Objective To investigate the anti-fibrogenesis property and mechanism of short hairpin RNA (shRNA ) targeting heat shock protein 47 (HSP47) in schistosomiasis liver fibrosis mice model . Methods Sixty female BALB/c mice (SPF level) were infected percutaneously with (16 ± 1) Schistosoma japonicum cercariae . Twelve mice which were not infected with Schistosoma japonicum were set as uninfected control .The 60 mice were randomly divided into five groups including 1 mg/kg HSP47-shRNA intervention group ,2 mg/kg HSP47-shRNA intervention group ,4 mg/kg HSP47-shRNA intervention group ,unrelated shRNA intervention group and infected control group ,with 12 mice each group .From 6 to 14 weeks post infection ,mice in HSP47-shRNA intervention groups were intravenously injected with HSP47-shRNA weekly and those in unrelated shRNA intervention group were intravenously injected with 2 mg/kg of unrelated shRNA vector weekly .Survival rate ,liver and spleen in general and liver histology of mice in each group were observed at week 14 which was considered as end of intervention . The expressions of HSP47 mRNA and protein were determined by real-time polymerase chain reaction (PCR) and Western blot .Collagen type Ⅰ ,collagen type Ⅲ ,tissue inhibitor of metalloproteinase-1 (TIMP-1) , matrix metalloproteinase-9 (MMP-9) ,plasminogen activator inhibitor-1 (PAI-1) ,transforming growth factor-β1 (TGF-β1 ) , connective tissue growth factor (CTGF ) , interleukin (IL )-13 and IL-17 at transcriptional level were measured by real-time PCR .Means among groups were compared using student-t test .Results In vivo intervention of HSP47-shRNA mainly localized in hepatic stellate cells of mice . The survival rate of 1 mg/kg ,2 mg/kg and 4 mg/kg HSP47-shRNA intervention groups were 25 .00% , 25 .00% and 33 .33% , respectively .Mice received 4 mg/kg dose of HSP47-shRNA had significantly higher survival rate than the infected controls (χ2 = 4 .168 ,P= 0 .043) .In both 4 mg/kg HSP47-shRNA intervention group and the infected control group , hematoxylin and eosin staining showed chronic granuloma change ,of which ova were wrapped by the spindle-shaped collagen and inflammatory cell infiltrated .The percentage of positive staining for Masson trichrome and sirius red showed the quantity of the collagen deposition was significantly reduced by the HSP 47-shRNA intervention ,compared to the infected control group (t = 3 .191 ,P = 0 .039) .HSP47-shRNA significantly reduced HSP47 expression , and reduced the transcriptional levels of collagen type Ⅰ ,collagen type Ⅲ ,TIMP-1 ,PAI-1 ,TGF-β1 , CTGF ,IL-13 and IL-17 (all P < 0 .01) ,and increased the expression of MMP-9 mRNA ( P < 0 .01) . Conclusion Delivery of shRNA targeting HSP47 to the hepatic schistosomiasis mice model can silence the expression of HSP47 and improve the liver fibrosis .Collagen degradation and related cytokines release through upregulation of MMP-9 and downregulation of PAI-1 may be one of the anti-fibrotic mechanisms in HSP47-shRNA intervention .

Spleen deficiency is an important part of the theoretical system of Traditional Chinese Medicine,which has experienced the process of origin,standardization,maturity,perfection and development in different historical periods.The physiological function of the spleen in Traditional Chinese Medicine involves"the spleen governs transportation and transformation,promotes blood circulation";The study of"spleen governing transportation and transformation"divided into"spleen governing transportation"and"spleen governing transformation"from the function of spleen,which is more conducive to explaining the scientific connotation of spleen governing transportation and transformation.Spleen governing transport and transformation is the basis of spleen governing clearing,and spleen governing clearing is the purpose of spleen governing transport and transformation.Spleen governing blood circulation is the outcome of spleen governing clearing,and there is a progressive logical hierarchy relationship between them.With the rise of proteomics,metabonomics and intestinal flora research,it provides technical support for the study of spleen deficiency syndrome;In addition,based on the correlation between spleen of Traditional Chinese Medicine and the functions of endoplasmic reticulum,the material basis of essence of spleen deficiency is discussed from the perspective of endoplasmic reticulum stress,which provides a new direction for the study of spleen deficiency.

The pathogenesis of ulcerative colitis(UC)is still unclear,and the pathogenesis based on intestinal mucosal immune imbalance is now widely recognized."Spleen as the defense"refers to the function of the spleen to protect the body and defend against pathogenic factors,which is highly consistent with modern mucosal immunology theory.The abnormal function of"Spleen as the defense"is the key reason for the immune imbalance of UC intestinal mucosa.In this paper,"spleen as the defense"as the starting point,to explore the mechanism of UC intestinal mucosal immune dysfunction,to consolidate the theoretical basis for the treatment of UC based on spleen,and to provide a theoretical basis for the treatment of UC from the perspective of restoring intestinal mucosal immune homeostasis.

The article reviewed the relevant studies on the treatment of spleen-deficiency syndrome with Chinese herbal formula for invigorating the spleen reported in the last 10 years,focusing on gastrointestinal motility disorders,mitochondrial dysfunction,visceral hypersensitivity,gastrointestinal mechanical barrier destruction,intestinal microecological disorders and immune imbalance.The progress and deficiency of the study on the mechanism of Spleen-Invigorating Traditional Chinese Medicine was summarized and analyzed,in order to provide theoretical support for the research on the related mechanism of the spleen-invigorating Chinese medicine compound,in order to provide reference for the study on the related effective mechanism of Spleen-Invigorating Traditional Chinese Medicine.

ObjectiveTo analyse the current implementation status of Chinese herbal medicine （CHM） placebo and systematically evaluate the placebo effect in randomised controlled trials （RCTs） of traditional Chinese medicine （TCM） for the treatment of functional dyspepsia （FD）. MethodsA combination of medical subject terms and free words was used to search six databases， including PubMed， EMBASE， Cochrane Library， Web of Science， China National Knowledge Infrastructure， and Wanfang， for RCTs with CHM placebo group for FD published from January 31st， 1994 to September 30th， 2023. The dosage forms， composition， and methodological quality were collected and evaluated. The quality of the included articles was evaluated by Cochrane risk of bias assessment tool， and meta-analysis was performed on the CHM placebo response rate of patients with FD， and subgroup analysis and meta-regression was performed according to diagnostic criteria， efficacy criteria， duration of treatment， type of placebo， whether it contained active ingredient， and whether it evaluated placebo effects. ResultsA total of 34 publications were included involving 5046 participants， of which 2221 FD patients received CHM placebo treatment. Granules were the predominant placebo preparation， accounting for 71% （24/34）； 32.35% （11/34） of the studies added real CHM to the placebo， and only 12 （35%） of the studies described appearance， odour， and taste. The placebo response rate in FD patients in the placebo group was 41% （95% CI： 0.35 to 0.47； P＜0.01， I² = 87%）； there was significant difference between groups with different diagnostic criteria and different treatment durations （P＜0.05 or P＜0.01）， but there was no significant difference between the different efficacy evaluation criteria， the different placebo preparation， the presence of a low-dose active ingredient， and the presence or absence of placebo assessment （P＞0.05）. ConclusionThere was a significant CHM placebo effect in patients with FD， with granules as the main preparation of placebop. Different diagnostic criteria and different treatment times may affect the response rate of patients， and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate. Clinical investigators have not paid enough attention to placebos， and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.