AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective CT scans combined with Mimics software were used to measure femoral offset(FO),rotation center height(RCH)and lower leg length discrepancy(LLD)following total hip arthroplasty(THA),and the relationship between FO,RCH and LLD after THA is discussed.Methods Retrospective analysis was performed on 40 patients with unilateral THA who met standard cases from October 2020 to June 2022.There were 21 males and 19 females,18 patients on the left side and 22 patients on the right side,aged range from 30 to 81 years old,with an average age of(58.90±14.13)years old,BMI ranged from 17.3 to 31.5 kg·m-2withan average of(25.3±3.4)kg·m-2.There were 30 cases of femoral head necrosis(Ficattype Ⅳ),2 cases of hip osteoarthritis(Tonnis type Ⅲ),2 cases of developmental hip dislocation combined with end-stage osteoarthritis(Crowe type Ⅲ),and 6 cases of femoral neck fracture(Garden type Ⅳ).Three-dimensional CT reconstruction of pelvis was taken preoperative and postoperative,and three-dimensional reconstruction model was established after processing by Mimics software.FO,RCH and LLD were measured on the model.The criteria for FO reconstruction were as follows:postoperative bi-lateral FO difference less than 5 mm;the standard for equal length of both lower limbs was as follows:postoperative LLD differ-ence less than 5 mm.Results Bilateral FO difference was positively correlated with LLD(r=0.744,P＜0.00l).Chi-square test was performed between the FO reconstructed group and the non-reconstructed eccentricity group:The results showed that the i-sometric ratio of lower limbs in the FO reconstructed group was significantly higher than that in the FO reconstructed group(x2=6.320,P=0.012).The bilateral RCH difference was significantly negatively correlated with LLD(r=-0.877,P＜0.001).There is a linear relationship between bilateral FO difference and bilateral RCH difference and postoperative LLD,and the lin-ear regression equation is satisfied:postoperative LLD=0.038x-0.099y+0.257(x:postoperative bilateral FO difference,y:post-operative bilateral RCH difference;Unit:cm),F=77.993,R2=0.808,P=0.009.Conclusion After THA,LLD increased with the increase of FO and decreased with the increase of RCH.The effect of lower limb isometric length can be obtained more easily by reconstruction of FO.There is a linear relationship between the bilateral FO difference and the bilateral RCH difference after THA and LLD,and the regression equation can provide a theoretical reference forjudging LLD.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.

Objective:To construct an intelligent medical emergency information platform for the 19th Hangzhou Asian Games events and evaluate its practical application.Methods:Addressing the medical support demands for Asian Games, based on the " Emergency medical service system for large-scale social activities" developed by Zhejiang Laboratory, a collaborative team comprising Hangzhou Emergency Center, the Second Affiliated Hospital of Zhejiang University,Zhejiang Lab and College of Biomedical Engineering and Instrument Science of ZhejiangUniversity developed an intelligent medical emergency information platform for the Asian Games. This system was implemented during the 19th Hangzhou Asian Games, collecting basic information, initial diagnosis locations, prognoses, severity grading, and occurrences of infectious diseases for all patients treated at support locations from September 16th to October 8th, 2023. The Modified Early Warning Score (MEWS) was employed for assessing patient conditions, and a symptom monitoring system was used to alert the occurrence of infectious diseases. Post-event, a satisfaction evaluation (on a 5-point scale) regarding the system's application was conducted.Results:The successful construction of the intelligent medical emergency information platform comprised a data dashboard display platform, a comprehensive command system on the management center, and a mobile platform covering on-site medical support, ambulances, and designated hospitals. ①A total of 11 068 patients were treated using this system, including 2 979 athletes, 3 429 staff members, 1 421 volunteers,1 051 spectators, and 2 188 others. The proportion of patients seeking treatment due to illnesses was significantly higher than those due to injuries. Among injury-related cases, athletes constituted 41.37%, while staff accounted for 32.5% of illness-related cases. ②The area under the ROC curve for MEWS regarding hospitalization rates was 0.81 for disease patients and 0.60 for injury patients. ③ There were 211 reported cases of infectious diseases during the event, constituting 1.91% of all treated cases.④ Satisfaction ratings: User-friendliness scored 4.47, completeness of functions scored 4.28, data security scored 4.38, and data accuracy scored 4.49. Compared to traditional paper-based reporting methods, 98.11% of users found the system more convenient, 92.45% were satisfied overall, and the recommendation rating was 4.36.Conclusions:The study findings confirm the critical role played by the information platform in enhancing comprehensive, accurate, timely, secure medical support information dissemination for the Asian Games and in early warning and control of infectious diseases.

Objective The aim of this study was to investigate the role of long chain non-coding RNA LINC-PINT in drug sensitivity of hypoxia induced in head and neck squamous cell carcinoma(HNSCC)through the Hippo/Yes-associated protein(YAP)signaling pathway.Methods The proliferative changes of HNSCC cell lines(AGZY-973 cells,HN4 cells,and HN30 cells)and nor-mal human oral keratinocytes(NHOKs)in hypoxic environment were detected by CCK-8 assay;HN30 cells in good condition were taken and set them as the normal group,hypoxia group,hypoxia+LINC-PINT overexpression group,and hypoxia+overexpression negative control group.The expression of LINC-PINT in HN30 cells was detected by qRT-PCR;CCK-8 assay was applied to de-tect the drug sensitivity of HN30 cells,and the effect of cisplatin on proliferation in HN30 cells;cell apoptosis was detected by flow cy-tometry;and Western blot was applied to detect the expression of hypoxia inducible factor-1α(HIF-1α),p-YAP,and YAP protein in HN30 cells.Results Under hypoxia conditions,the proliferative rates of AGZY-973 cells,HN4 cells and HN30 cells were obvi-ously higher than that of NHOKs cells(P＜0.05).Compared with the normal group,the IC50 value,the expression of HIF-1 α and p-YAP/YAP in the hypoxic group were obviously increased in HN30 cells,the rate of apoptosis,the rates of cell growth inhibition at 24 h and 48 h,and the expression of LINC-PINT protein were obviously decreased(P＜0.05);Compared with the hypoxia+overex-pression negative control group,the IC50 values,the expression of HIF-1α and p-YAP/YAP cells in the hypoxia overexpression of LINC-PINT group was obviously reduced in HN30,the rates of apoptosis,the rates of cell growth inhibition at 24 h and 48 h,and the expression of LINC-PINT protein were significantly increased(P＜0.05).Conclusion Overexpression of LINC-PINT can en-hance the hypoxia-induced cisplatin sensitivity in HNSCC,which may be related to the inhibition of the activation of Hippo/YAP sig-naling pathway.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.