The pathogenesis of metabolic dysfunction-associated steatotic liver disease （MASLD） is fundamentally rooted in spleen deficiency and is closely associated with phlegm turbidity， damp-heat and blood stasis. Clinically， liver constraint with spleen deficiency and internal retention of damp turbidity represent the predominant traditional Chinese medicine （TCM） syndrome patterns. Researches have indicated intrinsic connections between the syndrome patterns and biological indicators such as gut microbiota and metabolic profiles. Regarding treatment， classical famous formulas， modern empirical formulas， and newly developed TCM drugs show positive effects in regulating glucose and lipid metabolism， improving insulin resistance， and alleviating metabolic inflammation， exhibiting multi-target mechanisms of action； acupuncture and other external therapies also provide adjunctive value. Nevertheless， current researches still have limitations such as the lack of high-quality clinical evidence and insufficient systematic elucidation of the uncerlying mechanisms. Future efforts should focus on conducting high-quality TCM clinical trials with hard endpoint outcomes such as hepatic histology outcomes， and utilizing modern technologies like multi-omics to elucidate TCM's mechanisms of action， thereby advancing the position of TCM as a first-line therapeutic strategy for MASLD.

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.

OBJECTIVE: To investigate the effect of autologous osteochondral tissue and periosteum transplantation on tendon-bone healing of rotator cuff in rabbits. METHODS: Twenty-four male New Zealand white rabbits were randomly divided into autologous osteochondral tissue and periosteum transplantation group (experimental group, n=12) and simple suture group (control group, n=12). Both groups were subjected to acute supraspinatus tendon injury and repaired with corresponding techniques. At 4, 8, and 12 weeks after operation, 4 specimens from each group were taken from the right shoulder joint for histological examination (HE staining, Masson staining, and Safranin O-fast green staining), and the left shoulder was subjected to biomechanical tests (maximum tensile load and stiffness). RESULTS: Both groups of animals survived until the completion of the experiment after operation. At 4 weeks after operation, both groups showed less collagen fibers and disorder at the tendon-bone junction. At 8 weeks, both groups showed reduced inflammation at the tendon-bone junction, with more organized and denser collagen fibers and chondrocytes. The experimental group showed better results than the control group. At 12 weeks, the experimental group showed typical tendon-bone transition structure, with increased generation of collagen fibers and chondrocytes, and the larger cartilage staining area. Both groups showed an increase in maximum tensile load and stiffness over time ( P<0.05). The stiffness at 4 weeks and the maximum tensile load at 4, 8, and 12 weeks in the experimental group were superior to control group, and the differences were significant ( P<0.05). There was no significant difference in stiffness at 8, 12 weeks between the two groups ( P>0.05). CONCLUSION Autologous osteochondral tissue and periosteum transplantation can effectively promote the fiber and cartilage regeneration at the tendon-bone junction of rotator cuff and improve the biomechanical effect of shoulder joint in rabbits.
Animals ; Rabbits ; Male ; Wound Healing ; Transplantation, Autologous ; Periosteum/transplantation* ; Rotator Cuff Injuries ; Rotator Cuff/surgery* ; Tendons/surgery* ; Biomechanical Phenomena ; Chondrocytes/transplantation* ; Tendon Injuries/surgery* ; Tensile Strength

Objective To analyze the influence of drainage volume on prognosis of acute hydrocephalus(AHC)after aneurysmal subarachnoid hemorrhage(aSAH)by continuous lumbar drainage.Methods A retrospective trial was conducted on 82 AHC patients after aSAH admitted to the First Affiliated Hospital of Chongqing Medical University between January 2017 and January 2022.In 6 months after discharge,modified Rankin Scale(mRS)score was used to evaluate the prognostic outcomes.Univariate and multivariate logistic regression analyses were performed on demographic factors,severity of subarachnoid hemorrhage(SAH)at admission,medical history,cerebral vasospasm,and lumbar drainage data.Then a nomogram prediction model was constructed.Results Univariate analysis found that World Federation of Neurosurgical Societies(WFNS)score,Hunt-Hess grade,modified Fisher grade,time for continuous lumbar drainage,shunt dependence,cerebral vasospasm,and drainage volume were factors affecting the prognosis of the patients.Then logistic regression analysis revealed that high WFNS score(OR:3.25,95％CI:1.11～9.48),high modified Fisher grade(OR:3.66,95％CI:1.08～12.35),shunt dependence(OR:15.56,95％CI:1.22～198.57),and cerebral vasospasm(OR:22.24,95％CI:3.08～160.68)were independent predictors for mRS score,while volume of continuous lumbar drainage(OR:0.57,95％CI:0.40～0.82)was an independent protective factor.ROC curve analysis indicated a good predictive performance of the model(AUC=0.898,95％CI:0.935～0.861).Internal validation through Bootstrap method demonstrated excellent discriminatory ability of the model(C-index=0.950,95％CI:0.904～0.996;adjusted C-index:0.934).Conclusion Increased volume of lumbar drainage is an independent protective factor for poor prognosis following aSAH and can improve the prognosis of SAH patients.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective:To investigate the effect of dexmedetomidine(DEX)on the polarization of alveolar macrophages in-duced by lipopolysaccharide(LPS)and to explore the related mechanisms.Methods:Rat alveolar macrophages NR8383 were cul-tured in vitro.Experiment one was divided into control group,model group(1 μg/ml LPS),DEX low,medium and high dose groups(1,5,10 mg/kg DEX+10 mg/kg LPS).Experiment two was divided into DEX high dose group(10 mg/kg)and DEX high dose+Colive-lin(JAK2/STAT3 signaling pathway activator)group(10 mg/kg DEX+0.5 μmol/L Colivelin).The morphological changes of rat alveo-lar macrophages NR8383 were observed by inverted microscope;RT-PCR method was used to detect the expression levels of iNOS and Arg1 mRNA in NR8383 cells,and flow cytometry was used to detect the expression levels of CD86 and CD163 proteins in NR8383 cells;Western blot was used to detect the expression levels of surface marker proteins TNF-α,iNOS,SOCS,Arg1,TGF-β and JAK2/STAT3 signaling pathway related proteins in NR8383 cells.Results:Compared with control group,there were a lot of cell debris in the intercellular space of NR8383 in the model group,the proportions of iNOS mRNA,CD86 positive cells,and the expression levels of TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 were significantly increased,the proportions of Arg1 mRNA,CD163 positive cells,and the expression levels of SOCS and TGF-β were significantly reduced(P<0.05);compared with the model group,the NR8383 intercellular cell debris in the DEX low,medium,and high dose groups were decreased,the proportions of iNOS mRNA,CD86 positive cells,and the expression levels of TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 were significantly reduced,the proportions of Arg1 mRNA,CD163 positive cells,and the expression levels of SOCS and TGF-β were significantly increased(P<0.05).The reactivation of the JAK2/STAT3 signal pathway by Colivelin could weaken the role of DEX in LPS induced NR8383 cell polarization.Conclusion:DEX can inhibit the M1 polarization of NR8383 cells induced by LPS,which may be achieved by inhibiting the JAK2/STAT3 signaling pathway.

Objective:To observe any effect of percutaneous tibial nerve stimulation (PTNS) combined with electro-acupuncture on detrusor overactivity after a spinal cord injury.Methods:Forty spinal cord injury survivors with neurogenic detrusor overactivity were randomly assigned to a control group or an observation group, each of 20. Both groups received routine bladder training and electro-acupuncture modulating 3 sacral spinal nerves. The observation group also received 20 minutes of bilateral PTNS five times a week for 8 weeks. The frequency was 10Hz with a pulse width of 200μs. Before and after the treatment, both groups′ urination frequency, incontinence and average daily urine volume were assessed using a urodynamics analyzer, bladder diaries and an incontinence quality of life questionnaire (I-QOL).Results:After treatment, the average involuntary detrusor contraction volume (IDCV), maximum detrusor pressure at filling time (P det·max), bladder compliance (BC), residual volume and the TL value of the electromyogram of the urethral sphincter (LgTLR) had all improved significantly in both groups. The 1st IDCV, BC and LgTLR of the observation group were then significantly better than in the control group, on average, with the average P det·max and residual volume significantly lower than in the control group. The average daily single urine output and I-QOL score of both groups had increased significantly, while the average daily urination frequency and frequency of urinary incontinence had decreased significantly. Both were again significantly better in the observation group. Conclusion:Combining percutaneous electrical stimulation of the tibial nerves with electro-acupuncture can effectively inhibit detrusor overactivity after a spinal cord injury, reducing urinary incontinence.

【Objective】 To observe the effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway. 【Methods】 After flap operation, the survival of rat back flaps and flap survival rate were observed. HE staining, TUNEL staining, and qRT-PCR were used to detect the degree of nuclear destruction, as well as the distribution characteristics and mRNA expression levels of p38MAPK, PPARγ, and Nf-κB in vascular endothelial cells of rat flaps, respectively. 【Results】 The flap survival area in sham operation group was the largest, and it was the smallest in model control group and PPARγ inhibitor group. HE staining and TUNEL staining results showed that the flap tissue cells of rats in model control group and PPARγ inhibitor group were severely damaged and obvious apoptotic cells were seen. In model group, rats’ skin flap tissue cells were arranged in a single layer, and the nucleus was intact and clear. qRT-PCR experiment results showed that compared with model group, the expressions of p38MAPK and Nf-κb in the flap tissue of rats in Xiaozhong Zhicong Mixture group were inhibited (P<0.05), while the expression of PPARγ was increased (P<0.05). When the blocker was added, the expressions of p38MAPK, NF-κB and PPARγ in the flap tissue were further suppressed. 【Conclusion】 Xiaozhongzhitong Mixture can alleviate the infiltration of inflammatory cells in the rat model of skin flap ischemia-reperfusion injury, reduce inflammation and the production of apoptotic cells, thereby alleviating the ischemia-reperfusion injury of skin flaps and promoting the survival of the flaps. The mechanism may be related to the inhibition of p38MAPK-PPARγ/NF-κB signaling pathway.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone