This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

Objective To explore the CT imaging features and independent risk factors for cystic pulmonary nodules and establish a malignant probability prediction model. Methods The patients with cystic pulmonary nodules admitted to the Department of Thoracic Surgery of the First People's Hospital of Neijiang from January 2017 to February 2022 were retrospectively enrolled. They were divided into a malignant group and a benign group according to the pathological results. The clinical data and preoperative chest CT imaging features of the two groups were collected, and the independent risk factors for malignant cystic pulmonary nodules were screened out by logistic regression analysis, so as to establish a prediction model for benign and malignant cystic pulmonary nodules. Results A total of 107 patients were enrolled. There were 76 patients in the malignant group, including 36 males and 40 females, with an average age of 59.65±11.74 years. There were 31 patients in the benign group, including 16 males and 15 females, with an average age of 58.96±13.91 years. Multivariate logistic analysis showed that the special CT imaging features such as cystic wall nodules [OR=3.538, 95%CI (1.231, 10.164), P=0.019], short burrs [OR=4.106, 95%CI (1.454, 11.598), P=0.008], cystic wall morphology [OR=6.978, 95%CI (2.374, 20.505), P<0.001], and the number of cysts [OR=4.179, 95%CI (1.438, 12.146), P=0.009] were independent risk factors for cystic lung cancer. A prediction model was established: P=ex/(1+ex), X=–2.453+1.264×cystic wall nodules+1.412×short burrs+1.943×cystic wall morphology+1.430×the number of cysts. The area under the receiver operating charateristic curve was 0.830, the sensitivity was 82.9%, and the specificity was 74.2%. Conclusion Cystic wall nodules, short burrs, cystic wall morphology, and the number of cysts are the independent risk factors for cystic lung cancer, and the established prediction model can be used as a screening method for cystic pulmonary nodules.

Objective    To predict the probability of lymph node metastasis after thoracoscopic surgery in patients with lung adenocarcinoma based on nomogram. Methods    We analyzed the clinical data of the patients with lung adenocarcinoma treated in the department of thoracic surgery of our hospital from June 2018 to May 2021. The patients were randomly divided into a training group and a validation group. The variables that may affect the lymph node metastasis of lung adenocarcinoma were screened out by univariate logistic regression, and then the clinical prediction model was constructed by multivariate logistic regression. The nomogram was used to show the model visually, the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve to evaluate the calibration degree and practicability of the model. Results    Finally 249 patients were collected, including 117 males aged 53.15±13.95 years and 132 females aged 47.36±13.10 years. There were 180 patients in the training group, and 69 patients in the validation group. There was a significant correlation between the 6 clinicopathological characteristics and lymph node metastasis of lung adenocarcinoma in the univariate logistic regression. The area under the ROC curve in the training group was 0.863, suggesting the ability to distinguish lymph node metastasis, which was confirmed in the validation group (area under the ROC curve was 0.847). The nomogram and clinical decision curve also performed well in the follow-up analysis, which proved its potential clinical value. Conclusion    This study provides a nomogram combined with clinicopathological characteristics, which can be used to predict the risk of lymph node metastasis in patients with lung adenocarcinoma with a diameter≤3 cm.

Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P＜0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P＜0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P＜0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P＜0.05).There was no significant difference between Fer-1 group and con-trol group(P＜0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P＜0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.

BACKGROUND:Due to the sudden release and the rapid removal by proteases,platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site.In recent years,researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels. OBJECTIVE:To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. METHODS:The self-assembled polypeptide was synthesized by the solid-phase synthesis method,and the solution was prepared by D-PBS.Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions,so that the final mass fraction of polypeptides in the system was 0.1%,0.3%,and 0.5%,respectively.The hydrogel state was observed,and the release of growth factors in platelet-rich plasma was detected in vitro.The polypeptide self-assembly was stimulated by mixing 1%polypeptide solution with 1%human serum albumin solution,so that the final mass fraction of the polypeptide was 0.1%,0.3%,and 0.5%,respectively.The flow state of the liquid was observed,and the rheological mechanical properties of the self-assembled polypeptide were tested.The microstructure of polypeptide(mass fraction of 0.1%and 0.001%)-human serum albumin solution was observed by scanning electron microscope and transmission electron microscope. RESULTS AND CONCLUSION:(1)Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma.Compared with platelet-rich plasma hydrogels,0.1%and 0.3%polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor,and extend the release time to 48 hours.(2)After the addition of human serum albumin,the 0.1%polypeptide group still exhibited a flowing liquid,the 0.3%polypeptide group was semi-liquid,and the 0.5%polypeptide group stimulated self-assembly to form hydrogel.It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides.With the increase of the mass fraction of the polypeptide,the higher the storage modulus of the self-assembled polypeptide,the easier it was to form glue.(3)Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin.After the addition of human serum albumin,the polypeptide nanofibers became significantly longer and cross-linked into bundles,forming a dense fiber network structure.Under a scanning electron microscope,the polypeptides displayed a disordered lamellar structure before adding human serum albumin.After the addition of human serum albumin,the polypeptides self-assembled into cross-linked and densely arranged porous structures.(4)In conclusion,the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide.This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma,which can be used as a new biomaterial for tissue repair.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective:To explore the correlation between the dynamic changes of early immune cells in acute respiratory dis-tress syndrome(ARDS)caused by multiple injuries and lung infection.Methods:Multiple injury patients with ARDS(235 cases)ad-mitted to the First Affiliated Hospital of Hunan University of Chinese Medicine from October 2017 to February 2023 were selected as the research subjects and included them in the training set;according to simple clinical pulmonary infection scores(sCPIS),they were divided into a pulmonary infection group(94 cases,>6 points)and an uninfected group(141 cases,≤6 points).Another multi-ple injury patients with ARDS(78 cases)were selected to be included in the validation set to verify the effectiveness of the prediction model.Dynamic detection of lymphocytes were used flow cytometry.Compared and analyzed the clinical data of two groups of patients.Constructed a joint model and used Cox regression to analyze the relationship.Multi factor Logistic regression analysis of risk factors,construction of a simple risk scoring model and evaluation.Results:As the patient progresses,CD4+and CD8+first decrease and then increased,and the lowest stage was 3～15 d after onset;CD19+was gradually increasing;CD16+gradually decreased and fluctuated within a certain range.The joint model showed that for every 1 piece/μl longitudinal decrease in CD4+,CD8+,CD19+,and CD16+,the risk of pulmonary infection increased by 5.6%,4.1%,3.4% and 1.3%,respectively(P<0.05).Injury severity score(ISS),chest inju-ry as the main factor,emergency surgery,acutephysiology and chronic health evaluation Ⅱ(APACHE Ⅱ),broncho-alveolar lavage fluid(BALF)sTREM-1 level,and CD4+,CD8+,and CD19+level on the 15th day after onset all were independent influencing factors for the occurrence of pulmonary infection(P<0.05).The score of the simple risk scoring model is 0～36.7 points,which could be divid-ed into three risk levels:low(<16 points),medium(16～22 points),and high risk(>22 points);there was no significant difference in the incidence of pulmonary infection between the two episodes of patients(P>0.05).The evaluation results showed that the predic-tive model has good discrimination.Conclusion:The fluctuation of immune cells will increase the risk of pulmonary infection in pa-tients with multiple injuries ARDS;Baseline CD4+,CD8+,and CD19+levels are independent influencing factors for the occurrence of pulmonary infection;controlling high-level immune cells and maintaining stability is crucial for improving prognosis.

Humans ; Asthma/drug therapy* ; Biological Therapy

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*