Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

Objective:To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies.Methods:Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software.Results:From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% ( Z=7.35 , P<0.001). There was no significant upward trend in standardized incidence ( Z=1.64 , P=0.140), but the standardized incidence of male residents showed an increasing trend ( Z=2.76 , P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions:The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

Objective:To investigate the effect and molecular mechanism of tumor necrosis factor-α-inducible protein 8-like 2(TIPE2)on lipopolysaccharide(LPS)or interleukin-4(IL-4)-induced phenotypic switch of adipose tissue macrophages(ATM).Methods:The expression levels of TIPE2, inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein 1(MCP-1), CD206, and arginase 1(Arg-1)in the visceral adipose tissue of obese mice, TIPE2-knockout(KO)mice, and control mice were detected by immunohistochemistry, Western blotting, and real-time PCR(RT-qPCR). Peritoneal macrophages isolated from KO and wild-type mice and RAW 264.7 mouse macrophage cell line were cultured, and then stimulated with LPS(100 ng/mL)or IL-4(20 ng/mL)for 6 hours. The expression levels of TIPE2, iNOS, MCP-1, CD206, and Arg-1 were detected by Western blotting and RT-qPCR.Results:Obese mice showed down-regulated TIPE2 expression, up-regulated pro-inflammatory markers iNOS and MCP-1 expressions, and down-regulated anti-inflammatory markers CD206 and Arg-1 expressions. LPS decreased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages from mice, increased the expression of the classically activated macrophages(M1 phenotype)markers iNOS and MCP-1, and decreased the expression of the substituting activated macrophages(M2 phenotype)markers CD206 and Arg-1. IL-4 increased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages, decreased the expression of iNOS and MCP-1, and increased the expression of CD206 and Arg-1. During the M1 polarization of macrophages, LPS increased toll-like receptor(TLR4)expression as well as nuclear transcription factor κBα suppressor protein(IκBα) and NF-κB phosphorylations in macrophages. Knockout of TIPE2 further increased the expression of the TLR4/IκBα/NF-κB signaling pathway and M1 macrophage markers, and further reduced the expression of the M2 macrophage markers.Conclusion:TIPE2 regulates ATM phenotypic transformation through inhibition of the TLR4/IκBα/NF-κB signaling pathway, which ameliorates adipose tissue inflammation in obese states.

OBJECTIVE To compare the contents of the instructions of domestic and imported Chinese patent medicines as well as those from Hong Kong ，Macao and Taiwan ，and to explore the feasibility of Chinese patent medicines to strengthen the use of medicine according to disease differentiation . METHODS The domestic Chinese patent medicines included in national medical insurance list as well as imported Chinese patent medicines and those from Hong Kong ，Macao and Taiwan regions publicized on the official website of National Medical Products Administration were searched to statistically analyze the information of “functions”and“indications”in the instructions of Chinese patent medicines . RESULTS Finally，1 311 instructions of domestic Chinese patent medicine and 43 of imported Chinese patent regions were screened out . In the “functions”item contained in the instructions of Chinese patent medicines ，94.04% domestic Chinese patent medicines ，87.50% imported ones and those from Hong Kong ，Macao and Taiwan regions were expressed using the terms of traditional Chinese medicine ；4.89% and 12.50% were expressed using the terms of integrated Chinese and western medicine . The “functions” item were only expressed using the terms of western medicine in 1.07% of th e instructions of domestic Chinese patent medicines . The“functions” item was mostly expressed using the terms of integrated Chinese and western medicine in the instructions of imported Chinese patent medicines and those from Hong Kong ，Macao，and Taiwan regions ，but there was no expressed using the terms of western medicine alone . Among the expressions of “functions”item containing the terms of western medicine ，anti-inflammatory medicines accounted for the highest proportion ，and domestic Chinese patent medicines ，imported Chinese patent medicines and ones from Hong Kong ，Macao and Taiwan regions accounted for 37.18% and 75.00%，respectively. In the instructions of domestic Chinese patent medicines ，the“indications”item of which contained syndrome information accounted for 72.39%，and the instructions of imported Chinese patent medicines and those from Hong Kong ，Macao and Taiwan regions which did not include syndromes information accounted for 74.42%；in the instructions of domestic Chinese patent medicines ，imported ones and those from Hong Kong，Macao and Taiwan regions ，the“indications”item of which contained disease information ，accounted for 78.34% and 41.86%，respectively，and the “indications”item of which were mainly expressed using the terms of western medicine diseases ， accounted for 64.85% and 73.68%，respectively. CONCLUSIONS Most of the domestic Chinese patent medicines included in the national medical insurance list have the basis for the use of disease differentiation ；most of the imported Chinese patent medicines and those from Hong Kong ，Macao and Taiwan regions have the basis for the use of disease differentiation .

Algae are a large group of photosynthetic organisms responsible for approximately half of the earth's total photosynthesis. In addition to their fundamental ecological roles as oxygen producers and as the food base for almost all aquatic life, algae are also a rich source of bioactive natural products, including several clinical drugs. Cytochrome P450 enzymes (P450s) are a superfamily of biocatalysts that are extensively involved in natural product biosynthesis by mediating various types of reactions. In the post-genome era, a growing number of P450 genes have been discovered from algae, indicating their important roles in algal life-cycle. However, the functional studies of algal P450s remain limited. Benefitting from the recent technical advances in algae cultivation and genetic manipulation, the researches on P450s in algal natural product biosynthesis have been approaching to a new stage. Moreover, some photoautotrophic algae have been developed into "photo-bioreactors" for heterologous P450s to produce high-value added pharmaceuticals and chemicals in a carbon-neutral or carbon-negative manner. Here, we comprehensively review these advances of P450 studies in algae from 2000 to 2021.

Objective: To construct nomogram to predict the risk of bone metastasis in patients with non-small cell lung cancer(NSCLC). Methods: The clinical data of NSCLC patients diagnosed in the hospital were retrospectively analyzed, including the occurrence of bone metastasis, age, gender, pathological type, smoking status, PS score, TN stage, metastasis of other sites before bone metastasis, carcinoembryonic antigen(CEA) level, alpha fetoprotein(AFP) level, serum calcium(Ca2+), serum phosphorus(P), alkaline phosphatase(ALP) level, which were determined by univariate and multivariate logistic regression analysis. Receiver operating characteristic curve(ROC) and decision curve analysis were used, DCA was used to verify the accuracy and clinical benefit of the model, and nomogram was used to visualize the model. Results: Area under the ROC curve(AUC) showed that in the modeling group(n=138) and the validation group(n=92), the AUC value predicted by combined indicators(age, gender, pathological type, CEA, ALP)(modeling group=0.792, validation group=0.629) was higher than that predicted by single indicator. Conclusion The prediction model constructed in this study has good effect and can provide reference for clinical screening of high-risk patients with bone metastasis of NSCLC.

Objective: To learn the willingness and influencing factors of influenza vaccination among the community managed diabetic patients in Keqiao District, Shaoxing, so as to provide the basis for influenza vaccination promotion. Methods: A self-compiled questionnaire survey was conducted from October to December 2017 among all the managed diabetic patients in Keqiao District. The contents of questionnaire included the basic information of the respondents, awareness of influenza vaccine, vaccination status and vaccination intention. Logistic regression model was used to analyze the influencing factors for the willingness of influenza vaccination. Results: A total of 15 060 questionnaires were sent out and 13 781 valid ones were retrieved, the response rate was 91.51%. There were 3 888 patients with the awareness of influenza vaccine, accounting for 28.21%; 4 259 patients with the willingness to be vaccinated, accounting for 30.90%; 630 previously-vaccinated patients, accounting for 4.57%. The patients who were female (OR=1.157, 95%CI: 1.064-1.258) , were married (OR=1.242, 95%CI:1.107-1.393), were with other chronic diseases (OR=1.199, 95%CI: 1.103-1.303) , believed diabetic patients were more susceptible to influenza (OR=1.251, 95%CI: 1.102-1.419) , believed influenza aggravate diabetes status (OR=1.640, 95%CI: 1.445-1.860) , believed that the vaccination effectively prevent influenza (OR=3.129, 95%CI: 2.866-3.416) , knew about influenza vaccine (OR=1.111, 95%CI: 1.105-1.216) and ever received influenza vaccination (OR=1.316, 95%CI: 1.103-1.570) were more willing to be vaccinated. Conclusions The willingness of influenza vaccination among the community managed diabetic patients in Keqiao District is low. The patients＇gender, married status, other chronic diseases, awareness of influenza vaccine and the history of vaccination can affect the willingness of influenza vaccination.

Objective:To investigate the clinical efficacy of superficial temporal artery-anterior temporal artery bypass combined with encephalo-duro-arterio-synangiosis in the treatment of Moyamoya disease.Methods:A total of 42 patients with moyamoya disease, admitted to our hospital from January 2016 to January 2019, were selected and divided into observation group and control group according to surgical management. The patients in the observation group were treated with superficial temporal artery-anterior temporal artery bypass combined with encephalo-duro-arterio-synangiosis, and the patients in the control group were treated with superficial temporal artery-angular gyrus artery bypass combined with encephalo-duro-arterio-synangiosis. The clinical data of these patients were analyzed retrospectively, and the differences of efficacy and safety between the two groups were compared.Results:There was no significant difference in operation time between the two groups ([189.16±21.23] min vs. [179.46±16.95] min, P>0.05). One d after the operation, the patients in both groups were re-examined with CT angiography, and the anastomotic vessels were unobligated. Two patients in the observation group had cerebral infarction in the operative region and one patient in the control group had cerebral infarction in the operative region; no significant difference was noted in the incidence of postoperative complications between the two groups ( P>0.05). The modified Rankin scale (mRS) scores in both groups one month after surgery were significantly decreased as compared with those one d before surgery ( P<0.05); one month after surgery, the mRS scores in observation group (0.13±0.346) were significantly lower than those in the control group (0.42±0.515, P<0.05). Conclusion:The superficial temporal artery-anterior temporal artery bypass combined with encephalo-duro-arterio-synangiosis has definite clinical efficacy in the treatment of moyamoya disease.

In order to evaluate the intervention effect of the school-based salt reduction model, 28 primary schools were selected in Shandong Province in September 2014 and randomly divided into intervention group (1 361 students, 1 306 parents) and control group (1 364 students,1 340 parents). A series of "small hands and big hands" salt reduction intervention activities were conducted in intervention group for 8 months. After the intervention, the total awareness rate of salt reduction knowledge, the total holding rate of related beliefs and the total reporting rate of related behaviors were 70.65%, 80.30% and 67.03% among students, and 85.66%, 93.77% and 87.93% among parents, in the intervention group, which were higher than those in the control group (37.12%, 66.52% and 50.07% among students; 55.11%, 87.52% and 57.96% among parents) (all P values <0.05). The school-based salt reduction model is effective and feasible.

Objective : To explore the positive rates and influencing factors of depression and anxiety among managed diabetic patients in community and to provide evidence for the future mental health intervention. Methods: Random sampling method was used to select the diabetic patients from the local health information platform in Ningbo. The anxiety and depression symptoms of the diabetic patients were evaluated by 9-Item Patient Health Questionnaire（PHQ-9）and 7-Item Generalized Anxiety Disorder Scale（GAD-7）. Logistic regression model was applied to analyzing the influencing factors for anxiety and depression in diabetic patients. Results: A total of 1 032 diabetic patients were enrolled,with a response rate of 91.98%. The positive rate of depression was 9.01% and the positive rate of anxiety was 3.78%. The results of multivariate logistic regression analysis showed that divorced/widowed（OR=3.046,95%CI：1.522-6.100）,having two comorbidities or more（OR=6.723,95%CI：2.495-18.120）and suffering diabetes for more than ten years（OR=2.668,95%CI：1.406-5.062）were the risk factors for depression in diabetic patients,while having a college education or above（OR=0.288,95%CI：0.093-0.893）was the protective factor for depression in diabetic patients;unmarried（OR=13.244,95%CI：1.268-138.377）,having two comorbidities or more（OR=6.979,95%CI：2.164-22.503） and suffering diabetes for more than ten years（OR=3.109,95%CI：1.241-7.787）were the risk factors for anxiety in diabetic patients. Conclusion Marital status,the number of comorbidity,course of diabetes and education level could affect the occurrence of depression in diabetic patients;marital status,the number of comorbidity and course of diabetes could affect the occurrence of anxiety in diabetic patients.