Traditional treatment for type 1 diabetes mellitus （T1DM） primarily involves insulin replacement， yet some patients encounter issues such as significant blood glucose fluctuations， high risk of hypoglycemia， and weight gain. In recent years， the adjuvant therapeutic role of non-insulin hypoglycemic drugs in T1DM has gradually gained attention. This article reviews the mechanisms of action and clinical research progress of five types of non-insulin hypoglycemic drugs in the treatment of T1DM： amylin analogues （pramlintide）， biguanides （metformin）， sodium-glucose co-transporter 2 inhibitor， dipeptidyl peptidase-4 inhibitor， and glucagon-like peptide-1 receptor agonist. It is found that these drugs can enhance clinical benefits for T1DM patients by improving insulin sensitivity， delaying gastric emptying， promoting urinary glucose excretion， and regulating incretin levels， thereby reducing glycated hemoglobin levels， decreasing insulin dosage， and managing body weight. Simultaneously， these drugs also present limitations such as low patient compliance due to complex dosing regimens， increased risk of diabetic ketoacidosis， and heterogeneity in glycemic control. Future research could focus on developing individualized treatment strategies， combining pharmacogenomics with novel biomarkers to precisely identify subpopulations of patients who may benefit， and delving into the potential value of these drugs in delaying diabetic vascular complications and improving patients’ quality of life.

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.

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.

OBJECTIVE To evaluate the efficacy of intranasal branches neurotomy of vidian nerve in the treatment of persistent moderate to severe allergic rhinitis. METHODS Cases diagnosed as persistent moderate-severe allergic rhinitis in our department were collected. those treated with branches neurotomy of vidian nerve were selected as the treatment group,and those treated with conservative medicine were selected as the control group. The visual analogue scale(VAS),rhinoconjunctivitis quality of life questionnaire(RQLQ),Nitric oxide in nose(nNO) and medication score evaluation of two groups of cases were evaluated respectively short-term(<1 year),medium-term(1 to 3 years) and long-term prognosis of outcome(3 to 5 years). RESULTS The short-term,mid-term and long-term postoperative VAS(2.26±0.75,2.30±0.63,2.49±0.57),RQLQ(0.55±0.11,0.55±0.11,1.00±0.12),nNO[(464.62±75.84)ppb,(378.63±110.21)ppb,(368.23±104.25)ppb]and medication scores (2.50±1.03,2.54±0.99,2.95±0.93) were significantly lower than those before operation[6.76±0.58,3.35±0.40,(696.64±132.69)ppb,5.17±1.50)]. The VAS,RQLQ,nNO and medication scores of the control group were lower than those of the control group at the corresponding time points(all P<0.05). One patient developed blindness in the right eye after interventional treatment due to epistaxis 21 days after operation,but no serious complications directly related to intranasal branches neurotomy of vidian nerve occurred. CONCLUSION The branches neurotomy of vidian nerve have a positive outcome in short,medium and long-term for persistent moderate to severe allergic rhinitis,the operation is safe and effective.

OBJECTIVE To observe the curative effect of bacterial lysates(BLs)combined with intranasal corticosteroids(INCS)in the treatment of chronic rhinosinusitis(CRS).METHODS Cases diagnosed as CRS with nasal polyps(CRSwNP)and CRS without nasal polyps(CRSsNP)were collected and divided into four groups:CRSwNP with BLs group,CRSwNP control group,CRSsNP with BLS group and CRSsNP control group.All patients received surgical treatment,the control group received postoperative INCS therapy,and the BLs group received postoperative INCS+BLs oral therapy.Visual analogue scale(VAS),sino-nasal outcome test-20(SNOT-20),Lund-Kennedy score,Lund-Mackay score,eosinophilic(Eos)cell,IL-4,IgG,IgA,IgM and total IgE levels were evaluated before,1 month and 3 months after surgery.RESULTS Significant differences in IgG,IgA,IL-4 and Eos levels between CRSwNP and CRSsNP with BLs groups(P<0.05).There were significant differences in VAS and SNOT-20 between CRSwNP group and CRSsNP with BLs group at 1 and 3 months after treatment(P<0.05).At 1 month and 3 months after treatment,there were statistically significant differences in Lund-Kennedy score and Lund-Mackey score between the CRSwNP group and the CRSsNP with BLs group(P<0.05).The effective rate of disease control in the four groups after treatment was statistically significant(P<0.05).There were no serious complications directly related to the treatment.CONCLUSION The application of BLs can improve postoperative rhinorrhea,persistent inflammatory and mucosal recovery in patients with CRS,increase IgG and IgA levels,reduce Eos and IL-4 levels,reduce adverse reactions,and improve the therapeutic effect of CRS with high safety.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.