Ductular reaction （DR） refers to the adaptive pathological changes that occur after hepatobiliary injury， and it is essentially a repair response involving the proliferation， fibrosis， and inflammation of biliary epithelial cell （BEC）. With the understanding of the biological function of BEC， the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR， its potential as a therapeutic target， and future development directions， as well as novel therapies suggested by targeting these molecular mechanisms， in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.

Panvascular diseases represent systemic vascular disorders characterized by atherosclerosis as their core pathological feature. Their incidence rates continue to rise， posing significant challenges for clinical management. Based on Traditional Chinese Medicine （TCM） theory of ''positive deficiency phlegm stasis''， this study delved into the pivotal role of mitochondrial homeostasis dysregulation in the pathogenesis and progression of pan-vascular diseases， along with its intrinsic connection to TCM pathogenesis. Mitochondrial homeostasis dysregulation pervades the entire course of these diseases， with mitochondrial oxidative stress serving as the initiating factor. Excessive reactive oxygen species （ROS） trigger endothelial dysfunction， lipid accumulation， and inflammatory initiation. Additionally， the imbalance between mitochondrial autophagy and apoptosis constitutes a pivotal link in disease progression. Excessive or insufficient autophagy may lead to the accumulation of damaged mitochondria and excessive cellular apoptosis， thereby promoting plaque instability. Furthermore， mitochondrial metabolic reprogramming impairs energy supply and function in vascular wall cells， hindering subsequent vascular repair. These pathological processes constitute the microscopic manifestation of the core pathogenesis， which is characterized by ''the intermingle of phlegm and stasis and the deficiency of healthy Qi''. Specifically， the endogenous phlegm-turbidity drives mitochondrial oxidative stress injuries， the mutual entanglement of phlegm and stasis induces an imbalance between mitochondrial autophagy and apoptosis， while deficiency of healthy Qi propels mitochondrial energy metabolism disorders and reprogramming. In view of this， this study proposed to employ phlegm-resolving and turbidity-clearing methods to mitigate mitochondrial oxidative stress injuries， phlegm-resolving and blood-activating methods to regulate mitochondrial autophagy and apoptosis， and spleen-tonifying and kidney-nourishing methods to modulate mitochondrial metabolic reprogramming. This approach can prevent and treat panvascular diseases by multi-target regulation of mitochondrial homeostasis， providing a theoretical framework and therapeutic strategies for the prevention and treatment of panvascular diseases through integrated Chinese and Western medicine.

Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery（TORS） in treating human papillomavirus（HPV） -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage（≤T3 stage） oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival（OS） and progression-free survival（PFS）. Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients（60 males, 66.7%） were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years（range: 39-84 years） old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender（P>0.05）. Cox analysis identified surgical margins>2 mm as a significant factor improving PFS（HR=0.14, 95%CI 0.02-0.90, P=0.038）. Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Squamous Cell/virology* ; Human Papillomavirus Viruses/isolation & purification* ; Margins of Excision ; Oropharyngeal Neoplasms/virology* ; Papillomavirus Infections/virology* ; Prognosis ; Prospective Studies ; Robotic Surgical Procedures/methods*

This article provides a comprehensive review of the progress in the application of transoral robotic surgery（TORS） in the field of head and neck surgery. It elaborates on its developmental background and technical principles as a subset of natural orifice endoscopic surgery and highlights the technical characteristics and optimization trends of both general-purpose and specialized surgical robotic platforms. The review emphasizes the key advantages of TORS in addressing the limitations of traditional transoral surgery, improving surgical precision, and expanding the scope of surgical indications. This in-depth analysis serves as a valuable reference for the future development and wider adoption of TORS technology in head and neck surgery.
Humans ; Robotic Surgical Procedures/methods* ; Natural Orifice Endoscopic Surgery/methods* ; Mouth/surgery*

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Objective To observe the value of digital subtraction angiography(DSA)iFlow parameters for predicting major amputation in patients with acute lower limb ischemia(ALLI)within 30 days after revascularization operation.Methods Totally 310 ALLI patients who underwent revascularization operation were retrospectively included and divided into major amputation group(n=36)and non-major amputation group(n=274)according to major amputation within 30 days after revascularization operation or not.iFlow parameters,including time to peak(TTP)and the Peak were obtained after processing of DSA images after revascularization.Receiver operating characteristic(ROC)curves were used to screen the optimal cut-off value of TTP and Peak for predicting major amputation post operation,and then TTP and Peak were dichotomized.The dichotomized TTP and Peak variables and other variables were admitted into a multivariate logistic regression to identify independent predictors of major amputation.Results TTP was higher and Peak was lower in major amputation group than those in non-major amputation group(both P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of TTP and Peak for predicting major amputation within 30 days post operation was 0.831 and 0.712,respectively,and the optimal cut-off value was 16 s and 1.53,respectively.Multivariate logistic regression analysis revealed that atrial fibrillation(AF)[OR(95％CI)=3.048(1.076,8.632)],livid skin appearance[OR(95％CI)=6.035(2.323,15.677)],TTP≥16 s after revascularization operation[OR(95％CI)=8.414(3.116,22.723)]and high myoglobin levels measured 48 h after operation[OR(95％CI)=1.001(1.001,1.001)]were all independent predictors of major amputation within 30 days in ALLI patients,but dichotomized Peak variable was not an independent predictor[OR(95％CI)=0.485(0.183,1.283),P=0.145].Conclusion TTP obtained through DSA iFlow was valuable for predicting major amputation in ALLI patients within 30 days after revascularization operation.

Objective:To explore the predictive value of changes in prealbumin for the prognosis of patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) after artificial liver treatment.Methods:From January 1, 2018 to December 31, 2021, the clinical data (including prealbumin, platelet count, lymphocyte count, alanine transaminase (ALT), etc.) of 87 patients with HBV-ACLF who received artificial liver treatment at the Department of Gastroenterology of the General Hospital of Western Theater Command PLA were retrospectively collected. The 90-day survival status of all the patients was followed up, and the patients were divided into the survival group and the mortality group according to the survival status. The clinical characteristics and the changes of prealbumin on day 1 to 3, day 3 to 7, and day 1 to 7 after artificial liver treatment were compared between the 2 groups. Multivariate logistic regression analysis was used to analyze the independent influencing factors of the 90-day prognosis of HBV-ACLF patients after artificial liver treatment, and the nomogram prediction model was established and the receiver operating characteristic curve (ROC) was drawn to assess the area under the curve (AUC). Hosmer-Lemeshow goodness-of-fit test, calibration curve and clinical decision curve were performed to evaluate the goodness of fit, consistency and clinical value of the prediction model. Paired t-test and Mann-Whitney U test were used for statistical analysis. Results:There were 69 cases enrolled into the survival group, and 18 cases enrolled into the mortality group. The levels of albumin, prealbumin, platelet count, lymphocyte count, and ALT before treatment, and the level of prealbumin at the 3rd day after treatment of the survival group were all higher than those of the mortality group (32.5 (30.6, 35.2) g/L vs. 29.4 (27.6, 32.3) g/L, 66.0 (52.5, 81.5) mg/L vs. 56.5 (39.2, 65.0) mg/L, 103.0 (72.5, 145.0)×10 9/L vs. 63.5 (40.0, 92.5)×10 9/L, 1.1 (0.8, 1.4)×10 9/L vs. 0.9 (0.5, 1.1)×10 9/L, (514.7±86.4) U/L vs. (328.2±93.4) U/L, 90.0 (69.5, 102.5) mg/L vs.68.5(60.0, 75.8) mg/L), and the age, the level of total bilirubin, international normalized ratio, and prothrombin time before treatment of the survival group were all lower than those of the mortality group (48.0 (42.0, 57.0) years old vs. 48.5 (47.0, 56.0) years old, 323.9 (261.2, 409.2) μmol/L vs. 452.2 (405.8, 510.8) μmol/L, 1.5 (1.3, 1.9) vs. 1.9 (1.4, 2.1), 17.3 (14.6, 20.8) s vs. 21.4 (16.6, 23.2) s), and the differences were statistically significant ( Z=-3.38, -2.87, -2.38 and -2.01, t=2.39, Z=-4.11, 3.00, 3.64, 2.18 and 2.37; all P<0.05). The change of prealbumin on day 1 to 3 after treatment in the mortality group was greater than that in the survival group (-0.182 (-0.321, -0.026) vs. -0.043 (-0.133, 0.093)), and the difference was statistically significant ( Z=-3.42, P=0.001). The results of multivariate logistic regression analysis showed that the age, total bilirubin before treatment, and the change of prealbumin on day 1 to 3 after treatment were independent influencing factors for the 90-day prognosis in HBV-ACLF patients after artificial liver treatment (all P<0.05), and the nomogram model was established based on the above 3 factors. The results of ROC analysis showed that the AUC of the prediction model was 0.933 (95% confidence interval: 0.866 to 1.000, P<0.001), with a sensitivity of 0.933 and a specificity of 0.825. The results of the Hosmer-Lemeshow goodness-of-fit test showed that the prediction model had a good fit( P=0.700). The results of calibration curve analysis indicated that the actual curve of the prediction model was close to the calibration curve, with an average absolute error of 0.034, the consistency between the predicted probability and the actual probability was good. The clinical decision curve analysis suggested that the prediction model had significant clinical benefits. Conclusions:The changes of prealbumin after artificial liver treatment in HBV-ACLF patients can reflect the recovery of liver function. The nomogram prediction model based on the change of prealbumin on day 1 to 3 after treatment, age, and total bilirubin before treatment can better predict the 90-day prognosis of HBV-ACLF patients after artificial liver treatment.

Objective:To evaluate the clinical efficacy of transoral robotic surgery (TORS) in the treatment of malignant tongue base tumors.Methods:A multicenter study was conducted to collect and analyze the clinical data of patients with malignant tongue base tumors who underwent TORS at five otolaryngology-head and neck surgery centers in China, including Eye Ear Nose and Throat Hospital of Fudan University, Sun Yat-sen University Cancer Center, Tongji Hospital of Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the First Affiliated Hospital of China Medical University between January 2017 and January 2023. Among the patients, 38 were males and 11 were females, with a mean age of 59.0±8.8 years. Baseline characteristics, complications, and follow-up data were compared between groups. Independent sample t-tests or Mann-Whitney U tests was used for comparisons of continuous variables; chi-square tests or Fisher′s exact tests was applied for categorical variables. Survival analysis was performed using the Kaplan-Meier method to calculate overall survival and disease-free survival, and differences between groups were compared using the log-rank test. Results:Among the 49 patients, 41 (83.7%) were diagnosed with squamous cell carcinoma (SCC), with a p16 positive rate of 51.2% (21/41). There were no statistically significant differences between the p16-positive group ( n=21) and the p16-negative group ( n=20) in age, sex, or postoperative bleeding (all P>0.05). However, there was a significant difference in TNM stage between the two groups ( χ2=14.556, P=0.020), with the p16-positive group predominantly in stage I (66.7%) and the p16-negative group primarily in stages Ⅲ and Ⅳ (40.0% and 30.0%, respectively). The postoperative tracheotomy rate was 30.6% (15/49), and the incidence of postoperative bleeding was 6.1% (3/49). The 1-year and 3-year overall survival rates were 98.0% and 92.5%, respectively, while, the 1-year and 3-year disease-free survival rates were 89.2% and 84.9%, respectively. No significant differences were observed between the p16-positive and p16-negative groups in 3-year overall survival (100% vs. 83.8%, χ2=1.093, P=0.518) or 3-year disease-free survival (68.2% vs. 88.9%, χ2=2.161, P=0.382). Conclusion:TORS for malignant tongue base tumors demonstrates high clinical safety and favorable oncological outcomes.

Objective:To explore the clinical application value of transoral robotic surgery (TORS) in the treatment of tonsil squamous cell carcinoma (TSCC).Methods:A retrospective analysis was conducted. The clinical data of 157 TSCC patients were collected who received TORS at five medical centers, namely, the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Eye Ear Nose and Throat Hospital of Fudan University, the First Affiliated Hospital of China Medical University, and Tongji Hospital of Tongji Medical College, from January 1 2017 to July 31 2022. There were 130 males and 27 females, aged 24-85 years. All patients were followed-up at least for 2 years (2-year group), among them, 99 patients had a follow-up of 3 years (3-year group). The overall survival (OS), progression-free survival (PFS), clinical stage, human papillomavirus (HPV) infection status were analyzed. SPSS 25.0 and SAS 9.4 were used for statistical analysis.Results:The OS and PFS of the 2-year group were 91.7% and 87.9%, respectively. The OS and PFS of the 3-year group were 85.9% and 82.8%, respectively. The prognosis of patients with locally early-stage was better than that of locally advanced patients, with the OS of 94.4% for T1-2 vs. 78.0% for T3 ( P=0.005) and the PFS of 91.2% for T1-2 vs. 75.0% for T3 ( P=0.011) in the 2-year group; the OS of 91.1% for T1-2 vs. 65.0% for T3 ( P=0.004) and the PFS of 88.6% for T1-2 vs. 60.0% for T3 ( P=0.002) in the 3-year group; and also, the OS of 90.0% for stage Ⅰ-Ⅱ vs. 79.5% for stage Ⅲ-Ⅳ ( P=0.204) and the PFS of 86.7% for stage Ⅰ-Ⅱ vs. 76.9% for stage Ⅲ-Ⅳ ( P=0.188) in the 3-year group. The prognosis of HPV-positive TSCC patients was better than that of HPV-negative patients in the 3-year group, with the OS of 90.9% for HPV-positive vs. 80.5% for HPV-negative ( P=0.045) and the PFS of 90.9% for HPV-positive vs. 75.6% for HPV-negative ( P=0.047). The average time of postoperative tracheal cannula indwelling was 25.1 days. The indwelling rate and average indwelling time of the postoperative nasogastric tube were 94.3% (148/157) and 8.5 days, respectively. Conclusion:TORS has outstanding survival benefits for TSCC patients. HPV-positive TSCC patients have a better prognosis than HPV-negative patients. TORS treatment of TSCC patients has advantages in postoperative recovery and quality of life.

Objective:To investigate the efficacy and feasibility of transoral robotic surgery (TORS) for resection of tumors in the parapharyngeal spaces.Methods:The clinical data of 57 patients who underwent TORS for parapharyngeal space tumors from September 2018 to February 2024 were retrospectively analyzed. These patients were treated at five medical institutions: The First Affiliated Hospital of China Medical University, Eye & ENT Hospital of Fudan University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Sun Yat-sen University Cancer Center. The patients were 28 males and 29 females, aged 17-77 years (median age, 47 years). The pathological types, locations, and sizes of the tumors, operation time, intraoperative bleeding volumes, postoperative hospital stays, and postoperative complications were evaluated. The data were analyzed using SPSS 27.0 software.Results:Postoperative pathological examination revealed 11 types of benign tumors. Among 57 cases, 27 cases had their tumors in the prestyloid spaces, predominantly with pleomorphic adenoma ( n=17), and 30 cases in the retrostyloid spaces, predominantly with schwannoma ( n=22). The tumor volumes ranged from 0.6 to 130.1 cm3, the intraoperative bleeding volumes ranged from 5 to 1 000 ml, the operation time ranged from 20 to 390 min, and the postoperative hospital stays ranged from 2 to 25 days. The total costs for individual cases were 36 000-100 000 yuan, with the highest cost in the case suffering from cerebrovascular accident. Four patients(7.0%) had tracheotomy and 36(63.2%) had nasogastric tube placement. Among the 57 patients, 5 had postoperative cavity effusion, 2 had wound dehiscence, 2 had cerebrovascular accidents, 1 had Horner syndrome, and 2 had other complications. The patients were followed up for 1-67 months, with only 1 patient with intracranial and extracranial communication relapsed. Conclusion:TORS is a safe and feasible approach for treating parapharyngeal space tumors, offering advantages such as minimal invasiveness, reduced blood loss, and faster recovery. It is suitable for parapharyngeal space tumors of various pathological types and locations. The postoperative complications are manageable, with favorable long-term follow-up results and low recurrence rates.