AIM: To observe the effect of RBC preservation solution with sodium pyruvate on the morphology, structure and function of RBC stored in vitro in type 2 diabetes rats. METHODS: Thirty SPF male SD rats, were randomly divided into 3 groups (n=10): non-T2DM conventional RBC preservation solution (group A), T2DM conventional RBC preservation solution (group B) and T2DM sodium pyruvate RBC preservation solution (group C). The leukoreduced RBC from the tail vein and stored for 0 d (T0), 7 d (T1), 14 d (T2), 21 d (T3) and 28 d (T4) to detect the morphology, structure and the contents of 2, 3-DPG, reactive oxygen species (ROS), malondialdehyde (MDA) and lactic acid (LA) of RBC in group A, B and C. The RBC stored for 14 days in vitro were labeled with PKH26, and its survival rate were tested in vivo at 1, 4, 10 and 16 hours after intravenous infusion. RESULTS: At T0, the RBC morphology of group A was intact, which was better than that of group B and group C. With the extension of storage time, the morphology of RBC in each group gradually transformed into a spindle-spherical shape. Compared with group A, the incidence of acanthocytes in group B and group C was higher, and the incidence of acanthocytes in group C was lower than that in group B. Compared with group A, the content of 2, 3-DPG in group B and group C decreased, while ROS and MDA increased at different time points (P<0.05). The content of 2,3-DPG in group C was higher than that in group B (P<0.05), and the contents of ROS and MDA were lower than those in group B (P<0.05). LA content in group B was higher than that in group A and group C (P<0.05). At T2-T4, the LA content in group C was lower than that in group A (P<0.05). The survival rate of RBC in group A was higher than that in group B and C, and the survival rate of RBC in group B was lower than that in group C (P<0.05). CONCLUSION: Sodium pyruvate added RBC preservation solution has a certain protective effect on RBC stored in vitro in type 2 diabetic rats, and its mechanism may be related to its antioxidant effect.

Objective:To evaluate the effect of novel erythrocyte preservation solution on the quality of erythrocytes in stored blood of type 2 diabetes mellitus (T2DM) rats.Methods:Forty SPF male Sprague-Dawley rats, aged 8 weeks, weighing 180-220 g, were used in this study. Ten rats randomly selected served as conventional erythrocyte preservation solution group (group A). T2DM model was prepared in the remaining 30 rats. Twenty T2DM rats were divided into 2 groups ( n=10 each) using a random number table method: T2DM conventional erythrocyte preservation solution control group (group C) and T2DM novel erythrocyte preservation solution observation group (group Y). Erythrocyte preservation solution was prepared to simulate the preoperative autologous blood donation process, and blood was collected from the tail vein to isolate the red blood cells, and then the corresponding preservation solution was added. Immediately after blood collection (T 0) and at 7, 14 and 21 days of preservation (T 1-3), the morphological structure of erythrocytes was observed with a light microscope, and the concentrations of 2, 3-diphosphoglycerate (2, 3-DPG) and reactive oxygen species (ROS) were also determined by enzyme-linked immunosorbent assay at T 0-T 3 and 28 days of preservation (T 4). PKH26 was used to label the erythrocytes stored in vitro for 28 days, and then the erythrocytes were transfused back into rats. The survival rate of erythrocytes was detected by flow cytometry at 1, 7, 13 and 18 h after retransfusion. Results:The erythrocyte damage was aggravated at different time points of preservation in group C when compared with group A. Compared with group C, the damage to erythrocytes was significantly alleviated at different time points of preservation in group Y. Compared with group A, the concentration of 2, 3-DPG in erythrocytes was significantly decreased at T 0 and T 2-T 4, the concentration of ROS was increased at T 0-T 4, and the survival rate of erythrocytes was decreased at 1, 7 and 18 h after retransfusion in group C ( P<0.05). Compared with group C, the concentration of 2, 3-DPG in erythrocytes was significantly increased at T 0-T 4, the content of ROS was decreased at T 1, T 3 and T 4, and the survival rate of erythrocytes was increased at 1, 7 and 18 h after retransfusion in group Y ( P<0.05). Conclusions:The novel erythrocyte preservation solution can improve the quality of stored erythrocytes and increase the survival rate of erythrocytes in vivo after retransfusion in T2DM rats.

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

ObjectiveTo explore the effect of home visit based on empowerment education on psychotic symptoms， self-management ability and well-being of schizophrenia patients in home rehabilitation. MethodsA total of 87 cases of schizophrenia patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） and were recovering at home in Caiba town， Yibin city from January to July 2021 were selected by random sampling method as research subjects. They were divided into experimental group （n=43） and control group （n=44） according to the random number table method. The two groups received routine family visits， and the experimental group received family visits based on empowerment education. The intervention cycle of the two groups was 6 months. Before and after the intervention， the severity of psychotic symptoms， self-management ability and well-being of the patients in the two groups were assessed with the Brief Psychiatric Rating Scale （BPRS）， the Schizophrenia Self-Management Instrument Scale （SSMIS） and the Index of Well-Being Scale （IWB）. ResultsAfter intervention， the intra group comparison showed that the BPRS score in the experimental group was lower than that before the intervention （t=4.550， P<0.01）， the SSMIS scores in both groups were higher than those before intervention （t=-17.107， -6.367， P<0.01）， and the IWB score in the experimental group was higher than that before intervention （t=-9.239， P<0.01）. The comparison between groups showed that the BPRS score of the experimental group was lower than that of the control group， and the SSMIS and IWB scores were higher than those of the control group （t=-3.899， 10.564， 9.690， P<0.01）. ConclusionThe implementation of family visit based on empowerment education may help to improve the psychotic symptoms of home rehabilitation schizophrenia， and improve their self-management ability and well-being.

Objective:To observe the effect of project-based learning (PBL) in the clinical teaching of radiation physics.Methods:Thirty-two residents specializing in radiotherapy were included in the study. In the experimental group ( n=16), PBL was adopted, while traditional clinical teaching method was employed in the control group ( n=16). After the rotation, the assessment was conducted, as well as a questionnaire survey was performed, including five aspects: overall satisfaction, understanding of radiation physics knowledge, learning motivation, learning burden, and learning efficiency. Results:The assessment score in the experimental group was 86.31±5.41, which was higher than 75.28±5.91 in the control group, and the difference was statistically significant. Residents in the experimental group were satisfied with the effect of PBL.Conclusion:Compared with the traditional teaching method, PBL can improve the learning motivation, efficiency, and performance of radiotherapy residents, which is highly recognized by the residents.

Objective:To investigate the feasibility and adverse reactions of simultaneous integrated boost (SIB) in volumetric modulated arc therapy (VMAT) for early breast cancer after breast-conserving surgery.Methods:A total of 67 patients with early breast cancer after breast-conserving surgery at Zhongshan People's Hospital from September 2019 to May 2021 were enrolled. All patients received VMAT-SIB to the whole breast and tumor bed. The total breast dose and tumor bed dose were 40.5Gy/15 times every 3 weeks and 48 Gy/15 every 3 weeks respectively. The exposure dose of organs at risk and acute adverse reactions of radiotherapy were evaluated.Results:The average doses of planning target volume of the whole brease (PTV WB) and planning target volume of the boost(PTV BOOST) were (42.0±2.1) Gy and (49.9±0.8) Gy, respectively. The V 95% and V 105% of PTV WB and PTV BOOST were (98.8±1.2)% and (31.4±11.3)%, (99.8±0.6)% and (22.9±10.2)%, respectively. The V 5Gy, V 20Gy, V 30Gy and mean dose (D mean) of ipsilateral lung were (52.4±12.0)%, (15.3±4.5)%, (6.7±2.2)% and (11.0±2.4) Gy respectively. The V 18Gy, V 40Gy and D mean of heart were 3.80% (0.48%,9.60%), 0 (0,0.16%) and (6.7±2.1) Gy respectively. At the end of radiotherapy, 19 patients (29%) of all 67 patients had no acute skin toxicity, 41 patients (61%) showed radiation erythema, 5 patients (7%) had radioactive dry peeling and 2 patients (3%) had wet peeling mainly located in the nipple, areola area and breast folds. None of the patients had grade 3-4 acute skin reactions. Breast swelling and breast pain were found respectively in 9 patients (13%) and 7 patients (10%). No local recurrence or distant metastases were observed during the follow-up period. The 2-year disease-free survival rate was 100%. Conclusions:VMAT combined with SIB is feasible in the treatment of early breast cancer. The adverse reactions of radiotherapy are mild and well tolerated.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L^-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D₁. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D₁， β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD₁ were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD₁ were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.

This paper focuses on the practical necessity of discipline-integrated PBL curriculum in cultivating clinical thinking ability of college students majoring in clinical medicine. Through the teaching process of group discussion of some real and complete cases, this paper explains in detail how to cultivate medical students' clinical thinking ability by discipline-integrated PBL curriculum, discusses the implementation of ideological and political education associated with clinical medicine by heuristic teaching from close touching with clinical case and implicitly infiltration of the socialist core values such as dedication and integrity, and elaborates the humanistic quality and psychological comfort levels of medical students by being close to clinical patients. After five years of teaching practice, the teaching effect of discipline-integrated PBL curriculum has been approved by the national clinical medicine professional certification experts and praised by students. We believes that the development of discipline integrated PBL curriculum in medical college can strengthen students' problem-based autonomous learning ability, significantly improve the two-way integration ability between basic medical courses and basic medicine, and significantly build students' clinical thinking and clinical decision-making ability.