Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

OBJECTIVE To provide reference for Smilax glabra quality control. METHODS UPLC method was established to simultaneously determine the contents of 5-O-caffeoylshikimic acid， neoastilbin， astilbin， neoisoastilbin， isoastilbin， engelitin， resveratrol and isoengelitin in 20 batches of S. glabra from different areas （No. S1-S20）. The quality evaluation of 20 batches of samples was performed by chemometrics； the differential biomarkers that affected the quality of S. glabra were screened. RESULTS The measured 8 components had good linear relationship within the range of measured concentration （r≥0.999 6）. RSDs of precision， repeatability and stability tests （24 h） were all lower than 2.00% （n＝6）. The average recoveries varied between 97.60% and 106.40% （RSDs were all lower than 2.00%， n＝6）. Cluster analysis showed that the samples produced in Zhejiang （S1-S5） and Jiangxi （S6-S10） were clustered into one category； the samples produced in Hunan （S11-S15） were clustered into one category； the samples produced in Yunnan （S16-S20） were clustered into one category. Principal component analysis showed that the first two principal components could represent 85.60% information of 8 components in S. glabra. Partial least squares-discriminant analysis showed that variable importance projection values of 5-O-caffeoylshikimic acid， astilbin， isoastilbin and neoastilbin were all greater than 1. CONCLUSIONS There are differences in the contents of the above 8 components in S. glabra from different origins； 5-O-caffeoylshikimic acid， astilbin， isoastilbin and neoastilbin may be differential markers affecting the quality of S. glabra.

Objective To compare the cleaning abilities of ProTaper Gold(PTG)and TF-Adaptive(TFA).Methods Forty single-abstracted premolars were randomly divided into PTG and TFA groups.The debris and smear layer of the root coronal 1/3,middle 1/3 and apical 1/3 in the two groups were observed using scanning electron microscope(SEM).The cleaning abilities of the PTG and TFA rotary systems were scored according to the scoring standard developed by YAMASHITA.The scores of the two groups were compared and then analyzed.Results There was no significant difference found in the scores of the smear layer and debris at the root coronal 1/3 and the middle 1/3.The scores of the debris and smear layer at the apical 1/3 in the group PTG were higher than those in the TFA group(P<0.05).Conclusion PTG and TFA can effectively remove the root canal smear layer and debris at the root coronal 1/3,and the middle 1/3.However,at the apical 1/3,the cleaning efficiency of TFA is better than that of PTG.

Objective To explore the influencing factors of disability degree in elderly hospitalized patients with disability and the correlations of disability with malnutrition and sarcopenia. Methods A total of 234 elderly hospitalized patients with disability were selected as study subjects. The Activities of Daily Living (ADL) scale, Mini-nutritional Assessment Short Form (MNA-SF), and Sarcopenia Five-item Criteria with calf circumference (SARC-CalF) were used to investigate the status of disability, nutrition, and sarcopenia in patients. The clinical characteristics of different types of patients were compared, and correlations of disability with malnutrition and sarcopenia were analyzed using Pearson correlation analysis. Multiple linear regression analysis was used to explore the influencing factors of the degree of disability in patients. Results Of the 234 patients, 46.58%(109/234) had mild disability, 45.30%(106/234) had moderate disability, and 8.12%(19/234) had severe disability. The results of Pearson correlation analysis showed that the degree of disability (ADL score) in elderly hospitalized patients with disability was significantly correlated with the degree of malnutrition (MNA-SF score) and sarcopenia (SARC-CalF score) (r=0.177, -0.193, P=0.007, 0.003). Multiple linear regression analysis showed that malnutrition and sarcopenia were influencing factors of the degree of disability in elderly hospitalized patients with disability (P < 0.05). Conclusion There are correlations of disability with malnutrition and sarcopenia in elderly hospitalized patients with disability. The risk of exacerbation of disability is significantly increased in patients with malnutrition and sarcopenia. Therefore, clinicians need to identify high-risk patients as early as possible and provide targeted intervention measures.

Objective:To systematically assess the efficacy and safety of acupuncture therapy for essential hypertension.Methods:A computerized literature search of the Chinese National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Academic Journal Full-text Database(Wanfang),China Biology Medicine Disc(CBM),PubMed,Excerpta Medica Database(EMBASE),and Cochrane Library was conducted to retrieve randomized controlled clinical trials on acupuncture as the main intervention for the treatment of essential hypertension published from the inception of the database to 30 January 2021.The risk-of-bias assessment was carried out for each included study according to the Cochrane Handbook.Data analysis was performed using Review Manager 5.4.1 and Stata 15.0.Results:After the screening,46 randomized controlled trials involving a total of 3 859 subjects were included.Primary outcomes included changes in the diastolic blood pressure after intervention[eight studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[mean difference(MD)=1.45,95%confidence interval(CI)(0.48,2.43),P=0.004,fixed effects model;I2=39%]and changes in the systolic blood pressure after intervention{11 studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[MD=8.60,95%CI(7.12,10.07),P<0.00001,fixed effects model;I2=26%]}.The secondary outcome was antihypertensive efficacy,12 studies of acupuncture monotherapy group[risk ratio(RR)=1.20,95%CI(1.12,1.28),P<0.00001,fixed effects model;I2=36%]and 15 studies of acupuncture combined with antihypertensive drug group[RR=1.27,95%CI(1.20,1.34),P<0.00001,fixed effects model;I2=6%]showed better results than the antihypertensive drug monotherapy group in antihypertensive efficacy.In terms of the adverse events,four studies showed that the acupuncture monotherapy group had fewer adverse events than the antihypertensive drug monotherapy group[RR=0.10,95%CI(0.04,0.25),P<0.00001,fixed effects model;I2=0%].Conclusion:Acupuncture combined with antihypertensive drugs is superior to antihypertensive drugs alone in reducing blood pressure,and acupuncture therapy is effective and safe for the treatment of essential hypertension with fewer side effects.However,there is still a lack of high-quality multicenter randomized double-blinded controlled trials in this field.Rigorous large-sample clinical trials are needed to validate these findings.

Objective:To study the effect of splenic lymphocytes isolated from mouse models of colorectal carcinoma with liver metastases induced by oncolytic herpes simplex virus type Ⅱ(oHSV2) on the growth of pulmonary metastases of colorectal carcinoma.Methods:A total of 18 6-week-old BALB/c female mice were selected, colorectal carcinoma cell line CT26 of mice in logarithmic phase was inoculated at the right back (2×10 5 per mouse) and spleen (1×10 5 per mouse) of mice, and tumor cells had hematogenous metastasis to liver through splenic vein. CT26 colorectal carcinoma with liver metastases model was constructed. All mice were respectively divided into oHSV2 group and phosphatic buffered saline (PBS) group, 9 mice in each group according to the random number table method. Mice in oHSV2 group were treated with subcutaneous intratumoral multi-point injection of 100 μl oHSV2 (the multiplicity of infection was 1) for 6 cycles, while mice in PBS group were treated with subcutaneous intratumoral multi-point injection of 100 μl PBS for 6 cycles in total, once injection every other day; the survival of mice was analyzed by using Kaplan-Meier method and tumor growth was observed. The mice of both groups in mouse models of colorectal carcinoma with liver metastases were killed on day 20 and their splenic lymphocytes were isolated. After investigation of the most suitable inoculation number and the optimal observation time of colorectal carcinoma with pulmonary metastases CT26 cell lines, 9 6-week-old BALB/c female mice were divided into the experimental group, the negative control group and the blank control group according to the random number table method, with 3 mice in each group. Mice in the experimental group were injected with splenic lymphocytes (4×10 7 per mouse) and CT26 cells (2×10 5 per mouse) isolated from mouse models induced by oHSV2 via the tail vein, mice in the negative control group were injected with splenic lymphocytes (4×10 7 per mouse) and CT26 cells (2×10 5 per mouse) isolated from normal mice with same weeks old via the tail vein, and mice in the blank control group were injected with only CT26 cells (2×10 5 per mouse) via the tail vein. The above 3 groups were executed on day 10 after inoculation, and tumor growth, histopathological changes of mice were also observed; the survival of mice was analyzed by using Kaplan-Meier method. Results:In models of colorectal carcinoma with liver metastases, liver metastases lesions were not detected in 7 mice and 2 mice had 1-2 liver metastases lesions with long diameter less than 2 mm of oHSV2 group; in PBS group, 9 mice all had multiple liver metastases lesions with tumor long diameter ranging from 1 to 10 mm. And mice in oHSV2 group survived much longer than that of mice in PBS group ( P < 0.001). In models of pulmonary metastases, the optimal number of CT26 cells in mouse tail vein was 2×10 5 per mouse; the best observation time point was day 10 after tail vein injection. On day 24 after inoculation, all mice in the negative control group and the blank control group died, while mice in the experimental group all survived on day 60, and the difference of the overall survival in the above 3 groups was statistically significant ( P = 0.007). HE staining results showed that the lung tissues of the experimental group did not show clear tumor cells, whereas the lung tissues of the negative control group and the blank control group showed extensive diffuse tumor cells. Conclusions:Splenic lymphocytes produced by oHSV2 induction in mouse models of colorectal carcinoma with liver metastases can effectively inhibit the development of pulmonary metastases in colorectal carcinoma CT26 cell of mice.

Objective:To evaluate the effect of transitional care on the quality of life of patients with pancreatitis.Methods:We searched the following databases such as PubMed, Web of Science, Cochrane Library, CNKI, CBM, and WanFang Data electronically. Other sources as applying were also retrieved. Comprehensive collection of continuing care on the quality of life in patients with pancreatitis related research. According to the evaluation method of Cochrane system, the quality evaluation and data extraction were carried out, and the RevMan 5.3 software was used for Meta analysis.Results:A total of 21 randomized controlled trials involving 1 818 patients (910/908) were included. SF-36 health survey scale, analysis of 8 Meta subgroups showed that all groups P<0.05, and the combined effect was statistically significant. The results of the intervention with telephone as the main outcome indicator were: maintaining a regular lifestyle [weight mean difference ( WMD) value was 4.33, 95% confidence interval ( CI)2.52-7.44, P<0.01], quitting smoking and drinking ( WMD value was 5.95, 95% CI 3.69-9.59, P<0.01), maintaining a healthy diet ( WMD value was 8.62, 95% CI 5.07-9.59, P<0.01). Continuous nursing based on telephone intervention can reduce the recurrence rate ( WMD value was 0.20, 95% CI 0.13-0.31, P<0.01). Meta-analysis based on the intervention of establishing archives for continuous nursing showed that WMD value was 0.25, 95% CI 0.12-0.52, P<0.01, and archives and telephone showed that WMD value was 0.24, 95% CI 0.09-0.63, P=0.004, and the combined effect was statistically significant. Conclusions:Continuous nursing can improve the quality of life of patients with pancreatitis, improve the compliance with medical advice, and reduce the recurrence rate, but it needs to be further verified by a large sample, high-quality, multi-centered randomized controlled trial.

Objective To investigate the clinical significances of additional chromosome abnormalities and t(15;17) in acute promyelocytic leukemia (APL). Methods A total of 90 newly diagnosed APL patients in the Affiliated Hospital of Qingdao University from January 2007 to June 2014 were analyzed retrospectively. Patients with different chromosome karyotypes were divided into four groups: additional chromosome number abnormalities group (16 cases), additional chromosome structural abnormalities group (14 cases), additional chromosome number and structural abnormalities group (4 cases) and typical chromosome group (56 cases). According to whether the patient contained t(15;17), the patients were divided into group with t (15;17) and group without t (15;17). The short-term efficacy and survival of each group were analyzed and compared. Results The rate of complete remission in additional chromosome number abnormalities group, additional chromosome structural abnormalities group, additional chromosome number and structural abnormalities group and typical t(15;17) chromosome changes group were 56.3％(9/16), 100.0％(14/14), 25.0％(1/4) and 82.1％(46/56), the early mortality rates were 25.0％(4/16), 0 (0/14), 75.0％(3/4) and 8.9％ (5/56) respectively. Among them, the additional number and structural abnormalities group had lower complete remission rate and higher early mortality rate, and compared with other groups, the differences were statistically significant (all P< 0.05). The complete remission rates of the group with t (15;17) and the group without t (15;17) were 80.5％ (66/82) and 50.0％ (4/8), respectively, and the difference was not statistically significant (P= 0.070). Conclusions APL patients with karyotypes with additional number and structural changes have low complete remission rate, high early mortality rate and poor prognosis. Patients with t(15;17)have a high rate of complete remission.

Objective: To explore drug resistance of different viral loads, and investigate the relationship between drug resistance and CD4⁺T cell counts in patients with HIV antiretroviral therapy (ART) in China from 2003 to 2015. Methods: Data were extracted from the Chinese National HIVDR Surveillance database from 2003 to 2015. For this study, the data collected were as follows: having received ART for ≥12 months; 18 years or older; demographic characteristics, information of ART, CD4⁺T cell counts, viral load (VL) and HIV drug resistance of a total of 8 362 patients were collected. Multi-variables non-conditional logistic regression model was used to study the relationship between viral load, HIV drug resistance and CD4⁺T cell counts. Results: Participants with age of (41.8±10.5) years were enrolled in this study. Among them, 59.9% (5 009 cases) were men. The percentage of CD4⁺T cell counts <200 cells/μl in the total population was 17.9% (1 496 cases), the highest was in VL ≥1 000 copies/ml with drug resistance, which was 43.0% (397/923) , followed by VL 50-999 copies/ml with drug resistance, which was 31.1% (69/222), and the lowest was in VL 50-999 copies/ml without drug resistance 13.2% (273/2 068). Compared to VL 50-999 copies/ml without drug resistance, VL<50 copies/ml, VL 50-999 with drug resistance, VL≥1 000 copies/ml without drug resistance, and VL ≥1 000 copies/ml with drug resistance, the OR (95%CI) of CD4 <200 cells/μl were 0.9 (0.7-1.0), 3.2 (2.3-4.4), 2.6 (2.1-3.2), and 4.9 (4.0-5.9), respectively. Among 222 patients with VL 50-999 and HIVDR, the most frequent antiretroviral drugs were EFV and NVP, both of which were NNRTI, and whose percentage both were 94.1% (209 cases). The most frequent mutations were M184V/I (NNRTI), and the percentage was 26.1% (58 cases). The second one was K103N (NNRTI), and the percentage was 22.5% (50 cases). The percentage of V32L/E (PI) and V82A (PI) were lower, they were 0.9% (2 cases) and 0.5% (1 case) respectively. Conclusion Decreased CD4⁺T cell counts were associated with HIV drug resistance at low viraemia. In the case of low viral load, the most vulnerable were the NNRTI antiviral drugs such as EFV and NVP.