Objective: To study the efficacy of photosensitizer 8- methoxsalen (8-MOP) combined with ultraviolet radiation A (UVA) in inducing ferroptosis in mouse melanoma B16 cells, and to assess the resultant changes in immunogenicity, and their impact on subsequent immune activation after treatment. Methods: 1) Mouse melanoma B16 cells were cultured and treated with 8-MOP (100 ng/mL) and UVA (4 J/cm ), and then cultured in a constant temperature incubator (37℃, 5%CO ) for 24 hours after irradiation. 2) CCK8 (cell proliferation and toxicity) detection kit was used to detect the death rate of tumor cells. 3) LPO (lipid peroxide) and GSH (glutathione) detection kits were used to detect the degree of oxidative damage of tumor cells; Changes of Fe , mitochondrial membrane potential (JC-1) and BODIPY 581/591 C11 (lipid peroxidation detection kit) in tumor cells were detected by confocal microscope. Western blotting (WB) was performed to detect GPX4, SLC7A11 and NCOA4 to confirm ferroptosis. 4) The expression of HMGB1 (high mobility group protein 1), ATP and CRT (calreticulin) in the supernatant of tumor cell culture was detected by ELISA kit to evaluate the immunogenicity of tumor cells. 5) 1×10 B16 cells were injected subcutaneously into the skin of the back and neck of mice at a dose of 100 μL to construct a mouse melanoma model. Spleen mononuclear cells of tumor-bearing mice were extracted and immediately co-cultured with irradiated tumor cells for 48 h. Changes of dendritic cell (DC) maturity were detected by MHC-II, CD11c, CD80 and CD83 flow cytometry. Results: After UVAP, the survival rate of B16 cells decreased significantly (61.39±6.823 vs 84.81±7.026 vs 100.0±3.996, P<0.000 1, P<0.01). UVAP effectively induced ferroptosis in B16 cells, characterized by increased LPO and C11-bodipy lipid peroxidation, GSH depletion, Fe accumulation, mitochondrial membrane depolarization, decreased GPX4 and SLC7A11 protein expression, and increased NCOA4 expression, all in line with the trend of ferroptosis. UVAP also enhanced tumor cell immunogenicity, evidenced by elevated release of ATP, CRT, and HMGB1. The immunogenicity of B16 cells increased, the expressions of ATP, CRT and HMGB1 increased, and the DC maturity increased (CD80: 31.92±4.071 vs 19.77±3.177; CD83: 21.40±4.787 vs 12.19±1.487, P<0.001, P<0.01). Conclusion: The combined action of 8-MOP and UVA can induce ferroptosis in B16 tumor cells, enhance the immunogenicity of tumor cells, release more tumor antigens, promote the maturation of DC, present antigens better, thereby facilitating subsequent immune activation.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To understand the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Shandong province from 2010 to 2022, analyze the trends in morbidity and mortality, and provide a scientific basis for the prevention, control, diagnosis, and treatment of SFTS.Methods:The data on SFTS cases and deaths were retrospectively collected through the China Disease Control and Prevention Information System′s infectious disease surveillance system and the Shandong province all-cause mortality surveillance system. Descriptive epidemiological method was used for epidemiological analysis, and the Joinpoint regression model was applied to analyze trends in morbidity and mortality.Results:From 2010 to 2022, 6 714 SFTS cases were reported in Shandong, with an average crude incidence rate (CIR) and age-standardized incidence rate (ASIR) of 0.52/100 000 and 0.43/100 000, respectively. Among these, 1, 064 cases died within 30 days of onset, with an average crude mortality rate (CMR) and age-standardized mortality rate (ASMR) of 0.08/100, 000 and 0.06/100 000, respectively, and an average case fatality rate of 15.85%. The average incidence rates for males and females were 0.52/100 000 and 0.53/100 000, respectively, with no statistically significant difference ( P>0.05). The average annual mortality rate for males (0.09/100 000) was higher than that for females (0.08/100 000), and the average annual case fatality rate for males (17.21%) was higher than that for females (14.48%), with statistically significant differences ( P<0.05); 93.95% of the cases were over 45 years old, and 86.56% of the deaths were over 60 years old. Both cases and deaths were primarily among farmers, accounting for over 85% of the total. From 2010 to 2022, the incidence rate of SFTS in Shandong showed an overall upward trend, with an average annual percentage change (AAPC) in CIR of 23.58% and an AAPC in ASIR of 19.97%, P<0.05. The mortality rate of SFTS cases in Shandong from 2010 to 2022 showed a continuous and significant upward trend, with a CMR AAPC of 27.64% and an ASMR AAPC of 22.70%, P<0.05. SFTS incidence and mortality in Shandong exhibited clear seasonality, with high occurrence from May to October, primarily concentrated in the Jiaodong Peninsula and the hilly areas of central Shandong. The number of affected counties increased in a wave-like pattern, expanding from 6 in 2010 to 79 in 2021 for cases and from 2 in 2010 to 53 in 2022 for deaths. Conclusions:From 2010 to 2022, the incidence and mortality of SFTS in Shandong showed an upward and expanding trend, with a particularly heavy disease burden among middle-aged and elderly farmers.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To understand the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Shandong province from 2010 to 2022, analyze the trends in morbidity and mortality, and provide a scientific basis for the prevention, control, diagnosis, and treatment of SFTS.Methods:The data on SFTS cases and deaths were retrospectively collected through the China Disease Control and Prevention Information System′s infectious disease surveillance system and the Shandong province all-cause mortality surveillance system. Descriptive epidemiological method was used for epidemiological analysis, and the Joinpoint regression model was applied to analyze trends in morbidity and mortality.Results:From 2010 to 2022, 6 714 SFTS cases were reported in Shandong, with an average crude incidence rate (CIR) and age-standardized incidence rate (ASIR) of 0.52/100 000 and 0.43/100 000, respectively. Among these, 1, 064 cases died within 30 days of onset, with an average crude mortality rate (CMR) and age-standardized mortality rate (ASMR) of 0.08/100, 000 and 0.06/100 000, respectively, and an average case fatality rate of 15.85%. The average incidence rates for males and females were 0.52/100 000 and 0.53/100 000, respectively, with no statistically significant difference ( P>0.05). The average annual mortality rate for males (0.09/100 000) was higher than that for females (0.08/100 000), and the average annual case fatality rate for males (17.21%) was higher than that for females (14.48%), with statistically significant differences ( P<0.05); 93.95% of the cases were over 45 years old, and 86.56% of the deaths were over 60 years old. Both cases and deaths were primarily among farmers, accounting for over 85% of the total. From 2010 to 2022, the incidence rate of SFTS in Shandong showed an overall upward trend, with an average annual percentage change (AAPC) in CIR of 23.58% and an AAPC in ASIR of 19.97%, P<0.05. The mortality rate of SFTS cases in Shandong from 2010 to 2022 showed a continuous and significant upward trend, with a CMR AAPC of 27.64% and an ASMR AAPC of 22.70%, P<0.05. SFTS incidence and mortality in Shandong exhibited clear seasonality, with high occurrence from May to October, primarily concentrated in the Jiaodong Peninsula and the hilly areas of central Shandong. The number of affected counties increased in a wave-like pattern, expanding from 6 in 2010 to 79 in 2021 for cases and from 2 in 2010 to 53 in 2022 for deaths. Conclusions:From 2010 to 2022, the incidence and mortality of SFTS in Shandong showed an upward and expanding trend, with a particularly heavy disease burden among middle-aged and elderly farmers.

Objective:To analyze the surveillance data of population in rabies exposure and post-exposure prophylaxis (PEP) clinics in Shandong province from 2019 to 2023, explore risk factors for exposure, and provide a basis for further standardizing PEP.Methods:Based on surveillance data from the rabies exposure treatment clinic vaccination information system, population, and spatial administrative division data in Shandong province from 2019 to 2023, descriptive epidemiological methods were applied to analyze using SPSS 18.0.Results:The number of individuals receiving post-exposure treatment at PEP clinics in Shandong province from 2019 to 2023 was over 1 million annually and showed an increasing trend year by year, with the highest number of visits occurring from May to August each year. The number of female patients is increasing year by year. The 15-year-old and younger age group accounted for 31.69%-36.86% of clinic visits. Grade Ⅲ exposures accounted for 53.40%, and limbs accounted for approximately 89.81% of exposed areas. Approximately 1.94% is multi site exposure. The main injuring animals were dogs, followed by cats, and the proportion of cats is increasing year by year. The proportion of doctor′s office visitors who self-treated wounds increased from 32.32% to 45.46%, while the proportion of outpatient wound treatment decreased from 76.07% to 66.24%. The whole course vaccination rate after initial exposure is 63.79%. The whole course vaccination rate for the 15-29-year-old age group was lower than that for other age groups. The usage rate of passive immune preparations among grade Ⅲ exposed individuals is 35.66%. From 2019 to 2023, 8 cases of rabies were reported, none of whom received standard post-exposure treatment.Conclusions:The epidemic characteristics and exposure risk of people exposed to suspected rabies animals in Shandong province have changed. It is necessary to pay attention to the female population, the population with low vaccination rate between 15 to 29 years of age, cat bitten people, and carry out continuous monitoring on the exposed population, and timely adjust the prevention and control strategies.

Objective:To investigate the changes of left atrial structure and function in patients with apical hypertrophic cardiomyopathy (ApHCM) by three-dimensional (3D) echocardiography.Methods:From September 2020 to December 2022, 112 patients with ApHCM(ApHCM group) diagnosed at Tongji Hospital Tongji Medical College, Huazhong University of Science and Technology and 41 age- and sex-matched normal controls(control group) were finally enrolled. In 'pure’ ApHCM patients, cardiac hypertrophy was confined to the apical segment below the papillary muscle. The wall thickness of apical and intermediate segments in 'mixed’ ApHCM patients increased, but the wall thickness of apical segment was the largest. Two-dimensional(2D) and 3D volume and strain parameters of left atrium were compared between control group and ApHCM group, 'pure’ and 'mixed’ ApHCM patients.The correlations between 2D and 3D volume and strain parameters of left atrium and intraclass correlation coefficient (ICC) of those parameters were analyzed. The ROC curve was performed to determine the cutoff values of 3D left atrial volume abnormalities in all subjects. Logistics regression analysis was performed to analyze the impact factors of the left atrial enlargement in patients with ApHCM.Results:Compared with the control group, 2D left atrial maximum volume index (2D LAVimax), 2D left atrial minimum volume index (2D LAVimin), 3D left atrial maximum volume index (3D LAVimax), 3D left atrial minimum volume index (3D LAVimin), and 3D left atrial presystolic volume index (3D LAVipreA) significantly increased in ApHCM group( Z=-6.54, -6.38, -6.98, -7.40, -6.96; all P<0.001). However, 2D left atrial ejection fraction (2D LAEF) ( Z=-3.75, P<0.001), 2D left atrial expansion index (2D LAEI) ( t=-4.15, P<0.001), 3D left atrial ejection fraction (3D LAEF) ( Z=-5.09, P<0.001), 3D left atrial expansion index (3D LAEI) ( t=-5.49, P<0.001), 2D left atrial reservoir strain (2D LASr) ( t=-12.03, P<0.001), 2D left atrial conduit strain (2D LAScd) ( t=7.91, P<0.001), 2D left atrial contractile strain (2D LASct) ( t=6.06, P<0.001), 3D left atrial reservoir strain (3D LASr) ( t=-9.23, P<0.001), 3D left atrial conduit strain (3D LAScd) ( t=7.12, P<0.001) and 3D left atrial contractile strain (3D LASct) ( t=4.78, P<0.001) significantly decreased in ApHCM group. Compared with the 'pure’ ApHCM group, 2D LAVimax, 3D LAVimax, 2D LAVimin, 3D LAVimin, 3D LAVipreA in patients with mixed ApHCM increased more significantly, while 2D LAEF, 2D LAEI and 2D LASr decreased more significantly. The measurements of left atrial volume and strain by 3D echocardiography were significantly correlated with 2D measurements ( P<0.05). The correlations between 2D LAVimax and 3D LAVimax, 2D LAVimin and 3D LAVimin, 2D LAEF and 3D LAEF, 2D LASr and 3D LASr, 2D LAEI and 3D LAEI ( r=0.91, 0.93, 0.72, 0.76, 0.57; all P<0.05) were more than moderate. The repeatability of 3D left atrial strain was lower than 2D results, while the repeatability of 3D left atrial volume was higher than 2D results. ROC curve analysis showed that 3D echocardiography parameters could identify left atrial volume abnormality in all subjects. The cutoff values of 3D LAVimax, 3D LAVimin, 3D LAVipreA in all subjects were 36 ml/m 2, 18 ml/m 2 and 27 ml/m 2, respectively. Multivariate binary logistic regression analyses showed that ratio of LV systolic obliteration to cavity was independent factor affecting left atrial enlargement in ApHCM patients( OR=1.20, P<0.001). Conclusions:Three-dimensional echocardiography is significant for the accurate evaluation of left atrial structural changes in patients with ApHCM. Ratio of left ventricular systolic obliteration to cavity was an independent impact factor of left atrial enlargement in ApHCM patients.

【Objective】 To investigate the preventive effects of early apoptotic splenic mononuclear cells induced by extracorporeal photopheresis (ECP) on acute graft versus host disease (aGVHD) in mice and explore the underlying mechanisms. 【Methods】 1) Splenic mononuclear cells were extracted from C57BL/6 mice and treated with different concentrations of 8-MOP (50 ng/mL, 100 ng/mL, 200 ng/mL, 300 ng/mL, 600 ng/mL). After treatment, irradiate the cells with 2 J/cm² of ultraviolet light. Then, use the Annexin V-FITC/PI apoptosis detection kit to assess the early apoptosis rate of the cells and determine the optimal concentration of 8-MOP for the experiment.2) There were 35 SPF-grade female BALB/C mice (H-2Kd) aged 6-8 weeks. After whole-body irradiation with 8Gy X-rays, the mice were divided into five groups: sham irradiation group received intravenous infusion of 0.2 mL of normal saline, the syngeneic bone marrow transplantation group received intravenous infusion of 0.2 mL of BALB/C mouse bone marrow nucleated cell suspension (including a cell count of 1×10⁷), the allogeneic bone marrow transplantation group received intravenous infusion of 0.2 mL of C57BL/6 mouse bone marrow nucleated cell suspension (including a cell count of 1×10⁷), the aGVHD group received intravenous injection of a mixture of C57BL/6 mouse bone marrow nucleated cells (including a cell count of 1×10⁷) and splenic mononuclear cells (including a cell count of 1×10⁷) in 0.2 mL, the ECP prevention group received pre-transplant intravenous infusion of 0.2 mL of ECP-treated splenic mononuclear cells of C57BL/6 mice (including a cell count of 1×10⁷ ) 48 hours before transplantation, and on the day of transplantation, intravenous injection of a mixture of C57BL/6 mouse bone marrow nucleated cells (including a cell count of 1×10⁷) and splenic mononuclear cells (including a cell count of 1×10⁷ ) in 0.2 mL.The preventive effects of ECP on aGVHD were observed, and the concentrations of IFN-γ, IL-2, TNF, IL-4 and IL-6 in mouse serum were measured using CBA. Th1 cell counts were determined by flow cytometry. 【Results】 Different concentrations of 8-MOP (50 ng/mL,100 ng/mL, 200 ng/mL, 300 ng/mL, 600 ng/mL) were used to treat mouse splenic mononuclear cells. The early apoptosis rates (%), observed after treatment were as follows: (14.18±0.865) vs (16.76±0.407) vs (18.83±0.404) vs (19.27±0.404) vs (14.5±0.529). The appropriate concentration of 8-MOP was determined to be 200 ng/mL.In vivo experiment, the results showed that the aGVHD group had decreased survival rate, reduced body weight, and increased clinical scores compared to the syngeneic and allogeneic bone marrow transplantation groups (P<0.01), and the chimerism of bone marrow cells in mice after transplantation was over 90%. ECP significantly improved the survival rate of mice after transplantation, reduced clinical scores (P<0.05), and decreased the concentrations of Th1 cell cytokines in serum (P<0.05) and the counts of Th1 cells in the spleen (P<0.05). 【Conclusion】 ECP-induced early apoptotic single nuclear cells from the spleen can prevent the occurrence of aGVHD by reducing the Th1 response in mouse.

Humans ; Female ; Breast Neoplasms/pathology* ; Multiomics ; Trastuzumab ; Receptor, ErbB-2/genetics* ; Machine Learning

Objective:To investigate the risk factors of bone cement leakage after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A multi-center, large-sample, case-control study was carried out to analyze the clinical data of 2 273 OVCF patients (2 689 vertebrae) undergone PVP at four hospitals between May 2018 and October 2021, including 994 males and 1 279 females, with the age of 52-91 years [(69.1±3.1)years]. Of all, 581 patients (604 vertebrae) were allocated to leakage group and 1 692 patients (2 085 vertebrae) to no leakage group according to the occurrence of bone cement leakage. The gender, age, fracture sites, vertebral compression degree, endplate integrity of fractured vertebrae, surgical segments, surgical approaches and bone cement injection volume were recorded. Univariate analysis was used to investigate the correlation between those indicators with bone cement leakage. Multivariate Logistic regression analysis was used to identify the independent risk factors for bone cement leakage.Results:Univariate analysis showed that gender, age, fracture sites, vertebral compression degree, bone cement injection volume were related to bone cement leakage after PVP ( P<0.05 or 0.01), but no correlation was found in the endplate integrity of fractured vertebrae, surgical segments and surgical approaches (all P>0.05). Multivariate Logistic regression analysis showed that fracture sites ( OR=1.68, 95% CI 1.11-2.55, P<0.05), vertebral compression degree more than 40% ( OR=1.98, 95% CI 1.29-3.02, P<0.01), bone cement injection volume greater than or equal to 5.5 ml ( OR=1.55, 95% CI 1.07-2.26, P<0.05) were significantly associated with bone cement leakage after PVP. Conclusion:Thoracic vertebral fracture, vertebral compression degree more than 40% and bone cement injection volume greater than or equal to 5.5 ml are independent risk factors for bone cement leakage after PVP in OVCF.