Objective To investigate the effect of Rho kinase inhibitor,fasudil,on pulmonary fibrosis induced by paraquat in rats in order to elucidate the underlying mechanisms.Methods A total of 72 SpragueDawley male rats of specific pathogen free (SPF) were randomly (random number) divided into four groups:the normal control group (NS group,n =18),fasudil control group (FS control group,n =18),paraquat poisoning group (PQ poisoning group,n =18) and fasudil intervention group (FS intervention group,n =18).On days 7,14,28 after paraquat exposure,six rats were respectively selected from each group.These rats were anesthetized and sacrificed immediately,and their lung tissues were collected.The hydroxyproline (HYP) in the lung tissue was detected by using alkaline hydrolysis.The expressions of type Ⅰ,Ⅲ collagen protein,connective tissue growth factor (CTGF) and ROCK1 mRNA in Rho/ROCK signaling pathway were assayed by using the real-time quantitative PCR (RT-PCR),and the levels of type Ⅰ,Ⅲ collagen protein,connective tissue growth factor (CTGF) and Rho / ROCK signaling pathway ROCK1 protein were measured by using Western blotting.The pathological changes of lung tissue were observed under light microscope.Results There were no significant differences in the observed biomarkers between FS control group and NS group (P ＞ 0.05).While in PQ poisoning group and FS intervention group on days 7,14,28 (all P ＜ 0.05),the amount of HYP increased obviously (P ＜ 0.05),the expressions of type Ⅰ,Ⅲ collagen protein,CTGF,ROCK1 mRNA and protein levels were increased significantly (P ＜ 0.05).Compared with the PQ poisoning group,the amount of HYP decreased significantly,and the expressions of type Ⅰ,Ⅲ collagen protein,CTGF,ROCK1 mRNA and protein levels were decreased significantly in FS intervention group on days 7,14,28 (all P ＜ 0.05).The pathological changes of lung tissue revealed that the degree of pulmonary fibrosis in the PQ poisoning group were most serious on 28 d after paraquat exposure,and the degree of pulmonary fibrosis were lessened in FS intervention group on days 7,14,28.Conclusions ROCK inhibitor,fasudil,has obvious therapeutic effects on paraquat-induced lung fibrosis,by regulating Rho / ROCK signaling pathway with downregulated expression of CTGF,and decrease in the levels of type Ⅰ,Ⅲ collagen protein,thus reducing protein deposition.

Objective·To systematically integrate relevant influencing factors of advanced cancer patients'engagement behavior in advance care planning(ACP).Methods·The systematic search of Chinese and English literature on factors influencing ACP engagement behavior in advanced cancer patients from inception to December 2022 in China National Knowledge Infrastructure(CNKI),Wanfang,China Biomedical Literature Database(Sinomed),PubMed,Cochrane Library,Embase,CINAHL,and PsycINFO was conducted.After the literature quality evaluation,content extraction and summary were conducted by two researchers,and the data of quantitative research and qualitative research were extracted and integrated respectively.The final influencing factors of ACP engagement behavior of advanced cancer patients were obtained.With the help of the theoretical domain,they were mapped to the capability,opportunity,motivation-behavior(COM-B)model step by step.Results·A total of 21 studies were included and 27 factors were summarized,including 9 theoretical domains.Mapping to the COM-B model included 9 capability factors(knowledge of ACP,education level,accurate knowledge of prognosis,knowledge of the time of disease diagnosis,prior experience,subjective life expectancy,age,cancer site,and disease symptom burden),13 opportunity factors(gender,marital status,race/ethnicity,religious belief,dependent children,family economic condition,place of living,housing type,family support,social support,doctor-patient relationship,acculturation,and whether or not to establish a hospice service center)and 5 motivational factors(ACP attitude,ACP belief,ACP motivation,anxiety and depression,and death attitude).Among them,doctor-patient relationship,religious belief,ACP attitude,educational level,marital status,family support,knowledge of ACP,accurate knowledge of prognosis,age,place of living,attitude toward death,prior experience,and race/ethnicity were more influential factors on ACP engagement behavior.Conclusion·Based on the COM-B model,the influencing factors of ACP engagement behavior in advanced cancer patients can be comprehensively summarized.Future studies can use the above factors as an entry point to design continuous,multifaceted,and comprehensive interventions based on the COM-B model to promote the practice of ACP engagement behavior in advanced cancer patients.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.