1.892,P=0.169).No severe adverse effects was observed.Conclusion NTG can effectively prevent post-ERCP hyperamylaemia,but its effect on PEP is limited.

Objective To investigate the value of MRI in thmmbolytic thempy of hyperacute cerebral arterial thrombosis.Methods One hundred and sixteen patients with acute cerebral arterial thrombosis were recruited.plain CT and multi.modal MRI were performed in all patients.Thirty-three patients with hyperacute cerebral infarction were treated bv recombinant tissue plasminogen activator(rt-PA) and followed-up periodically using MRI.Results The 33 patients with thrombolysis selected by MRI demonstrated clinical improvement.90 d moclified Rankin scale scores(mRs)were less than 2 and life quality Barthal indexes(BI)were from 80 to 100.The complication included one asymptomatic parenchymal hematoma(PH1)one weeks after thrombolytic therapy and 4(12.2%)hemorrhagic infarction(HI)6 to 24 hours after thrombolytic therapy.Condusions MRI has significant clinical value for the screening and follow-up of intravenous thrombolytic therapy of hyperacute ischemic stroke.MRI-based thrombolysis is a safe and effective method for hyperacute ischemic stroke.

OBJECTIVETo evaluate the role of nuclear factor-kappa B (NF-kappaB) and inhibitory kappaB alpha (IkappaBalpha) in hepatocellular cacinoma (HCC) SMMC7721 cells, the consequence of NF-kappaB inhibition in SMMC7721 cells transfected with mutated IkappaBalpha (mIkappaBalpha) plasmid and the effect of stable inhibition of NF-kappaB activity in combination with Doxorubicin.

METHODSWestern blot was used to determine the expression of NF-kappaB and IkappaBalpha in SMMC7721 cells and normal liver cells. Nuclear protein was used to evaluate the binding of the (32)P-labeled tandem kappaB sequence using electrophoretic mobility shift assay and the expression of NF-kappaB using Western blot between SMMC7721 cells transfected with mIkappaBalpha plasmid (SMMC7721-MT) and control cells. Furthermore, cell viability was plotted between SMMC7721-MT and control cells. The binding of kappaB sequence and cell viability between SMMC7721-MT and control cells at different concentrations of Doxorubicin were also investigated.

RESULTSWestern blot analysis for nuclear extract showed more P50 (NF-kappaB1) and P65 (RelA) expression in SMMC7721 cells compared with normal liver cells. The expression of cytosolic IkappaBalpha protein in SMMC7721 cells was less than that in normal cells. SMMC7721-MT cells inhibited NF-kappaB nuclear translocation at 0, 24, 48 and 96 hours. Furthermore, NF-kappaB cannot be detected in the nuclear protein of SMMC7721-MT cells by Western blot. By calculating cell viability, the proliferation of SMMC7721-MT cells was shown to be suppressed more significantly than that of control cells. NF-kappaB in untransfected cells was activated by Doxorubicin in a dose-dependent manner, but that in SMMC7721-MT cells was not induced at low concentrations of Doxorubicin. Compared with untransfected cells, the viability of SMMC7721-MT cells was significantly suppressed at the same concentration of Doxorubicin (P < 0.01).

CONCLUSIONSThe present study demonstrates that upregulation of NF-kappaB and downregulation of inhibitory kappa B (IkappaBalpha) in SMMC7721 cells are related with the growth of hepatocellular cacinoma cells. Stable expression of mIkappaBalpha in SMMC7721-MT cells can inhibit NF-kappaB nuclear translocation and suppress cell growth. Furthermore, stable inhibition of NF-kappaB activity in combination with Doxorubicin can significantly inhibit cell proliferation in SMMC7721-MT cells. Thus, modulation of NF-kappaB may represent an improvement in the efficacy of HCC therapies and be worthy of further research and investigation.

Antineoplastic Agents ; pharmacology ; Blotting, Western ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Division ; Doxorubicin ; pharmacology ; Electrophoretic Mobility Shift Assay ; Humans ; I-kappa B Proteins ; biosynthesis ; Liver Neoplasms ; metabolism ; pathology ; NF-kappa B ; biosynthesis ; physiology ; Tumor Cells, Cultured