AIM: To detect the distribution and expression of vascular endothelial growth factor(VEGF)in radiation retinopathy(RR)through fluorescence targeted imaging.METHODS:Covalent binding of fluorescein FITC with VEGF antibody ranibizumab to prepare targeted fluorescent imaging probe ranibizumab-FITC. SD rats were randomly divided into three groups based on the principle of weight balance: a normal control group(Con group), a low-dose radiation group(10 Gy group), and a high-dose radiation group(30 Gy group). Medical linear accelerators and lead blocks were used to locally irradiate the rat eyeballs for modeling. Western blot and qRT-PCR were used to detect the expression levels of VEGF-A in each group and to screen for appropriate modeling dose. The inverted fluorescence microscope and the confocal microscope were used to observe the distribution of VEGF and imaging probes in the retinas of control and RR model group rats, and to verify the effectiveness of targeted probes.RESULTS:The expression level of VEGF-A in the retina of rats in the high-dose radiation group(30 Gy group)was higher than that in the normal control group(Con group). In early RR, VEGF expression was observed to be associated with microaneurysms and abnormal microvessels in the retina. VEGF accumulation was observed at the site of capillary wall damage. When retinal capillary endothelial damage occurred, targeted probes gathered on the outer surface of the vessel wall.CONCLUSION:The expression level of VEGF in the retina of RR model rats is elevated, and fluorescent targeted molecular imaging probes can detect the spatial distribution of VEGF at the microvascular lesions in the retina of RR rats.

ObjectiveThis paper aims to analyze the damage degree of muscle tone in rats with spasticity of cerebral apoplexy （SCA） and the expression of Nestin and β-catenin in the M1 region of the cerebral cortex， thereby investigating the action mechanism of different doses of Shaoyao Gancaotang on rats with SCA. MethodsThe rats were randomly divided into a blank group， a model group， a positive control group （baclofen， 5.25 mg·kg^-1）， and low， medium， and high-dose groups of Shaoyao Gancaotang （2.1， 4.2， 8.4 g·kg^-1）， with nine rats in each group. A rat model with SCA was established by using a modified phrenic nerve block combined with intraventricular injection of anhydrous ethanol. Following behavioral scoring to confirm model validity， drug interventions were conducted. Neurological deficits and muscle tone were evaluated by behavioral assessments. The open field test was used to measure locomotor distance. Transmission electron microscopy was employed to examine the synaptic structures. Skeletal muscle adenosine triphosphate （ATP）ase staining was used to analyze myofibrillar changes. Hematoxylin and eosin （HE） staining was used to observe the histomorphological changes. Immunohistochemistry， Real-time polymerase chain reaction （Real-time PCR）， and Western blot were employed to detect mRNA levels and protein expressions of Nestin and β-catenin in the M1 region of the cerebral cortex. ResultsCompared with the blank group， rats in the model group exhibited significantly increased neurological deficit scores （P<0.01）， markedly elevated muscle tone scores （P<0.01）， substantially reduced locomotor distance （P<0.01）， prominent structural swelling and blurring， severe destruction of cerebral cortical cells， a significant increase in the proportion of skeletal muscle ATPase type Ⅰ fibers （P<0.01）， a significant decrease in mRNA levels and protein expression of Nestin （P<0.01）， and a significant increase in mRNA levels and protein expression of β-catenin （P<0.01）. Compared with the model group， the Shaoyao Gancaotang group exhibited reduced neurological deficit scores and muscle tone scores in rats with SCA （P<0.01） and increased locomotor distance （P<0.01）. Transmission electron microscopy revealed clearer and more intact synaptic structures in the rats from the Shaoyao Gancaotang group， with increased vesicle numbers and improved morphology. HE staining revealed intact neuronal cell structures with regular arrangement and reduced vacuolated cells in the rats from Shaoyao Gancaotang. ATPase staining result indicated a decreased proportion of type Ⅰ muscle fibers in the rats from the Shaoyao Gancaotang group （P<0.01）. Real-time PCR results demonstrated increased mRNA expressions of Nestin and β-catenin in the rats from the Shaoyao Gancaotang group （P<0.01）. Immunohistochemistry and western blot analyses indicated elevated protein expressions of Nestin and β-catenin in rats with SCA from the Shaoyao Gancaotang group （P<0.05， P<0.01）. ConclusionShaoyao Gancaotang may improve neurological function impairment and limb spasticity in model rats with SCA by regulating the proliferation and differentiation of neural stem cells in the cerebral cortex M1 region.

ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp^-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp^-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp^-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp^-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp^-/- mice through the MAPK signaling pathway.

BACKGROUND:Plate fixation is the mainstream method for the surgical treatment of distal femoral fractures.The intramedullary nailing has the advantages of minimally invasive,such as less soft tissue injury and bone blood supply destruction.At the same time,it is a central fixation and has better biomechanical effect.Therefore,retrograde intramedullary nailing has become another option for the internal fixation of distal femoral fractures.OBJECTIVE:The biomechanical characteristics of new retrograde intramedullary nail on lateral femur condyle,common femoral retrograde intramedullary nail,and lateral femur condyle anatomical locking plate for the treatment of A2-type distal femoral fractures were compared using finite element analysis,and the advantages of new retrograde intramedullary nail on lateral femur condyle was studied.METHODS:A new retrograde intramedullary nail on lateral femur condyle was designed,which was inserted into the bone cortex in front of the insertion point of the lateral collateral ligament of the lateral femoral condyle.A CT scan was performed on the lower limb bone of a male volunteer,and a three-dimensional model of the femur was established.The model was then segmented to create a three-dimensional model of a femoral distal A2-type fracture,The three-dimensional models of small(small group),standard type retrograde intramedullary nail on the lateral femoral condyle(standard group),common retrograde intramedullary needle(common group),and lateral femur condyle anatomical locking plate(plate group)were established respectively.The axial stresses of 600,1 800 N and the torsional load of 4 000,8 000 N·mm were applied to the models,and the displacement and stress of femur and the displacement,stress and shear force of internal fixators were observed in each group.RESULTS AND CONCLUSION:(1)When subjected to axial load of 600 and 1 800 N,the femoral peak displacement,the femoral peak stress,and the peak stress of interal fixation in the standard group were the lowest among the four groups.(2)When subjected to torsional load of 4 000 and 8 000 N·mm,the femoral peak displacement and peak displacement of the internal fixation in the standard group were the lowest among the four groups.(3)Compared with femoral lateral condylar locking plate and common retrograde intramedullary needle,the new retrograde intramedullary needle on lateral femur condyle has mechanical advantages of reducing stress concentration and decreasing the risk of internal fixation failure.

BACKGROUND:Plate fixation is the mainstream method for the surgical treatment of distal femoral fractures.The intramedullary nailing has the advantages of minimally invasive,such as less soft tissue injury and bone blood supply destruction.At the same time,it is a central fixation and has better biomechanical effect.Therefore,retrograde intramedullary nailing has become another option for the internal fixation of distal femoral fractures.OBJECTIVE:The biomechanical characteristics of new retrograde intramedullary nail on lateral femur condyle,common femoral retrograde intramedullary nail,and lateral femur condyle anatomical locking plate for the treatment of A2-type distal femoral fractures were compared using finite element analysis,and the advantages of new retrograde intramedullary nail on lateral femur condyle was studied.METHODS:A new retrograde intramedullary nail on lateral femur condyle was designed,which was inserted into the bone cortex in front of the insertion point of the lateral collateral ligament of the lateral femoral condyle.A CT scan was performed on the lower limb bone of a male volunteer,and a three-dimensional model of the femur was established.The model was then segmented to create a three-dimensional model of a femoral distal A2-type fracture,The three-dimensional models of small(small group),standard type retrograde intramedullary nail on the lateral femoral condyle(standard group),common retrograde intramedullary needle(common group),and lateral femur condyle anatomical locking plate(plate group)were established respectively.The axial stresses of 600,1 800 N and the torsional load of 4 000,8 000 N·mm were applied to the models,and the displacement and stress of femur and the displacement,stress and shear force of internal fixators were observed in each group.RESULTS AND CONCLUSION:(1)When subjected to axial load of 600 and 1 800 N,the femoral peak displacement,the femoral peak stress,and the peak stress of interal fixation in the standard group were the lowest among the four groups.(2)When subjected to torsional load of 4 000 and 8 000 N·mm,the femoral peak displacement and peak displacement of the internal fixation in the standard group were the lowest among the four groups.(3)Compared with femoral lateral condylar locking plate and common retrograde intramedullary needle,the new retrograde intramedullary needle on lateral femur condyle has mechanical advantages of reducing stress concentration and decreasing the risk of internal fixation failure.

OBJECTIVE: To systematically evaluate the effect and safety of the combination of Compound Xuanju Capsules (CXC) and Western medicine (WM) in the treatment of type Ш prostatitis complicated by ED. METHODS: We searched for randomized controlled trials (RCT) on the treatment of type Ш prostatitis complicated by ED with CXC+WM or WM in the Chinese and English databases CNKI, VIP, Wanfang Digital, Duxiu Academic Search and Chaoxing Electronic Book Information Retrieval, Fangzheng Apabi Electronic Book, Google Scholar Search, Web of Science, Scopus, PubMed, and others from their establishment to April 2024. According to the Cochrane Handbook requirement, we subjected the identified RCTs to meta-analysis using the RevMan 5.3 software. RESULTS: A total of 16 eligible studies were identified, involving 742 cases treated by combination therapy of CXC+WM and another 742 with WM alone. The results of meta-analysis showed that the rate of clinical effectiveness was dramatically higher in the CXC+WM than in the WM group (P<0.01, MD = 6.19, 95% CI: 4.63－8.28), and so were the IIEF-5 scores (P < 0.004, MD = 2.90, 95% CI: 0.90－4.89), while the quality of life (QOL) scores were significantly lower in the former group than in the latter (P<0.01, MD = －1.94, 95% CI: －2.47－－1.40), and so were the NIH-CPSI scores (P<0.01, MD = －3.92, 95% CI: －4.94－－2.91). No statistically significant difference was reported in the adverse reactions between the two groups (P = 0.12, MD = 0.03, 95% CI: －0.01－0.08). Publication bias analysis on the effectiveness rate of the results revealed an incomplete symmetry between the two sides of the funnel plot, indicating the possibility of publication biases. CONCLUSION The combination therapy of CXC+WM is superior to WM alone in the treatment of type Ш prostatitis complicated by ED for its high safety and effect of improving the patients' erectile function, but inferior to the latter in improving the QOL and NIH-CPSI scores of the patients.
Male ; Humans ; Prostatitis/complications* ; Erectile Dysfunction/complications* ; Drugs, Chinese Herbal/therapeutic use* ; Capsules ; Randomized Controlled Trials as Topic ; Drug Therapy, Combination ; Treatment Outcome ; Quality of Life ; Phytotherapy

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE: To investigate the clinical effects of thread-dragging therapy on gangrene of non-ischemic diabetic foot ulcers (NIDFU). METHODS: A total of 136 patients with NIDFU were recruited from the Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between June 21, 2021 and February 1, 2023, and randomized into an intervention group and a control group, with 68 cases in each group. Both groups received basic treatment. The intervention group was treated with thread-dragging therapy, while the control group was treated with debridement combined with routine dressing changes after surgery. Both groups were treated continuously for 2 months. The amputation rates and changes in the ulcer area were compared between the groups. The inflammatory response index including peripheral white blood cells (WBCs), neutrophil percentage (NEUT%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin 6 (IL-6) were compared between the two groups. RESULTS: After treatment, the ulcer areas in the intervention group were significantly smaller than that of the control group (8.50±3.88 cm² vs. 10.11±4.61 cm², P<0.05). The amputation rates of the two groups were not statistically significant (4.4% vs. 5.9%, P>0.05). Differences of WBCs count, CRP, and ESR before and after therapy in the intervention group were better than the control group (P<0.05). However, there were no significant differences in changes of NEUT%, PCT, and IL-6 between the two groups (P>0.05). CONCLUSION Thread-dragging therapy may be effective in the treatment of NIDFU, with the additional advantages of less tissue damage after healing. (Registration No. ChiCTR2100047496).
Humans ; Diabetic Foot/blood* ; Male ; Female ; Middle Aged ; Gangrene/therapy* ; Medicine, Chinese Traditional/methods* ; Aged ; C-Reactive Protein/metabolism* ; Amputation, Surgical ; Wound Healing ; Treatment Outcome ; Interleukin-6/blood*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

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.