BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal

OBJECTIVE To evaluate the clinical value of dose-escalated postoperative radiotherapy(PORT)in improving local control and survival outcomes for head and neck adenoid cystic carcinoma(ACC)patients.METHODS This retrospective study analyzed 336 ACC patients treated with surgery plus PORT at Beijing Tongren Hospital from January 2015 to January 2021.Cohort stratification compared high-dose(>60 Gy,n=146)and conventional-dose(≤60 Gy,n=190)regimens.Survival analysis employed Kaplan-Meier estimates with log-rank testing,complemented by multivariate Cox regression for risk adjustment.RESULTS The cohort demonstrated 39.29%(132/336)cumulative local failure rate.The overall survival rates at 1,3,and 5 years after surgery were 98.81%,94.05%,and 90.48%,respectively.Dose-response relationships revealed:1.Significantly reduced local recurrence with high-dose PORT(28.08%vs.47.89%,P<0.001),corresponding to 41.37%lower recurrence risk(a HR=0.59,95%CI=0.38-0.91;P=0.041);2.Superior progression-free survival in the high-dose group(3-year:86.99%vs.76.32%;5-year:82.19%vs.66.32%,all P<0.05);3.Comparable overall survival between groups(median OS:200 vs.160 months,P=0.292).CONCLUSION Dose escalation beyond 60 Gy significantly enhances locoregional control and progression-free survival in head and neck ACC without conferring overall survival advantage,likely reflecting the disease's characteristic indolent metastatic progression.These results establish>60 Gy as an optimal dose threshold for PORT in high-risk ACC management.

Circular RNAs(circRNAs)are a class of closed-loop non-coding RNAs(ncRNAs)formed by head-to-tail covalent bonds.CircRNAs participate in the development of osteoarthritis by regulating extracellular matrix degrada-tion,inflammatory response and homeostasis of chondrocytes;It regulates the osteogenic differentiation of bone mar-row mesenchymal stem cells,the activity of bone microvascular endothelial cells and angiogenesis to affect femoral head necrosis;It regulates the differentiation of bone marrow stem cells,osteoblasts and osteoclasts to cause osteo-porosis and it affects the invasion,metastasis and drug resistance of osteosarcoma through different pathogenesis.CircRNAs are expected to become a new clinical diagnostic marker in the future.

Objective:To introduce the experience of reconstructing the pelvic floor with a pedicled large omental flap combined with a basement membrane biological mesh in combined pelvic organ resection for locally advanced or locally recurrent rectal cancer combined with sacrococcygeal resection, and to discuss the feasibility, safety, and near-term therapeutic efficacy of this technique.Methods:For patients with sacrococcygeal resection of combined pelvic organs, a basement membrane mesh was used to rebuild the pelvic floor with a pedicled greater omentum flap to isolate the abdominopelvic cavity. The main operation was to pull the greater omentum, which preserved the double vascular arches, to the pelvic floor to cover the pelvic floor, and then the mesh was used to cover the posterior peritoneal defect and pelvic inlet with absorbable sutures of 2-0 or thicker.Results:In this study, a retrospective cohort study was used to collect clinical data through the China Rectal Cancer Combined Pelvic Organs Resections Case Database. Twenty patients with locally advanced or locally recurrent rectal cancer without extra-pelvic metastasis or only oligometastases underwent combined pelvic organ and sacrococcygeal resection in the Department of Anal and Intestinal Surgery of the Second Affiliated Hospital of the Naval Military Medical University during the period of July 1, 2022, to June 30, 2023, and 10 patients underwent simple basement membrane resection with a simple basement membrane. Among them, the pelvic floor were reconstructed by basement membrane mesh alone in 10 cases (mesh only group), and 10 cases were reconstructed the pelvic floor by pedicled large omental flap combined with basement membrane mesh (omental flap-combined mesh group). The recent outcomes of the two groups of patients were studied comparatively. Comparison of baseline data and intraoperative conditions between the two groups showed no statistically significant differences (all P>0.05); the drain removal time in the omental flap-combined mesh group was 26.7 (19-42) days, which was shorter than that in the mesh only group, which was 40.4 (24-56) days ( U=4.125, P=0.001); The empty pelvis healing time in the omental flap-combined mesh group was 29.4 (23~43) days, which was shorter than that of 42.2 (27~58) days in the mesh-only group ( U=4.043, P=0.001); the differences were all statistically significant. The postoperative complication rate of grade ≥III in the omental flap-combined mesh group was 1/10, which was lower than that of 6/10 in the mesh-only group; the difference was not statistically significant when comparing the two groups ( P = 0.057). Follow-up ended on 09/30/2023, with a median follow-up of 9.5 (3-15) months in 20 patients, and all 20 cases survived during the follow-up period, with no tumor recurrence at the surgical site. Conclusion:In locally advanced or locally recurrent rectal cancer undergoing combined pelvic organ resection with sacrococcygeal, compared with reconstruction of the pelvic floor by basement membrane mesh alone, reconstruction of the pelvic floor and isolation of the abdominopelvic cavity by a pedicled greater omentum flap combined with a basement membrane mesh is safe and feasible.

Objective:A mouse silicosis model was constructed by injecting silicon dioxide (SiO 2) particles into the trachea to explore the effect and mechanism of Cordyceps cicadae polysaccharides (CCP) on ameliorating pulmonary fibrosis in silicosis mice. Methods:In May 2023, CCP were extracted and isolated, the monosaccharide composition and functional group composition were analyzed by high performance liquid chromatography and Fourier transform infrared spectroscopy. C57BL/6J mice were injected with 50 μl 50 mg/ml SiO 2 suspension to construct silicosis mouse model, which were then randomly divided into model group, CCP intervention groups [low dose group (LCCP group), medium dose group (MCCP group) and high dose group (HCCP group) ], the control group was administered by physiological saline, 8 mice in each group. Mice in the CCP intervention groups received oral gavage administration once daily with CCP solution (100, 200 and 400 mg/kg), while control group and model group received physiological saline, lasted for 30 days. The body weight of mice was recorded and the lung coefficient was calculated. The pathomorphological changes of mouse lung tissue were determined by HE and Masson staining. The contents of fibrosis indexes [hydroxyproline acid (HYP), connective tissue growth factor (CTGF) and matrix metallopeptidase 2 (MMP-2) ] of lung tissue and the pro-inflammatory factors[tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) ] of lung tissue and alveolar lavage fluid were determined by ELISA. The expression level of Collagen Ⅰ was determined by immunohistochemistry. The relative protein expression levels of transforming growth factor-β1 (TGF-β1), P-Smad2, α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κBp65) and myeloid differentiation primary response gene 88 (MyD88) in lung tissue were determined by Western blot. Results:The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was decreased, lung coefficient was increased, the contents of HYP, CTGF and MMP-2 in lung tissue were increased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were increased ( P<0.05). The mice lung showed massive inflammatory cell infiltration and collagen fiber deposition, and the silicosis fibrosis was severe. The expression of CollagenⅠin lung tissue of model group was increased, and the proteins expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were increased in mouse lung tissue ( P<0.05). Compared with the model group, the body weights of mice in the MCCP and HCCP groups were increased, the lung coefficients were decreased, the contents of HYP, CTGF and MMP-2 in lung tissue were decreased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were decreased ( P<0.05). The inflammatory cell infiltration in the lung was reduced, and the degree of fibrosis was improved to varying degrees. The expression level of CollagenⅠwas down-regulated in the lung tissue of MCCP and HCCP groups, and the protein expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were decreased in lung tissue ( P<0.05) . Conclusion:The CCP could reduce the levels of fibrosis-related indicators and pro-inflammatory factors in lung tissue, ameliorating mouse lung inflammation and silicosis fibrosis caused by SiO 2 particles by inhibiting the activation of TGF-β1/Smad pathway and TLR4/nuclear factor kappa-B (NF-κB) pathway.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Aim To investigate the effect of artificial intelligence(AI)assisting doctors with different seniority in predicting the enlargement of hematoma in the early stage of cerebral hemorrhage.Methods A total of 108 patients diagnosed with cerebral hemorrhage in Central Hospital Affiliated to Dalian University of Technology were retrospectively collected.CT images at admission and 24 hours after admission were collected.DICOM images obtained from plain CT scan were input into AI-CAD model developed by Biomind in collaboration with Temple of Heaven.A total of 9 doctors of different senior-level were selected in neurosurgery department of our hospital.Firstly,independent prediction was applied in the patients and then the study predicted whether patients would delelop hematoma enlargement within 24 hours combined with the results of auxiliary AI.The accuracy of independent prediction of doctors with different seniority and assisted AI prediction of aneurysm stability was calculated respectively.McNemar of paired samples was used to test the significance of difference between independent prediction coincidence rate and assisted AI prediction accuracy among differ-ent doctors.Results The accuracy of high,middle and low seniority doctors independently predicting the early expan-sion of cerebral hemorrhage was 58.95％,50.62％and 38.89％,respectively,and the accuracy of prediction was signifi-cantly improved after assisted AI(P＜0.001),the highest increase rate was low seniority doctors(25.92％),followed by middle seniority doctors(19.75％)and high seniority doctors(11.73％).The ability of senior physicians to independ-ently predict the expansion of intracerebral hemorrhage was strongest in patients and non-patients,with sensitivity of 18.75％(95％CI:9.44％～33.10％)and specificity of 65.94％(95％CI:59.98％～71.45％).The sensitivity of middle seniority doctors was 16.67％(95％CI:7.97％～30.76％),the specificity was 56.52％(95％CI:50.44％～62.42％),and the sensitivity of low seniority doctors was 8.33％(95％CI:2.70％～20.87％),the specificity was 44.20％(95％CI:38.29％～50.28％).However,after AI assisted the prediction of senior doctors,the sensitivity and specificity of each seniority group of doctors increased.The sensitivity of high seniority doctors was 60.42％(95％CI:45.29％～73.88％),the specificity was 72.46％(95％CI:66.72％～77.57％),the sensitivity of middle seniority doc-tors was 64.58％(95％CI:49.40％～77.45％),the specificity was 71.38％(95％CI:65.59％～76.56％),and the sensitivity of low seniority doctors was 68.75％(95％CI:53.60％～80.91％),the specificity was 64.13％(95％CI:58.13％～69.73％).Conclusion AI-CAD assisted doctors with high,middle and low seniority can improve the ac-curacy of predicting the enlargement of hematoma in early stage of cerebral hemorrhage,especially the ability of doctors with low seniority to find patients can be significantly improved,which can make up for the lack of work experience of doc-tors with low seniority to a certain extent.

【Objective】 To improve the understanding and diagnosis and treatment level of ALK negative anaplastic large cell lymphoma (ALK-ALCL) by sharing the diagnosis and treatment process of a patient with ALK-ALCL treated in Hangzhou Bay Hospital of Ningbo. 【Methods】 The clinical data and diagnosis and treatment process of the patient were retrospectively analyzed, and relevant literature was reviewed. 【Results】 The patient was a young male, with recurrent gross hematuria and right low back pain as the initial symptoms.Imaging examination indicated bladder tumor.After resection, the tumor was reduced and confirmed to be ALK-ALCL.After chemotherapy and autologous hematopoietic stem cell transplantation, the patient’s condition continued to improve.During the follow-up, no recurrence was observed. 【Conclusion】 Primary ALK-ALCL in the bladder is very rare and prone to misdiagnosis and missed diagnosis in clinical practice.The successful diagnosis and treatment experience of this patient can provide clinical reference.