The primary clinical manifestation of osteoarthritis (OA) is pain, yet considerable variability exists in the pain experience among OA patients. This narrative review aims to explore the mechanisms driving OA pain heterogeneity to inform the development of targeted interventions that improve treatment efficacy and patient outcomes. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Google Scholar) for papers published between January 1, 2020, and December 31, 2024. Inclusion criteria focused on studies addressing pain mechanisms and therapeutic interventions in OA. This review identifies key mechanisms of OA pain, including joint alterations, angiogenesis, nervous system involvement, peripheral and central sensitization, and psychosocial factors. It highlights the underlying distinct mechanisms in OA pain, which contribute to the variability in individuals' responses to treatment. It was suggested that interactions between neuroimmune and neurovascular systems are key contributors to chronic pain in OA. This narrative review emphasizes the complexity of OA pain, highlighting the importance of thoroughly understanding the underlying mechanisms for developing personalized and effective pain management strategies. Additional research is required to refine treatment approaches and explore long-term effects.
Humans ; Osteoarthritis/complications* ; Pain Management/methods* ; Chronic Pain/etiology*

ObjectiveTo investigate the role of sphingosine-1-phosphate （S1P） in abnormal ossification in ankylosing spondylitis （AS）， clarify the relationship between S1P and “angiogenesis-osteogenesis” coupling， and provide new strategies for AS treatment. MethodsFemoral heads from AS patients and patients undergoing routine hip replacement were collected for immunohistochemical （IHC） staining to evaluate osteogenesis and H-type vessel formation. In vitro， ELISA was used to quantify the synthesis of S1P and analyze the expression changes of S1P signaling pathway-related molecules during the osteogenic differentiation of mesenchymal stem cells derived from patients with ankylosing spondylitis （ASMSCs） and those from healthy donors （HDMSCs）， to evaluate the activation status of S1P pathway during osteogenesis. Sphingosine kinase 1 （SK1） expression was knocked down in MSCs， and the S1P receptor inhibitor FTY720 was applied to block S1P signaling. Alkaline phosphatase （ALP） activity and Alizarin Red S （ARS） quantification were used to assess the effect of S1P on ASMSCs osteogenesis. Conditioned medium from osteogenically induced MSCs was used to treat human umbilical vein endothelial cells （HUVECs） to evaluate the effect of S1P on angiogenesis. An AS mouse model （SKG mice） was treated with FTY720 or the SK1 inhibitor PF-543 citrate. IHC staining and micro-CT scanning were used to assess abnormal ossification and spinal fusion， and immunofluorescence was used to evaluate H-type vessel formation. ResultsCompared with Osteonecrosis of the Femoral Head（ONFH） patients， AS patients exhibited excessive osteogenesis and H-type vessel formation （OCN P＜0.001， CD31 P＜0.001， EMCN P＜0.001）. During osteogenic differentiation， S1P expression and secretion were significantly higher in ASMSCs than in HDMSCs （P=0.0179）. Inhibition of S1P signaling with FTY720 or SK1 knockdown significantly suppressed osteogenic differentiation （compared with ASMSC， ARS： HDMSC P=0.001 8， FTY720 P＜0.001， si-SK1 P＜0.001； ALP： HDMSC P=0.032 8， FTY720 P=0.001 6， si-SK1 P＜0.001） of ASMSCs and the angiogenesis of HUVEC（compared with ASMSC， cell-covered area， total loops， total tube length and total branch points P＜0.001）. Treatment with FTY720 or PF-543 markedly inhibited abnormal ossification and spinal fusion（compared with Curdlan， arthritis index score， P＜0.001； OCN：control P=0.002， PF-543 P=0.010 7， FTY720 P=0.015 9 ） in AS mice and reduced H-type vessel formation （CD31⁺EMCN⁺： compared with curdlan， control P＜0.001， PF-543 P=0.001 7， FTY720 P=0.002 1）. ConclusionIncreased S1P synthesis in ASMSCs promotes osteogenic differentiation via autocrine mechanisms and further enhances ossification by facilitating H-type angiogenesis. Inhibiting S1P secretion in ASMSCs significantly suppresses abnormal ossification in AS.

Objective:To discuss the infection status and clinical outcomes in the patients with bullous pemphigoid(BP),and to analyze the risk factors for infection in hospitalized BP patients,as well as to construct and evaluate the risk prediction model.Methods:A total of 126 patients first diagnosed with BP were selected.According to the occurrence of infection,the patients were divided into infection group(52 cases)and non-infection group(74 cases).The infection status and outcomes of the patients in two groups were recorded;statistical analysis was performed on the general data,laboratory examination results,FRAIL scale scores for frailty screening,NRS2002 scores,and skin lesion severity of the patients in two groups;multivariate Logistic regression model was used to identify the risk factors for infection in the patients;the goodness-of-fit test was used to evaluate the model;receiver operating characteristic(ROC)curve was used to evaluate the predictive value of the model for infection.Results:Among the 126 hospitalized BP patients,52 cases had infection,with an infection rate of 41.27％.The mortality rate of the patients in infection group was higher than that in non-infection group(P＜0.05),and the remission rate of the patients in non-infection group was higher than that in infection group(P＜0.05).The FRAIL scale score for frailty screening,NRS2002 score,serum albumin level,prealbumin level,number of hospitalization,skin lesion severity,and time of hospital stay of the patients in infection group were significantly higher than those in non-infection group(P＜0.05).The multivariate Logistic regression analysis results derived the regression equation:Logistic(P)=-7.63+0.922× skin lesion severity+2.565×FRAIL scale score for frailty screening+1.214×NRS2002 score.The area under the curve of the Logistic regression model was 0.916.Conclusion:The FRAIL scale score for frailty screening,NRS2002 score,and skin lesion severity are the risk factors for infection in the hospitalized BP patients.The constructed infection risk prediction model based on these factors has good predictive value and may provide new ideas for the prevention and control of infection in the hospitalized BP patients.

By combining the origin and research progress of the combination of disease and syndrome, the core pathogenesis, this article explored the research ideas and methods of the core pathogenesis of TCM. It is found that modern TCM is mostly guided by the idea of classification-staging-syndrome differentiation, the main prescription of the main disease, the special prescription of the special disease, and the idea of "dynamic-fixed sequential". The tongue image syndrome differentiation method, clustering analysis method, drug test syndrome method, compound pathogenesis method, "evidence-based pathogenesis-syndrome treatment system" research model, and the integration of traditional Chinese and Western medicine theory were used to explore the core pathogenesis of TCM under the condition of disease. Combined with the advantages of modern medical disease differentiation and TCM syndrome differentiation, the individualized diagnosis and treatment methods of integrated traditional Chinese and Western medicine have been continuously improved, in order to solve the stage contradictions of different clinical stages, effectively delay the progression of the disease and improve the prognosis of the disease.

Objective To compare the efficacy and safety of computed tomography (CT)-guided percutaneous versus electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) for the treatment of pulmonary nodules. Methods A retrospective analysis was conducted on the data of high-risk pulmonary nodule patients who underwent MWA at the Nanjing Drum Tower Hospital between 2022 and 2023. The pathological diagnosis rate, complications, and progression-free survival (PFS) rate were compared between the CT group and the ENB group. Results There were 61 patients in the CT group, including 30 males and 31 females, with an average age of (67.22±9.13) years. There were 53 patients in the ENB group, including 29 males and 24 females, with an average age of (65.29±13.76) years. The pathological diagnosis rate in the CT group was slightly higher than that in the ENB group (88.52% vs. 71.69%, P=0.03). However, the ENB group exhibited a lower incidence of perioperative complications, including pneumothorax (16.39% vs. 3.77%, P=0.03), hemoptysis (19.67% vs. 5.66%, P=0.05), and pain (22.95% vs. 7.55%, P=0.03). There was no statistically significant difference in PFS rate between the two groups [HR=1.17, 95%CI (0.23, 5.81), P=0.85]. Conclusion Both CT-guided and ENB-guided MWA are effective treatment modalities for high-risk pulmonary nodules.

Objective:The obesity rate among middle-aged and young adults in China is increasing annually,and the incidence of cardiovascular diseases is becoming more prevalent in younger populations.However,it has not yet been reported whether obesity is associated with early vascular aging(EVA).This study aims to explore the correlation between obesity and EVA in middle-aged and young adult health check-up populations,providing a reference for the prevention of cardiovascular diseases. Methods:A total of 15 464 middle-aged and young adults aged 18-59 who completed brachial-ankle pulse wave velocity(baPWV)test in the Third Xiangya Hospital of Central South University from January to December 2020 were included.Among them,1 965 individuals with normal blood pressure and no cardiovascular risk factors were selected as the healthy population.The baPWV thresholds for determining EVA in each age group for males and females were calculated based on the baPWV values of the healthy population.The number and percentage of individuals meeting the EVA criteria in the middle-aged and young adult health check-up populations were statistically analyzed by age and gender.The differences in obesity indicators[visceral adiposity index(VAI),body mass index(BMI),waist circumference(WC)]between the EVA and non-EVA groups for males and females were compared.Using EVA as the dependent variable,VAI,BMI,and WC were included as independent variables in a Logistic model to analyze the correlation between each obesity indicator and EVA before and after adjusting for other influencing factors.Furthermore,the correlation between each obesity indicator and EVA in each age group was analyzed. Results:In the health check-up populations,the detection rate of EVA in different age groups was 1.65%-10.92%for males,and 1.16%-10.50%for females,the detection rate of EVA increased with age in both males and females.Except for the 40-<50 age group,the EVA detection rate was higher in males than in females in all other age groups.Regardless of gender,obesity indicators VAI,BMI,and WC were significantly higher in the EVA group than in the non-EVA group(all P<0.01).Before and after adjusting for other influencing factors,VAI and WC were both correlated with EVA(both P<0.05).BMI was a risk factor for EVA before adjusting for other influencing factors(P<0.01),but after adjustment,the correlation between BMI and EVA was not statistically significant(P=0.05).After adjusting for other influencing factors,the correlation between VAI and EVA was statistically significant in the 18-<40 and 50-<60 age groups(both P<0.05),while the correlation between BMI and WC with EVA was not statistically significant(both P>0.05).In the 40-<50 age group,the correlation between VAI and BMI with EVA was not statistically significant(both P>0.05),but the correlation between WC and EVA was statistically significant(P<0.01). Conclusion:VAI is closely related to the occurrence of EVA in middle-aged and young adults aged 18-<40 and 50-<60 years,while WC is closely related to the occurrence of EVA in those aged 40-<50 years.

Objective:To investigate the role of modification level of lysine trimethylation at position 27 of histone 3 (H3K27me3) on expression of anti-apoptotic protein B lymphocyte tumor-2 gene (BCL2) during arsenic-induced hepatocyte apoptosis.Methods:Rat liver BRL-3A cells were cultured in vitro. According to the arsenic treatment factor, the experiment was divided into two parts, in the first part arsenic was not added, the experiment was divided into normal, transfection reagent, negative transfection, H3K27me3 specific demethylase (JMJD3) small interfering RNA (siRNA) transfection and H3K27me3 methyltransferase (EZH2) siRNA transfection groups. In the second part arsenic was added, the experiment was divided into control, arsenic treatment, arsenic + negative transfection, arsenic + JMJD3siRNA transfection and arsenic + EZH2siRNA transfection groups. When arsenic was not added, the corresponding siRNA and transfection reagent was used to transfect cells at a ratio of 100 pmol : 7.5 μl for 6 h [the normal group was treated with phosphate buffer solution (PBS) of the same volume as transfection reagent], then the medium was changed and the cells were incubated for a total of 48 h. After 24 h of treatment with the above transfection and culture method in arsenic added group, a final concentration of 30 μmol/L sodium arsenite (NaAsO 2) was added and the cells were incubated for 24 h (the control group was treated with PBS with the same volume of NaAsO 2 for 24 h). Real-time cell analysis (RTCA) was used to measure the proliferation of BRL-3A cells in arsenic added group. Apoptosis of BRL-3A cells was analyzed by flow cytometry in arsenic added group. Western blotting was used to detect JMJD3, EZH2, H3K27me3 and BCL2 in no-arsenic and arsenic-added BRL-3A cells. The modification levels of H3K27me3 in BCL2 gene promoter regions were detected by chromatin immunoprecipitation of the cells exposed to arsenic. Results:There were statistically significant differences of the proliferation rates [control, arsenic treatment, arsenic + negative transfection, arsenic + JMJD3siRNA transfection and arsenic + EZH2siRNA transfection groups: (100.00 ± 10.43)%, (12.19 ± 3.37)%, (31.86 ± 1.95)%, (24.58 ± 3.64)%, (11.53 ± 1.11)%] and the apoptosis rates [(1.15 ± 0.04)%, (13.06 ± 1.33)%, (17.39 ± 0.22)%, (23.90 ± 1.66)%, (15.07 ± 0.88)%] between groups ( F = 146.50, 194.30, P < 0.001), correspondingly. The protein expression level of H3K27me3 in JMJD3siRNA transfection group was higher than that of normal, transfection reagent and negative transfection groups, while EZH2siRNA transfection group had an opposite result ( P < 0.05). The protein expression level of BCL2 in JMJD3siRNA transfection group was lower than that of normal, transfection reagent and negative transfection groups, while EZH2siRNA transfection group had an opposite result ( P < 0.05). The protein expression levels of H3K27me3 and BCL2 were not statistically significant differences between normal, transfection reagent and negative transfection groups ( P > 0.05). The protein expression levels of JMJD3, EZH2, H3K27me3 and BCL2 among control, arsenic treatment, arsenic + negative transfection, arsenic + JMJD3siRNA transfection and arsenic + EZH2siRNA transfection groups were compared, and the differences were statistically significant ( F = 26.56, 7.82, 9.81, 31.19, P < 0.05). Compared with control group, the protein expression levels of JMJD3 and EZH2 in arsenic treatment group were significantly reduced ( P < 0.05), and the protein expression level of H3K27me3 was higher ( P < 0.05), meanwhile the protein expression level of BCL2 was lower ( P < 0.05). Compared with arsenic + negative transfection group, the protein expression level of JMJD3 was significantly reduced in arsenic + JMJD3siRNA group, and the protein expression level of EZH2 was significantly reduced in arsenic + EZH2siRNA group ( P < 0.05). In addition, arsenic + JMJD3siRNA increased the level of H3K27me3 modification while reducing the protein expression of BCL2, while arsenic + EZH2siRNA had an opposite result ( P < 0.05). Compared with control group, the enrichment levels of H3K27me3 in BCL2 gene promoter regions (CHIP1 and CHIP2) in arsenic treatment group were significantly higher ( P < 0.05). Conclusion:Arsenic may inhibit the expression of BCL2 by increasing the enrichment level of H3K27me3 in the promoter regions of BCL2 gene, and promoting hepatocyte apoptosis.

Objective To compare the dose difference of intensity-modulated radiotherapy (IMRT) with different gantry angle between target volumes and surrounding normal tissues in lumbar spinal metastases therapy. Methods Ten patients with lumbar spinal metastases were enrolled in the study. Three plans with the same prescription dose of 3000 cGy/10f were designed by seven-equal beams (plan-A), five-back beams (plan-B) and seven-back beams (plan-C). All the plans were designed with the same objective function and dose limiting condition. The difference of dosimetric parameters of planning target volume (PTV), organ at risk (OAR), normal tissues, and treatment parameters in all the plans were compared with SPSS 21.0 statistical software. Results All the plans satisfied the clinical requirement. There was no significant difference in the D_mean, D_2%, D_98%, CI and HI of PTV between plan-A and plan-C (P >0.05), and these parameters of plan-A and plan-C were better than plan-B (P < 0.05). Compared with the other two plans, plan-B reduced the dosimetric parameters of bilateral kidney (P < 0.05), whereas plan-B increased the D_max of spinal cord (P < 0.05). The V₅ and V₁₀ of normal tissue of plan-B were lower than the other two plans while the V₁₅, V₂₀ and V₂₅ showed inverse relationship (P < 0.05). plan-B had certain advantages in shortening the monitor units and treatment time (P < 0.05).. Conclusions The seven-equal beams (plan-A) and seven-back beams (plan-C) IMRT plans can provide better target dose distribution, and reduce the D_max of spinal cord. Five-back beams (plan-B) IMRT plan had certain advantages in protecting bilateral kidney and shortening treatment time.

Objective:To investigate the current situation of students' academic procrastination behavior in medical colleges and universities and its influencing factors, and to put forward suggestions to reduce the academic procrastination of medical students.Methods:A total of 1 327 undergraduate students from three medical colleges and universities in Heilongjiang Province were randomly selected to receive questionnaire investigation on life satisfaction, anxiety, and academic procrastination. SPSS 23.0 was used for data analysis.Results:①The total procrastination scores of medical students were (35.00±8.92) points. ②There were statistical differences in the academic procrastination of medical students with different genders, whether the only children, the reasons for choosing the major, and the level of achievement ( P < 0.05). There was no statistical difference in academic procrastination among medical students of different ages and grades ( P > 0.05). ③Medical students' procrastination was positively correlated with their anxiety level ( r = 0.102, P < 0.01), and negatively correlated with life satisfaction ( r = -0.117, P < 0.01). ④Regression analysis showed that the following six predictive variables including the level of achievement, gender, life satisfaction, anxiety, reasons for choosing the major, and whether the only children could effectively explain the variance of 14.2% academic procrastination of medical students. Conclusion:The overall degree of academic procrastination of medical students is higher than that of non-medical students. And the students' achievement level, gender, life satisfaction, anxiety, the reasons for choosing this major and whether the only child are the influencing factors of academic procrastination.

Objective:To investigate the changes of microRNA-153 (miR-153) expression and the mechanism of regulating histone H3 lysine 4 (H3K4) methyltransferase (SET7/9) and histone H3K4 methylation (H3K4me1) in the process of arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis.Methods:Human normal hepatocytes (L-02 cells) were cultured in vitro and divided into control, arsenic treatment, arsenic + negative transfection, arsenic + miR-153 up-regulation and arsenic+ miR-153 down-regulation groups according to different treatment methods. Arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were transfected with transfection plasmid and transfection reagent according to a certain proportion (3 μg: 8 μl). After 24 h, arsenic treatment, arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were all treated with 100 μmol/L sodium arsenite (NaAsO 2) as the final concentration for 24 h. The control group was treated with phosphate buffer solution (PBS) of the same volume as NaAsO 2 for 24 h. The expression of miR-153 was detected by real-time quantitative polymerase chain reaction (RT-qPCR); cell apoptosis and cell cycle were detected by flow cytometry; real-time cell dynamic analyzer (RTCA) was used to detect cell proliferation; Western blotting was used to detect the expression of endoplasmic reticulum marker proteins glucose regulatory protein 78 (GRP78), SET7/9 and H3K4me1. Results:The expression levels of miR-153 in each group were significantly different ( F = 10.73, P < 0.05). Compared with the control group [(41.10 ± 6.08)%], the expression level of miR-153 in arsenic treatment group [(4.35 ± 0.20)%] was significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group [(10.00 ± 2.40)%], the expression level of miR-153 in arsenic+ miR-153 up-regulation group [(157.70 ± 42.70)%] was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group [(4.20 ± 0.28)%] was significantly decreased ( P < 0.05). There were significant differences in the total cell apoptosis rate and G1 phase cell proportion among the five groups ( F = 29.69, 104.32, P < 0.05). Compared with the control group, the total cell apoptosis rates and G1 phase cell proportions in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the total cell apoptosis rate and G1 phase cell proportion in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic+ miR-153 down-regulation group were significantly increased ( P < 0.05). The difference of cell proliferation rate in each group was statistically significant ( F = 799.35, P < 0.05). Compared with the control group, the cell proliferation rates in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group, the cell proliferation rate in arsenic+ miR-153 up-regulation group was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group was significantly decreased ( P < 0.05). The protein expression levels of SET7/9, GRP78 and H3K4me1 in each group were significantly different ( F = 78.52, 52.13, 54.32, P < 0.05). Compared with the control group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic treatment group were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic + miR-153 down-regulation group were significantly increased ( P < 0.05). Conclusion:miR-153 plays an important role in arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis, the expression and regulation are related to the changes of SET7/9 and H3K4me1 levels.