Objective To compare the dosimetric differences in the heart and its substructures between two hybrid plans for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. Methods A total of 46 patients with early-stage left-sided breast cancer who underwent hypofractionated whole-breast radiotherapy were randomly selected. Two hybrid radiotherapy plans were used, including hybrid intensity-modulated radiotherapy (H_IMRT) and hybrid volumetric-modulated arc therapy (H_VMAT). The heart and its substructures were contoured, including left anterior descending (LAD), left ventricle (LV), right coronary artery (RCA), and right ventricle (RV). The heart and substructure doses, as well as monitor units, were compared between H_IMRT and H_VMAT. Results Both hybrid plans met the clinical requirements. H_IMRT significantly outperformed H_VMAT for the heart (V₁₀, V₃₀, and D_mean), LAD (V₃₀, V₄₀, D_max and D_mean), LV (V₁₀, V₂₀ and D_mean), RCA (D_max, D_mean), and RV (V₅, V₁₀, D_mean) (P < 0.001). Additionally, H_IMRT was significantly superior to H_VMAT for heart V₅, LAD V₂₀, and RV V₂₀ (P = 0.005, 0.035 and 0.037). For LAD (V₁₅, V₄₀) and LV (V₅, V₂₅), H_IMRT was slightly better than H_VMAT, and the difference was not statistically significant. Conclusion Both H_IMRT and H_VMAT hybrid radiotherapy plans are suitable for hypofractionated whole-breast radiotherapy after breast-conserving surgery in patients with early-stage left-sided breast cancer. H_IMRT is slightly better than H_VMAT in dose sparing for the heart and its substructures.

Purpose To investigate the independent risk factors for early papillary gastric adenocarcinoma(EP-GA)and construct a diagnostic nomogram.Methods A retrospective analysis was performed on the clinicopathologi-cal characteristics of 325 cases of early differentiated gastric adenocarcinoma.Taking EPGA as the case group and early well-moderately differentiated tubular gastric adenocarcinoma(ETGA)as the control group,the independent risk fac-tors for the occurrence of EPGA were identified through univariate and multivariate analyses,and a nomogram was con-structed.The diagnostic performance of the nomogram was evaluated using the receiver operating characteristic(ROC)curves,Hosmer-Lemeshow goodness-of-fit tests,and calibration curves.Results Among the 325 cases of early differ-entiated gastric adenocarcinoma,there were 121 cases of EPGA and 204 cases of ETGA.Univariate analysis showed that elevated appearance(56.3％),ulcer formation(11.5％),tumor maximum diameter of 2.15(1.60,3.00)cm,moderately-differentiated(55.2％),submucosal invasion(21.9％),lymphovascular invasion(10.4％),high ex-pression of MUC5AC(75.0％),microsatellite instability-high(15.6％),and wild-type expression of p53(59.4％)were significantly associated with an increased risk of EPGA.Multivariate analysis revealed that gross appearance,ul-cer formation,tumor maximum diameter,and the expression of MUC5AC was independent risk factors for EPGA.A di-agnostic nomogram was constructed,and the area under the ROC curve(AUC)was calculated.In the training and val-idation cohorts,the AUC values were 0.847(95％CI=0.799-0.896)and 0.830(95％CI=0.733-0.927),re-spectively.The Hosmer-Lemeshow goodness-of-fit tests showed that x2=13.498,P=0.096,and x2=7.138,P=0.415,respectively.Conclusion The nomogram,based on independent risk factors,exhibits good accuracy for diag-nosing EPGA and can help pathologists in achieving rapid and precise EPGA diagnosis.

Purpose To investigate the independent risk factors for early papillary gastric adenocarcinoma(EP-GA)and construct a diagnostic nomogram.Methods A retrospective analysis was performed on the clinicopathologi-cal characteristics of 325 cases of early differentiated gastric adenocarcinoma.Taking EPGA as the case group and early well-moderately differentiated tubular gastric adenocarcinoma(ETGA)as the control group,the independent risk fac-tors for the occurrence of EPGA were identified through univariate and multivariate analyses,and a nomogram was con-structed.The diagnostic performance of the nomogram was evaluated using the receiver operating characteristic(ROC)curves,Hosmer-Lemeshow goodness-of-fit tests,and calibration curves.Results Among the 325 cases of early differ-entiated gastric adenocarcinoma,there were 121 cases of EPGA and 204 cases of ETGA.Univariate analysis showed that elevated appearance(56.3％),ulcer formation(11.5％),tumor maximum diameter of 2.15(1.60,3.00)cm,moderately-differentiated(55.2％),submucosal invasion(21.9％),lymphovascular invasion(10.4％),high ex-pression of MUC5AC(75.0％),microsatellite instability-high(15.6％),and wild-type expression of p53(59.4％)were significantly associated with an increased risk of EPGA.Multivariate analysis revealed that gross appearance,ul-cer formation,tumor maximum diameter,and the expression of MUC5AC was independent risk factors for EPGA.A di-agnostic nomogram was constructed,and the area under the ROC curve(AUC)was calculated.In the training and val-idation cohorts,the AUC values were 0.847(95％CI=0.799-0.896)and 0.830(95％CI=0.733-0.927),re-spectively.The Hosmer-Lemeshow goodness-of-fit tests showed that x2=13.498,P=0.096,and x2=7.138,P=0.415,respectively.Conclusion The nomogram,based on independent risk factors,exhibits good accuracy for diag-nosing EPGA and can help pathologists in achieving rapid and precise EPGA diagnosis.

Objective:To discuss the differential expression of microRNA(miR)-125a-5p in peripheral blood mononuclear cells(PBMCs)of the patients with mycobacterium tuberculosis(MTB)infection and its effect on macrophage polarization,and to clarify its clinical significance.Methods:A total of 40 patients with active tuberculosis(ATB)(ATB group),35 patients with latent tuberculosis infection(LTBI)(LTBI group),and 40 healthy physical examinees(control group)clinically diagnosed from July 2022 to June 2023 were selected.The fasting blood samples of the subjects in three groups were collected next morning after 12 h of fasting,and then serum was separated.Enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of inflammatory factors in the serum of the subjects in various groups.Simultaneously,the PBMCs were extracted from the subjects in various groups;flow cytometry was used to detect the expression levels of CD80 and CD206 proteins in the PBMCs of the subjects in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of microRNA(miR)-125a-5p and interleukin-6(IL-6)mRNA in PBMCs of the subjects in various groups.Results:There were no statistically significant differences in the general information of the subjects among three groups(P>0.05).Compared with control group,the erythrocyte sedimentation rate(ESR),percentages of monocytes(MONO),tumor necrosis factor-α(TNF-α)levels,and interleukin-10(IL-10)levels in serum of the patients in ATB group and LTBI group were significantly increased(P<0.05),and the percentages of lymphocytes(LY)were significantly decreased(P<0.05);compared with ATB group,the ESR and level of IL-10 in serum of the patients in LTBI group were significantly decreased(P<0.05),and the percentage of LY was significantly increased(P<0.05);there were statistically significant differences in the counts of white blood cell(WBC)of the subjects among various groups(P>0.05).The flow cytometry results showed that compared with control group,the expression levels of CD80 and CD206 proteins in PBMCs of the patients in ATB group and LTBI group were significantly increased(P<0.05).Compared with ATB group,the expression level of CD206 protein in the PBMCs of the patients in LTBI group was significantly increased(P<0.05),and the expression level of CD80 protein was significantly decreased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of miR-125a-5p and IL-6 mRNA in the PBMCs of the patients in ATB group and LTBI group were significantly increased(P<0.05);compared with ATB group,the expression levels of miR-125a-5p and IL-6 mRNA in PBMCs of the patients in LTBI group were significantly increased(P<0.05).The correlation analysis results showed that the miR-125a-5p expression level was positively correlated with the TNF-α level and IL-6 mRNA expression level(r=0.406,P<0.05;r=0.351,P<0.05),and negatively correlated with the IL-10 level(r=-0.368,P<0.05).The area under the receiver operating characteristic(ROC)curve(AUC)value of miR-125a-5p expression level for diagnosing LTBI patients was 0.89(P<0.01),with a sensitivity of 0.85 and a specificity of 0.88.Conclusion:The expression level of miR-125a-5p in PBMCs of the patients in LTBI group is significantly increased,and it can affect the macrophage polarization to M1,promote the inflammatory response process of macrophages and participate in the occurrence and development of pulmonary tuberculosis.

Atherosclerosis(AS)is a multifactorial disease,in which mitochondrial dysfunction of macrophages plays a key role.Mitochondrial dysfunction of macrophages affects polarization direction of macrophages and leads to severe inflammatory reac-tions,is a potential therapeutic target for AS.This article mainly reviews the latest research progress on role of macrophage mitochon-drial dysfunction in occurrence and development of AS,as well as treatment methods for improving macrophage mitochondrial function.

Atherosclerosis(AS)is a multifactorial disease,in which mitochondrial dysfunction of macrophages plays a key role.Mitochondrial dysfunction of macrophages affects polarization direction of macrophages and leads to severe inflammatory reac-tions,is a potential therapeutic target for AS.This article mainly reviews the latest research progress on role of macrophage mitochon-drial dysfunction in occurrence and development of AS,as well as treatment methods for improving macrophage mitochondrial function.

From the perspective of state differentiation and treatment， it is believed that the pathogenesis of acute respiratory distress syndrome （ARDS） is that evil poisons injured the lungs， and the lung qi suddenly collapsed， then blocked and exhausted， and the qi failure to control blood and liquid， then the fluids overflow outside the vessels， and damp phlegm， stasis， and toxins became knotted up in the body， which ultimately leads to qi dysfunction， and a series of symptom arise， so qi impairment is the principal mechanism of ARDS. A combination of Chinese and Western medicine was proposed to treat ARDS by combining tangible qi and intangible qi， using Chinese herbal medicine to boost qi and relieve collapse， percolate and drain dampness with bland medicinals， resolve toxins and dissolve stasis， and regulate qi， and combining with Western medicine to assist qi circulation to improve qi's consolidation， propulsion， and transformation， so as to make the evil qi go away， the positive qi restored， the viscera qi circulated， qi， blood， yin， and yang connected， and the activities of life maintained， and thus to achieve the goal of treating ARDS by integrated Chinese medicine and Western medicine.

Objective:To evaluate the effect of different reconstruction points of intrauterine applicator on the source dwell positions and plan dosimetry in intracavitary brachytherapy for cervical cancer.Methods:Clinical data of 43 patients with cervical cancer who had completed radical radiotherapy in Liuzhou Workers' Hospital from May 2020 to October 2022 were retrospectively analyzed. Among 43 patients, aged 32-79 years, 40 cases were diagnosed with squamous carcinoma and 3 cases of adenocarcinoma. All patients received external irradiation for 50.4 Gy / 28 fractions and CT-guided intracavitary brachytherapy (45° intrauterine applicator) was 36 Gy / 6 fractions. Brachytherapy was performed by using Fletcher applicator, the curvature of intrauterine applicator were 15°, 30°and45°. Two sets of brachytherapy plans were simulated for each patient. One set of plans extracted the simulated CT positioning images and the original plan of the patient's brachytherapy. The reconstruction point of the curved part of the 45° intrauterine applicator was adjusted to slice-by-slice reconstruction. The plan was optimized to meet clinical requirements according to the prescription, which was called the slice-by-slice group. In the other set of plans, slice-by-slice group was used as a template. The reconstruction points of the curved section of the 45° intrauterine applicator were adjusted to 1, 3, 5, and 7, without modifying the applicator weights and other parameters, which was called the average group 1, 3, 5 and 7. The deviation analysis of 15°, 30° and 45° intrauterine applicator with different number of reconstruction points was carried out, the reconstruction deviation of 45°, 30° and 15° intrauterine applicator at different reconstruction points was compared. Paired-sample t-test or Wilcoxon signed rank test were used to compare the differences in high-risk clinical target volume (HR-CTV) D 50%, D 90%, D 100%, V 100%, V 150%, V 200% and conformity index (CI) as well as D 2 cm3, D 1 cm3 and D 0.1 cm3 in bladder, rectum, and small intestine between two groups of 45° intrauterine applicator. Results:The reconstruction deviation in the average group was mainly from the vertical direction of the 45° intrauterine applicator. The mean reconstruction deviations of 45° (1, 3, 5, 7 reconstruction points), 30° (1, 3, 5 reconstruction points) and 15° (1, 2 reconstruction points) were 1.30 mm, 0.32 mm, 0.14 mm and 0.08 mm; 0.57 mm, 0.14 mm and 0.06 mm; 0.14 mm and 0.06 mm, respectively. There was no significant difference in the parameters of high-risk clinical target volume (HR-CTV) in the slice-by-slice group compared with the average group 5 and 7 (all P>0.005), and no significant difference was found between the average group 5 and 7 (all P>0.005). There were no statistically significant differences in bladder and rectum doses between the slice-by-slice group and the average groups or within the average groups (all P>0.005). The parameters of small intestine in the slice-by-slice group were higher than those of the average group 1, the difference was statistically significant ( P=0.002,<0.001,<0.001). The dose of small intestine in the slice-by-slice group was not statistically significant compared with those in the average group 5 and 7 (both P>0.005). The dose of small intestine in the average group 5 was not statistically significant compared with that in the average group 7 ( P>0.005). The small intestine dose deviations of D 0.1 cm3, D 1 cm3 and D 2 cm3 in the average groups at 1 reconstruction point were 2.41%±1.70%, 1.95%±1.27% and 1.71%±1.10%, respectively. Conclusion:The number of reconstruction points is recommended to be no less than 1, 3 and 5 of the curved part of the 15°, 30°and 45° Fletcher intrauterine applicator, respectively, during intracavitary brachytherapy for cervical cancer.

Objective To explore the effect and mechanism of berberine combined with curcumin on ath-erosclerosis(AS)by mediating M1 macrophages polarization.Methods M1-type macrophages were obtained from mouse mononuclear macrophages(RAW264.7)induced by lipopolysaccharide(LPS,100 ng/mL)and interferon(IFN)-γ(20 ng/mL).A cell model was established.The cells were divided into a control group,model group,berberine group,curcumin group and berberine plus curcumin group.Concentrations of berberine and curcumin were detected by CCK-8 assay.The expression levels of M1-type macrophage markers iNOS,TNF-α,CXCL9 and p-STAT6/STAT6 in macrophage supernatant were detected by ELISA.Levels of iNOS,TNF-α and CXCL9 mRNA were detected by RT-PCR.Levels of iNOS,STAT6 and p-STAT6 proteins in each group were detected by Western blot.After down-regulation of STAT6 level by siRNA technology,expression of p-STAT6 protein was detected by Western blot.Expression levels of iNOS,TNF-α,CXCL9 and p-STAT6 were detected by ELISA.Results In the polarization of M1 macrophages induced by LPS and IFN-γ,berberine(25 μmol/L)and curcumin(20 μmol/L)were the best concentrations as compared with other drug concentration groups,and neither alone nor combined use could significantly inhibit the viability of RAW264.7 cells(P<0.05).As compared with the normal group,iNOS,TNF-α and CXCL9 mRNA and protein levels were increased in the model group,while P-STAT6/STAT6 levels were decreased,with statistical differences(P<0.05).As compared with the model group,iNOS,TNF-α and CXCL9 mRNA and protein levels in the berberine group,curcumin group,and berberine plus curcumin group were decreased,while P-STAT6/STAT6 levels were increased,and the changes were more obvious in berberine plus curcumin group,with statistical difference(P<0.05).After transfection of STAT6 siRNA in M1 macrophages in the berberine plus curcumin group,P-STAT6 levels were down-regulated,while expressions of iNOS,TNF-α and CXCL9 were up-regulated,with statistical differences(P<0.05).Conclusions Both berberine and curcumin can inhibit the activity of M1-type macrophages and reduce inflammatory response.The action of berberine combined with curcumin is more advantageous than that of either drug alone,which may be the main mechanism of action through activation of STAT6.

ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.