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.

Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective To explore the mechanism of ferroptosis induced by endoplasmic reticulum stress(ERs)in acute respiratory distress syndrome(ARDS).Methods In order to determine the effects of LPS on oxidative stress and Fe2+level of mouse capillary alveolar epithelial cells(MLE12 cells),the cells were treated with LPS(0,1,2,5 μg/ml)for 24 h.To verify the role of ferroptosis in lipopolysaccharide(LPS)-induced cell death,MLE12 cells were divided into control(Con)group,iron removal inhibitor(Fer-1)group,LPS group and LPS+Fer-1 group.LPS+Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h,then the cells were exposed to 5 μg/ml LPS for 24 h.Con group was treated with solvent DMSO for 24 h.Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h,and then treated with DMSO for 24 h.The cells in LPS group were exposed to 5 μg/ml LPS for 24 h.The MLE12 cells were divided into three groups:Con+Vector group,Con+sequence similarity family 134 mem-ber B(FAM134B)group,LPS+Vector group and LPS+FAM134B group.After transfected with vector or FAM134B overexpression plasmid for 48 h,the cells were exposed or not exposed to 5 μg/ml LPS for 24 h.Cell vi-ability was measured by CCK-8.The levels of malondialdehyde(MDA),glutathione and iron,the protein levels of ferroptosis markers[cyclooxygenase 2(PTGS2),glutathione peroxidase 4(GPX4)]and ERs markers[glucose reg-ulatory protein 78(GRP78),activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)]were measured in different groups.In order to further confirm the results of in vitro cell experiments,40 mice were randomly divided into Con+Vector group,Con+FAM134B group,LPS+Vector group and LPS+FAM134B group,with 10 mice in each group.LPS-induced sepsis models were established in LPS+Vector group and LPS+FAM134B group,and the levels of GPX4 and ERs in lung tissue were evaluated by immunofluorescence staining and protein blot.Results LPS treatment increased the levels of PTGS2 and MDA,and decreased the levels of GPX4 and GSH in MLE12 cells in a dose-dependent manner.Compared with LPS group,the cell viability,GPX4 and GSH levels in LPS+Fer-1 group increased significantly(P<0.05),while the PTGS2 protein level and MDA level decreased significantly(P<0.05).Compared with LPS+Vector group,LPS+FAM134B group significantly increased cell viability(P<0.05),decreased PTGS2 protein level(P<0.05)and increased GPX4 level(P<0.05).At the same time,the level of MDA in LPS+FAM134B group was lower than that in LPS+Vector group(P<0.05),and the level of GSH was higher than that in LPS+Vector group(P<0.05).In animal experiment,compared with LPS+Vector group,the expression levels of 4-HNE,ATF4 and CHOP in lung tissue of LPS+FAM134B group decreased significantly(P<0.05),and the expression levels of GPX4,FAM134B group in-creased significantly(P<0.05).Conclusion LPS induces ferroptosis and ERs in MLE12 cells in a dose-depend-ent manner.Activating the endoplasmic reticulum autophagy associated FAM134B receptor helps to inhibit ERs and alleviate cell ferroptosis.

[Objective]To identify the relationship between tumor tissue interleukins(ILs)and non-small cell lung cancer(NSCLC)patients with poor response to immune checkpoint blockade(ICB)therapy,and to investigate the differ-ential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis.[Methods]A total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study.We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment.Us-ing bioinformatics methods,we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment.We evaluated the efficacy of ICB treatment using progressive-free survival(PFS)and assessed the prognosis using overall sur-vival(OS).The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients.[Results]The results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P<0.1.Further multivariate analysis revealed that high expression of IL-11,IL-17D,and IL-36A was significant-ly associated with poor prognosis in these patients(P<0.05).The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients.Specifically,patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low ex-pression patients[95%confidence interval(CI)(1.178,3.655),P=0.009].Similarly,the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group[95%CI(1.116,4.392),P=0.018].ROC curve showed that the prediction performance was favorable[AUCPFS=0.702,95%CI(0.562,0.842),P=0.027;AU-COS=0.684,95%CI(0.550,0.818),P=0.014].Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients,the median PFS and OS were notably shortened to 2.2 months(P=0.003)and 3.0 months(P<0.001),respectively,when high expression of IL-11 and IL-36A was combined with high expression of IL-17D.The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients[AUCPFS=0.748,95%CI(0.615,0.880),P=0.007;AUCOS=0.703,95%CI(0.573,0.833),P=0.007].[Conclu-sion]The results suggest that high expression of IL-11,IL-17D,and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

Proteolysis targeting chimera (PROTAC) is a drug discovery strategy using ubiquitin proteasome system (UPS) to degrade the target protein. Unlike traditional small molecule drugs utilizing occupancy-driven pharmacology as the mode of action (MOA) to regulate protein activity, PROTACs function through forming stable target protein-PROTAC-E3 ubiquitin ligase ternary complex and use ubiquitin proteasome system to degrade the target protein. However, only a few E3 ubiquitin ligases have been used in PROTAC drug design now, and the space of target proteins that PROTAC can target needs to be further expanded. On the other hand, the complicated system of ternary crystal structures is difficult to capture and identify, computational simulation provides modeling of PROTAC-mediated ternary complex formation with effective approaches. In view of this, this review describes the recent progress of bioinformatics on expanding the landscape of E3 ubiquitin ligases and target proteins, and summarizes the methods of computation simulation in modeling PROTAC ternary complex. Finally, the trend of development about PROTAC is prospected.