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: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.

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: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:To summarize the clinical characteristics of patients with renal angiomyolipoma(RAML)combined with inferior vena cava(IVC)tumor thrombus,and to explore the feasibility of par-tial nephrectomy and thrombectomy in this series of patients.Methods:The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed,and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Elec-tronic Medical Record System,including age,gender,surgical methods,and follow-up time,etc.The clinical characteristics between classic angiomyolipoma(CAML)patients with IVC tumor thrombus and epithelioid angiomyolipoma(EAML)patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients.Results:A total of 11 patients were included in this study,in-cluding 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus.There were 9 females(9/11,81.8％)and 2 males(2/11,18.2％),with an average age of(44.0±17.1)years.9 patients(9/11,81.8％)experienced clinical symptoms,including local symp-toms including abdominal pain,hematuria,abdominal masses,and systemic symptoms including weight loss and fever;2 patients(2/11,18.2％)with RAML and IVC tumor thrombus did not show clinical symptoms,which were discovered by physical examination.Among the 11 patients,10 underwent radical nephrectomy with thrombectomy,of whom,3 underwent open surgery(3/10,30.0％),2 underwent laparoscopic surgery(2/10,20.0％),and 5 underwent robot-assisted laparoscopic surgery(5/10,50.0％).In addition,1 patient underwent open partial nephrectomy and thrombectomy.The patients with EAML combined with I VC tumor thrombus had a higher proportion of systemic clinical symptoms(100％vs.0％,P=0.003),more intraoperative bleeding[400(240,3 050)mL vs.50(50,300)mL,P=0.036],and a higher proportion of tumor necrosis(75％vs.0％,P=0.024)compared to the patients with CAML combined with I VC tumor thrombus.However,there was no statistically significant difference in operation time[(415.8±201.2)min vs.(226.0±87.3)min,P=0.053]between the two groups.Conclusion:Compared with the patients with CAML and IVC tumor thrombus,the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis.In addi-tion,in the selected patients with CAML with IVC tumor thrombus,partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.

OBJECTIVE To assess the clinical profile,prognosis,and risk factors of extrapulmonary metastasis in adenoid cystic carcinoma patients.METHODS A retrospective analysis was conducted on 126 patients diagnosed with adenoid cystic carcinoma at Beijing Tongren Hospital between January 2002 and December 2020.Of these patients,21 cases had metastases outside the lungs as their initial site of metastasis,while 105 cases had lungs as the initial site of distant metastasis.In addition,clinical data of patients diagnosed with adenoid cystic carcinoma from the Surveillance,Epidemiology,and End Results(SEER)database in the United States from 2010 to 2019 were analyzed for prognosis.RESULTS Univariate analysis showed that factors such as N stage,neurological symptoms,pathological subtype,grading,Ki67,neural invasion,and p63 status were associated with extrapulmonary metastasis(χ2=5.385,9.888,20.485,15.579,8.711,5.476,5.280;all P values<0.05).Multivariate logistic regression analysis indicated that N stage,pathological grading,and neurological symptoms were correlated with an increased risk of extrapulmonary metastasis.Survival analysis indicated lower cumulative survival and progression-free survival rates in the initial extrapulmonary metastasis group(both P values<0.05).CONCLUSION The initial metastasis site in adenoid cystic carcinoma is associated with multiple factors including N stage,pathological grading,and neurological symptoms.Patients displaying a solid subtype and those accompanied by high-grade transformation are more prone to extrapulmonary metastasis.Patients with extrapulmonary metastasis as their initial diagnosis typically exhibit poorer prognosis.

OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.

BACKGROUND:Calcaneal defects are common in clinical practice.It is difficult for surgeons to evaluate the effect of calcaneal reconstruction due to the complex anatomical structure and motor function of the heel.Finite element analysis has become an effective method for biomechanical behavior simulation and numerical analysis. OBJECTIVE:To compare the clinical effect and biomechanical characteristics of total calcaneal reconstruction with the Ⅱ-shaped and V-shaped fibular flap. METHODS:CT images of one left foot of a healthy 50-year-old male were acquired.Mimics software was used to obtain the preliminary three-dimensional model.Geomagic software was used to trim and curve the model.The model was imported into Solidworks software to simulate calcaneal reconstruction and complete the pre-processing of finite element calculation.Finally,Ansys software was used to solve the problem.The simulation results were compared with previous literature results to verify the effectiveness of the model.The surgical effect and biomechanical characteristics of the foot in different gait phases based on the simulated stress results were analyzed. RESULTS AND CONCLUSION:(1)Both Ⅱ-shaped and V-shaped fibular flaps could be used to reconstruct completely missing calcaneus,which could restore the length,width and height of normal calcaneus,and fill up the missing calcaneus bone.(2)Compared with the normal calcaneus,both configurations of fibular flaps showed a tendency for over-concentration of stress after loading.The normal calcaneus stress was mostly concentrated around the calcaneus nodule,the subtalar process and the calcaneus groove,while the stress of the two fibular flaps was mostly concentrated at the junction between the bone flap with the talus and cuboid bones.(3)The maximum stress of calcaneus was different between the two models and normal calcaneus under different simulation conditions,with statistically significant differences(P＜0.05).Compared with the V-shaped fibular flaps,Ⅱ-shaped fibular flaps had less force change in different gaits and were closer to the normal calcaneus.The V-shaped fibular flap bore excessive stress during the period of push-off,and the grafted bone material may yield under this condition and have the risk of fractures.