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Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.
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Examining mechanisms involved in the mutual regulation between the muscular system and the skeletal system, elucidating the key issues responsible for loss of muscle and bone mass and strength, and thus halting the progression of these conditions are critical measures for reducing fractures caused by falls and subsequent disability and mortality.At present, most studies have treated the muscular system and the skeletal system separately, often ignoring the mutual regulation and connections between them.This article reviews the current research progress on the mechanisms of interaction between the two systems, aiming to provide a basis for the prevention, diagnosis and treatment of disuse-related diseases in the elderly population.
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Retinoblastoma is a kind of malignant eye tumor commonly seen in children, which is one of the main causes threatening children's vision and life. The diagnosis and evaluation of retinoblastoma has always been a hot topic in clinic. In the past few years, the application of artificial intelligence(AI)technology has made significant progress in the medical field, providing new opportunities and challenges for the diagnosis and treatment of retinoblastoma, for example, the use of AI algorithms to analyze massive clinical data, which can help doctors diagnose the disease more accurately and provide personalized treatment plans. In addition, AI technology also plays an important role in medical image analysis, genomics research and other aspects, which can help the development of new drugs and improve patient prognosis. This article reviews the application progress of AI in retinoblastoma.
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Objective To analyze the influence from material and size of the filling block on stress distributions of the tibial osteotomy model. Methods The filling blocks with three different materials (iliac bone, cancellous bone and polyetheretherketone (PEEK)) and five different sizes were established and implanted to the tibial osteotomy models, respectively. The mechanical loads were applied on the model, the stress distribution and edge displacement of the model were analyzed. Results For three kinds of materials, the stress at proximal end of the tibia and the plate, as well as edge displacement in the model implanted with filling block by iliac bone material were lower than those of the cancellous bone and PEEK, but the filling block by iliac bone material had the highest stress. When the filling blocks with different sizes were implanted in osteotomy space, the stress distribution on each part of the tibial osteotomy and edge displacement were different. Especially when the width of the filling block was reduced from 30 mm to 10 mm, the peak stress of the proximal tibia, steel plate and filling block was increased by 49. 3% , 92. 7% and 54. 4% on average. Conclusions Different filling block parameters will affect the stress distribution in different parts of the tibial osteotomy. The research results provide the theoretical basis for parameter selection of the tibial osteotomy filling block in clinic.
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Objective To compare the differences in kinematic parameters and plantar pressures for two types of knee varus with tibial and femoral origins in gait analysis, so as to provide biomechanical theoretical basis for different types of genu varus. Methods Twenty-six patients with unilateral knee osteoarthritis (KOA) varus genu were enrolled, with 13 from femoral and 13 from tibial sources. Using Noraxon MyoMotion three-dimensional (3D) motion capture system and Footscan plantar pressure test system, the gait of the subjects during natural walking was measured, the temporal and spatial parameters of the gait, the kinematics parameters of lower limb joints and plantar pressures were collected, to make comparative analysis between the two groups. Results The range of knee flexion and extension of tibial varus, the peak of hip abduction, the range of motion (ROM) of hip adduction and abduction and the peak of ankle pronation were larger than those of femoral lateral genu varus. The peak of knee flexion and hip adduction was smaller than that of femoral lateral genu varus. Compared with femoral varus, subjects with tibial varus had increased stress time and peak pressure on the plantar of the 4th and 5th metatarsals (P<0.05). In the 3rd metatarsal region, the impulse of healthy femoral limb was greater than that of healthy limb with tibial deformity. While in the medial calcaneal region, the impulse of healthy femoral limb was smaller (P<0.05). Conclusions There are some differences in kinematic parameters and plantar pressures between two different types of unilateral genu varus patients. The results of this study are helpful to understand the abnormal gait caused by genu varus, and provide reliable reference for postoperative rehabilitation and limb exercise for different types of genu varus.
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The sources of common knee valgus deformities were classified in order to better plan the orthopedic methods, matching prostheses and soft tissue repair of knee valgus deformities.Based on the analysis of typical clinical cases and the operability of classification standards in practical clinical practice, it is of great significance to establish a reasonable morphological classification of knee valgus deformity, in order to grasp the characteristics and patterns of the onset of valgus deformity. According to the origin of the deformity and the tension of the medial and lateral collateral ligaments, the classification of the genu valgus deformity can be divided into the classification of the traditional Genu valgum deformity origin and the classification of the new Genu valgum deformity origin. Although both of them highlight the skeletal characteristics and soft tissue conditions of the valgus deformity, they are quite different. Traditional classification is based on femoral tibial angle, valgus angle, etc; The new classification is divided into mechanical angle, anatomical angle, distal condylar angle, etc. The origin of Genu valgum deformity is generally complex. The traditional classification cannot fully reflect the origin of valgus deformity and the tension state of soft tissue. The new classification, especially based on the classification of anatomical angle valgus deformity, can not only reflect the morphological and anatomical details of knee valgus deformity, but also reflect the tension state of the medial and lateral collateral ligaments and local soft tissue stress state that determine the stability of the knee joint. At present, the commonly used surgical methods for valgus deformity of the knee include periarticular osteotomy of the knee and total knee Joint replacement. The former focuses on correcting extraarticular deformity without over repairing ligaments, and the latter focuses on force line correction, which is the final treatment for terminal valgus deformity. The application of digital technology in clinical orthopedics can improve the accuracy of implant placement. Implant placement needs to be based on the patient's bone characteristics and degree of deformity. For patients with severe deformity, the application of digital technology can improve the accuracy of implant placement and assist in the treatment of knee valgus deformity.
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Objective:To analysis the prevalence and characteristics of comorbid insomnia and sleep disordered breathing (SDB) in community population.Methods:This is a cross-sectional study. Cluster sampling was applied. Community residents in Shantou and Meizhou were investigated during April to May, 2021. Essential information collection, sleep related health investigation, and sleep study were conducted. Insomnia was defined as the insomnia severity index (ISI)≥8. A type Ⅳ wearable intelligent sleep monitor was applied for sleep study. Comorbid insomnia and SDB was defined as both diagnosis of insomnia and SDB. Statistical analysis was conducted by SPSS 25. Prevalence and characteristics of insomnia only, SDB only and comorbid insomnia and SDB were analyzed. Logistic regression was conducted to analyze the relationship between sleep disorders and unrestored sleep, abnormal glucose metabolism, hyperlipidemia, and cardiovascular disease.Results:There were 3 730 residents completed the investigation. The median age was 55.0 (46.0, 63.0) years. The prevalence of insomnia only, SDB only, and comorbid insomnia and SDB were 26.0%, 20.2%, and 10.4% respectively. The incidence of unrestored sleep in insomnia only and comorbid insomnia and SDB were 2.900 times and 3.777 times of that in no insomnia or SDB (both P<0.001); the risk of hyperlipidemia was elevated in insomnia only, SDB only and comorbid insomnia and SDB ( OR=1.553, 1.415, and 1.868; all P<0.05); the risk of cardiovascular disease increased 40.8% in SDB only ( P=0.001), and 42.1% in comorbid insomnia and SDB ( P=0.007), after adjusted by age, sex, body mass index (BMI), smoking, drinking, abnormal glucose metabolism, and hyperlipidemia. Stratified analysis revealed that young female (age<60 years) with normal BMI (<25 kg/m 2) and comorbid insomnia and SDB were associated with higher risk of cardiovascular disease. Female with normal body weight and insomnia only or comorbid insomnia and SDB were associated with higher risk of hyperlipidemia. Conclusions:The prevalence of comorbid insomnia and SDB is high in community population. Patients with comorbid insomnia and SDB present with more significant unrestored sleep, and are correlated with higher risk of hyperlipidemia and cardiovascular diseases.
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Posttransplant diabetes mellitus(PTDM)is a prevalent metabolic disorder after solid organ transplantation. As a major risk factor for cardiovascular disease and even death, PTDM shares the same characteristics with T2DM(obesity & insulin resistance, etc.). Immunosuppressants is also a predisposing factor for transplantation.Screening, prevention and management of PTDM should be performed pre-transplantation, peri-operation and during stable period post-transplantation. In recent years, several novel blood glucose monitoring techniques and anti-diabetic agents have been developed for a more precise treatment of PTDM. In the near future, a multi-disciplinary team should be formulated for optimizing the management of PTDM and improving the outcomes of solid organ transplantation recipients.
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The clinical data of 5 patients with occupational contact dermatitis caused by methyl chlorobutyrate treated in the Affiliated Hospital of Jining Medical College and Mamiao Township Hospital of Jinxiang County from September to October 2021 were retrospectively analyzed. Patients were all males aged 33-47 years with a history of exposure to methyl chlorobutyrate 1 to 4 d before the onset of symptoms. Three patients were hospitalized and 2 patients were treated in outpatient clinic. The clinical manifestations were erythema on the trunk or extremities of varying degrees, scattered with blisters and bullae of different sizes, with thin and clear blisters, local ulceration and exudation; no erosion or ulceration was found in the oral cavity and vulva. All 5 patients had elevated white blood cell counts, and 2 patients had abnormal liver function. All patients received symptomatic treatment with topical drugs. Three hospitalized patients were given methylprednisolone and loratadine; in addition, 1 case also received human immunoglobulin and moxifloxacin hydrochloride injection and 2 cases received hepatoprotective drugs. Two outpatients were given prednisone acetate and loratadine for treatment. Three hospitalized patients were all improved and discharged after 14-30 d of treatment. The rash of 2 outpatients subsided after 14 d of treatment, and there was no recurrence after 1-month follow-up. The occupational contact dermatitis caused by methyl chlorobutyrate is primary irritant contact dermatitis, often manifested as erythema and blisters on the trunk or limbs, and timely anti-allergic treatment can effectively control the disease.
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Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.
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Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.
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Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
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This study aims to explore the improvement and the mechanism of the Alisma plantago-aquatica Linn. (ApL) on chronic glomerulonephritis (CGN). All animal experiments were followed the regulation of the Experimental Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine. CGN mouse model was established by a single tail-vein injection of doxorubicin (Dox) (20 mg·kg-1). One week after Dox administration, the mice received water extract of ApL (85 and 255 mg·kg-1) by gavage once a day for 14 days. At the end of experiment, the urine albumin-to-creatinine ratio (ACR), serum albumin (ALB), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected, kidney histopathological H&E staining was analyzed. Active ingredients and action targets of ApL were collected from TCMSP database, and CGN-related targets were obtained from Genecards database. STRING platform was employed to perform protein-protein interaction (PPI), and Metascape platform was used for KEGG pathway and GO enrichment analysis. The results of experiments demonstrated that ApL (85 and 255 mg·kg-1) could reduce the ACR and the content of SCr and BUN, and increase the content of ALB in mice. Network pharmacology results predicted that nuclear factor kappa-B (NF-κB)-related pathway and biological process of oxidoreductase activity regulation may be involved in the ApL-provided amelioration on CGN. The verification results showed that ApL could inhibit the activation of NF-κB and the expression of inflammatory factors in mice, and reduce the activity of renal myeloperoxidase (MPO). Meanwhile, ApL promoted the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream gene mRNA, and reduced the level of renal malondialdehyde (MDA) and reactive oxygen species (ROS), and further elevated renal glutathione (GSH) level. Based on network pharmacology combined experiments, this study found that ApL may improve CGN in mice through multiple targets and multiple pathways, in which the inhibition of NF-κB signaling and the activation of Nrf2 signaling may be important mechanisms involved.
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Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.
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Humans , Early Detection of Cancer , Risk Factors , Colorectal Neoplasms/genetics , Asia , China/epidemiologyالملخص
OBJECTIVE@#To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms.@*METHODS@#3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo.@*RESULTS@#The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01).@*CONCLUSION@#Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.
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Animals , Mice , NF-kappa B/metabolism , Lipopolysaccharides , Zebrafish , NF-KappaB Inhibitor alpha/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/metabolism , STAT3 Transcription Factor/metabolism , Inflammation/metabolism , Anti-Inflammatory Agents/therapeutic useالملخص
OBJECTIVES@#Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy.@*METHODS@#The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 μmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels.@*RESULTS@#Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05).@*CONCLUSIONS@#p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.
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Animals , Humans , Mice , Carboxymethylcellulose Sodium/pharmacology , Diabetes Mellitus, Type 2/metabolism , Endothelium, Vascular/metabolism , Glucose/metabolism , Human Umbilical Vein Endothelial Cells , Mice, Inbred C57BL , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Phosphorylation , Pyruvate Kinase/metabolism , Vasodilationالملخص
As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.
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In 2022,Chinese Society of Gastroenterology,Chinese Medical Association updated the consensus on chronic gastritis in China(2017,Shanghai)and formulated the guidelines for diagnosis and treatment of chronic gastritis in China(2022,Shanghai)(herein after referred to as the"2022 guidelines for gastritis").Totally 53 recommendations were put forward on 9 clinical problems related to chronic gastritis in the 2022 guidelines for gastritis.This article interprets the 2022 guidelines for gastritis on gastric cancer risk stratification and endoscopic surveillance strategies for atrophic gastritis.
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Background:With the increasing incidence of antibiotic resistance and adverse reactions to Helicobacter pylori(Hp),it is difficult for proton pump inhibitor-based quadruple therapy to meet the actual clinical treatment needs,so it is necessary to seek another effective combination therapy program on this basis.In recent years,the application of microecological preparations represented by Bifid triple viable capsule has been widely valued in clinical practice with its unique advantages.Aims:To evaluate the efficacy and safety of Bifid triple viable capsule combined with quadruple therapy in the treatment of Hp infection.Methods:The databases of CNKI,Wanfang,VIP,CBM,PubMed,Web of Science from January 2012 to April 2023 were searched by computer,to collect the relevant literature published at home and abroad on the treatment of Hp infection with Bifid triple viable capsule combined with quadruple therapy,and to screen the included literature for quality evaluation using the Cochrane risk bias tool,and to extract relevant data.Data were Meta-analyzed with RevMan 5.4.Results:Ten randomized controlled trials were included,including 1 828 patients with or without underlying disease who were Hp positive.Meta-analysis showed that the eradication rate of Hp in Bifid triple viable capsule combined with quadruple therapy was significantly higher than that in quadruple therapy group(RR=1.23,95%CI:1.19-1.29,P<0.000 01),while the incidence of adverse reactions was significantly decreased(RR=0.37,95%CI:0.28-0.48,P<0.000 01).Conclusions:Bifid triple viable capsule combined with quadruple therapy can significantly increase the eradication rate of Hp and reduce the adverse drug reactions,which has practical significance to guide clinical application.
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Post-transplant diabetes mellitus (PTDM) is a common endocrine and metabolic disorder after adult solid organ transplant (SOT), affecting 10% to 40% of recipients. PTDM has been associated with increased mortality, heightened risk of infections, graft-related complications and cardiovascular diseases, all of which seriously threaten the quality of life and long-term survival of recipients. According to recent studies and the domestic healthcare system, this consensus provides a comprehensive overview of the epidemiology, risk factors, pathogenesis, screening and diagnosis, treatments, prevention strategies, cardiovascular risk factor management and microvascular complications associated with PTDM, in order to further standardize the diagnosis and treatment of PTDM. The objective is to standardize the comprehensive management of PTDM with the aim of enhancing the long-term quality of life and clinical outcomes for SOT recipients.