ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 （Fas）/cysteine protease-8 （Caspase-8）/cysteine protease-3 （Caspase-3） signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury （CLI）. MethodsAmong 48 Wistar rats，12 rats were randomly selected as the blank group，and the other rats were administered alpha-naphthalene isothiocyanate （ANIT） by gavage to induce a CLI model. The modeling rats were randomly divided into the model group， the ursodeoxycholic acid group（0.1 g·kg^-1） and the Yinchenhao Tang group（9.23 g·kg^-1），with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），gamma-glutamyl transpeptidase （γ-GT），total bilirubin （TBil） and total bile acid （TBA） in serum were detected. The levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3，B-cell lymphoma-2 （Bcl-2） associated X protein （Bax） and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with those in the blank group，the levels of ALT，AST，ALP，γ-GT，TBA and TBil in serum of the model group were significantly increased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased （P<0.01）. The arrangement of hepatocytes was disordered，and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly increased（P<0.05，P<0.01），while the protein and mRNA expressions of Bcl-2 were significantly decreased （P<0.05，P<0.01）. Compared with those in the model group，the levels of ALP，γ-GT，TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased（P<0.05，P<0.01）. The protein and mRNA expressions of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the mRNA expression of Bcl-2 was significantly increased （P<0.05，）. The levels of ALT，AST，γ-GT，TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased （P<0.01）. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased （P<0.05，P<0.01）. The protein expression of Fas and Bax and the mRNA expression of Fas，Caspase-8，Caspase-3 and Bax in liver tissue were significantly decreased （P<0.05，P<0.01），while the protein and mRNA expression of Bcl-2 were significantly increased （P<0.05，P<0.01）. Hepatocyte injury，inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI，and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.

ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury （CLI） by inhibiting toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） pathway via regulating farnesol X receptor （FXR）. MethodsA total of 40 Wistar male rats were randomly selected， with 10 as a blank group，and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate （ANIT）. After modeling，they were randomly divided into the model group， the ursodeoxycholic acid （0.1 g·kg^-1） group and the Yinchenhao Tang （9.23 g·kg^-1） group，with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），γ-glutamyl transpeptidase （γ-GT），total bile acid （TBA），total bilirubin （TBil） and direct bilirubin （DBil） levels in serum were detected. Tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6） levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR，TLR4，MyD88，NF-κB，F4/80，TNF-α，IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR，TLR4，MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin （HE） staining. ResultsCompared with those in the blank group，ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the model group were significantly increased （P<0.01）. The levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were significantly increased （P<0.01），and the mRNA and protein expressions of FXR in liver tissue were decreased （P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased （P<0.05，P<0.01）. Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group，ALT，ALP，γ-GT，TBA，TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.05，P<0.01）. The mRNA and protein expressions of TLR4，MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased （P<0.05，P<0.01）. ALT，AST，ALP，γ-GT，TBA，TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased （P<0.05，P<0.01），and the levels and mRNA expression of TNF-α，IL-1β and IL-6 in liver tissue were obviously decreased （P<0.01）. The mRNA and protein expressions of FXR in liver tissue were significantly increased，and the mRNA expressions of TLR4，MyD88，NF-κB，and F4/80， as well as the protein expressions of TLR4 and NF-κB were obviously decreased （P<0.05，P<0.01）. The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI，and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.

ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

This paper summarizes the experience of professor LIU Shangyi in differentiating and treating rectal carcinoma from the perspective of "treating ulcers as tumors". It is believed that the manifestations of rectal cancer， such as anal itching， cauliflower-like or ulcerative tumors， and bloody stools， are similar to external skin itching， skin ulceration， swelling， and skin bleeding. Therefore， the treatment principles of sores and ulcers department can be applied to treat tumors. Following the diagnostic and treatment approach of dermatology regarding the clinical typical symptoms， for anal itching， the main treatment is to dispel wind and remove dampness， clear heat to relieve itching， using "skin medicinals" such as Difuzi （Fructus Kochiae） and Baixianpi （Cortex Dictamni）， as well as wind medicinals such as Shengma （Rhizoma Cimicifugae） and Fangfeng （Radix Saposhnikoviae）. For constipation， the method of clearing heat and resolving toxins， unblocking the bowels and discharging heat can be used， commonly using Baitouweng （Radix Pulsatillae）， Donglingcao （Herba Rabdosiae Rubescentis） and Dahuang （Radix et Rhizoma Rhei）. In terms of mucosal ulcers， it is critical to differentiate between yin and yang； the treatment of yang ulcers should focus on clearing heat and resolving toxins， commonly using modified Xianfang Huoming Beverage （仙方活命饮）； for yin ulcers， emphasis should be placed on removing dampness and resolving phlegm， commonly with modified Yiyi Fuzi Baijiang Powder （薏苡附子败酱散）. For bloody stool， differentiation is made between deficiency and excess， with the use of Diyu （Radix Sanguisorbae） and Huaihua （Flos Sophorae） for excess syndrome to cool and stop blee-ding， and both herbs dry-fried until charred combined with liver-tonifying medicinals for deficiency syndrome

This paper explores the immune-inflammatory regulatory mechanism of colorectal cancer cachexia and corresponding traditional Chinese medicine （TCM） intervention strategies based on the TCM theory of reinforcing healthy qi and dispelling pathogenen. It is proposed that depletion of healthy qi is the root cause of colorectal cancer cachexia， while cancer toxins exuberance is the symptomatic manifestation of the disease， and failure of the spleen and stomach is the core pathogenesis. In terms of treatment， a TCM treatment system is constructed based on the principles of reinforcing healthy qi to consolidate the foundation and regulate immunity， and dispelling pathogen to remove toxins and alleviate inflammation. The system clarifies the healty qi-reinforcing method as fortifying spleen and boosting qi to enhance immune function， and nourishing blood and enriching yin to consolidate yin essence and healthy qi. It also emphasizes the pathogen-dispelling method as clearing heat and removing toxins to regulate the secretion of inflammatory cytokines， and promoting blood circulation and resolving stasis to improve the immune microenvironment and microcirculation. This therapeutic approach may provide valuable insights for TCM interventions in colo-rectal cancer cachexia.

Cholestatic liver injury （CLI） is a hepatic disorder characterized by the abnormal accumulation of bile acids in the body due to various etiologies， and without timely intervention， it can progress to liver fibrosis， liver cirrhosis， and liver failure and even lead to death. Studies have shown that modulating oxidative stress can alleviate lipid peroxidation and cellular damage， thereby suppressing inflammation and cell apoptosis. In recent years， remarkable progress has been made regarding the active components and compound prescriptions of traditional Chinese medicine in the treatment of CLI by regulating oxidative stress. This article systematically reviews the current status of research on the mechanism of action and clinical application of traditional Chinese medicine in the treatment of CLI by regulating oxidative stress.

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

Abstract Cholestasis can be seen in many acute and chronic liver diseases. If not intervened in time, persistent cholestasis can further progress to liver fibrosis, liver cirrhosis, liver failure, and even death. The pathogenesis of cholestasis is complex, and there is currently a lack of effective therapeutic drugs. Bile acids(BAs), the main component of bile, are synthesized from cholesterol in the liver as primary bile acids. After entering the intestine through the enterohepatic circulation, they are reshaped into secondary bile acids by gut microbiota. BAs can directly or indirectly affect the composition and function of gut microbiota, which in turn can regulate the synthesis and metabolism of BAs. The interaction between BAs and gut microbiota plays an important role in the pathogenesis and treatment of cholestasis. This review elucidates the bidirectional regulatory mechanisms between BAs and gut microbiota and their roles in the pathogenesis and treatment of cholestasis, aiming to provide insights and references for basic research and clinical practice related to cholestasis-associated diseases.

Hepatic resection and liver transplantation usually adopt the controlled low central venous pressure(CLCVP)technique and liver blood flow blocking technique,which can reduce hepatic venous pres-sure,thus effectively reduce intraoperative blood loss and blood transfusion,as well as decrease the risk of sur-gery,therefore have been widely used in clinical practice.However,intraoperative hypotension may occur when applying CLCVP and hepatic portal blockade,which increases the risk of acute kidney injury,myocardial injury and neurologic complications,moreover increases the postoperative mortality rate of the patients.The goal-di-rected fluid therapy(GDFT)is a novel fluid infusion measure that optimizes the vital organ perfusion,reduces the risk of monitoring central venous pressure and effectively improves the patient's prognosis.This article discussed the use of CLCVP technique in hepatic resection,challenges and the advantages of GDFT in periop-erative fluid management.

Objective Investigate the prevalence and epidemiological characteristics of flatfoot among a sample of adolescents(grade 3,5 and 7)in the Northeastern Chongqing,analyze the influencing factors,to provide a scientific basis for selecting intervention strategies.Methods Utilizing plantar optical observation mirrors and questionnaires,a flatfoot screening was conducted among grade 3,5 and 7 school-aged adolescents from 10 urban and rural schools in Wanzhou District,Chongqing.Relevant parameters were recorded,and uni-variate logistic regression analysis was performed considering gender,genetics,BMI,exercise duration,foot-wear,history of ankle trauma,awareness of risks,medical consultation history,and knowledge of preventive measures for flatfoot prevalence.Variables with statistically significant differences in the univariate logistic a-nalysis were included in the multivariate logistic regression analysis.Results In a sample of 5 058 school-age adolescents,2 163 were diagnosed with flatfoot,yielding a prevalence rate of 42.76%(2 163/5 058).Urban and rural areas difference:urban areas had a rate of 43.70%(1 444/3 304),while rural areas had a rate of 40.99%(719/1 754),no statistically significant difference was found between the two(χ2=3.334,P=0.068).Gender difference:males had a rate of 45.56%(1 212/2 660),and females had a rate of 39.66%(951/2 398),the prev-alence rate was higher in males than in females,with a statistically significant difference(χ2=17.730,P<0.001).Grade difference:the prevalence rate in grade 3 was 49.45%(822/1 662),in grade 5 was 42.78%(727/1 699),and in grade 7 was 36.18%(614/1 697),there was a statistically significant among different grades(χ2=60.473,P<0.001),while the prevalence rate in grade 3 was significantly higher than that in grade 5 and 7,and it showed a decreasing trend with the increase of the students'grade level(χ2 trend=24.223,P<0.001).Genetic differences:the proportion of individuals with a positive genetic predisposition to flat feet was 15.53%(336/2 163),the influence of genetics on the occurrence of flat feet was statistically significant(χ2=70.232,P<0.001);furthermore,there was a higher genetic tendency towards severe flatfoot,with statistically significant difference(χ2trend=44.976,P<0.001).BMI difference:comparison of flatfoot severity across differ-ent BMI strata showed a significant difference(χ2trend=21.118,P=0.002),indicating that varying BMI levels affect the prevalence of flatfoot.Multivariate logistic regression analysis showed that gender,genetics,and BMI(18.5-<25.0 kg/m2)were the influencing factors of flatfoot among adolescents in Northeastern Chongqing(P<0.05).Conclusion The incidence of flatfoot among school-age adolescents decreases with in-creasing grade,with lower rates among girls than boys,and there is a genetic predisposition.Most flatfoot are mild,and BMI is a high-risk factor.Early intervention should be implemented for flatfoot in adolescents.