BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

Objective To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective To explore the distribution and characteristics of traditional Chinese medicine(TCM)syndromes in patients with adenomyosis.Methods A retrospective analysis was conducted on the data collected from patients with adenomyosis between December 2019 and April 2022 based on a cross-sectional survey.Variables included age,body mass index(BMI),disease duration,geographical region,dysmenorrhea,menstrual flow,diagnosis and treatment goals,history of adenomyosis-related surgery,postoperative recurrence,and carbohydrate antigen 125(CA125)and carbohydrate antigen 199(CA199)levels.The distribution pattern of TCM syndromes,including general information of patients with different syndromes,CA125 and CA199 levels,were analyzed.The relationship between syndromes and age,BMI,duration of disease,geographic region,and history of adenomyosis-related surgery were analyzed using the multinomial logistic regression.Results A total of 1,816 patients with adenomyosis were included.The most common TCM syndrome was syndrome of cold coagulation and blood stasis(36.84%).The other four TCM syndromes,ranked by frequency,were syndrome of qi stagnation and blood stasis(25.39%),syndrome of blood stasis due to qi deficiency(17.35%),syndrome of kidney deficiency and blood stasis(15.97%),and syndrome of intermin-gled phlegm and blood stasis(4.46%).Significant differences in age,disease duration,and BMI were observed among patients with different TCM syndromes(P<0.05).Patients with syndrome of cold congelation and blood stasis,syndrome of kidney deficiency and blood stasis,were younger than those with syndrome of qi stagnation and blood stasis.Patients with syndrome of cold congelation and blood stasis had a longer disease duration than those with syndrome of blood stasis due to qi deficiency.Patients with syndrome of blood stasis due to qi deficiency had lower BMI(P<0.05)than those with syndrome of intermin-gled phlegm and blood stasis.The most common symptom in North China,East China,Southwest China,Northwest China,and Northeast China was syndrome of cold congelation and blood stasis,accounting for 45.39%,35.98%,30.33%,41.38%,and 50.00%,respectively.The most common syndrome in Southern and Central China was syndrome of qi stagnation and blood stasis,accounting for 31.34%and 36.23%respectively.Differences in syndrome distribution were observed between patients in East,Southwest,South,and Central China and those in North China(P<0.05).Syndrome distribution also varied significantly across different diagnosis and treatment goals,as well as menstrual conditions(P<0.05).For treatment goals such as pain relief,lesion control,menstrual flow reduction,and recurrence prevention,the dominant syndromes were syndrome of cold congelation and blood stasis(40.67%,37.13%,36.95%,and 43.35%,respectively)and syndrome of qi stagnation and blood stasis(29.35%,26.39%,26.10%,and 25.75%,respectively).Among patients seeking assisted pregnancy,the primary syndromes were syndrome of cold congelation and blood stasis(41.12%)and syndrome of kidney deficiency and blood stasis(18.69%).Patients with dysmenorrhea were mostly diagnosed with syndrome of cold congelation and blood stasis(39.95%)and syndrome of qi stagnation and blood stasis(28.52%).Differences in syndrome distribution were observed between patients with small and large menstrual volume,with a higher proportion of syndrome of kidney deficiency and blood stasis in patients with small menstrual volume(P<0.05).However,no significant difference was noted in the distribution of TCM syndromes in different treatment stages.Additionally,no statistical significance was observed in the CA125 and CA199 levels among patients with various TCM syndromes.Multinomial logistic regression analysis revealed that compared with syndrome of cold congelation and blood stasis,the course of disease was the influencing factor of syndrome of blood stasis due to qi deficiency,BMI was the influencing factor of syndrome of qi stagnation and blood stasis and syndrome of intermin-gled phlegm and blood stasis,and geography was the influencing factor of syndrome of blood stasis due to qi deficiency,syndrome of qi stagnation and blood stasis,syndrome of kidney deficiency and blood stasis,and syndrome of intermin-gled phlegm and blood stasis.Conclusion Syndrome of cold coagulation and blood stasis is the most prevalent TCM syndrome among patients with adenomyosis,and the distribution of TCM syndromes has a specific regularity.The syndromes are independently correlated with region,disease duration,and BMI.

Objective:To discuss the correlation of International Society of Urological Pathology (ISUP) pathological grading with 18F-prostate specific membrane antigen (PSMA)-1007 positron emission tomography-computed tomography (PET/CT) parameters and serum total prostate specific antigen (tPSA) in prostate cancer, and assess the clinical value of PET/CT combined with tPSA in predicting the ISUP pathological grade of prostate cancer. Methods:The correlation of ISUP pathological grade with primary parameters of PET/CT images and serum tPSA of 117 patients diagnosed with prostate cancer at Shanxi Cancer Hospital from August 2018 to February 2023 and taken 18F-PSMA-1007 PET/CT imaging were retrospectively analyzed. Univariate and multivariate logistic regressions were used to identify the independent influencing factors for ISUP pathological grading of prostate cancer. The receiver operating characteristic (ROC) curves were used to predict the efficacy between the high and low ISUP grades for prostate cancer. Results:Of the 117 patients, 20 were in ISUP Group 1, 25 in Group 2, 18 in Group 3, 32 in Group 4, and 22 in Group 5. Of these, 63 were in the low-grade group (Groups 1-3) and 54 were in the high-grade group (Groups 4-5). The tumor long diameter was 3.10 (2.05, 4.25) cm, the prostate volume was 40.11 (33.13, 51.85) cm 3, the serum tPSA was 19.71 (12.25, 42.83) ng/ml, the prostate specific antigen density (PSAD) was 0.51 (0.31, 1.01) ng·ml -1·cm -3, the maximum standard uptake value of the lesion (SUVmax) was 15.24 (10.87, 22.03), and the tumor/spleen uptake ratio (TSR) was 1.61 (1.08, 2.15) in the 117 patients. The correlation analysis displayed that the SUVmax, TSR, and tPSA were positively correlated with ISUP groups ( r=0.640, 0.619, and 0.500, P＜0.01). The differences among SUVmax, TSR, long diameter, tPSA, and PSAD were statistically significant when compared among the five ISUP groups ( H=48.98, 45.63, 26.82, 33.95, and 23.81, P＜0.001). The differencesin serum tPSA ( z=5.19), PSAD ( z=4.64), long diameter ( z=3.19), SUVmax ( z=5.57), and TSR ( z=5.53) of the patients between the low-grade group and the high-grade group were statistically significant ( P＜0.01). In multivariate analysis, TSR ( OR=4.172, 95% CI: 2.095-8.308, P＜0.001) and the serum tPSA ( OR=1.042, 95% CI: 1.014-1.070, P＜0.01) were independent influencing factors for ISUP grades. ROC analysis revealed that the area under the curve for the 18F-PSMA-1007 PET/CT parameters SUVmax and TSR to predict low- or high-grade ISUP for prostate cancer was 0.800 (95% CI: 0.717-0.883) and 0.797 (95% CI: 0.713-0.881), respectively. Among the 70 patients who underwent radical prostatectomy, the postoperative recurrence rate of high-grade ISUP patients was higher than that of low-grade patients (54.8% and 25.6%, χ 2=6.21, P＜0.05). Conclusions:18F-PSMA-1007 PET/CT has good application in predicting ISUP grading of prostate cancer. TSR and the serum tPSA are independent predictors for the pathological grade.

Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective:To assess the attitudes toward and factors influencing starting insulin use among community-based patients with type 2 diabetes (T2D).Methods:A cross- sectional study. This secondary analysis used baseline data from patients with T2D recruited through convenience sampling from a community-based peer support intervention study implemented in nine community health service centers in Shanghai since 2017. Attitudes toward insulin use were assessed using the Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ); the higher the score, the more negative the attitude toward starting insulin use. Multiple linear regression was used to analyze the factors influencing attitudes toward starting insulin use.Results:A total of 336 patients with T2D were included in the survey. The patients had a mean age of (67.7±7.9) years, mean disease duration of (13.62±7.73) years, relatively low levels of depression [Patient Health Questionnaire 8 (PHQ-8): 2 (0, 5)] and diabetes distress [Diabetes Distress Scale 4 (DDS-4): 1.97±0.95], and suboptimal target achieving rates of risk factors including body mass index, blood pressure, blood glucose, and lipid levels. The total score on the Ch-ASIQ among all patients was 1.84±0.55. Multivariate analyses showed that refusing insulin use was positively significantly associated with higher scores on the Ch-ASIQ and the three sub-dimensions of "Factors promoting self-efficacy," "Fear of pain or needles," and "Time and family support" [ β (95% CI): 0.515 (0.355-0.674), 0.728 (0.470-0.986), 0.273 (0.030-0.515), 0.909 (0.606-1.213), all P<0.05]. In addition, disease duration [ β (95% CI):-0.011 (-0.019 to -0.004)] was independently negatively associated with the Ch-ASIQ score. In comparison, age [ β (95% CI): 0.011 (0.003-0.018)], DDS-4 [0.129 (0.069-0.190)], and PHQ-8 [0.015 (0.000-0.029)] were independently positively associated with the Ch-ASIQ score (all P<0.05). There were slight differences in the factors influencing the four sub-dimensions of the Ch-ASIQ scale. Conclusions:Community-based patients with T2D had moderate negative attitudes toward starting insulin treatment. Refusing insulin use, shorter diabetes duration, older age, higher diabetes distress, and higher levels of depression were associated with higher negative attitudes towards starting insulin use.

Synovium is the target organ of rheumatoid arthritis.The excessive proliferation of synovial cells and insufficient apoptosis lead to synovial hyperplasia,which in turn causes damage to the surrounding tissues of the joint and bone destruction."Yang transforming qi and yin forming elements"is derived from Su Wen and is a highly summarized description of the functions of yin and yang,which runs through the entire course of the disease.This article elucidated the theoretical connotation of"yang transforming qi and yin forming elements"and its connection with synovial hyperplasia,proposing that the insufficiency of"yang transforming qi"is the root of synovial hyperplasia,while the excess of"yin forming elements"is the manifestation of synovial hyperplasia.Based on this,it put forward that"assisting yang qi as the priority,and according to the bias of pathogenic factors of yin,supplementing the method of reducing yin forming elements"is an important principle for treating this disease,which could provide new ideas for the treatment of the disease.

Objective:To analyze the evaluation value of contrast-enhanced ultrasound (CEUS) combined with automatic volumetric ultrasound in the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer.Methods:A retrospective study was conducted on 98 female patients with breast cancer admitted to Shaanxi Provincial Cancer Hospital from January to December 2022. All patients received 4 cycles of NAC, and underwent conventional ultrasound, automatic volumetric ultrasound, CEUS, and histopathological examination before and after treatment. Based on the post-treatment histopathological efficacy, patients were divided into the effective group ( n=67) and the ineffective group ( n=31). The CEUS and automatic volumetric ultrasound parameters before and after treatment, as well as the evaluation efficacy of these two types of parameters for NAC efficacy in breast cancer, were compared. The value of CEUS combined with automatic volumetric ultrasound in evaluating NAC efficacy for breast cancer was analyzed. Results:After NAC treatment, the CEUS parameters [time to peak (TTP) and arrival time (AT) of contrast agent] were longer than those before treatment, while the peak intensity (PI) was lower than that before treatment (all P<0.05); the automatic volumetric ultrasound parameters (tumor volume, area, thickness, length, and width) after NAC treatment were all smaller than those before treatment (all P<0.05). After treatment, the PI, volume, area, thickness, length, and width in the effective group were significantly smaller than those in the ineffective group, while the TTP and AT were significantly longer than those in the ineffective group (all P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of CEUS parameters and automatic volumetric ultrasound parameters for predicting effective NAC efficacy in breast cancer was 0.837(0.749-0.904) and 0.864(0.780-0.925), respectively, with no statistically significant difference between the two ( P=0.674). The AUC of the combined parameters for predicting effective NAC efficacy was 0.942(0.875-0.979), which was significantly higher than that of CEUS parameters or automatic volumetric ultrasound parameters alone ( Z=2.947, 2.135, P=0.003, 0.033). Conclusions:The combination of CEUS and automatic volumetric ultrasound parameters has high value in the efficacy evaluation of NAC for breast cancer and can be used as a clinical reference.