Objective To investigate the effect of combination therapy of Gabapentin and Cobamamide in treatment of painful diabetic neuropathy (PDN).Methods A total of 96 patients with type 2 diabetes (T2DM) and PDN were enrolled in this study and randomly divided into control group (Con,n=32),Cobamamide group,(n=32),and Gabapentin+Cobamamide group,(n=32).FPG and HbA1c were actively controlled in each group.Con group was treated with vitamin B1.Clinical and biochemical data of all the subjects were collected.The degree of pain was assessed by visual analogue scale (VAS).The changes of median nerve,peroneal nerve motor nerve conduction velocity (MNCV),and sensory nerve conduction velocity (SNCV) were evaluated by EMG assessment.The assessment of sleep quality was done by Pittsburgh sleep quality index scale (PSQI).Results There was no significant differences of baseline MNCV,SNCV and the degree of pain among the three groups (P>0.05).After treatment,all the above index were improved in both Cobamamide group and Gabapentin+Cobamamide group.MNCV and SNCV were higher in Gabapentin+Cobamamide group than in Cobamamide group (P<0.05).There were no significantly improvement of MNCV and SNCV in Con group (P>0.05).Conclusion The combination therapy of Gabapentin and adenosine cobalt amine could reduce pain,improve nerve conduction velocity,and improve the quality of sleep.

Objective To investigate the carboprost ammonia butyl alcohol three plus motherwort injection on prevention of high risk maternal postpartum hemorrhage effect .Methods 120 cases of cesarean section operation and potential bleeding symptom of women were selected as the research object ,and randomly divided into two groups , the observation group of 60 cases using carboprost ammonia butyl alcohol three joint of leonurus heterophyllus injec -tion for prevention and treatment ,the control group of 60 cases used oxytocin for prevention and treatment ,prevention and treatment effects were compared between the two groups .Results After treatment,the observation group 2h,24h postpartum hemorrhage were (422.41 ±213.49)mL,(35.29 ±16.44)mL,were significantly less than those in the control group (589.64 ±345.21)mL,(69.31 ±29.47)mL(t=6.732,8.915,all P<0.05);the observation group 1 cases without production after bleeding ,control group 5 cases of postpartum hemorrhage ,statistically significant differ-ences between the two groups (χ2 =4.973,P<0.05).Conclusion Carboprost ammonia butyl alcohol three plus motherwort injection on prevention of high risk maternal postpartum hemorrhage has a significant effect ,which can re-duce the cesarean section uterine bleeding and reduce the amount of bleeding ,promote uterine involution ,conducive to maternal rehabilitation .

Pachycarpine given intravenously (10~20mg/kg) to anesthetized rabbits markedly increased the force of contraction of the anterior tibialis musculi for 30 minsimultaneously. It significantly increased the work made by rabbit anterior tibialis musculi. It markedly plo-longed the mice swimming time. It also significantly increased the muscle evoked action potential induced by electrical stimulation on anterior tibialis musculi of rabbit.

Objective To investigate the expression and relationship of TIP30(HIV-1 Tat interactive protein 2), vascular endothelial growth factor (VEGF) and MVD (detected by CD34) in the angiogenesis of human brain astrocytomas. Methods Expression of TIP30, VEGF and CD34 in 19 cases of normal brain tissue and 71 cases of astrocytoma were immunohistochemically examined with Elivision plus two-step method. Results The positive expression of TIP30 could be seen in cytoplasm of neuroglial cells and neurons of 19 normal brain tissues. The positive expression rate of TIP30 in 71 cases of astrocytoma was 33.80 % (24/ 71). The positive expression rate of TIP30 in astrocytoma of different grades was 52 % for grade Ⅱ, 34.78 % for grade Ⅲ and 13.04 % for grade Ⅳ. The positive expression rate of TIP30 in high grade (Ⅲ+Ⅳ) of astrocytoma was found significantly lower than that in low grade(Ⅱ) (χ2=5.71, P <0.05); The expression of VEGF and MVD detected by CD34 in astrocytomas were higher than that in normal brain tissue and increased as the tumor grade increased; In astrocytoma, the negtive correlation was found between the expression of TIP30 and VEGF (r=-0.428, P<0.05); no correlation was found between TIP30 and MVD(r=-0.065, P 0.05); the positive correlation was found between VEGF and MVD(r=0.684, P<0.01). Conclusion The positive expression rate of TIP30 in normal brain tissue is significantly higher than that in astrocytoma. The positive expression rate of TIP30 significantly decreases as the pathological grade of the astrocytoma increases; The expression of TIP30 and VEGF is negatively correlated in astrocytoma.

Objective To investigate the effect of targeted interruption of cyclooxygenase-2 (COX-2) gene by small interference RNA (siRNA) on the expression of COX-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in eutopic and ectopic endometrial stromal cells (ESC) with endometriosis, and the effect on the content of 6-keto-prostaglandin-F1α (6-keto-PGF1α, metabolites of COX) and the apoptosis of eutopic and ectopic ESC with endometriosis. Methods Ectopic and eutopic ESC from 30 women with endometriosis were isolated and cultured respectively. Then, ESC were classified into three groups: interference group, negative control group and blank control group. ESC in interference group were injected into siRNA transfection complex while ESC in negative control group were injected into negative control transfection complex. ESC from 10 participants without endometriosis were the normal control group. The mRNA and protein expression of COX-2, VEGF, MMP-9 in pre-transfected and post-transfected eutopic and ectopic ESC were detected through real time reverse transcription PCR and western blot. The content of 6-keto-PGF1α was determined by ELISA, the apoptotic cells were detected by flow cytometry. Results After interruption of COX-2 gene, there were no significant difference in the mRNA and protein expression of COX-2, VEGF and MMP-9 between the negative control group and blank control group (P>0.05); the mRNA and protein expression of the three genes in interference group were significantly lower than those in negative control group and blank control group (P<0.05); the mRNA expression of the three genes in interference group of eutopic ESC were 0.87±0.06, 1.76±0.59, 1.04±0.32, in interference group of ectopic ESC were 0.75±0.12, 1.62±0.47, 0.88±0.25, the protein expression of the three genes in interference group of eutopic ESC were 0.457 ± 0.019, 0.500 ± 0.012, 0.361 ± 0.008, in interference group of ectopic ESC were 0.323 ± 0.018, 0.474 ± 0.016, 0.339 ± 0.009;the mRNA and protein expression of the three genes in ectopic ESC had a more reduction than those in eutopic ESC (P<0.05). The results from ELISA revealed that the content of 6-keto-PGF1α in the normal control group [(17.7 ± 1.9) pg/ml] were significantly lower than those in the blank control group (P<0.05), the content of 6-keto-PGF1α in ectopic ESC were significantly higher than that in eutopic ESC (P<0.05), the content of 6-keto-PGF1α in the blank control group of eutopic and ectopic ESC were (32.4±2.6) pg/ml, (38.2±3.7) pg/ml;there was no significant difference in the content of 6-keto-PGF1α between the negative control group and blank control group (P>0.05);compared with those of negative control group and blank control group, the content of 6-keto-PGF1αin interference group decreased significantly (P<0.05), the content of 6-keto-PGF1α in interference group of eutopic and ectopic ESC were (17.1 ± 2.4) pg/ml, (20.9 ± 2.7) pg/ml; the content of 6-keto-PGF1α in eutopic ESC had a slightly more reduction than that in ectopic ESC (P>0.05). The results from flow cytometry displayed that, there was no significant difference in apoptotic cells between the negative control group and blank control group (P>0.05);compared with those of negative control group and blank control group, more apoptotic cells were detected in interference group and the difference was significant (P<0.01);the apoptotic cells in ectopic ESC were significantly more than that in eutopic ESC (P<0.05); the apoptosis rate in interference group of eutopic and ectopic ESC were (33.76 ± 0.06)%, (47.18 ± 0.12)%. Conclusions Our results suggested the targeted interruption of COX-2 gene by siRNA effectively inhibited the mRNA and protein expression of COX-2, VEGF and MMP-9 in both eutopic ESC and ectopic ESC with endometriosis, greatly increased the apoptotic rate of cells and obviously reduced the content of 6-keto-PGF1αby inhibiting the activity of COX-2. And the changes in ectopic endometrium were more evident than those in eutopic endometrium.

Objective? To explore the process and experience of self-management among patients with schizophrenia by interview so as to provide examples and inspirations for clinical nursing and improving self-management among patients with schizophrenia. Methods? From February to April 2018, we collected information in 14 schizophrenia outpatients at a ClassⅢ Grade A psychiatric hospital in Beijing by semi-structured depth interview. The information was analyzed and summarized with the method of content analysis. Results? The interview results were divided into two aspects. On the one hand, the cognition of schizophrenia patients on self-management limited the self-management ability development of patients including lack of knowledge on self-management and family dysfunction. On the other hand, the experience of self-management also limited the ability involving lack of symptom management ability, skills and knowledge on treatment management, poor emotion management, low daily life management initiative, poor interpersonal management and inadequate social support resource use. Conclusions? Medical staff should actively understand the self-management of schizophrenia patients, strengthen training and education so as to improve disease self-management and promote recovery from disease.

Objective To analyze the heterogeneities of hepatitis B virus ( HBV ) reverse transcriptase domain (RT) gene mutations related to nucleos (t)ide analogues (NAs) resistance.Methods Blood samples from 2765 chronic hepatitis B patients with virological breakthrough or poor drug response treated in Ningbo No .2 Hospital and Ningbo Fourth Hospital from April 2011 to March 2018 were collected . According to the medication status , it was divided into LAM monotherapy group ( n =603 ) , LdT monotherapy group (n=147), ADV monotherapy group (n=68), ETV monotherapy group (n=10) and the sequential or combined drug resistance of NAs group (n=365).The resistance mutation sites and drug resistance patterns (pathways) of each group were analyzed .The SPSS 19.0 software was used to analyze the data.Results Among 2765 serum samples, the NAs-related HBV-RT resistance mutations were detected in 1193 cases with an overall mutation rate of 43.15％.The mutation rate of LAM monoclonal resistance group was 62.62％ (603/963) with 19 mutation types, the most common single point mutation was rtM204I/V (40.30％, 243/603).The mutation rate of LdT monoclonal resistance group was 45.51％(147/323), and there were 3 mutation types, with the single point mutation rtM204I/V being the most common (59.86％, 88/147).The mutation rate of the ADV monoclonal resistance group was 17.80％(68/382), mainly rtA181T single point mutation (64.71％, 44/68).The mutation rate of the ETV monoclonal resistance group was 4.06％(10/246), and the single point mutation of rtT184A/G/S/I/L/F was the most common one (80.00％, 8/10).The mutation rate of the sequential or combination therapy group was 41.91％ (365/871), among which the mutation rate of the LAM/LdT poor response or the resistance with the sequential ADV group was 63.39％(142/224), and the most single mutation point was rtA181V/T ( 35.21％, 50/142 );the mutation rate of LAM/LdT poor response or drug-resistant with combined ADV group was 42.19％ (54/128), and the most common mutation point was rtA181V/T (46.30％, 25/54);the mutation rate of LAM/LdT with poor response or resistance after sequential ETV 1.0 mg was 44.66％(117/262), and the most common mutation point was rtL180M+M204I/V+S202G/I (31.62％, 37/117);the LAM/LdT poor response or the drug-resistant ETV combined with ADV group had a mutation rate of 7.14％(5/70), all of which were multi-site mutations;the mutation rate of poor response to ADV or resistant with sequential ETV 0.5 mg group was 28.14％(47/167), all of which were multi-site mutations.Secondary ( compensation ) sites such as rtV173L, rtL180M, and rtV214A, and single-point mutations such as rtV207I/L/G, rtS213Tand rtN238T, which were not fully defined , were detected.The resistance patterns ( pathways ) of NAs monotherapy were relatively simple , and the resistance patterns ( pathways ) of NAs experienced patients ( sequential or combined treatment group ) were complex and diverse, and multiple resistance patterns (pathways) existed, along with NAs increasing in species.Non-first-line NAs-related resistance patterns ( pathways ) showed an overall downward trend sand ETV-related drug-resistant mutation showed an overall upward trend .Conclusion The NAs-related HBV resistance mutation sites ( patterns ) are complex and diverse , especially multi-site mutations , refractory drug resistance mutations, multidrug resistance mutations and cross-resistance mutations.Therefore, the optimization of antiviral treatment strategies and drug resistance management concepts need to be continuously updated .

Tumor neoantigens generated from somatic mutations can be presented by major histo-compability complex (MHC) molecules and elicit specific immune response against cancer. Therapeutic vac-cines and specific T cells targeting tumor neoantigens will realize the potential of precision immunotherapy in cancer treatment. Along with the development of methods for predicting neoantigens, individualized cancer immunotherapy strategies will be widely adopted. In the present review, we discuss the current state of the prediction approaches and clinical applications of neoantigens, as well as the challenges that remain to be ad-dressed in order to improve immunotherapy targeting neoantigens.