Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

OBJECTIVE To study the regulation effects and mechanism of liquiritin （LIQ） on immune function in gastric cancer-bearing mice based on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Gastric cancer cells MFC were injected subcutaneously to establish gastric cancer-bearing model of mice. The model mice were divided into model group， LIQ low-dose group （LIQ-L group， 20 mg/kg）， LIQ high-dose group （LIQ-H group， 40 mg/kg）， and high-dose LIQ+JAK2 activator coumermycin A1 group （LIQ-H+coumermycin A1 group， 40 mg/kg LIQ+1 mg/kg coumermycin A1）， with 12 mice in each group. Another 12 mice without modeling were set as normal group. Mice in each group were given the corresponding drug or normal saline by intragastric administration/intraperitoneal injection， once a day， for consecutive 14 days. After the last administration， the volume and mass of gastric cancer tumor and organ index were measured. The percentages of CD4+ and CD8+T lymphocytes were detected in peripheral blood. The histopathological morphology of gastric cancer tumor tissues was observed， and the expression levels of JAK2/STAT3 signaling pathway-related proteins and interleukin-6 （IL-6） protein in gastric cancer tumor tissues were detected. RESULTS Compared with the normal group， the thymus index， spleen index， and the percentage of CD8 T lymphocyte in the peripheral blood of mice were obviouslyincreased in model group （P＜0.05）， while the percentage of CD4+T lymphocyte in the peripheral blood were decreased （P＜0.05）. Compared with model group， the above indexes in LIQ-L group and LIQ-H group were significantly reversed （P＜0.05）， while the volume and mass of gastric cancer tumor， the phosphorylation levels of JAK2 and STAT3 protein and the expression level of IL-6 protein were significantly decreased in tumor tissue （P＜0.05）， and the effect of LIQ was in a dose-dependent manner （P＜0.05）； the tumor cells showed varying degrees of loose arrangement， vacuolization， and uneven distribution. JAK2 activator coumermycin A1 weakened the improvement effect of LIQ on the immune function of gastric cancer-bearing mice and its inhibitory effect on gastric cancer tumors （P＜0.05）. CONCLUSIONS LIQ can improve the immune function of gastric cancer-bearing mice by inhibiting the activation of JAK2/STAT3 signaling pathway， thus playing an anti-tumor role.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

【Objective】 To achieve supervision and management of the whole business process of blood center, raise productivity and ensure blood quality by enabling blood center managers comprehensively grasp the key business operation situation of the whole process at anytime and anywhere. 【Methods】 A whole business process supervision and management system was established covering background of preparation, business scope, content of position supervision and management, overall framework design, interface design of management and supervision management, physical database design, program development and online debugging, and was integrated with the blood bank management information system. The display and management were through a mobile APP to record key indicators of business process from blood collection to blood supply timely and comprehensively. Statistical analysis was conducted on total collection volume, total preparation volume and total supply volume, as well as discarding rate of test unqualified and of non-test unqualified (lipemic blood excluded) in 2023 and 2022. 【Results】 We established a mobile APP based on a blood bank management information system for business supervision and management of whole process, and achieved management by phones. After its implementation in 2023, the total collection volume, total preparation volume and total supply volume in 2023 were all higher than those in 2022, with growth rates of 5.88% (13 247/225 454 U), 4.73% (24 156/510 698 U), and 6.70% (34 814/519 914 U), respectively. The discarding rate in 2023 was lower than that in 2022 (0.54%, 2 868/534 854 U) vs (0.60%, 3 047/510 698 U) (P<0.01), and the non-test unqualified discarding rate (lipemic blood excluded) in 2023 was significantly lower than that in 2022(0.12%, 649/534 854 U) vs (0.19%, 991/510 698 U)(P<0.01). 【Conclusion】 The construction of supervision and management system of a whole business process based on blood bank management information system can meet the standardized service needs of managers at anytime and anywhere, continuously raise productivity and the standardization and scientific level of blood bank management, thus ensuring blood supply.

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 efficacy and safety of venetoclax (VEN) combined with hypomethylating agents (HMA) in the treatment of blastic plasmacytoid dendritic cell neoplasms (BPDCN).Methods:A retrospective case series study was conducted. The clinical data of 5 patients with BPDCN treated with VEN combined with azacitidine (AZA) or decitabine (DAC) in the First Affiliated Hospital of Soochow University and Suzhou Hongci Blood Disease Hospital from February 2017 to July 2023 were collected, and the therapeutic effect, adverse reaction and prognosis of all 5 patients were summarized.Results:All 5 BPDCN patients were male with the median onset age [ M ( Q1, Q3)] of 66 years (51 years, 73 years), of which 4 cases were presented with skin lesions and 1 case was presented with lymphadenopathy as the primary symptom. As for the treatment, 3 patients were initially treated with VEN in combination with AZA induction regimen, among which 2 patients achieved complete remission with incomplete blood count recovery (CRi) after 2 cycles of treatment, survived for 26.5 months and 14.6 months, respectively and finally died, and 1 patient achieved partial remission after 1 cycle of treatment and he still survived after 3-month follow-up; 1 patient was initially treated with VEN in combination with DAC induction regimen, and achieved clinical complete remission of non-active disease with residual skin abnormalities after 2 cycles of treatment followed by allogeneic hematologic stem cell transplantation (allo-HSCT) and he was in the state of disease-free survival for 15-month; and another 1 patient experienced a relapse after treatment with acute lymphocytic leukemia-like regimen in combination with allo-HSCT and again achieved CRi after 2 treatment courses of VEN in combination with AZA regimen, and he was in the state of disease-free survival for 30-month follow-up. Treatment-related haematological adverse effects of VEN combined with HMA were mainly neutropenia with fever, reduction of hemoglobin and thrombocytopenia; and non-haematological adverse effects were mainly gastrointestinal reactions such as nausea and vomiting. These adverse events improved with symptomatic supportive therapy, and no treatment-related deaths occurred. Conclusions:BPDCN patients who are unable to tolerate intensive chemotherapy regimens at initial time of diagnosis may attempt induction therapy with VEN+HMA regimen, which has a manageable adverse reaction and may serve as a bridge to allo-HSCT.

Objective To investigate whether recombinant Newcastle disease virus(rL-RVG)induces iron death in gastric cancer cells through Nrf2-GCLC-GPX4 pathway.Methods After human gastric cancer HGC-27 cells were treated with rL-RVG,Newcastle disease virus(NDV)and PBS solution(control group),respectively,cell proliferation,invasion and migration were detected by CCK-8 assay and Transwell invasion assay and cell scratch test.Ferroptosis accelerator(erastin),and nuclear factor E2 related factor 2(Nrf2)accelerator(TBHQ)and inhibitor(ML385)were added respectively as controls.The content of malondialdehyde(MDA)in each treatment group was detected by lipid oxidation kit.The content of reactive oxygen species(ROS)was detected by DCFH-DA fluorescent probe and flow cytometry.Western blotting and immunofluorescence assay were employed to measure the expression levels of Nrf2-GCLC-GPX4 pathway related proteins.Results Compared with the control group,the survival rate of HGC-27 cells were significantly decreased after rL-RVG and NDV treatment in a dose-and time-dependent manner,and the effect was more significant in the rL-RVG treatment group(P＜0.05).The migration and invasion abilities of HGC-27 cells were obviously inhibited in the NDV and rL-RVG treatment groups,and the latter had more notable inhibition than the former.The protein levels of Nrf2,GCLC,SLC7A11 and GPX4 were statistically decreased(P＜0.05),and the contents of MDA and ROS were increased(P＜0.05)in the virus treatment groups than the control group,with the increasing or decreasing trend more significant in the rL-RVG group than the NDV group.What's more,the protein levels of SLC7A11 and GPX4 were decreased in the erastin group(P＜0.05).Compared with the control group,those of Nrf2,GCLC,SLC7A11 and GPX4 were increased in the TBHQ group and decreased in the ML385 group(P＜0.05),while the contents of MDA and ROS were decreased and increased respectively in the above 2 groups(P＜0.05).Compared with the rL-RVG group,the rL-RVG+TBHQ group and rL-RVG+ML385 group had enhanced and reduced protein expressio of Nrf2,GCLC,SLC7A11 and GPX4,respectively(P＜0.05),while the contents of MDA and ROS were in opposite trends(P＜0.05).Conclusion rL-RVG can induce ferroptosis of gastric cancer cells through Nrf2-GCLC-GPX4 pathway,and then inhibit the growth of tumor cells.

Objective To investigate the role of sodium-hyaluronate-modified calcium peroxide nanoparticles(SH-CaO2 NPs)in inducing pyroptosis in human gastric cancer cells and its possible mechanisms.Methods Transmission electron microscopy(TEM),X-ray diffraction(XRD),infrared spectroscopy,and zeta potential test were used to confirm the synthesis of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay were employed to observe the impacts of SH-CaO2 NPs on the migration and proliferation of human gastric cancer cell line HGC-27.The generation of reactive oxygen species(ROS)was observed with confocal laser scanning microscopy(CLSM)and quantified with flow cytometry in the cells after SH-CaO2 NPs treatment or with pretreatment with ROS inhibitor NAC.Furthermore,the effects of pretreatment of NLRP3 inhibitor(MCC950)and Caspase-1 inhibitor(VX765)on the proliferative activity and on expression of their own and their downstream GSDMD in HGC-27 cells were also investigated with CCK-8 assay,immunofluorescence assay and Western blotting.Results TEM images,XRD,infrared spectroscopy,and zeta potential test confirmed the successful preparation of SH-CaO2 NPs.Cell scratch assay and CCK-8 assay showed that application of SH-CaO2 NPs for 24 h significantly inhibited the proliferation of HGC-27 cells(P＜0.001),while,CLSM and flow cytometry indicated the treatment also promoted the production of ROS(P＜0.001).Pretreatment of ROS inhibitor NAC resulted in up-regulation of NLRP3,and increased expression levels of cleaved Caspase-1 and N-terminal fragment of GSDMD(P＜0.001),while pretreatment of both NLRP3 inhibitor and Caspase-1 inhibitor could reverse the process.Conclusion SH-CaO2 NPs inhibit cell viability of human gastric cancer,which may mediate the inflammatory response and pyroptosis by activating the ROS/NLRP3/Caspase-1/GSDMD signaling pathway.