Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the therapeutic effect of Bupiqiangli compound on experimental myasthenia gravis with sub-clinical hypothyroidism in rats and the influence of hypothalamus-pituitary-thyroid-thymus(HPTT)axis.Methods:SPF Lewis rats were randomly divided into normal group,model group,Bupiqiangli compound low-dose,medium-dose and high-dose groups.Model rats were immunized with AchR-α subunit 97-116 peptide sequence to construct an experimental myasthenia gravis model,and then methimazole was used to prepare an experimental myasthenia gravis with subclinical hypothyroidism model.Bupiqiangli compound low-dose,medium-dose and high-dose groups were given 4.57 g/kg,7.12 g/kg and 9.49 g/kg of Bupiqiangli compound by gavage,nor-mal group and model group were given an equal volume of normal saline by gavage,once a day,for 4 weeks.After the last gavage,Lennon scores of rats in each group were recorded;HE staining was used to detect pathological changes of thymus and thyroid;ELISA was used to detect expression levels of acetylcholine receptor antibody(AchRab),thyroid stimulating hormone(TSH),thyrotropin releasing hormone(TRH),free thyroxine(FT4)and thyroxine(T4)in serum;mRNA level of TRH in hypothalamus and TSH in pituitary tissue were detected by qPCR;Western blot detected changes of protein expressions of Cleaved Caspase3,Bcl2 associated X protein(Bax)and B-cell lymphoma-2(Bcl2)in thymus.Results:Compared with normal group,model group showed obvious symp-toms of muscle weakness,Lennon score increased significantly(P<0.05),obvious pathological changes in thymus and thyroid tissues,while no significant changes in expressions of FT4 and T4 in serum(P>0.05),expressions of AchRab,TSH and TRH in serum were significantly increased(P<0.05),expressions of TRH in hypothalamus and TSH in pituitary were significantly increased(P<0.05),protein expressions of Cleaved Caspase3 and Bax in thymus were significantly decreased(P<0.05),while expression of Bcl2 protein in thymus increased significantly(P<0.05).Compared with model group,myasthenia symptoms of compound high-dose group were im-proved,Lennon score was significantly decreased(P<0.05),pathological changes of thymus and thyroid tissues were improved,ex-pressions of FT4 and T4 in serum had no significant changes(P>0.05),expressions of AchRab,TSH and TRH in serum were signifi-cantly decreased(P<0.05),expressions of TRH in hypothalamus and TSH in pituitary were significantly decreased(P<0.05),expres-sions of Cleaved Caspase3 and Bax in thymus were significantly increased(P<0.05),while expression of Bcl2 in thymus was signifi-cantly decreased(P<0.05).Conclusion:Bupiqiang compound can improve clinical symptoms of experimental myasthenia gravis with subclinical hypothyroidism in rats,and its mechanism may be related to the regulation of HPTT axis.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective This study aimed to examine the risk factors and prognostic factors of brucellar spondylitis for early prevention and treatment of the disease,and improving the outcomes of patients.Methods A retrospective case-control study was conducted on the patients with brucellosis who were hospitalized in the Third Hospital of Hebei Medical University from June 2020 to June 2022.Patients were assigned to brucellosis without spondylitis group or brucellar spondylitis group according to the presence of spondylitis.The patients in brucellar spondylitis group were followed for 1 year.Then they were stratified into a subgroup of good or poor prognosis according to clinical outcomes.The dataset for the demographic and clinical variables of patients were analyzed using SPSS 26.0 software.Results A total of 300 patients with brucellosis were enrolled,including 113 cases of brucellosis without spondylitis and 187 cases of brucellar spondylitis.Multivariate analysis showed that age,time from onset to diagnosis,low back pain,and erythrocyte sedimentation rate were independent risk factors for brucellar spondylitis(P＜0.05).Of the 154 cases of brucellar spondylitis with known outcomes,121 cases showed good prognosis and 33 cases had poor prognosis.COX regression analysis showed that the time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment were independent risk factors for poor prognosis in patients with brucellar spondylitis(P＜0.05).Conclusions Old age,prolonged time from onset to diagnosis,low back pain,and increased erythrocyte sedimentation rate are independent risk factors for spondylitis in patients with brucellosis.Prolonged time from onset to diagnosis,diabetes mellitus,paravertebral abscess,and neurological impairment are independent risk factors for poor prognosis of brucellar spondylitis.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.

Objective:To construct a competency-oriented assessment index system based on entrustable professional activities (EPAs) for 5-year undergraduate clinical medical students in oncology internship.Methods:From June to December 2023, the scoping review approach and Bicomb 2.0 were used to construct and manage an item pool. The draft of EPAs and competencies was designed based on truncated word frequency. SPSS 25.0 was used for cluster analysis and UCINET 6.0 was used for visualization. Combining the characteristics and consensus of oncology, a multi-center expert group used the KJ method to draft the framework of EPAs and competencies. Subsequently, the expert group defined milestones and mapped the milestones to the framework to establish the assessment system.Results:Based on 26 included studies, a draft was created containing 19 EPA indicators and 72 competency characteristic indicators. After cluster analysis, 13 experts from 6 medical institutions established a framework including 13 EPAs and 10 competencies as well as 50 milestones, leading to the construction of the "EPAs-competencies-milestones" assessment system.Conclusions:The "EPAs-competencies-milestones" assessment system aligns with the trend of reform, demonstrating universality, specificity, and scientificity. It provides a reference for the development and assessment of oncology internship courses in medical universities.

This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

Objective This study aimed to investigate the relationship between multiple inflammatory markers and poor outcome in patients with intracerebral hemorrhage,and to compare their predictive abilities.Methods We retrospectively analyzed the patients with intracerebral hemorrhage admitted to the Department of Neurology of the First Affiliated Hospital of Nanchang University from January 1,2015 to March 31,2023.According to the Modified Rankin Scale at 90 days after onset,the patients were divided into good outcome(mRS≤2 points)and poor outcome(mRS score≥3 points).Clinical information,laboratory examinations and follow-up data were compared between the two groups.Inflammatory markers include neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),monocyte to high-density lipoprotein ratio(MHR),systemic inflammatory response index(SIRI),systemic immune-inflammation index(SII),white blood cell count to mean platelet volume ratio(WMR),lymphocyte to monocyte ratio(LMR),and systemic coagulation-inflammation index(SCI).Univariate and multivariate logistic regression analysis were used to analyze the predictors of poor prognosis after intracerebral hemorrhage,and receiver operating characteristic curve(ROC)was constructed to compare their predictive ability.Results A total of 510 patients with intracerebral hemorrhage were included.Of those,297(58.2%)had good outcome,and 213(41.8%)had poor outcome.Comparison of baseline characteristics demonstrated that patients with poor prognosis had higher levels of white blood cells,neutrophils,high-density lipoprotein,fibrinogen,NLR,PLR,SIRI,SII,WMR at admission,larger baseline hematoma volume and baseline perihematomal edema volume,a higher proportion of lobar hemorrhage,older age,and lower levels of platelets,lymphocytes,LMR,and SCI(P<0.05).Multivariate regression analysis showed that NLR(OR:1.081,95%CI:1.032～1.1131,P=0.001),SIRI(OR:1.089,95%CI:1.014～1.169,P=0.019),SII(OR:1.000,95%CI:1.000～1.001,P=0.011),WMR(OR:2.627,95%CI:1.267～5.445,P=0.009)were independently associated with poor prognosis in patients with ICH.In ROC analysis,the area under the curve of NLR(0.729,95%CI:0.685～0.774)was higher than SIRI(0.692,95%CI:0.645～0.738),SII(0.688,95%CI:0.641～0.735)and WMR(0.65,95%CI:0.602～0.698)for predicting poor outcomes.Conclusion NLR,SIRI,SII and WMR at admission are independently associated with poor outcomes in patients with intracerebral hemorrhage,and NLR has the strongest predictive ability.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.