BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

Objective To develop a Nomogram clinical prediction model for the pathological occurrence of extraprostatic extension(EPE)after radical prostatectomy in prostate cancer patients,using simplified site-specific magnetic resonance imaging(MRI)indicators and other clinical parameters.Methods A total of 181 prostate cancer patients[mean age(69.0±7.3)years]who underwent radical prostatectomy were included.These patients had received 3-Tesla multi-parametric magnetic resonance imaging(3-T mpMRI)within 6 months prior to surgery.Based on mpMRI measurements[capsular contact length(CCL)>15 mm,capsular bulging/irregularities,diameter of index lesion(dIL),and evident extraprostatic extension(eEPE)],the dIL?sEPE grading system was derived.The optimal cut-off value of dIL(denoted as dIL)was determined using the Youden J index,and categorized it into a binary variable.A Logistic regression model was established based on the dIL?sEPE grading and clinical scores.The predictive performance of clinical indicators,MRI indicators,and combined clinical and MRI indicators were compared.Finally,a clinical prediction model integrating both clinical and MRI data was developed.Results Pathological EPE was found in 46 out of 181 cases(25.4% ).A Nomogram prediction model for EPE was established with a combination of the dIL?sEPE grading and clinical indicators.Conclusion The combination of dIL?sEPE grading with clinical indicators accurately predicts extracapsular extension in prostate cancer.The Nomogram model that established,based on MRI imaging characteristics and clinical indicators has good performance and is easy to use.It is beneficial to stratifying management for prostate cancer patients,and it provides valuable guidance for patients suitable for nerve-sparing surgery.

Both the androgen receptor pathway and PI3K/AKT pathway play pivotal roles in the progression of prostate cancer.There are intricate interactions between these two pathways,showing a negative regulatory relationship of mutual restriction between them.In view of the above,a combined inhibition strategy targeting these two pathways is expected to become a significant therapeutic approach for prostate cancer.This article aims to comprehensively review the molecular mechanisms underlying the interactions between the androgen receptor and PI3K/AKT pathways,to provide new perspectives and insights for research in the fields.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

Objective To investigate the cognition of both doctors and patients in the neurology department of a tertiary hospital in Linyi City regarding graded diagnosis and treatment,and to explore its influencing factors.Methods Convenient sampling was used to select 456 survey subjects from 20 medical institutions within the medical consortium of a tertiary hospital in Linyi City,including 191 medical staffs and 265 patients;A total of 35 medical staffs and patients were interviewed.Results The overall awareness of graded diagnosis and treatment among medical staff and patients was(3.731±0.563)points and(3.136±0.367)points,respectively.The influencing factors of medical staff on grading diagnosis and treatment are professional title,years of work experience,and hospital grade.The influencing factors of patient on grading diagnosis and treatment are age,type of medical insurance,average monthly income,and whether they had a transfer experience.Conclusion While strengthe-ning information technology construction,government supervision and investment,and enhancing the capacity building of grassro-ots medical institutions,it is also necessary to actively promote the construction of close medical consortia to accelerate the forma-tion of a standardized and orderly new system for medical treatment and diagnosis.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

Objective:To assess the predictive value of the percentage of Gleason pattern 4 (G4%) in prostate biopsy for adverse pathology and biochemical recurrence.Methods:We retrospectively analyzed consecutive patients who underwent radical prostatectomy in our institution between January 2019 and December 2023, and included those who were diagnosed with ISUP 2-3 cancer at biopsy. A total of 109 patients were included in this study. The average age of patients was (67.40±6.11) years, and the average BMI of patients was (25.36±2.97) kg/m 2. 49 Cases (45.0%) had a PI-RADS score of 5, and the median prostate volume was 32.60 (24.57, 45.63) ml. The median of most recent tPSA before biopsy was 9.76 (6.89, 12.95) ng/ml, the median PSAD was 0.28 (0.17, 0.44) ng/ml 2, and the median f/tPSA was 0.11 (0.08, 0.16). Clinical T 2b or higher stage was found in 84 cases (77.1%). The total biopsy core length was (22.91±5.18) cm, with a median of 24 (20, 24) biopsy cores and a median of 6 (4, 9) positive cores. Gleason score 3+ 4 was found in 52 cases (47.7%), and Gleason score 4+ 3 in 57 cases (52.3%). Cribriform was present in 30 cases (27.5%). G4% was calculated based on the proportion of Gleason grade 4 tumor relative to total tumor, tumor proportion relative to total tissue, and tissue length. Patients were divided into high-G4% (≥2.45%) and low-G4% (<2.45%) groups based on the median G4% value, with 55 and 54 cases, respectively. No significant differences were observed in baseline characteristics between the two groups ( P>0.05). The main risk factor of adverse pathology was analyzed by logistic regression, and receiver operating characteristic (ROC) curve and area under curve (AUC) were performed. Patients were further stratified by the G4% cutoff value from ROC, and Kaplan-Meier survival curves were plotted to compare biochemical recurrence free survival (BCRFS) between groups. The main risk factor affecting BCRFS was analyzed by Cox regression. Adverse pathology was defined as postoperative Gleason score ≥4+ 3 or pathological stage ≥T 3a. Results:Adverse pathology occurred in 44 (80.0%) high-G4% and 16 (29.6%) low-G4% patients ( P<0.01). Multivariate analysis identified G4% as an independent risk factor for adverse pathology ( OR=1.23, 95% CI 1.02-1.50, P=0.033). The highest ROC AUC value was seen for G4% (0.799), significantly outperforming Gleason score (0.799 vs. 0.641, P=0.003), tPSA (0.799 vs. 0.615, P=0.003), PSAD (0.799 vs. 0.679, P=0.038), positive cores (0.799 vs. 0.677, P=0.009), clinical T stage (0.799 vs. 0.607, P=0.001) and cribriform (0.799 vs. 0.639, P=0.001). The G4% cutoff value for predicting biochemical recurrence was 10.97%. The median BCRFS was significantly higher in the low G4% (<10.97%) group than that in the high G4% (≥10.97%) group (55 vs. 28 months, P=0.002). Cumulative recurrence free survival rates at 1 and 3 years were 94.6% vs. 74.1% and 78.0% vs. 47.6%, respectively. Multivariate Cox regression analysis indicates that G4% was an independent risk factor affecting BCRFS ( HR=1.11, 95% CI 1.00-1.23, P=0.041). Conclusions:For patients with ISUP 2-3 nmPCa, a higher G4% in biopsy specimens demonstrates strong predictive ability for adverse pathology and biochemical recurrence, outperforming traditional clinical indicators such as Gleason score and PSA.

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts