The activation of the P2X7 receptor as an ATP-gated ion channel,triggers the release of pro-inflammato-ry cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons,thereby exacerbating the transmission of pain.In preclinical cancer pain models,it has the potential to serve as a new therapeutic target for cancer pain management.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM_2.5 exposure. Objective To investigate the association between long-term exposure to PM_2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM_2.5 and diet on diabetes. Methods The study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM_2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM_2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM_2.5 exposure. Results The mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM_2.5 was (38.10±4.67) μg·m⁻³. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L⁻¹ for each 1 μg·m⁻³ increase in PM_2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits <1 time per week, individuals who consumed fruits 1-3 times per week and ≥4 times per week exhibited a reduced risk of diabetes by 16.4% (OR=0.836, 95%CI: 0.702, 0.998) and 18.2% (OR=0.818, 95%CI: 0.700, 0.959) respectively. Fasting blood glucose decreased by 0.202 (95%CI: -0.304, -0.101) mmol·L⁻¹ in participants who ate vegetables 1-3 times per week. The effect of salty taste on diabetes and fasting blood glucose was not significant. The results of stratified analysis by dietary factors and PM_2.5 concentration showed that the risks of diabetes were increased in the low PM_2.5 pollution-low vegetable intake frequency group and the high PM_2.5 pollution-low vegetable intake frequency group compared with the low PM_2.5 pollution-high vegetable intake frequency group, with OR values of 3.987 (95%CI: 2.943, 5.371) and 1.433 (95%CI: 1.143, 1.796) respectively. The risk of diabetes was 50.1% higher in participants with high PM_2.5 pollution and low fruit intake frequency than in participants with low PM_2.5 pollution and high fruit intake frequency (OR=1.501, 95%CI: 1.171, 1.926). No interaction was found between salty taste and PM_2.5 on diabetes. Conclusion Long-term exposure to ambient PM_2.5 is associated with an increased fasting blood glucose and an elevated risk of diabetes in rural Ningxia population. Increasing the frequency of weekly consumption of vegetables or fruits may have a certain protective effect against diabetes occurrence, as well as a moderating effect on diabetes and fasting blood glucose levels associated with long-term exposure to atmospheric PM_2.5.

Objective:To understand the real experience and needs of early exercise rehabilitation in elderly patients with total hip arthroplasty (THA), so as to provide a preliminary basis for intervention research to meet the needs of patients.Methods:Using the purposive sampling method, a total of 12 elderly patients with THA from the First Affiliated Hospital of Naval Medical University from June to September 2021 were selected as the research objects for semi-structured in-depth interviews. Colaizzi 7-step method was used to analyze, summarize and extract the data.Results:The early exercise rehabilitation experience and needs of elderly THA patients could be summarized into four themes such as postoperative exercise being a difficult journey, the need for professional support, the need for external support and internally driven needs and 14 sub themes.Conclusions:There are various problems and needs for early exercise rehabilitation in elderly patients undergoing THA. It is necessary to strengthen communication among doctors, nurses and patients, understand their true feelings and provide personalized care and rehabilitation guidance to improve their treatment experience and enhance their satisfaction.

Objective To observe the value of Zero-Shot Noise2Noise(ZS-N2N)based on Z-axis correlation for reducing noise of low dose CT(LDCT)images.Methods CT data of the cancer imaging archive were enrolled,including normal dose CT(NDCT)images and LDCT images,with 3 sets of chest and 3 sets of abdominal images.Noise on LDCT images were reduced with ZS-N2N method based on Z-axis correlation,and the peak signal-to-noise ratio(PSNR),structural similarity(SSIM)and time-consuming of reducing noise were compared with those of Self2Self,simple ZS-N2N and traditional Block-matching and 3D filtering(BM3D).Results After reducing noise,noise on Self2Self denoised images remained significant,the structure edges on BM3D denoised images were blurry with some details lost,while simple ZS-N2N and ZS-N2N based on Z-axis correlation denoised images preserved more details and had better quality.PSNR and SSIM of Self2Self denoised images were poor and the time-consuming were longer.PSNR,SSIM and time-consuming of the other 3 methods were similar,among which PSNR of ZS-N2N based on Z-axis correlation were slightly higher than BM3D and simple ZS-N2N,but the time-consuming were also slightly longer.Conclusion ZS-N2N based on Z-axis correlation had high value for reducing noise of LDCT images.

OBJECTIVE: To comprehensively assess the occurrence of residual symptoms in patients with axial spondyloarthritis who have successfully attained the treatment goal of low disease activity, and to conduct a thorough analysis of the related factors. METHODS: An analysis was performed on axial spondyloarthritis patients who achieved low disease activity for the first time during their visits at the Rheumatology and Immunology Department of Peking University Third Hospital, spanning from May 1, 2021, to February 29, 2024. Based on the ankylosing spondylitis disease activity score-C-reactive protein (ASDAS-CRP), the patients who achieved low disease activity were divided into a non-remission low disease activity group and a remission group. The occurrence of residual fatigue and pain symptoms in both groups was assessed, and binary Logistic regression analysis was used to evaluate the related factors. RESULTS: In the study, 201 patients achieved low disease activity during treatment. The gender distribution was skewed towards males, with 151 male patients (75.1%) and 50 female patients (24.9%). The median age of the patients who achieved low disease activity was 32.0 (28.0, 37.0) years, and the median disease duration was 6.7 (3.8, 11.5) years. Notably, 140 patients (69.7%) achieved low disease activity but did not experience complete remission, while 61 patients (30.3%) attained remission. A substantial proportion of the patients, 45.8%, reported residual fatigue visual analogue scale (VAS) ≥4, with a marked difference between the non-remission low disease activity group and the remission group (53.6% vs. 27.9%, P=0.001). Similarly, 24.4% of the patients had residual pain VAS ≥4, with a significant disparity between the non-remission low disease activity group and the remission group (30.0% vs. 11.5%, P=0.005). Binary Logistic regression analysis revealed that C-reactive protein levels had a notable negative influence on residual fatigue symptom (B=-0.142, P=0.008, OR=0.868), whereas ASAS-HI had a positive effect on residual fatigue (B=0.288, P < 0.001, OR=1.334). Gender was found to have a significant impact on residual pain symptoms, with females exhibiting a higher risk (B=1.135, P=0.002, OR=3.112). CONCLUSION The residual fatigue and pain symptoms are common in axial spondyloarthritis patients who have achieved low disease activity, particularly among female patients. More assessment and recognition of the residual disease burden in these patients will be needed to optimize the treatment strategies.
Humans ; Female ; Male ; Adult ; C-Reactive Protein/analysis* ; Axial Spondyloarthritis ; Fatigue/etiology* ; Severity of Illness Index ; Spondylitis, Ankylosing/physiopathology* ; Remission Induction ; Pain/etiology* ; Logistic Models

OBJECTIVE: To investigate the current status of methotrexate (MTX) application in rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of RA patients who attended in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 1, 2022 to November 31, 2023 were collected retrospectively. In order to figure out the relationship between MTX use and RA disease control, we recorded information including the starting dose, maximum dose, current dose, reasons of discontinuation of MTX, etc. The t test, Mann-Whitney U test, Chi-square test, Fisher' s exact probability and multivariable Logistic regression were used for analysis. RESULTS: A total of 239 RA patients were enrolled, including 201 females and 38 males with a mean age of (54.5±14.3) years. Among them, 101 patients reached the therapeutic target [clinical remission or low disease activity assessed by 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR)], accounting for 42.2% of the RA patients. Twenty-six patients met the European League Against Rheumatism (EULAR) definition of difficult-to-treat (D2T) RA, accounting for 10.9% of RA patients. The proportion of the RA patients who had ever used MTX was 84. 1%, and those who were currently on it accounted for only 39.7%. The MTX dose was generally low, with a starting dose of (9.5±3.0) mg/week, the maximum dose of 15.0 (10.0, 15.0) mg/week, and the current dose being (12.4±2.7) mg/week. The most common reasons for MTX dose reduction or discontinuation were adverse reactions, mainly including abnormalities of hepatic function, gastrointestinal discomfort, leucopenia, etc. Those who were currently on MTX had a higher rate of treatment to target (52.6% vs. 35.4%, P>0.05), lower disease activity score (DAS28-ESR, 3.6±1.8 vs. 4.2±1.8, P < 0.05), and fewer tender joint counts (4.8±8.3 vs. 8.6±10.4, P < 0.05) as compared with those who were not taking the drug, while swollen joint count, pain visual analog score and patient' s global score, C-reactive protein (CRP) level and ESR level were not significantly different between the two groups. Compared with those who did not reach the target of treatment, those who did had a higher rate of current MTX application (48.5% vs. 33.3%, P < 0.05), but the history of MTX did not differ between the two groups (84.2% vs. 84.1%, P>0.05). The maximum dose of MTX (median 15.0 mg/week vs. 13.7 mg/week, P>0.05) and the current dose [(12.9±2.5) mg/week vs. (11.8±2.8) mg/week, P>0.05] was higher in those who achieved the target, while the starting dose [(9.6±2.8) mg/week vs. (9.5±3.1) mg/week, P>0.05] and the rate of prior MTX (84.2% vs. 83.3%, P>0.05) was comparable between the two groups. The D2T RA patients had a higher rate of previous MTX use (96.2% vs. 82.6%, P < 0.05) and a higher starting dose [(11.6±4.3) mg/week vs. (9.8±2.7) mg/week, P>0.05], while the maximum dose (median 12.5 mg/week vs. 15.0 mg/week, P>0.05) and the current dose were both lower [(11.6±3.2) mg/week vs. (12.5±2.6) mg/week, P>0.05] than the non-D2T RA patients. CONCLUSION The proportion of regular use of MTX among RA patients was low and the dose was generally small. The RA patients with regular use of MTX had a higher rate of achieving treatment target and lower disease activity. Those who achieved the target had a higher rate of current MTX use, higher maximum and current doses than those who did not. The D2T RA patients had lower maximum and current doses of MTX than the non-D2T RA patients. Therefore, increasing the usage and dosage of MTX in RA patients may help to improve the rate of achieving treatment targets.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/therapeutic use* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Adult ; Blood Sedimentation ; Severity of Illness Index ; Remission Induction

We reported the diagnostic and therapeutic process of a young male patient with systemic lupus erythematosus (SLE) who presented with severe hyponatremia as the main manifestation upon admission, and analyzed and discussed the case. The patient was a 19-year-old young male with a subacute course of disease, fever ≥38.3 ℃ that could not be explained by other causes, acute and subacute cutaneous lupus erythematosus, oral ulcers, arthritis, leukopenia (< 4×10⁹/L), low C3+low C4, and positive anti-double-stranded DNA (anti-dsDNA). According to the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, the score was 27 points. The patient was admitted to the hospital with SLE. After admission, further diagnosis of lupus was confirmed, excluding infection, tumor, endocrine disease, etc. Hyponatremia was the main complication of this lupus patient. Hyponatremia was a rare complication of lupus, only a few cases have been reported. In this study, the paient ' s blood osmotic pressure was significantly reduced, which was considered to be hypotonic hyponatretic, urine osmotic pressure increased, maximum urine dilution caused by excessive water intake such as primary polydipsia, hypoosmotic fluid intake, and beer drinking were excluded, and 24 h urine volume and sodium were improved. The urinary sodium concentration was close to 20 mmol/L although with severe hyponatremia, considering the possibility of isovolemic hypotonic hyponatremia, the syndrome of improper secretion of antidiuretic hormone or adrenal cortical insufficiency. The patient had no manifestations, such as hypotension, typical site pigmentation, and high potassium, and there was little possibility of adrenal cortical insufficiency, and syndrome of inappropriate antidiuretic hormone secretion (SIADH) was considered for hyponatremia in the patient. The etiological mechanism of hyponatremia in lupus patients is not clear, but it is related to acute kidney injury, drugs and systemic inflammation. In this case, we reported for the first time that SLE was associated with abnormal hypothalamic signals, suggesting a possible mechanism of lupus hyponatremia. The patient underwent water restriction, intravenous and oral sodium supplementation, and the blood sodium quickly returned to normal after pulse therapy. The abnormal signal of the head magnetic resonance imaging (MRI) fornix column was improved after 1 month of treatment, further confirming our diagnosis. SLE complicated with hyponatremia is rare, but severe hyponatremia can be life-threatening, and attention should be paid to it. The possibility of neuropsychiatric lupus should be vigilant in patients with lupus combined with hyponatremia.
Humans ; Hyponatremia/etiology* ; Lupus Erythematosus, Systemic/diagnosis* ; Male ; Young Adult

Sjögren's syndrome （SS）， a disorder of immune system， is one of the dominant diseases treated by traditional Chinese medicine （TCM）. China Association of Chinese Medicine organized experts in the field of TCM and western medicine rheumatology and pharmacology to discuss the advantages and optimal regimens of TCM for the treatment of SS. The experts generally agreed on the low early diagnosis rate of SS and the lack of targeted therapeutic drugs. In addition， autoimmune abnormality is the key factor in the occurrence of SS and deficiency of both Qi and Yin is the core pathogenesis. SS has unique tongue manifestations， which is expected to allow for the early diagnosis and treatment with integrated traditional Chinese and western medicine. TCM has advantages in treating SS in terms of alleviating clinical symptoms and systemic involvement， individualized treatment， relieving sleep and mood disorders， preventing the occurrence in the early stage， and enhancing the effectiveness and reducing toxicity in the treatment by integrated TCM and western medicine. In general， TCM has advantages in different stages of SS. Internal and external use of TCM， acupuncture， and acupotome are all available options. The optimal regimens should be determined on the basis of pattern identification， stage of disease， and the advantages of TCM. Clinical characteristics and biomarkers of SS should be studied to classify patients， so as to design precision evidence-based TCM regimens for SS. On the basis of unique tongue manifestations of SS， models for early diagnosis and poor prognosis identification of SS should also be established to achieve early prevention and treatment and to improve the prognosis. In the future， we should vigorously carry out high-quality evidence-based medical research on the treatment of SS by TCM and integrated traditional Chinese and western medicine and develop relevant guidelines to optimize and standardize current diagnosis and treatment， thereby laying a basis for clarifying and explaining the advantages of TCM in treating SS.

Background The contribution of long-term ambient PM_2.5 exposure to hypertension should not be ignored. However, the conclusions of whether dietary factors play a role in regulating PM_2.5-related hypertension are still inconsistent. Objective To explore the correlation between long-term exposure to ambient PM_2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure) in adults in Ningxia and a potential moderating effect of dietary factors. Methods A set of cross-sectional survey data from March, 2013 to May, 2018 was retrieved from the China Northwest Cohort-Ningxia, and the average ambient PM_2.5 concentration in the previous three years was also collected to estimate the long-term exposure of the participants. Binary logistic regression model was used to validate the correlation between long-term exposure to ambient PM_2.5 and hypertension in Ningxia, and linear model was used to study the correlation between long-term exposure to ambient PM_2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure), and to explore the influence of dietary factors on ambient PM_2.5-related hypertension. Results A total of 11470 participants were included in the study, 42.2% male and 57.8% female. The three-year average ambient PM_2.5 concentration before the baseline survey was 37.0 μg·m⁻³. Each 1 μg·m⁻³ increase in ambient PM_2.5 was associated with an increased risk of hypertension (OR=1.111, 95%CI: 1.097, 1.125), and increased systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure by 0.886 (95%CI: 0.783, 0.990), 0.570 (95%CI: 0.500, 0.641), 0.676 (95%CI: 0.600, 0.751), and 0.316 (95%CI: 0.243, 0.389) mmHg, respectively. The stratified analysis showed that the OR and 95%CI of hypertension were 1.171 (1.097, 1.254), 1.117 (1.064, 1.174), and 1.160 (1.116, 1.207) respectively for each 1 μg·m⁻³ increased in PM_2.5 with low frequency of vegetable and fruit consumption and salty taste respectively. The OR and 95%CI of hypertension were decreased when the moderate and high frequency of vegetable and fruit intake and moderate and light taste applied, the values were 1.091 (1.062, 1.121) and 1.114 (1.097, 1.131), 1.105 (1.082, 1.129) and 1.111 (1.092, 1.13), 1.115 (1.090, 1.140) and 1.102 (1.083, 1.121) respectively. Compared with low frequency of vegetable and fruit intake and salty taste, the increase degree of ambient PM_2.5 related systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure also decreased in middle and high frequency of vegetable and fruit intake and moderate and light taste. Conclusion Long-term exposure to ambient PM_2.5 is significantly associated with increased risks of hypertension and blood pressure in Ningxia area. Increasing the frequency of vegetable and fruit intake and decreasing salty taste may reduce the effect of ambient PM_2.5 on hypertension and blood pressure.

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.