Hyperbranched polymers (HBPs) have drawn great interest in the biomedical field on account of their special morphology, low viscosity, self-regulation, and facile preparation methods. Moreover, their large intramolecular cavities, high biocompatibility, biodegradability, and targeting properties render them very suitable for anti-tumor drug delivery. Recently, exploiting the specific characteristics of the tumor microenvironment, a range of multifunctional HBPs responsive to the tumor microenvironment have emerged. By further introducing various types of drugs through physical embedding or chemical coupling, the resulting HBPs based delivery systems have played a crucial part in improving drug stability, increasing effective drug concentration, decreasing drug toxicity and side effects, and enhancing anti-tumor effect. Here, based on different types of tumor microenvironment stimulation signals such as pH, redox, temperature, etc., we systematically review the preparation and response mechanism of HBPs, summarize the latest advances in drug delivery applications, and analyze the challenges and future research directions for such nanomaterials in biomedical clinical applications.

Background Arsenic is a well-known environmental toxicant. Hepatic fibrosis could occur dueto excessive or long-term exposure to arsenic, while associated molecular mechanisms remain undefined. Mitogen-inducible gene 6 (Mig-6) exhibits a protective effect on numerous diseases or cancers. However, the specific role of Mig-6 in the mechanisms of arsenite-induced hepatic fibrosis remains indistinct. Objective To investigate the specific role of Mig-6 in the activation of hepatic stellate cells (HSC) and the deposition of extracellular matrix (ECM) induced by sodium arsenite (NaAsO₂). Methods Human hepatic stellate cells (Lx-2) were treated with 0, 1.875, 3.75, 7.5, and 15 μmol·L⁻¹ of NaAsO₂ for 24 h, or with 7.5 μmol·L⁻¹ NaAsO₂ for 0, 12, 24, 48, and 72 h. Additionally, Lx-2 cells were transfected by pcDNA3.1(+)/Mig-6, then treated with 7.5 μmol·L⁻¹ NaAsO₂ for 24 h; a blank control group, a pcDNA3.1(+)-control group, a pcDNA3.1(+)/Mig-6 group, and an arsenic (7.5 μmol·L⁻¹ NaAsO₂) group were also set up. After transfection, the cells and culture supernatants were collected, and the protein levels of Mig-6, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) in Lx-2 cells were identified by Western blotting analysis; moreover, the secretion levels of main ECM components in supernatants such as hyaluronic acid (HA), laminin (LN), collagens IV (COL-IV), and procollagen-III (PIIINP) were tested by ELISA. Results The Mig-6 expression decreased in the 3.75, 7.5, and 15 μmol·L⁻¹ NaAsO₂ groups (0.561±0.095, 0.695±0.048, and 0.401±0.030) compared to the control group (1.000±0.000) in Lx-2 cells (P<0.05). After administration with 7.5 μmol·L⁻¹ of NaAsO₂ for 24, 48, and 72 h, the Mig-6 expression (0.856±0.036, 0.515±0.077, 0.491±0.060) decreased compared with the 0 h group (1.000±0.000) (P<0.05). After over-expression of Mig-6, the results of Lx-2 activation related protein levels showed that compared to the control group, the α-SMA and TGF-β1 expression were up-regulated in the arsenic group (P<0.05); meanwhile, the α-SMA and TGF-β1 in the Mig-6 over-expression combined arsenic exposure group reduced compared to the arsenic (7.5 μmol·L⁻¹) group (P<0.05). The results of ELISA showed that compared with the control group, the HA, LN, PIIINP, COL-IV in the arsenic group were up-regulated (P<0.05); while compared to the arsenic group, the HA, LN, PIIINP, and COL-IV in the Mig-6 over-expression combined with arsenic exposure group were decreased (P<0.05). Conclusion Arsenic down-regulates Mig-6 expression in HSC, and over-expression of Mig-6 can reverse the activation of HSC and ECM deposition induced by arsenic exposure. It suggests that Mig-6 plays a protective role in arsenic-induced HSC activation and ECM deposition.

Objective:To explore the influencing factors of anxiety and depression in patients with coronary heart disease after percutaneous coronary intervention (PCI), so as to provide theoretical basis for psychological intervention.Methods:This study was a cross-sectional study. From November 2021 to March 2022, 150 patients with coronary heart disease after PCI were selected from the Department of Cardiovascular, Zhongnan Hospital of Wuhan University by convenience sampling. The patients were investigated with the General Information Questionnaire, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Social Support Rating Scale (SSRS). Pearson correlation was used to explore the relationship among anxiety, depression and social support in patients with coronary heart disease after PCI.Results:Among 150 patients with coronary heart disease after PCI, the total score of social support was 31.0 (28.0, 36.0), including 33 cases of anxiety (33/150, 22.0%), 47 cases of depression (47/150, 31.3%), and 27 cases of anxiety and depression (27/150, 18%). Pearson correlation analysis showed that the total score and each dimension score of SSRS of patients with coronary heart disease after PCI were negatively correlated with SAS and SDS scores ( P<0.05) . Conclusions:Patients with coronary heart disease after PCI are prone to anxiety and depression. While paying attention to patients' physical diseases, medical and nursing staff should pay attention to patients' psychological conditions, find negative emotions as early as possible and give targeted intervention and treatment.

Objective:To evaluate the prediction power of HIV infection risk assessment tool and the applicability in MSM in Guizhou province.Methods:MSM were recruited through snowball sampling method. Questionnaire surveys were conducted among the MSM using HIV infection risk assessment tool, and combined with HIV serologic test results, the risk prediction power of HIV infection risk assessment tool was evaluated.Results:A total of 3 379 MSM were recruited from January 2018 to December 2019 in Guizhou. The HIV infection rate was 3.3%(111/3 379). The mean risk scores of HIV positive and HIV negative MSM were (12.15±3.08) and (12.07±3.07), respectively. The difference in risk score was significant between MSM with different HIV status ( t=8.69, P<0.001). According to the principle of decision tree, individual risk scores were divided into following three categories: ≤11.96, 11.97-14.80 and >14.80, the HIV infection rate was 0.8%, 4.3% and 8.6% respectively, suggesting that the higher the individual risk score was, the higher the HIV infection rate was (trend χ 2=88.18, P<0.001). Multivariate logistic regression analysis showed that the higher the individual risk score was, the higher the risk of HIV infection was. Compared to the total score ≤11.96, the a OR values at total scores of 11.97-14.80 and >14.80 were 6.34 (95% CI: 3.38-11.88) and 14.07(95% CI: 7.44-26.61), respectively. The risk of HIV infection in Miao ethnic group was higher than that in Han ethnic group (a OR=1.83, 95% CI:1.04-3.21), and the risk of HIV infection in those with education level of primary school and below was higher than that in undergraduates or those with education level of junior college and above (a OR=2.50, 95% CI:1.06-5.88), and the risk of HIV infection was higher in those who had bisexual behaviors than in those who had homosexual behaviors (a OR=1.95, 95% CI:1.19-3.19). The risk of HIV infection was higher in those who had never received HIV testing (a OR=1.53, 95% CI:1.01-2.33). The area under the receiver operating characteristic (ROC) curve and area under ROC (AUC) for HIV infection prediction was 0.751 (95% CI:0.710-0.792, P<0.001). The maximum Youden's index was individual risk score of 12.56, and the sensitivity of the risk assessment tool was 0.838, and its specificity was 0.412. Conclusions:The results of HIV infection risk assessment tool in Guizhou indicated that in MSM the higher the individual risk score, the higher the risk of HIV infection is. The tool can be used to evaluate the risk of HIV infection in MSM, but the specificity should be improved.

Morinda genus of Rubiaceae has been widely used in medicine at home and abroad. Many parts of Morinda tree are utilized in research, mainly including roots, stems, leaves, branches and seeds. Through the research of online databases, the chemical components and biological activities of the iridoids in Morinda genus were summarized in this paper. Up to now, more than 50 kinds of iridoids have been identified. In addition, more and more studies proved that Morinda iridoids might benefit human via such anti-inflammatory, antinociceptive, anti-oxidation, anti-tumor and bone protection. The theoretical basis was provided for the further development and utilization of the iridoids in Morinda genus.

Objective:To explore the relations among childhood trauma,autistic traits and dysexecutive functions in college students.Methods:Totally 2757 college students were assessed with the Childhood Trauma Questionnaire (CTQ).Sixty-three college students were randomly selected as the abused group according to the subscale cutoff point of CTQ Scale defined by Bernstein,and 93 students were randomly selected from students without history of childhood trauma as the control group.They were assessed with the Self-Rating Depression Scale (SDS),Autism Spectrum Quotient (AQ) and Dysexecutive Questionnaire (DEX) to measure depression,autistic traits and abnormality of executive functions,respectively.The individuals from the top and below 27％ of CTQ and AQ scores were defined as higher or lower-level different types of abused group and higher or lower-level autistic traits group,respectively.Results:The differences of DEX scores between higher or lower-level four types of CTQ (emotional abuse,physical abuse,sexual abuse,emotional neglect and physical neglect) and between higher or lower-level autistic traits group were significant (Ps ＜0.05).DEX scores in all higher-level groups were higher than all lower-level groups.Regression analysis showed that DEX score could be positively predicted by scores of emotional abuse,AQ and SDS (β =0.17-0.32,P ＜0.05).SDS score was a mediator between scores of emotional abuse and DEX,and between scores of autistic traits and DEX (95％ confidence interval were 0.05-0.32 and 0.07-0.55,respectively).Conclusion:Childhood trauma and autistic traits may positively predict dysexecutive function,and depression may play a mediating role between emotional abuse and dysexecutive function,and between autistic traits and dysexecutive function.

Objective Continuous nursing intervention was conducted in patients with chronic hepatitis B by means of Weixin platform. The effect of this intervention on compliance of oral nucleoside (acid) analogues (NA) in patients with chronic hepatitis B was studied and analyzed.Methods A total of 240 patients with chronic hepatitis B treated in the Third People's Hospital of Guangyuan in Sichuan Province from October 2014 to December 2016 were recruited. According to the different nursing methods, all the research subjects were divided into experimental group (n=120) and control group (n=120). For the experimental group, a nursing WeChat team and related WeChat group was established to provide professional counseling, authoritative scientific diagnostic information, appointment registration and other continuous nursing intervention for 6 months. Patients in the control group were given routine nursing. All patients were given oral NA treatment. The score of compliance after 6 months' intervention, the rate of review at 1st, 3rd and 6th month after discharge, and the recurrence rate at 12th month after discharge.Results The score of compliance of the control group was (52.37±7.65), and experimental group (63.85±8.57) after intervention. The difference in compliance was statistically significant (t=10.947,P<0.05). After intervention, the number of high compliance patients was 51 in the experimental group, which was higher than 29 in the control group, and the difference was statistically significant (χ2=9.075,P<0.05). The rates of review at 1st, 3rd and 6th month after discharge of the experimental group were all 100.00％, which were higher than those of the control group (96.67％, 92.50％ and 82.50％). The recurrence rate at 12th month after discharge of the experimental group was 8.33％,which was lower than 20.00％ of the control group, and the difference was statistically significant (P<0.05). Conclusions With the help of WeChat platform, continuous nursing can significantly improve the compliance of oral NA, improve the degree of re-visit and reduce the recurrence rate after 1 years in patients with hepatitis B.

Objective To develop a method for determination of iridoid glycosides in Morinda officinalis How.and optimize the extraction methods for iridoid glycosides in Morinda officinalis How.Methods The iridoid glycosides, including monotropein, deacetyl asperulosidic acid,asperulosidic acid and asperuloside as standards, HPLC method was developed to determine the content of iridoid glycosides in Morinda officinalis How.The separation was performed on Venusil MP C18 (250 mm×4.6 mm, 5 μm) column.The mobile phase was acetonitrile (A)-0.2% phosphoric acid and 0.01 disodium hydrogen phosphate buffer salt (B) with gradient elution (0-12 min, 1%-2% A;12-30 min, 2%-25% A).The detection wavelength was 235 nm.The flow rate was set at 1.0 ml/min and the column temperature at 25 ℃.The injection volume was 20 μl.Single factor analysis and orthogonal test were used to optimize extraction method of iridoid glycosides in Morinda officinalis How.Results Monotropein, deacetyl asperulosidic acid, asperulosidic acid and asperuloside showed good linearity (r>0.999 5) in the ranges of 0.375-12 μg, 0.13-4.16 μg, 0.016-0.516 μg and 0.012-0.384 μg, respectively.This validated method has good repeatability, precision, recovery and stability.It was conformed to meet the requirements and regulation.The optimal extraction method included soaking the raw materials with 16 times of 10% ethanol for 9 h, and then extraction by percolation with the flow rate of 0.8 BV/h.Conclusion The HPLC method sensitively and precisely determined the content of iridoid glycosides in Morinda officinalis How.The optimized extraction method extracted these constituents effectively.

OBJECTIVE:To observe clinical efficacy and safety of mesalazine combined with Kangfuxin solution retention en-ema in the treatment of active ulcerative colitis(UC). METHODS:A total of 120 patients diagnosed as active UC selected from gastroenterology department of our hospital during Mar. 2012 to Aug. 2014 were divided into observation group and control group according to random number table,with 60 cases in each group. Both groups received conventional treatment of active UC. Control group was additionally given Mesalazine enteric coated tablets 1 g,tid,on the basis of routine treatment.Observation group was ad-ditionally given Kangfuxin solution 30 mL diluted with normal saline 150 mL for enema,qd,on the basis of control group. Both groups were treated for 30 d. The serum levels of TNF-α,IL-1,IL-8,IL-10,SOD,NO and LPO were observed in 2 groups be-fore and after treatment;clinical efficacies,recurrence rates,colonoscopy efficacies and the occurrence of ADR were compared be-tween 2 groups. RESULTS:Before treatment,there was no statistical significance in the serum levels of TNF-α,IL-1,IL-8, IL-10,SOD,NO or LPO between 2 groups(P>0.05).After treatment,the serum levels of TNF-α,IL-1,IL-8,NO and LPO in 2 groups were decreased significantly,while the serum levels of IL-10 and SOD were increased significantly;the serum levels of TNF-α,IL-1,IL-8,NO and LPO in observation group were significantly lower than control group,while the serum levels of IL-10 and SOD were significantly higher than control group,with statistical significance(P<0.05). Clinical response rate,recur-rence rate and colonoscopy response rate of observation group were 83.3%,11.7% and 88.3%,which were significantly better than 66.7%,30.0%,70.0%of control group,with statistical significance(P<0.05).There was no statistical significance in the in-cidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Mesalazine combined with Kangfuxin solution can effectively alle-viate inflammatory reaction in patients with active UC,and reduce oxygen free radical damage with good safety.

Objective To observe and evaluate the clinical efficacy and safety of Xiaoerzhili syrup in attention deficit/hyperactivity disorder(ADHD) in children.Methods This study was performed by a multicenter self-controlled clinical observation trial.A total of 1 833 children with ADHD selected from 18 clinical centers from June 2013 to December 2015 were treated by Xiaoerzhili syrup for 6 months,and the clinical efficacy and safety were evaluated.Chinese Version of ADHD Rating Scale-Ⅳ-Parent(ADHDRS-Ⅳ-P) and Clinical Global Impression (CGI) were used to evaluate the clinical efficacy,and the registration form of side reaction and the questionnaire of drug safety grade were used to assess the safety.Results Compared with the scores before treatment,the total scores of ADHDRS-Ⅳ-P,attention deficit subscale scores and hyperactivity impulsivity subscale scores decreased with statistically significant differences after treatment with Xiaoerzhili syrup in the total ADHD group,male ADHD group,female ADHD group,mild ADHD group,moderate ADHD group and severe ADHD group(all P ＜0.01).The statistically significant differences in the total scores of ADHDRS-Ⅳ-P,attention deficit subscale score and hyperactivity impulsivity subscale scores were not found in different gender before and after treatment (all P ＞ 0.05).According to the results of CGI-Ⅰ,the proportion of "improved obviously" and above were 80.98％ (1 379 cases),79.95％ (1 089 cases) and 85.05％ (290 cases),in the total poptlation group,male group and female group,respectively.The side effects of drugs were found in six male cases.After treatment,safety problems were not found in the analysis of the safety evaluation.Conclusion Xiaoerzhili syrup treatment is effective in children with ADHD treatment,and security problems are not found.