Objective To observe the effect of Sishen Pills on the expression of TREK-1 signaling pathway in rats of irritable bowel syndrome with diarrhea(IBS-D);To explore its mechanism in treating IBS-D.Methods Ten SPF-grade SD rats were randomly selected as the normal group,and the remaining 30 rats were used to prepare the IBS-D rat model by senna gavage combined with water stress avoidance method,and then the modeled rats were randomly divided into the model group,Western medicine group(15.23 mg/kg pivoxyl bromide)and Chinese medicine group(7.32 g/kg Sishen Pills).The medication groups were gavaged by corresponding drugs,and the normal group and model group were given equal volume of pure water,once a day,for consecutive 14 d.The general state of the rats was observed,the contents of serum cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phosphorylated extracellular signal-regulated kinase(p-ERK)were detected by ELISA,the positive expressions of biportal potassium channel TREK-1 and p-ERK in colonic tissue were detected by immunofluorescence,the expressions of cAMP,PKA and p-ERK protein were detected by Western blot.Results Compared with the normal group,the body mass of rats in the model group was significantly reduced,and loose stool rate significantly increased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly increased(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue were significantly reduced,while the positive expression of p-ERK significantly increased(P<0.01),and the expressions of cAMP and PKA proteins significantly increased(P<0.01).Compared with the model group,the body mass of rats in Chinese medince group significantly increased,and loose stool rate significantly decreased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly reduced(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue significantly increased(P<0.01),while the positive expression of p-ERK significantly decreased(P<0.05),and the expressions of cAMP and PKA proteins significantly decreased(P<0.01).Conclusion Sishen Pills may regulate intestinal motility by affecting the expression of the TREK-1 signaling pathway,thereby treating IBS-D.

Objective To observe the effect of Sishen Pills on the expression of TREK-1 signaling pathway in rats of irritable bowel syndrome with diarrhea(IBS-D);To explore its mechanism in treating IBS-D.Methods Ten SPF-grade SD rats were randomly selected as the normal group,and the remaining 30 rats were used to prepare the IBS-D rat model by senna gavage combined with water stress avoidance method,and then the modeled rats were randomly divided into the model group,Western medicine group(15.23 mg/kg pivoxyl bromide)and Chinese medicine group(7.32 g/kg Sishen Pills).The medication groups were gavaged by corresponding drugs,and the normal group and model group were given equal volume of pure water,once a day,for consecutive 14 d.The general state of the rats was observed,the contents of serum cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phosphorylated extracellular signal-regulated kinase(p-ERK)were detected by ELISA,the positive expressions of biportal potassium channel TREK-1 and p-ERK in colonic tissue were detected by immunofluorescence,the expressions of cAMP,PKA and p-ERK protein were detected by Western blot.Results Compared with the normal group,the body mass of rats in the model group was significantly reduced,and loose stool rate significantly increased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly increased(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue were significantly reduced,while the positive expression of p-ERK significantly increased(P<0.01),and the expressions of cAMP and PKA proteins significantly increased(P<0.01).Compared with the model group,the body mass of rats in Chinese medince group significantly increased,and loose stool rate significantly decreased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly reduced(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue significantly increased(P<0.01),while the positive expression of p-ERK significantly decreased(P<0.05),and the expressions of cAMP and PKA proteins significantly decreased(P<0.01).Conclusion Sishen Pills may regulate intestinal motility by affecting the expression of the TREK-1 signaling pathway,thereby treating IBS-D.

Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

Objective To explore the effects of Jianpi Yichang Powder on the expressions of interleukin(IL)-1β and IL-18 of NLRP3 signaling pathway in ulcerative colitis(UC)model rats.Methods Ten rats were randomly selected from 40 SD rats as the normal group,and the other rats freely drank 5%dextran sulfate solution for 7 days to replicate UC rats model.The model rats were randomly divided into model group,sulfasalazine group and Jianpi Yichang Powder group,with 10 rats in each group.Jianpi Yichang Powder group and sulfasalazine group were given corresponding liquid medicine for gavage,and the normal and model groups were given equivalent volume distilled water for gavage for consecutive 14 d.The general status was observed,and the disease activity index(DAI)was scored,the contents of NLRP3,apoptosis-associated spotted proteins(ASC),and Caspase-1 in serum were detected by ELISA,the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were detected by immunohistochemistry,Western blot and RT-PCR respectively.Results Compared with the normal group,the general status of the rats in model group was relatively worse,and DAI score significantly increased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum were significantly increased(P<0.01),the expressions of IL-1β and IL-18 protein and mRNA in colon tissue were significantly increased(P<0.01).Compared with the model group,the general status of the rats in Jianpi Yichang Powder group and sulfasalazine group were significantly improved,DAI score significantly decreased(P<0.01),the contents of NLRP3,ASC and Caspase-l in serum significantly reduced(P<0.05,P<0.01),and the expressions of IL-1β and IL-18 protein and mRNA in colon tissue significantly decreased(P<0.05,P<0.01).Conclusion Jianpi Yichang Powder can inhibit IL-1β and IL-18 expression of NLRP3 signaling pathway to reduce colon immune inflammatory damage,thus play a role in treating UC.

Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.

Objective To explore the mechanism of protective effect of Jianpi Yichang Powder on intestinal mucosa by observing its effect on the expression of autophagy-related molecules in colon of ulcerative colitis(UC)model rats.Methods SD rats were randomly divided into normal group,model group,Jianpi Yichang Powder group and sulfasalazine group.UC rat model was established by 2,4,6-trinitrobenzene sulfonic acid/ethanol solution.After the model was successfully reproduced,the rats were given drugs orally once a day for 14 days.The general condition of rats was observed and the disease activity index(DAI)score was calculated.The pathological morphology of colonic tissue in all groups was observed by hematoxylin eosin(HE)staining.Autophagy of colonic epithelial cells was examined by transmission electron microscope.The expressions of myosin-like BCL2 interacting protein(Beclin1)and microtubule-associated protein 1 light chain 3(LC3)in colonic tissue were detected by immunofluorescence staining and Western Blot.The mRNA expressions of autophagy protein 5(Atg5),autophagy protein 7(Atg7)and ubiquitin-binding protein 62(p62)were detected by real-time quantitative polymerase chain reaction(Real-time PCR).Results Compared with the normal group,the general situation of the model group was worse,and the DAI score increased significantly(P<0.000 1).There was obvious epithelial cell damage in colonic tissue,and the number of autophagosomes decreased obviously under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue decreased significantly(P<0.000 1),while the expression of p62 mRNA increased significantly(P<0.000 1).Compared with the model group,the general condition of rats in Jianpi Yichang Powder group had recovered significantly,and the DAI score decreased significantly(P<0.000 1).Pathological damage of colonic tissue has been improved in different degrees,and the number of autophagosomes increased significantly under electron microscope.The expressions of Beclin1 and LC3-Ⅱ/LC3-Ⅰ protein as well as Atg5 and Atg7 mRNA in colonic tissue were significantly increased(P<0.01,P<0.001,P<0.000 1),while the expression of p62 mRNA was significantly decreased(P<0.01).Conclusion Jianpi Yichang Powder can protect UC colon mucosa from injury by up-regulating the expression of autophagy-related molecules including Beclin1,LC3,Atg5 and Atg7,down-regulating the expression of p62 and enhancing autophagy.

Objective To investigate the effects of Jianpi Yichang Powder on regulating the NLRP3 inflammasome signaling pathway to inhibit dendritic cells(DCs)inflammatory injury induced by TNF-α;To explore its mechanism in the treatment of ulcerative colitis.Methods C57BL/6 mice DCs were primitively isolated and cultured.The cultured DCs were randomly divided into the normal group,model group,negative control group,positive drug group and TCM group.DCs inflammatory microenvironment model was established by TNF-α induction.After corresponding treatments were given to each group,CCK-8 method was used to detect cell proliferation ability,immunofluorescence and Western blot were used to detect the protein expressions of NLRP3,ASC and Caspase-1 in DCs respectively,Western blot and RT-PCR were used to detect the protein and mRNA expressions of IL-1β and IL-18 in DCs.Results Compared with the normal group,the proliferation ability in DCs of model group significantly decreased(P<0.01),the positive expressions of NLRP3,ASC and Caspase-1 significantly increased,the expressions of NLRP3,ASC,Caspase-1,IL-18,IL-1β protein and IL-18,IL-1β mRNA in DCs significantly increased(P<0.01).Compared with the model group and negative control group,the proliferation ability of DCs significantly increased in positive drug group and TCM group(P<0.01),the positive expressions of NLRP3,ASC,and Caspase-1 significantly decreased(P<0.01),the protein expressions of NLRP3,ASC,Caspase-1,IL-1β and IL-18 significantly decreased(P<0.05,P<0.01),and the mRNA expressions of IL-1β and IL-18 significantly decreased(P<0.01).The cell proliferation ability,Caspase-1 positive expression,and IL-18 mRNA expression of TCM group were significantly higher than those of the positive drug group(P<0.05),while the mRNA expression of IL-1β was lower than that of the positive drug group(P<0.05).Conclusion Jianpi Yichang Powder can inhibit the inflammatory response of DCs induced by TNF-α,and its mechanism in the treatment of ulcerative colitis may be related to regulating the expressions of the NLRP3 inflammasome signaling pathway,including the expressions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β.

Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Background::Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear.Methods::The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference.Results::A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories.Conclusions::The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.