HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.

Objective To study the relationship between the C677T polymorphisms of N5,N10-methylenetetrahydrofolate re-ductase(MTHFR)gene and type 2 diabetic nephropathy(T2DN).Methods By using PCR-RFLP method,the C677T polymor-phisms of MTHFR was analyzed in 163 cases of type 2 diabetes mellitus(T2DM),which included diabetic nephropathy(DN group, n=82)and diabetes without complications(DM group,n=81),and 77 cases of healthy people as the control group(CON).Plasma total Hcy levels were also measured for all the subjects.Results The frequencies of MTHFR TT and CT homogenetic type and al-lele T(4.9%,37.8%,23.8%)in the DN group were significantly higher than those in the DM(2.5%,28.4%,16.7%)group or the CON group(0.0%,29.8%,14.9%).However,there was no significant difference in MTHFR genotype and allele frequency be-tween the DM group and the CON group.Moreover,plasma Hcy levels were markedly higher in the patients with allele TT and CT genotype than those in the patients with CC genotype,the difference showing statistical significance (P <0.01).The univariate lo-gistic regression analysis showed that the C677T polymorphism of MTHFR gene was closely associated with the development of DN.The odds ratio was 1 .660 and the 95% confidence interval was 1.038 and 2.655 respectively.Conclusion The C677T polymor-phisms of MTHFR gene is associated with T2DN in Southeast Guangxi and the allele T might be the susceptibility gene for DN.

Objective To evaluate the effectiveness and safety of ultrasound-enhanced thrombolysis for acute ischemic stroke.Methods Fifty stroke patients with acute middle cerebral artery occlusion were randomly divided into either a ultrasound-enhanced thrombolysis group (recombinant tissue-plasminogen activator [rtPA] +2 MHz ultrasound monitoring for 2 h) or a standard thrombolysis group (rtPA alone).The demographic characteristics,vascular risk factors,blood pressure before treatment,thrombolysis in brain ischemia (TIBI) grade before thrombosis,and vascular occlusion site of the patients were collected.The primary outcome endpoint was the good outcome rate (defined as the modified Rankin Scale score 0-1) at 3 months.The secondary outcome endpoints were complete recanalization at 2 h after thrombolysis,sustained complete recanalization,symptomatic intracerebral hemorrhage,and mortalitY.Results The good outcome rate of the ultrasound-enhanced thrombolysis group at 3 months after treatment was significantly higher than that of the standard thrombolysis group (64％ vs.36％;P=0.011).The sustained complete recanalization rate (40％ vs.8％;P =0.018) and complete recanalization rate (48％ vs.12％;P =0.012) of the ultrasound-enhanced thrombolysis group were significantly higher than those of the standard thrombolysis group,but there were no significant differences in the reocclusion rate (8％ vs.12％;P =0.637),incidence of symptomatic intracerebral hemorrhage (4％ vs.4％;P=1.000),and mortality (4％ vs.4％;P=1.000) compared with the standard thrombolysis group.Conclusions Ultrasoundenhanced thrombolysis can improve the sustained complete recanalization rate,complete recanalization rate,and good outcome rate after using rtPA within 2 h,and it does not increase the risks of symptomatic cerebral hemorrhage and death.It is a safe and effective adjunctive thrombolytic therapy.

Objective To investigate the effects of EMP exposure to male BABL/c mice on the reproduction and its sex ratio.Methods Thirty-three male BALB/c mice were randomly divided into sham-exposed group,10 000 pulses/d exposed group,and 100 000 pulses/d exposed group with 50 Hz static magnetic field of 35 kV/m for 2 weeks consecutively,then the male mice were mated with unexposed females (1 male vs.2 female).Mated males were sacrificed to examine the exposure effects on sperm number and testis index after 7 days of mating.The sex ratio of embryos collected from unexposed mated females was investigated by PCR.Results The sex ratio of offspring was 0.298 (14/47) in the 10 000 pulses/d exposed group,significantly lower than 0.871 (27/31) in the sham-exposed group.No statistical changes were observed in the sex ratio of offspring,sperm number,the weights of testis and testis index after 100 000 pulses/d exposure.Conclusions The exposure of male mice to 35 kV/m EMP at 10 000 pulses/d for 2 weeks consecutively may change the sex ratio of mice's offspring.

Objective: To observe whether an Xingnaojing 醒脑静 injection could improve the prognosis of patients, by increasing rifampicin penetration through the blood-brain barrier. Methods: Patients with severe tuberculous meningitis were enrolled in this study. The concentrations of Xingnaojing in cerebrospinal fluid and blood in patients treated with Xingnaojing and control were determined by high performance liquid chromatography. The changes in cerebrospinal fluid and the improvement of clinical symptoms and signs, were evaluated two weeks after admission. The long-term prognosis of the patients in the two groups were evaluated by the Glasgow Outcome Scale (GOS). Results: The concentration of rifampicin in cerebrospinal fluid was significantly higher in the Xingnaojing group (1.77±0.17 μg/mL), than in the control group (1.27±0.16 μg/mL, p<0.05). The difference in concentration of rifampicin in the blood was not significant (P>0.05). The short-term effective rate of the Xingnaojing group was 92.5% (37/40), which was significantly higher than that of the control group (80%, 32/40, p<0.05). After 6 months, 75% (30/40) of the Xingnaojing group had good prognosis according to the GOS score, whereas that of the control group was 50% (20/40) showing significantly better long-term treatment effect of the Xingnaojing group compared to the control group (P<0.05). Conclusion: Xingnaojing injection improved rifampicin penetration into the central nervous system. The increase in rifampicin concentration in cerebrospinal fluid improved outcomes in patients with severe tuberculous meningitis.

Objective To explore the influencing factors of device-related pressure injuries (DRPI) in critically ill patients, construct a risk prediction model, and validate its effectiveness. Methods A retrospective analysis was conducted on the clinical data of 136 critically ill patients. Based on the occurrence of DRPIs, the patients were divided into occurrence group (32 patients) and non-occurrence group (104 patients). Univariate analysis and binary Logistic regression analysis were used to investigate the influencing factors of DRPIs, and a binary Logistic regression model was constructed. The Hosmer-Lemeshow test was used to assess the goodness of fit of the model, and the area (AUC) under the receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model.Additionally, the Bootstrap method was employed for internal validation of the model. Results Univariate analysis revealed statistically significant differences between the two groups in terms of age, diabetes, ICU stay duration, duration of non-invasive ventilation mask use, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Braden scale score, use of vasoactive drugs, prone position ventilation, hemoglobin levels, and lactate levels (P < 0.05). Binary Logistic regression analysis indicated that age, diabetes, ICU stay duration, APACHE Ⅱ score, duration of non-invasive ventilation mask use, use of vasoactive drugs, prone position ventilation, lactate levels, Braden scale score, and hemoglobin levels were independent influencing factors for DRPIs in critically ill patients (P < 0.05). A binary Logistic regression model for predicting the risk of DRPIs in critically ill patients was constructed based on these independent factors. The overall prediction accuracy of the model was 99.26%. The Hosmer-Lemeshow goodness-of-fit test showed that the model had good fitness (χ² < 0.001, P>0.999). Internal validation using the Bootstrap method and ROC curve analysis showed that the AUC of the model for predicting DRPIs in critically ill patientswas 0.952, with a sensitivity of 87.5% and a specificity of 93.3%. Conclusion The risk prediction model for DRPIs in critically ill patients constructed in this study demonstrates good stability and predictive performance. It can assist clinical healthcare professionals in screening high-risk patients and formulating personalized intervention plans.

Objective To discuss the cause and management of delayed hemorrhage after minimally invasive percutaneous nephrolithotomy (PCNL). Methods From 2004 to 2009,there were 13 cases (10 men and 3 women, mean age 47 years) developed severe bleeding following PCNL. The cause of hemorrhage and treatments were retrospectively analyzed and summarized. Results The time of hemorrhage was 5-40 d. In 7 of 13 cases, the bleeding were was controlled by complete bed rest,hemostatic,balloon compression and clamped nephrostomy tube. Six of 13 underwent selective renal arteriography after ineffective with conservative treatment. The DSA showed 4 were false aneurysm and 2 were arteriovenous fistula. All the 6 cases were treated by the super-selective arteriolar embolization. The hematuria was disappeared 1- 3 d later. The intravenous pyelogram revealed the renal function kept well during follow-up visit. Conclusions Delayed hemorrhage is one of the severe complications, which may be caused when the renal puncture passage established as forming false aneurysm and arteriovenous fistula. The renal arteriography and super-selective arteriolar embolization could be a safe and effective treatment for the severe hemorrhage after PCNL.

Objective:To evaluate the role of ErbB2 interacting protein (Erbin) in sepsis-associated encephalopathy (SAE) in mice and the relationship with nod-like receptor thermoprotein domain associated protein 3 (NLRP3) inflammasomes.Methods:Sixty SPF-grade healthy male wild-type C57BL/6 mice and 60 Erbin (-/-)C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=30 each) by a random number table method: wild-type sham operation group (WT+ Sham group), wild-type SAE group (WT+ SAE group), Erbin (-/-) sham operation group (EKO+ Sham group) and Erbin (-/-) plus SAE group (EKO+ SAE group). The model of SAE was established by cecal ligation and perforation in anesthetized mice.Open field test (total distance moved) was performed at 7 days after establishing the model, new object recognition test (recognition index) was performed at 8 days after establishing the model, and Morris water maze test (time of staying at target quadrant) was performed at 10 days after establishing the model.The mice were sacrificed, and hippocampal tissues were removed for microscopic examination of pathologic changes (by HE staining) and for determination of neuron count, expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot), the number of NLRP3 positive cells (by immunohistochemistry), and contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-18 (by enzyme-linked immunosorbent assay). The cell survival rate was calculated. Results:Compared with group WT+ Sham, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group WT+ SAE ( P<0.05). Compared with group EKO+ Sham, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group EKO+ SAE ( P<0.05). Compared with group WT+ SAE, the time of staying at target quadrant was significantly shortened, the recognition index and cell survival rate were decreased, the contents of IL-1β, IL-18 and TNF-α and the number of NLRP3 positive cells were increased, and the expression of NLRP3, caspase-1 and ASC was up-regulated in group EKO+ SAE ( P<0.05). There was no significant difference in total distance moved between the four groups ( P>0.05). Conclusion:Erbin can exert endogenous protection by inhibiting the activation of NLRP3 inflammasomes in mice with SAE.

Objective This study aims to develop a mandibular impression technique for type four edentulous jaws. Methods Twenty patients with type four edentulous jaws were selected for this study. The mandibular impression for each patient was made using both a traditional impression technique and the impression technique with a tissue-stop area. After the cast was made for each impression, the temporary denture bases were constructed on each cast. When the patients wear temporary denture bases, they must appreciate the degree of comfortability provided by each denture base. Whether the soft tissues that had been pushed away was also recorded. For 10 of the randomly selected patients, a complete denture was made using the traditional impression technique; the remaining ten subjects were given complete dentures constructed by the im-pression technique with a tissue-stop area. The number of times a review for misfit was recorded. The tissue fitness of each denture was also recorded. Results A paired t-test showed that the soft tissues that stacked on the residual ridge were more readily pushed away by the impression technique with a tissue-stop area than by the traditional impression technique. However, for all patients, the degree of comfortability did not vary when different techniques were used. The independent t-test results indicated that the differences between the fitness of dentures constructed using different impression techniques were not signi-ficant. The number of times a review for misfit conducted by the impression technique with a tissue-stop area was considerably lower than that for patients wearing traditionally dentures. Conclusion Using the impression technique with a tissue-stop area can more readily push away the soft tissues packed on the residual ridge and reduce the times of review for misfit com-pared with using the traditional technique. However, the degree of comfortability and fitness of denture are not improved.

Objective To analyze the epidemiological characteristics of an outbreak caused by human brucellosis in a farm in Yantai City,to explore the causes and transmission routes,and to provide evidence for prevention and control of brucellosis in Yantai City.Methods In 2014,an on-site investigation was conducted in a farm where brucellosis occurred in Yantai City,and case searches were conducted on exposed populations in the farm.According to the investigation questionnaire on epidemiology of brucellosis in Shandong Province,general information,clinical manifestation and high-risk behavior exposure information of the cases were collected;blood samples were collected and tested by tiger red plate agglutination test (RBPT) and tube agglutination test (SAT).Brucellosis was diagnosed according to the "Diagnostic Criteria for Brucellosis" (WS 269-2007).Results The first case was male,58 years old,farm worker.A total of 38 suspected cases were found.Eleven patients with positive RBPT and SAT≥1:100 (++) were confirmed cases.The confirmed cases were all male,with a median age of 52 years,ranging from 40 to 60 years old;5 farm workers and 6 construction workers;the onset time was mainly in June and July,a total of 7 cases;clinical manifestations mainly included excessive sweating,muscle and joint pain,fatigue,testicular swelling,etc.Of the 147 sheep in the farm,47 were positive by laboratory tests,accounting for 31.97％,which were the main sources of infection.High-risk exposures for farm workers included hand-delivered births (5 cases) and breeding for livestock (1 case);high-risk exposures for construction workers included entry and exit of sheep houses (6 cases) and handling of supplies in sheep houses (6 cases).Conclusions The epidemic is caused by direct contact with Brucella-infected sheep or caused by respiratory contact with brucellosis contaminated environment.It is necessary to strengthen the health education for prevention and control of the disease in key populations and improve the awareness of the disease.