Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To investigate the clinical effect of LUO's Nephropathy Recipe Ⅲ(composed of Sargassum,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Rehmanniae Radix Praeparata,calcined Ostreae Concha,Houttuyniae Herba,Schizonepetae Spica,etc.)combined with conventional western medicine in treating stage 3-5 non-dialysis chronic kidney disease(CKD)of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type.Methods A total of 180 patients with stage 3-5 non-dialysis CKD of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type were randomly divided into observation group and control group,with 90 cases in each group.The control group was given conventional western medicine for symptomatic treatment,and the observation group was treated with LUO's Nephropathy RecipeⅢon the basis of treatment for the control group.The course of treatment for the two groups covered one month.Before and after treatment,the levels of serum inflammatory factors,renal function indicators and urine protein parameters in the two groups were observed.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate in the observation group was 95.56%(86/90)and that in the control group was 81.11%(73/90).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammatory factors of transforming growth factor β1(TGF-β1),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function indicators of blood urea nitrogen(BUN),serum creatinine(Scr),blood uric acid(UA),and cystatin C(Cys-C)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of 24-hour urine protein quantification and urine microalbumin in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.44%(4/90),which was significantly lower than that of 15.56%(14/90)in the control group,and the difference was statistically significant between the two groups(P＜0.05).Conclusion LUO's Nephropathy Recipe Ⅲ combined with conventional western medicine exerts satisfactory efficacy in treating stage 3-5 non-dialysis CKD patients with spleen-kidney deficiency with turbidity-toxin-stasis obstruction syndrome type,and the therapy can significantly alleviate the inflammatory response,improve the renal function,decrease the urinary protein excretion of the patients,with high safety profile.

The essence of cirrhosis is the over-repairing reaction of liver tissue damage in the process of chronic liver disease.During repair,the liver parenchyma is gradually replaced by fibrosis tissue,resulting in changes in liver tissue morphology,followed by portal hypertension and other related manifestations.Liver failure are serious disorder of liver functions(synthesis,metabolism,transformation,regeneration,etc.)caused by various factors,often mainly manifested as jaundice,coagulation disfunction,hepatic encephalopathy,ascites,etc.The naming and typing of the two are different,and they can exist independently of each other or intersect with each other.In recent years,with the in-depth exploration of cirrhosis and liver failure,many new definitions and classification methods have been put forward in the research.However,due to the confusion of classification methods,there is still a lack of summary,so this article briefly reviews the current progress of clinical classification of liver cirrhosis and liver failure and their differences and intersections.

Objective To construct a lentiviral vector for overexpression of bone morphogenetic protein 7(BMP7)in mice,and the effect of BMP7 overexpression on the expression of Jagged1 in mouse aortic endothelial cells and the calcification of the co-cultured vascular smooth muscle cells(VSMCs)were analyzed.Methods According to the target gene information Mouse-BMP7(NM_007557.3)and plasmid information pLVX-zsGreen-C1,gene sequence synthesis was carried out to construct BMP7 overexpression lentivirus.The efficiency of BMP7 overexpression lentivirus infection was detected by qPCR;the expression of Jagged1 protein in aortic endothelial cells from infected mice was detected by Western blot.The endothelial cells with lentivirus overexpressing BMP7 were co-cultured with VSMCs,and the calcification of VSMCs was observed by alizarin red staining.Results BMP7 overexpression lentiviral vector was successfully constructed and transfected into aortic endothelial cells.qPCR test results showed that the expression level of BMP7 mRNA was significantly increased in the BMP7 overexpression group than that in the normal control group(P<0.01),while there was no significant difference in the expression of BMP7 mRNA between the empty vector control group and the normal control group(P>0.05).Western blot results showed that the expression level of Jagged1 protein in endothelial cells of mouse in the BMP7 overexpression group was significantly lower than that in the normal control group(P<0.01),while there was no significant difference in the expression level of Jagged1 protein in endothelial cells between the empty vector control group and the normal control group(P>0.05).The results of alizarin red staining showed that the calcification of VSMCs was significantly increased after co-cultured with endothelial cells infected with BMP7 lentivirus.Conclusion Mouse BMP7 overexpression lentiviral vector was successfully constructed,and overexpression of BMP7 can reduce the expression of Jagged1 in mouse aortic endothelial cells and promote the calcification of co-cultured VSMCs.

Trichinosis is a global food-borne zoonotic parasitic disease caused by Trichinella spiralis(T.spiralis),which causes serious harm to animal production,and the public health safety of humans and animals.T.spiralis has a complex devel-opment history,and its entire life cycle is completed in the same host.To coexist with the host,it has evolved various immune escape mechanisms for avoiding immune clearance by the host,thus establishing long-term chronic infection.In this study,to aid in understanding the pathogenic mechanism of T.spiralis,the immune escape mechanism of Trichinella is discussed from three aspects:the molecular role of antigens in various stages,the immune regulatory effect on the host,and the formation of cysts to generate immune isolation.

Objective:To clarify the spatio-temporal characteristics and changing trends of provincial health resources and medical pressure,and to provide suggestions for the high-quality development of medical and health services in China.Methods:Based on the panel data of 31 provincial administrative units from 2010 to 2020,a comprehensive evaluation system of provincial health resources and medical pressure was constructed.The global entropy method and exploratory spatial analysis were used to reveal the spatio-temporal differentiation and correlation pattern,and the Tapio decoupling index was illustrated to explain the evolution characteristics and trends.Results:During the observation period,health resources and medical pressure in the vast majority of provinces in China rose steadily,with positive spatial correlation and agglomeration,and a close relationship with economic development and population demand;the mainstream decoupling state of the country shifted from a negative decoupling to a positive decoupling,with an obvious progressive decoupling trend,and the development of regional health continued to improve.Conclusions and suggestions:Provinces need to take into account the status quo of health development in their own provinces,focus on the spatio-temporal coupling of elements and structures,and optimize the structure of health resource allocation and enhance the resilience of the health system as a means of bringing into play the comparative advantages of the regional health system.

Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.

Cardiovascular and cerebrovascular diseases, usually result from atherosclerosis, has the highest mortality rate globally. Lipid metabolism disorder is the main cause of atherosclerotic cardiovascular and cerebrovascular diseases, which not only lead to acute diseases such as myocardial infarction, stroke, acute pancreatitis, but also chronic kidney disease. In recent years, the advancement of gene therapy technologies has provided novel means for lipid metabolism study, and has also made it possible to cure patients with congenital lipid metabolism abnormalities. Adeno-associatd virus has a wide host range, high safety, low immunogenicity, and especially the ability of long-term stable expression in vivo, making it the preferred delivery tool for gene therapy of monogenic genetic diseases. Alipogene triprivec, also known as Glybera, was approved by the European Medicines Agency in 2012. It is the first gene therapy drug that uses recombinant AAV1 vector to directly deliver a highly active LPL protein S447X mutant to muscle cells for the treatment of patients with hereditary LPL deficiency. To enhance the targeted transduction efficiency of AAV carriers, recombinantAAV8.TBG.hLDLR utilizes the tissue tropsim of AAV8 to liver, meanwhile utilizes a liver specific thyroxine binding globulin promoter to control gene transcription, thereby achieving liver cell specific high expressionof human low-density lipoprotein receptors (LDLR). In patients with familial hypercholesterolemia,AAV8.TBG.hLDLR treatment effectively lower the level of plasma LDL for a long time, thus preventing the occurrence of atherosclerosis.Proprotein convert subunit kexin 9 (PCSK9) is secreted by liver cells. PCSK9 binds and transports LDLR to lysosomes for degradation, preventing the circulation and regeneration of LDLR, leading to accelerated degradation of LDLR and finally resulting in the accumulation of low-density lipoprotein cholesterol in plasma. Using AAV to deliver Cas9 of Staphylococcus aureus and gRNA targeting the Pcsk9 gene can knock out Pcsk9 in mouse liver, leading to a long-term significant decrease in plasma cholesterol levels in mice. Hepatocyte specific angiopoietin related protein 3 (Angptl3) is an endogenous inhibitor of LPL. Using the AAV9 mediated AncBE4max system and the dCas9 mediated single base gene editing system to introduce early termination codons, the knockout of Angptal3 in liver cells was achieved with an average knockout efficiency of 63.3%. After 2-4 weeks of administration in mice, the Angptl3 protein was completely undetectable in the peripheral blood, and serum triglycerides and total cholesterol decreased by 58% and 61%, respectively. Ring finger containing protein 130 (RNF130) is an E3 ubiquitin ligase. Research has shown that overexpression of RNF130 using AAV2/8 leads to ubiquitination degradation and redistribution of LDLR on the cell membrane, significantly reducing LDLR expression on liver cells and increasing plasma LDLC levels, while knocking out Rnf130 gene using the AAV-CRISPR system results in the opposite effect. This AAV mediated RNF130 function study proves that RNF130 is a posttranslational regulatory protein of LDLR and plays an important role in the regulation of serum LDLC. As mentioned above, recently, various lipid-lowering gene therapy drugs carried by different serotypes of adeno-associated virus have been applied in clinic or are undergoing clinical trials, and adeno-associated virus has emerging to be an important tool for lipid metabolism research.This article reviews the new progress of adeno-associated virus vectors in lipid metabolism study and lipid-lowering gene therapy.