Ulcerative colitis （UC）， a chronic relapsing inflammatory bowel disease， involves multifaceted pathological mechanisms such as intestinal barrier dysfunction， immune dysregulation， and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism， inflammatory regulation， and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine （TCM） prevented and treated UC through the regulation of the AMPK signaling pathway， with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk， alleviating oxidative stress， restoring intestinal immune balance， repairing the intestinal barrier， and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity， TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC， this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

BACKGROUND: The achievement of an optimal return to sport (RTS) has remained a key goal after sports-related injuries, with the ongoing debate on the effectiveness of different surgical approaches for anterior cruciate ligament (ACL) rupture. This study aims to assess clinical outcomes and RTS across various surgical methods, such as anatomical single-bundle reconstruction (ASBR), central-axial single-bundle reconstruction (CASBR), and double-bundle reconstruction (DBR). METHODS: A randomized clinical trial was conducted, comprising 191 patients who underwent ACL rupture. These patients were divided into three groups based on the ACL reconstruction techniques they received (ASBR, CASBR, DBR). Over the 2-year follow-up period, the study assessed RTS through four single-hop tests, isokinetic extension tests, and limb asymmetry indices. Postoperative graft status was determined using the signal-to-noise quotient (SNQ), while knee function was evaluated using the International Knee Documentation Committee 2000 (IKDC-2000) score, Lysholm score, Tegner score, and degree of knee laxity. A binary logistic regression model was developed to forecast the factors influencing ideal RTS. RESULTS: DBR (67.63%) and CASBR (58.00%) exhibited higher RTS passing rates compared to ASBR (30.39%; χ2 = 19.57, P <0.05). Quadriceps strength symmetry in the lower limbs was identified as the key determinant of RTS ( χ2 = 17.08, P <0.05). The RTS rate was influenced by SNQs of the graft's tibial site (odds ratio: 0.544) and quadriceps strength of the reconstructed knee joint at 60°/s (odds ratio: 6.346). Notably, the DBR group showed enhanced knee stability, evidenced by superior results in the Lachman test ( χ2 = 13.49, P <0.01), objective IKDC-2000 ( χ2 = 27.02, P = 0.002), and anterior instability test ( χ2 = 9.46, P <0.01). Furthermore, DBR demonstrated superior clinical outcomes based on the Lysholm score (DBR: 89.57 ± 7.72, CASBR: 83.00 ± 12.71, ASBR: 83.21 ± 11.95; F = 10.452, P <0.01) and IKDC-2000 score (DBR: 90.95 ± 7.00, CASBR: 84.64 ± 12.68, ASBR: 83.63 ± 11.41; F = 11.78, P <0.01). CONCLUSION: For patients with ACL rupture, more ideal RTS rate and clinical outcomes were shown in the DBR group than in the ASBR and CASBR groups. Autograft status and quadriceps strength are postively related to RTS. TRIAL REGISTRATION ClinicalTrials.gov (NCT05400460).
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Male ; Female ; Adult ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Return to Sport ; Adolescent ; Anterior Cruciate Ligament/surgery* ; Treatment Outcome

Objective To determine the effects of dexmedetomidine(Dex)in anesthesia on brain function,cerebral oxygen uptake rate(CERO2),difference in glucose content between cerebral ar-terial and venous blood(A-VDG)and jugular bulb oxygen saturation(SjvO2)and stress response in elderly patients with hypertensive cerebral hemorrhage.Methods A total of 96 elderly patients with hypertensive cerebral hemorrhage admitted to our hospital from January 2021 to June 2024 were recruited,and according to different anesthesia schemes,they were divided into the group A(propofol,remifentanil,sevoflurane combined with rocuronium anesthesia,48 cases)and group B(same anesthesia regimen as group A plus Dex).Glasgow coma(GCS)score and restlessness-sedation score 48 h after operation,postoperative recovery,stress indexes and cerebral glucose and oxygen metabolism before(T1)and at the end of operation(T2),and adverse reactions during the study were compared between the two groups.Results When compared with the group A,the group B had significantly higher GCS score 48 after surgery(13.95±0.28 vs 12.89±0.41,P＜0.01),and shorter awakening time,time to regain spontaneous breathing,extubation time and response time(P＜0.01).At T2,the levels of CERO2,A-VDG and SjvO2 were notably higher,while levels of cortisol,norepinephrine and epinephrine,and activity of renin were remarkably lower in the group B than the group A(P＜0.01).At T2,the both groups obtained increased levels of cortisol,norepinephrine,epinephrine and renin activity and SjvO2,while decreased CERO2 and A-VDG levels than the corresponding levels at T1(P＜0.05).The incidences of nausea and vomiting,cough,chills,restlessness and delirium was obviously lower in the group B than the group A(P＜0.05,P＜0.01).Conclusion For elderly patients with hypertensive cerebral hemorrhage,application of Dex in anesthesia can improve cerebral glucose and oxygen metabo-lism,reduce stress response,maintain the stability of perioperative vital signs,decrease the severi-ty of coma and incidences of delirium,nausea and vomiting,cough,chills,restlessness and other adverse reactions,and thus promote postoperative recovery.

Objective:To analyze the risk factors for in-hospital malignant ventricular arrhythmia (MVA) in acute myocardial infarction (AMI) and to construct and validate a risk prediction model.Methods:This study was a retrospective cohort study. Patients aged≥18 years who were admitted to Qilu Hospital of Shandong University with a diagnosis of AMI and underwent coronary angiography (CAG) from May 2016 to March 2023 were selected, and the patients' clinical routine test indicators and CAG results were collected. Univariate and bidirectional stepwise logistic regression were used to screen out the risk factors for constructing the best prediction model. The prediction model was constructed by combining the results of multivariate logistic regression. The Hosmer-Lemeshow test and ROC curve, calibration curve, and decision curve were drawn to evaluate the model. The nomogram was drawn to visualize the model, and the Bootstrap self-sampling method was used for internal validation. The ROC curve was drawn to evaluate the predictive performance of each risk factor and prediction model. Finally, a multicollinearity test was performed.Results:Among the 4 205 patients finally included in the study, 115 patients (2.735%) developed MVA during hospitalization. The predictive factors screened out included age (X1), diastolic blood pressure (X2), respiratory rate (X3), blood glucose (X4), serum potassium (X5), logarithmic NT-proBNP (X6), myocardial infarction type (NSTEMI=X7, unclassified=X8), J wave (X9), Killip grade (Ⅱ=X10, Ⅲ=X11, Ⅳ=X12), and the regression equation was ln(p/1-p)=-4.699+0.029×X1-0.012×X2+0.059×X3+0.148×X4-1.175×X5+0.866×X6-1.427×X7-0.475×X8+0.758×X9+0.294×X10+0.902×X11+1.815×X12. The area under the ROC curve (AUC) of the model was 0.855 (95% CI: 0.816-0.894), and the Hosmer-Lemeshow test ( χ2=14.178, P=0.077) and the calibration curve showed that the predicted probability was consistent with the actual probability. The probability threshold of 0% to 65% had a better clinical net benefit. The area under the internal validation ROC curve (AUC) was 0.855, 95% CI: 0.813-0.891. The prediction performance of the nine variables was stronger than that of any single variable. There was no multicollinearity between the variables. Conclusions:Age, diastolic blood pressure, respiratory rate, blood glucose, serum potassium, NT-proBNP, type of AMI, J wave, and Killip class are forecasting indicator for in-hospital MVA in AMI. The risk prediction model based on the above factors has good predictive performance.

Background and Aims:To overcome the limitations of the transoral endoscopic thyroidectomy vestibular approach,such as restricted operative space and high complication risks,our team proposed a modified technique—endoscopic thyroidectomy via oral vestibule and submandibular approach(ETOSA).Preliminary studies have confirmed its safety and feasibility.This study aims to systematically evaluate the key factors affecting postoperative complications and operative time in ETOSA,explore the interactions among these variables,and construct a learning curve model to support its broader clinical adoption.Methods:A retrospective analysis was conducted on 125 patients with papillary thyroid carcinoma who underwent ETOSA at Xiangya Hospital,Central South University,between March 2022 and March 2023.Clinical characteristics,surgical parameters,and postoperative complications were extracted.A random forest model was employed to identify the major influencing factors for complications and operative time,as well as their interaction effects.Partial dependence plots based on case sequence were used to generate the learning curve.Results:All 125 patients successfully underwent ETOSA with no conversion to open surgery.The median operative time was 95.0 min,and the median intraoperative blood loss was 15.0 mL.The overall postoperative complication rate was 16.0%,with no cases of permanent hypoparathyroidism or hypocalcemia.The average neck appearance score was 1.05,indicating high patient satisfaction.The random forest analysis identified case number,surgical extent,lymph node yield(LNY),Hashimoto's thyroiditis(HT),and body mass index(BMI)as the key predictors of postoperative complications,while surgical extent,case number,LNY,HT,and blood loss were the key factors affecting operative time.A significant positive interaction was observed between case number and both surgical extent and HT,particularly in the first 20 cases,suggesting a higher risk during the early learning phase.The learning curve analysis indicated that surgical proficiency stabilized after 20 cases.Operative time and complication rate in the proficient phase were significantly lower than those in the learning phase(90.0 min vs.102.5 min;11.4%vs.40.0%,both P<0.05).Conclusion:ETOSA is a safe and feasible technique characterized by minimal invasiveness,favorable cosmetic outcomes,and a relatively short learning curve.case number,surgical extent,LNY,HT,BMI,and blood loss are key factors affecting complications and operation time.

Background and Aims:To overcome the limitations of the transoral endoscopic thyroidectomy vestibular approach,such as restricted operative space and high complication risks,our team proposed a modified technique—endoscopic thyroidectomy via oral vestibule and submandibular approach(ETOSA).Preliminary studies have confirmed its safety and feasibility.This study aims to systematically evaluate the key factors affecting postoperative complications and operative time in ETOSA,explore the interactions among these variables,and construct a learning curve model to support its broader clinical adoption.Methods:A retrospective analysis was conducted on 125 patients with papillary thyroid carcinoma who underwent ETOSA at Xiangya Hospital,Central South University,between March 2022 and March 2023.Clinical characteristics,surgical parameters,and postoperative complications were extracted.A random forest model was employed to identify the major influencing factors for complications and operative time,as well as their interaction effects.Partial dependence plots based on case sequence were used to generate the learning curve.Results:All 125 patients successfully underwent ETOSA with no conversion to open surgery.The median operative time was 95.0 min,and the median intraoperative blood loss was 15.0 mL.The overall postoperative complication rate was 16.0%,with no cases of permanent hypoparathyroidism or hypocalcemia.The average neck appearance score was 1.05,indicating high patient satisfaction.The random forest analysis identified case number,surgical extent,lymph node yield(LNY),Hashimoto's thyroiditis(HT),and body mass index(BMI)as the key predictors of postoperative complications,while surgical extent,case number,LNY,HT,and blood loss were the key factors affecting operative time.A significant positive interaction was observed between case number and both surgical extent and HT,particularly in the first 20 cases,suggesting a higher risk during the early learning phase.The learning curve analysis indicated that surgical proficiency stabilized after 20 cases.Operative time and complication rate in the proficient phase were significantly lower than those in the learning phase(90.0 min vs.102.5 min;11.4%vs.40.0%,both P<0.05).Conclusion:ETOSA is a safe and feasible technique characterized by minimal invasiveness,favorable cosmetic outcomes,and a relatively short learning curve.case number,surgical extent,LNY,HT,BMI,and blood loss are key factors affecting complications and operation time.