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.

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.

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.

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.

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.

Objective To investigate the protective effect of berberine (BBR) against ionizing radiation injury in rats and its mechanism of action. Methods Sprague-Dawley rats were divided into seven groups: normal control group, 1-Gy radiation group, 1-Gy radiation plus low-dose BBR (50 mg/kg) group, 1-Gy radiation plus high-dose BBR (150 mg/kg) group, 3-Gy radiation group, 3-Gy radiation plus low-dose BBR (50 mg/kg) group, and 3-Gy radiation plus high-dose BBR (150 mg/kg) group. All the groups except the normal control group were exposed to external irradiation with a medical electron linear accelerator, followed by BBR administration by gavage for consecutive ten days. The serum levels of superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) were measured by using the micromethod. The pathological changes of the bone marrow and small intestine were observed with HE staining. Results Compared with the normal control group, the radiation groups showed significantly increased MDA levels (P < 0.05), significantly decreased SOD and GSH levels (P < 0.05), and more severe pathological damage of the bone marrow and small intestine. Compared with the radiation groups, the BBR groups showed significantly decreased MDA levels (P < 0.05), significantly increased SOD and GSH levels (P < 0.05), and reduced pathological damage to the bone marrow and small intestine, which were more marked in the high-dose BBR group. Conclusion BBR has a certain protective effect against radiation injury in rats, which may be through increasing the activity of antioxidant substances, enhancing free radical clearance, and thereby alleviating free radicals-caused oxidative damage.

The massive accumulation of β-amyloid （Aβ） in the brain is believed to be the first pathological mechanism of Alzheimer's disease （AD）， and the accumulation is mainly resulted from the overproduction and dysfunction in the clearance. Extensive and in-depth research has been carried out on AD. In addition to the drugs which are commonly used in clinical settings to improve cognitive function， Aβ monoclonal antibody aducanumab （Aduhelm） has been successfully marketed in the US， which may delay the progress of AD. Thus， it is a potential method for the treatment of AD to target Aβ， but it is expensive， with many adverse reactions and contraindications， which hinders the clinical promotion. Traditional Chinese medicine， featuring multiple components， multiple targets， multiple pathways， and high safety， can regulate the level of Aβ deposition in the brain， alleviate neurotoxicity， and prevent and treat AD by inhibiting the production and aggregation of Aβ and promoting the clearance in the brain. Berberine， gallic acid， osthole， scutellaria barbata flavonoids， Huannao Yicong decoction and Ditantang can promote α-secretase and inhibit the activity and expression of β- and γ-secretase， thus reducing production of Aβ. Baicalein， aloe-emodin， gallic acid， and curcumin can suppress the aggregation of Aβ， promote its depolymerization， and reduce the toxic effect of Aβ on nerve cells by interacting with the hydrophobic structure of Aβ and the H bond， salt bridge， and β-sheet that mediate the aggregation of Aβ. Curcumin and resveratrol can promote the expression of triggering receptor 2 in bone marrow cells of microglia and the migration and phagocytosis of Aβ in microglia. Bilobalide， Kaixinsan and curcumin can up-regulate the expression of encephalin-degrading enzyme and insulin degrading enzyme to promote Aβ degradation， and geniposide， dihydrotanshinone， dihydroartemisinin， and curcumin can degrade Aβ in cells by activating normal autophagy or inhibiting abnormal autophagy. Cycloastragenol， Danggui Shaoyaosan， Yizhi Fangdai formula and Linggui Zhugan decoction can promote the outflow of Aβ and inhibit the inflow of Aβ by improving the integrity and permeability of the blood-brain barrier （BBB）. Yizhi Fangdai formula and Xueshuantong can promote the polarization of aquaporin 4（AQP4）， allow Aβ to be cleared through the lymphatic system， and reduce the aggregation of Aβ in the brain， thereby relieving or preventing nerve cell damage and improving cognitive function. The above summary aims to provide more sufficient evidence and ideas for the clinical treatment of AD with traditional Chinese medicine.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Objective:To evaluate the effect of obesity on in-hospital prognosis of patients with mechanical ventilation in PICU.Methods:We enrolled 301 patients who received mechanical ventilation treatment in PICU at Chongqing Medical University Affiliated Children′s Hospital, between June 2015 and June 2020, and stratified them into obese group(49 cases), overweight group(96 cases)and normal weight group(156 cases). Obesity was determined by reference to the growth and development standards published by the World Health Organization.Indicators included PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital and the rates of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers were observed.The influence of obesity on hospitalized prognosis of children in PICU was analyzed.Results:In obesity group, overweight group and normal weight group, PICU hospital mortality(2.0%, 10.4%, 12.2%), the rate of tracheal reintubation(14.3%, 5.2%, 9.0%), the rate of tracheotomy (2.0%, 1.0%, 2.6%), the rate of deep venous thrombosis(8.2%, 3.1%, 5.8%), and the rate of pressure ulcers(4.1%, 7.3%, 1.9%) did not have significant difference(all P>0.05). No ventilator-associated pneumonia and central venous catheter infection occurred in three groups.There were no significant differences in the PICU hospital mortality, duration of mechanical ventilation, length of stay in the PICU, length of stay in hospital among the three groups(all P>0.05). Obesity was not an independent risk factor for in-hospital death in PICU patients on mechanical ventilation( B=1.975, SE=1.038, OR=7.206, 95% CI 0.942~55.127, P=0.057). Conclusion:Obesity does not prolong the duration of mechanical ventilation, length of stay in PICU and total length of stay in hospital, as well as not increase the rate of duration of mechanical ventilation>21 days, re-intubation, tracheotomy, ventilator-associated pneumonia, central venous catheter infection, deep venous thrombosis and pressure ulcers.Obesity is not an independent influencing factor for in-hospital death in patients with mechanical ventilation in PICU.

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.