BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Systemic inflammatory response (SIR) evoked by cardiopulmonary bypass (CPB) is still one of the major causes of postoperative multiple organs injuries. Since the concentrations of circulating inflammatory factors are positively associated with postoperative adverse events, removal or inhibition of inflammatory factors are considered as effective treatments to improve outcomes. After more than 20 years of research, however, the results are disappointed as neither neutralization nor removal of circulating inflammatory factors could reduce adverse events. Therefore, the role of circulating inflammatory factors in CPB-related organs injuries should be reconsidered in order to find effective therapies. Here we reviewed the association between circulating inflammatory factors and the outcomes, as well as the current therapies, including antibody and hemadsorption. Most importantly, the role of circulating inflammatory factors in SIR was reviewed, which may be helpful to develop new measures to prevent and treat CPB-related organs injuries.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

During the 14th Five-Year Plan period, the population of China has turned into a stage of negative growth, the fertility rate gradually declined, and the infertility rate gradually increased. The most effective treatment for infertility is assisted reproductive technology (ART), which has brought hope for fertility to many patients. However, the current promotion of the utilization of ART is still fraught with many obstacles. In this context, focusing on the realistic challenges of ART on its development in China, we will take a problem-oriented approach, utilize the relevant policies of ART in foreign countries as references, and put forward policy recommendations for the further implementation of ART, such as coordinating the balanced distribution of ART resources in the region, strengthening policy safeguards for ART, enhancing the institutional functioning of professional associations in medical ethics, and standardizing the application of ART treatments.

Objective:To investigate the feasibility and optimal expansion width of replacing the left anterior descending coronary artery (LADCA) with the region of heart sparing (RHS) to reduce cardiac radiation dose during breast cancer radiotherapy.Methods:Retrospective analysis was conducted on data from 88 patients with left-sided breast cancer who underwent radiotherapy at 2 centers: Nanfang Hospital of Southern Medical University (50 cases for the training set, 15 cases for the internal test set) and Ganzhou Hospital of Nanfang Hospital (23 cases for the external test set) from March 2022 to January 2024. All patients had left-sided invasive ductal carcinoma with axillary lymph node metastasis, and had undergone modified radical mastectomy and chemotherapy. Based on simulation CT images, 2 radiation oncologists delineated the LADCA and 8 RHSs. The RHSs were delineated by expanding the LADCA contour by 0.5 cm increments, totaling 8 expansions. The RHS widths were defined as 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 cm. The nnU-Net model was trained for 3D automatic segmentation of the LADCA and RHSs. Model performance was evaluated using the Dice similarity coefficient (DSC), relative volume error (RVE), sensitivity, specificity, and 95% Hausdorff distance (HD95). Additionally, the minimum, maximum, and average relative dose variations (RDV) as well as V5% and V20% indicators were calculated for the LADCA and each RHS. Correlation analysis was performed using the least squares regression, with the slope and coefficient of determination ( R2) employed to evaluate the accuracy of the model fitting, the relationship between the LADCA and RHS, and the degree of their correlation, thereby assessing the substitutive effect of the RHS for the LADCA. Results:The DSC for the LADCA was 0.415, while the DSCs for RHS widths of 0.5 cm and 4.0 cm were 0.718 and 0.835, respectively. Overall, the automatic segmentation performance improved with increasing RHS width. The DSC, RVE, sensitivity, specificity, and HD95 for the external test set were largely consistent with those of the internal test set, demonstrating the model's good robustness across different datasets. All RDVmin values were negative, while RDVmax and RDVmean showed a positive correlation with RHS width. RDVmean increased from 39.01% to 75.89% as the RHS width increased. In the correlation analysis, the slopes for RHS widths of 1.5 cm and 2.0 cm were 0.95 and 1.05, respectively, with R2 values and coefficients of variation of 0.79 and 0.73, and 21.11% and 24.03%, respectively. Conclusions:The automatic segmentation model trained on nnU-Net can accurately segment RHSs. Based on geometric and dosimetric indicators, a 1.5 cm-wide RHS is the most suitable substitute for the LADCA, effectively limiting the radiation dose to the LADCA without compromising target dose coverage.

Objective:To review the clinicopathological features of TFE3-rearranged renal cell carcino-ma(TFE3-RCC)with venous tumor thrombus(VT)(TFE3-VT),to explore treatment strategies and to prognostic characteristics,and to provide diagnostic and therapeutic references for TFE3-VT patients.Methods:Patients who underwent surgery at Department of Urology,Peking University Third Hospital from January 2013 to January 2024 were enrolled,including three cohorts:Pathologically confirmed TFE3-VT patients,TFE3-RCC patients without VT(TFE3-non-VT),and non-TFE3-rearranged renal cell carcinoma patients with VT(non-TFE3-VT).Clinical history,imaging data,pathological data,and follow-up records were collected.Primary and secondary endpoints were progression-free survival(PFS)and overall survival(OS),respectively.(1)Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients.Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test;non-normally distributed variables were expressed as M(P25,P75)and analyzed with Mann-Whitney U test;categorical variables were described as frequency and percentage[n(％)]and compared by x2 test or Fisher's exact test.(2)Clinical history,radiological presenta-tions,surgical data,and histopathological features of the TFE3-VT patients were comprehensively charac-terized.(3)Survival analysis was performed for the TFE3-VT patients.Follow-up data of the TFE3-VT patients were described in detail,and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients.When compared with the TFE3-non-VT counterparts,Kaplan-Meier method was used to generate PFS and OS curves among:(1)the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ;(2)TFE3-VT versus TFE3-non-VT cohorts;(3)stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients.Intergroup survival differences were statistically evaluated using Log-rank tests.For comparisons with the non-TFE3-VT patients,a 1∶1 propensity score matching(PSM)was implemented to balance baseline characteristics between the two cohorts.Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups,with Log-rank tests employed to determine statistical significance of survival disparities.All statistical analyses were conducted with R software(v 4.2.3),and two-tailed P＜0.05 was considered statistically significant.Results:The study included 45 TFE3-RCC patients:13 TFE3-VT and 32 TFE3-non-VT cases.Additionally,523 non-TFE3-VT patients were enrolled.Among the 13 TFE3-VT patients,9 were female(69.2％)and 4 male(30.8％),with a mean age of(37.9±14.4)years,mean BMI of(22.2±3.5)kg/m2,median age-adjusted Charlson comorbidity index(aCCI)of 1.0(0.0,1.0),and preoperative creatinine level of(75.3±15.9)μmol/L;tumors were located in the left kidney in 7 patients(53.8％)and right kidney in 6(46.2％);preoperative distant metastasis(M1 stage)was present in 6 patients(46.2％),while 7(53.8％)showed no metastasis;VT distribution by Mayo level comprised 7 cases(53.8％)at level 0,1 case each at levels Ⅰ and Ⅳ(7.7％respectively),and 2 cases each at levels Ⅱ and Ⅲ(15.4％respectively);surgical approaches comprised open surgery(n=2,15.4％),laparoscopic surgery(n=6,46.1％),and robot-assisted laparoscopic surgery(n=5,38.5％);mean operative time was(273±79)min,and intraoperative blood loss was(722±570)mL;mean maximum tumor diameter was(10.8±2.4)cm.All the 13 patients underwent TFE3 protein immunohistochemistry(IHC)staining,with 7 confirmed by fluorescence in situ hybridization(FISH).Tumor recurrence or metastasis occurred in 11 patients(84.6％),and 9(69.2％)patients died during follow-up.Median PFS was 4 months(1 year PFS rate:31％),and median OS was 13 months(1 year OS rate:54％).Survival analysis of 45 TFE3-RCC pa-tients revealed statistically significant differences in PFS and OS across all the clinical stages(P＜0.001).The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients(P＜0.001),with persistent significance in stage Ⅲ subgroup analysis(P＜0.05).After PSM,TFE3-VT pa-tients showed significantly inferior PFS compared with non-TFE3-VT(P=0.01),though no significant difference was shown between the OS curves(P=0.11).Conclusion:TFE3-VT predominantly occurs in young females with frequent preoperative metastases.Strongly-positive staining of TFE3 protein in IHC stai-ning and red-green split signals in FISH tests are reliable diagnostic markers.TFE3-VT patients exhibit in-ferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.

Hashimoto's thyroiditis(HT)is an autoimmune thyroid disease characterized by diffuse enlargement of thyroid gland and elevated thyroid autoantibodies.HT is closely related to emotional factors,conveyance and dispersion function of the liver,and the qi movement of the five zang organs.This paper explores the approach to the differentiation and treatment of HT based on Professor Yang Shuyu's view of regulation of both mind and body.In the view of regulation of both mind and body,the regulation of mind is to harmonize emotions,and the regulation of body refers to the conveyance and dispersion function of zang-fu organs.Based on the view of regulation of both mind and body,the pathological changes of HT are characterized by the disordered conveyance and dispersion of qi movement,and the stable phase,hyperthyroid phase,and hypothyroid phase of HT correspond to obstructed conveyance and dispersion,excessive conveyance and dispersion,and insufficient conveyance and dispersion,respectively.The emotional disorders caused by the failure of mind regulation exist throughout the disease course.Therefore,the treatment of HT can be conducted by using the therapies of unblocking,suppressing,and tonifying separately for stable phase,hyperthyroid phase,and hypothyroid phase to address the root cause,and then the conveyance and dispersion of visceral qi movement are restored.Besides,the therapeutic method of resolution is used to alleviate symptoms by removing goiter and dissipating nodules.Simultaneously,emotional regulation therapy is incorporated to achieve a comprehensive efficacy for harmonizing physique-spirit and mind-body through the regulation of emotions,conveyance and dispersion of qi movement,and visceral functions.The view of regulation of both mind and body provides new methods and approaches for traditional Chinese medicine management of HT.

Objective To investigate the correlations of CALLY index in early pregnancy with the onset and severity of preeclampsia.Methods A total of 987 pregnant women were prospectively en-rolled as study subjects,with 42 lost during follow-up,resulting in a final inclusion of 945 subjects.Based on the occurrence and severity of preeclampsia during follow-up,the pregnant women were di-vided into preeclampsia group(n=47),severe preeclampsia group(n=49),and normal group(n=849).General information and laboratory test results were collected from all pregnant women,and the CALLY index was calculated.The Pearson correlation analysis was used to explore the correlation be-tween CALLY index and severity of preeclampsia(mean arterial pressure);the receiver operating characteristic(ROC)curve was plotted to analyze the predictive efficacy of each indicator for pre-eclampsia;Cox regression analysis was used to explore the influencing factors for the onset of preeclamp-sia.Results The mean arterial pressure and 24-hour urine protein levels were higher in the severe pre-eclampsia group than those in the preeclampsia group and normal group,and higher in the preeclampsia group than those in the normal group(P＜0.05).The CALLY index was lower in the severe preeclamp-sia group than in the preeclampsia group and normal group,and lower in the preeclampsia group than in the normal group(P＜0.05).Pearson correlation analysis showed a negative correlation between CALLY index and mean arterial pressure(r=-0.571,P＜0.001).The ROC curve showed that the area under the curve(AUC)of CALLY index for predicting preeclampsia was 0.941(95％CI,0.900 to 0.981).Multivariate Cox regression analysis showed that an increased CALLY index was an independent protective factor for the onset of preeclampsia(HR=0.185,95％CI,0.092 to 0.374,P＜0.001).Conclusion The CALLY index is negatively correlated with the severity of preeclampsia and is an independent influencing factor for the onset of preeclampsia,which can be used as an auxiliary indicator to assess the onset and severity of preeclampsia in pregnant women.