Objective To construct a nomogram prediction model based on anti-cyclic citrullinated peptide antibody(anti-CCP an-tibody)and rheumatoid factor(RF)to predict the probability of cardiovascular disease(CVD)in patients with rheumatoid arthritis(RA).Methods A total of 437 RA patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to February 2024 were selected as the study objects,the clinical data of the patients were collected,and they were divided into RA+CVD group(n=88)and RA group(n=349)according to the follow-up results.The risk factors of CVD in RA patients were screened by univariate and multivariate Logistic regression analysis,and the prediction model of CVD in RA patients was constructed and internally validated.Results Multivariate Logistic regression analysis showed that age,course of disease,uric acid,C-reactive protein,hyperten-sion and diabetes,anti-CCP antibody and RF were independent risk factors for CVD in RA patients(P＜0.05).The constructed mod-el was internally validated.The area under the area(AUC)of the training set and the validation set were 0.891(95％CI:0.851-0.930)and 0.867(95％CI:0.790-0.944).Conclusion The prediction model constructed in this paper has good predictive and dis-crimination ability,and has a high predictive value for whether RA patients are complicated with CVD.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

Objective:To evaluate the relationship between the mechanism of mild hypothermia-induced reduction of neuronal apoptosis during cerebral ischemia-reperfusion (I/R) and calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in rats.Methods:Forty SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 5 groups ( n=8 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (IR group), hypothermia + cerebral I/R group (HIR group), hypothermia + cerebral ischemia-reperfusion + solvent group (HIR-DMSO group) and hypothermia + ischemia-reperfusion + CaMKK2 inhibitor STO-609 group (HIR-STO609 group). A global cerebral I/R injury model was established using the four-vessel occlusion method. In HIR group, HIR-DMSO group, and HIR-STO609 group, an ice blanket was used to reduce the body temperature immediately after cerebral ischemia, bringing the core body temperature down to 32.5-33.5 ℃, and rewarming was carried out 4 h later. One hour before developing the model, STO-609 solution 4 μl was injected into the lateral ventricle in HIR-STO609 group, and the equal volume of dimethyl sulfoxide solution was given instead in HIR-DMSO group. At the end of reperfusion, the modified neurological severity score (mNSS) was performed. Then the rats were sacrificed under deep anesthesia, and the hippocampal tissues were taken to observe the pathological results of the hippocampal tissues (using HE staining and Nissl staining) and to determine the apoptosis rate of neurons (by TUNEL method) and expression of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X (Bax), CaMKK2, phosphorylated AMPK (p-AMPK) and AMPK (by Western blot). Results:Compared with Sham group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, and the ratio of p-AMPK/AMPK was decreased in IR group ( P<0.05). Compared with IR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly decreased, the expression of Bax was down-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was up-regulated, and the ratio of p-AMPK/AMPK was increased in HIR group ( P<0.05). Compared with HIR group, the mNSS and apoptosis rate of neurons in the hippocampal tissues were significantly increased, the expression of Bax was up-regulated, the expression of Bcl-2, CaMKK2 and p-AMPK was down-regulated, the ratio of p-AMPK/AMPK was decreased ( P<0.05), and no significant change was found in the aforementioned parameters in HIR-DMSO group ( P>0.05). Conclusions:Mild hypothermia can inhibit neuronal apoptosis by up-regulating the CaMKK2/AMPK signaling pathway, thus reducing cerebral I/R injury in rats.

Objective:To evaluate the role of peptidylarginine deiminase 4 (PAD4)-mediated development of neutrophil extracellular traps (NETs) in lung ischemia-reperfusion injury (LIRI) in mice.Methods:Ninety-six clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=24 each) using a table of random numbers: sham operation group (group S), sham operation + PAD4 specific inhibitor GSK484 group (group S+ G), lung ischemia-reperfusion group (group L), and lung ischemia-reperfusion + GSK484 group (group L+ G). After anesthesia and mechanical ventilation, mice were subjected to left hilum occlusion for 1 h followed by 2 h of reperfusion to establish the LIRI model in L and L+ G groups. Mice underwent thoracotomy for 3 h without left hilum occlusion in S and S+ G groups. In S+ G and L+ G groups, GSK484 4 mg/kg was intraperitoneally injected once a day for 3 days before developing the model. At the end of reperfusion, blood samples were collected from the abdominal aorta for blood gas analysis to record arterial partial pressure of oxygen (PaO 2). Mice were then sacrificed to collect bronchoalveolar lavage fluid (BALF) and to obtain lung tissues. The concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) in BALF were measured using enzyme-linked immunosorbent assay. The wet/dry lung weight (W/D) ratio was calculated. The lung tissues were obtained for microscopic examination of pathological changes (with a light microscope) which were scored after hematoxylin-eosin staining and for determination of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) (by colorimetric assay) and expression of PAD4, neutrophil elastase (NE), high-mobility group box 1 (HMGB1), and citrullinated histone 3 (Cit-H3) (by Western blot). Results:Compared with group S, lung injury scores and W/D ratios were significantly increased, PaO 2 was decreased, the concentrations of IL-1β, IL-6, TNF-α and MPO in BALF were increased, the content of SOD was decreased, the content of MDA was increased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was up-regulated in L and L+ G groups ( P<0.05), and no significant changes were observed in the aforementioned parameters in group S+ G ( P>0.05). Compared with group L, lung injury scores and W/D ratios were significantly decreased, PaO 2 was increased, concentrations of IL-1β, IL-6, TNF-α, and MPO in BALF were decreased, the content of SOD was increased, the content of MDA was decreased, and the expression of PAD4, NE, HMGB1 and Cit-H3 was down-regulated in group L+ G ( P<0.05). Conclusions:Up-regulated PAD4 expression can promote the development of NETs and aggravate oxidative stress and inflammatory responses in lung tissues, thereby participating in LIRI in mice.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

The intestine in a hypoxic state is an essential physiological organ,and its primary func-tions include digestion,absorption,excretion,hormone secretion,and providing barrier and immune protec-tion.Hypoxia-inducible factor-2α(HIF-2α)represents one of the important physiologicalregulators for the intestine,partaking in the regulation of iron homeostasis,oxygen homeostasis and energy metabo-lism in the intestinal environment.Recent studies have shown that HIF-2α is closely associated with the onset and progression of various intestinal-related diseases,including iron-relatedblood diseases,inflam-matory bowel disease(IBD),colorectal cancer(CRC),and obesity-related metabolic diseases.Thus,HIF-2α may be a novel target for the treatment.HIF-2α is currently a hot topic in drug development,and numerous studies have revealed that it has therapeutic potential for intestinal-related diseases.HIF-2α is a key transcription factor that regulates intestinal iron absorption and systemic iron homeostasis.Aberrant expression of HIF-2α has been closely linked to various hematological disorders associated with iron metabolism dysregulation.In the pathological hypoxic microenvironment of the intestine,sustained activation of HIF-2α induces inflammatory response and impairs epithelial barrier function,thereby exacerbating the progression of IBD.Within the tumor microenvironment,HIF-2α contributes to CRC progression through multiple mechanisms,including metabolic reprogramming,angiogenesis,enhanced prolifera-tion,migration,and invasion of tumor cells,as well as inflammation,iron accumulation,and immune evasion.Moreover,HIF-2α is involved in the regulation of obesity,insulin resistance,and glucose-lipid metabolism via the gut-liver axis.Although seven HIF-2α modulators have been approved for clinical use,adverse effects such as anemia and thrombosis remain concerns.Therefore,developing next-generation HIF-2α-targeted strategies with improved specificity and safety profiles is critical to future research.This article is an overview of the recent advancements in understanding the role and mecha-nisms of HIF-2α in intestinal health and associated diseases while analyzing the challenges to develop-ment and application of HIF-2α modulators in the future,in hopes of offering novel therapeutic avenues for intestinal-related ailments.

Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.

Objective To investigate the effects of transcranial magnetic stimulation(TMS)combined with human umbilical cord mesen-chymal stem cells(hUC-MSCs)on ferroptosis following spinal cord injury(SCI)in rats.Methods Allen percussion was used to estab-lish the SCI model.A total of 60 SD rats were randomly divided into sham,SCI,TMS,hUC-MSC,and TMS+hUC-MSC groups,with 12 rats in each group.Motor function was evaluated using the Basso-Beattie-Bresnahan(BBB)score.Spinal cord tissues were sampled and stained with hematoxylin and eosin(HE)as well as Nissl to observe tissue damage as well as the changes in neurons and Nissl bodies,respectively.The colorimetric method was used to detect the contents of ferrous ions(Fe2+)and reduced glutathione(GSH).Transmission electron microscopy was applied to observe the ultrastructure of the mitochondria.Western blotting was performed to detect the expres-sion levels of SLC7A11,GPX4,and ACSL4.Results The SCI group had lower BBB scores,higher Fe2+and ACSL4 protein expression levels,and lower GSH,SLC7A11,and GPX4 protein expression levels than the sham group(P<0.05).The mitochondrial cristae reduced with membrane shrinkage,neuronal damage was severe,and Nissl bodies were absent in the SCI group.The TMS,hUC-MSC,and TMS+hUC-MSC groups had higher BBB scores,lower Fe2+and ACSL4 protein expression levels,and higher GSH,SLC7A11,and GPX4 protein expression levels than the SCI group(P<0.05).The mitochondrial cristae increased with an intact membrane structure,the pathological damage was attenuated,neuronal morphology was restored,and Nissl bodies were clearly visible in TMS,hUC-MSC,and TMS+hUC-MSC groups.Conclusion TMS combined with hUC-MSC inhibits ferroptosis through activating the SLC7A11/GSH/GPX4 pathway,alleviates secondary injury after SCI,and promotes functional recovery and neural remodeling in rats.

Objective Based on the phosphatidylinositol kinase(PI3K)/protein kinase B(AKT)pathway and M2 polarization of macrophages,the effects of polydatin on malignant phenotype of osteosarcoma cells were investigated.Methods The macrophages were divided into M0 group,M2 group,polydatin group,and polydatin+PI3K pathway agonist 740Y-P group.The expression of arginase-1(Arg-1)and CD206 mRNAs and proteins in macrophages were detected by RT-qPCR and Western blot.Western blot was used to detect p-PI3K/PI3K and p-AKT/AKT protein expression in macrophages.The osteosarcoma cells MG-63 were divided into control group,control group(RPMI-1640 medium culture),CM-M0 group(M0 group M0 macrophage supernatant is collected for osteosarcoma cells),CM-M2 group(M2 group M2 macrophage supernatant is collected for osteosarcoma cells),CM-polydatin group(M2 macrophage supernatant in the polydatin group was collected on osteosarcoma cells),and CM-polydatin+740Y-P group(M2 macrophage supernatant was collected on osteosarcoma cells in the CM-polydatin+740Y-P group).Edu staining assay was used to detect the proliferation of MG-63 cells.Scratches and Transwell assays were used to detect the migration and invasion of MG-63 cells.Results Compared with the M0 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the M2 group significantly(P<0.05).Compared with the M2 group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT decreased in the polydatin group significantly(P<0.05).Compared with the polydatin group,the Arg-1,CD206,IL-10,p-PI3K/PI3K,p-AKT/AKT increased in the polydatin+740Y-P group significantly(P<0.05).Compared with the CM-M0 group,the proportion of Edu-positive cells in the CM-M2 group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Compared with the CM-M2 group,the proportion of Edu-positive cells in the CM-polydatin group decreased significantly(P<0.05),and MG-63 cell migration and invasion rates decreased significantly(P<0.05).Compared with the CM-polydatin group,the proportion of Edu-positive cells in the CM-polydatin+740Y-P group increased significantly(P<0.05),and MG-63 cell migration and invasion rates increased significantly(P<0.05).Conclusion Polygonum cuspidatum can inhibit the proliferation,migration and invasion of osteosarcoma cells by inhibiting the M2 polarization of macrophages,and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.