BACKGROUND:While antivenom has provided hope for treating snakebites,it is not always effective for local tissue damage caused by venomous snakes.Additionally,antivenom has several limitations,including the risk of hypersensitivity,immune reactions like"serum sickness,"and accessibility issues in some regions.Consequently,there is an urgent need to explore complementary or alternative therapies and therapeutic targets for snakebites in clinical settings.OBJECTIVE:To observe the effect of the 717 Jiedu Decoction on the expression of extracellular matrix proteins and matrix metalloproteinases/tissue inhibitors of metalloproteinases in the local tissues of rats bitten by Agkistrodon halys.METHODS:SD rats were randomly divided into a control group,a model group,an anti-viper venom serum group,and 717 Jiedu Decoction low-,medium-and high-dose groups.Except for the control group,all other groups received an injection of 1.25 mL/kg of viper venom into the gastrocnemius muscle of the left hind limb to create a model.The 717 Jiedu Decoction low-,medium-and high-dose groups were administered a preventive oral gavage of 1.98,3.96,and 7.92 g/kg daily for seven consecutive days prior to the viper venom injection.The anti-viper venom serum group received a tail vein injection of 0.6 mL of antivenom serum two hours after the venom injection.Twenty-four hours post-injection,the pathological changes in the gastrocnemius muscle were observed using hematoxylin-eosin staining.The expression levels of matrix metalloproteinase-2,matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1,and tissue inhibitor of metalloproteinase-2 proteins,as well as their mRNA in serum and gastrocnemius muscle,were evaluated using ELISA and qPCR.The expression levels of type Ⅰ collagen,type Ⅳ collagen,fibronectin,laminin,α-smooth muscle actin,transforming growth factor-β1,CD31,and vascular endothelial growth factor in the gastrocnemius muscle were analyzed by immunohistochemistry.RESULTS AND CONCLUSION:(1)Compared to the control group,the model group displayed significant local inflammatory cell infiltration,hemorrhage,muscle structure disruption,and myocyte degeneration and necrosis.The protein and mRNA levels of matrix metalloproteinase-2,matrix metalloproteinase-9,and tissue inhibitor of metalloproteinase-1 in serum and gastrocnemius muscle were elevated(P＜0.05 or P＜0.01),while the mRNA expression of tissue inhibitor of metalloproteinase-2 was reduced(P＜0.01).The protein levels of type Ⅰ collagen and type Ⅳ collagen in the gastrocnemius muscle were significantly decreased(P＜0.01),whereas the protein levels of laminin,vascular endothelial growth factor,and CD31 were increased(P＜0.05 or P＜0.01);however,there were no significant changes in the protein levels of fibronectin,α-smooth muscle actin,and transforming growth factor-β1(P＞0.05).(2)In contrast to the model group,the 717 Jiedu Decoction low-,medium-and high-dose groups and the anti-viper venom serum group demonstrated alleviated myocyte damage,with improved reduction in inflammatory cell infiltration and hemorrhage.The levels of matrix metalloproteinase-2,matrix metalloproteinase-9,and tissue inhibitor of metalloproteinase-1 in serum and gastrocnemius muscle were significantly reduced(P＜0.05 or P＜0.01).In the high-dose 717 Jiedu Decoction group,the protein level of tissue inhibitor of metalloproteinase-2 was upregulated(P＜0.05).Type Ⅰ collagen,type Ⅳ collagen,laminin,α-smooth muscle actin,and transforming growth factor B1 protein expression were elevated(P＜0.05 or P＜0.01),and there was a dose-effect relationship;vascular endothelial growth factor expression was decreased(P＜0.05 or P＜0.01),there was no significant difference in the expression of fibronectin(P＞0.05);the expression of CD31 protein was elevated in the 717 Jiedu Decoction low-dose group(P＜0.01).The results showed that 717 Jiedu Decoction could promote the production of α-smooth muscle actin and transforming growth factor β1 by regulating the expression of matrix metalloproteinase 2,matrix metalloproteinase 9 with tissue metalloproteinase inhibitory factor 1,and tissue metalloproteinase inhibitory factor 2,so as to make the synthesis of extracellular matrix greater than the degradation,maintain the extracellular matrix homeostasis,and then promote the repair of local tissue damage in pit viper bites.

Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

Objective To investigate the role of the GPR120 gene in the progression of sepsis,explore the molecular mechanisms through which GPR120 gene regulates NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome activation and macrophage polarization.Methods The blood and pleural fluid samples were collected from the sepsis patients and the control group.The expression of inflammatory factors and the associated proteins were detected by flow cytometry and ELISA.C57BL/6 mice and monocyte-macrophage cell line(Raw264.7)were treated with lipopolysaccharide(LPS)to construct the sepsis models.After the intervention of GPR120 agonist TUG891,the expression of GPR120 gene,NLRP3 inflammasome protein and macrophage polarization protein were detected between the control group and the sepsis group.Results The expression of inflammatory factors,such as IL-1β in the serum of septic patients,significantly increased compared with the control(P<0.001).And the expression of inflammasome proteins such as NLRP3,Caspase-1 and IL-1β in the pleural fluid also increased(all P<0.05).In vivo,LPS could induce severe inflammation in lung tissue,the GPR120 gene expression decreased in lung tissue,and inflammatory factors were up-regulated in mouse serum(P<0.01).The inflammasome-associated protein and M1 type polarization of macrophages were enhanced,the TUG891 could reduce the inflammatory response,inhibit the NLRP3 inflammasome activating,and promote the M2 polarization of macrophages(P<0.01).In vitro,LPS could inhibit the intracellular GPR120 expression.The inflammatory factors secreted more in LPS-induced sepsis cells.TUG891 could promote the up-regulation of GPR120 protein and alleviate the secretion of inflammatory factors(P<0.05).Conclusion In sepsis,GPR120 gene activation could inhibit the NLRP3 inflammasome activation,promote macrophage polarization,and reduce the inflammatory damage,thereby delay the rapid progression of sepsis.

The medulla oblongata,situated at the caudal portion of the brainstem,serves as a critical regulatory center responsible for maintaining fundamental vital functions including respiratory and cardiovascular homeostasis.As a pivotal hub within the autonomic nervous system,it orchestrates the coordinated control of afferent and efferent neural pathways.Dysfunction of this region may precipitate life-threatening cardiorespiratory arrest,associated with substantial mortality rates.This case report presents a patient who developed acute extensive anterior myocardial infarction during treatment with dual antiplatelet therapy and moderate-intensity statins following acute medullary infarction.It is hypothesized that the pathogenesis may involve the acceleration of plaque erosion by the stroke-heart syndrome.This clinical case provides valuable insights into the complex neurocardiac interplay,particularly highlighting the imperative for enhanced recognition of brain-heart axis interactions in cerebrovascular pathology.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

With the deepening of the public hospital reform and the implementation of a series of policies,the external environment of the hospital has undergone profound changes,and the operation and management of the hospital has faced unprecedented pressure.Against this background,the case hospital has set up a special operation management team,established an operation evaluation index system that integrates business and finance,written an analysis report on"one policy for one department",set up an"operation management MDT clinic",and issued a list of operation problems to functional departments.A series of measures,such as the establishment of a set of operation management system with multi-line synergy,big data support,lean operation and evidence-based decision-making,have strongly guaranteed the scientific decision-making and efficient implementation of the hospital's operation management,and played a good role in the hospital's medical business,operation efficiency,cost structure,and management of the medical insurance fund,etc.The practical exploration of the operation management model has further improved the medical service level of the hospital and accelerated the pace of improving quality and increasing efficiency of the hospital.It is necessary to pay more attention to the refined management,continuously optimize the operation management system,and continuously promote the high-quality development of the hospital.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Aim To investigate the effects of circ_0071653 targeting miR-197-3p on the proliferation and metastasis of esophageal squamous cell carcinoma(ES-CC)cells.Methods The circular structure of circ_0071653 was confirmed by Sanger sequencing and ribo-nuclease R tolerance experiments.Real-time quantita-tive polymerase chain reaction(RT-qPCR)and tissue fluorescence in situ hybridization assay were performed to detect the circ_0071653 expression levels and ana-lyze its clinical relevance.Cell fluorescence in situ hy-bridization and nuclear cytoplasmic separation assays were used to verify the subcellular localization of circ_0071653 and miR-197-3p.Bioinformatics analysis,dual luciferase reporter gene and RT-qPCR assays were conducted to validate the interactions between circ_0071653 and miR-197-3p.Moreover,the cell counting Kit-8(CCK-8),colony formation,scratch,Transwell invasion and subcutaneous tumor formation in nude mice assays were used to evaluate the effects of circ_0071653 and miR-197-3p on cell viability,prolifera-tion,migration,and invasion and in vivo tumorigenesi-sability.Results Circ_0071653 was a circular RNA,which showed high expression in ESCC cell lines and tissues.The expression of circ_0071653 was signifi-cantly correlated with lymph node metastasis and clini-cal stage of ESCC patients.Circ_0071653 and miR-197-3p were mainly localized in the cytoplasm.The databases predict that circ_0071653 had complementa-ry binding sites with miR-197-3p,and their binding were confirmed by dual luciferase reporter geneand RT-qPCR assays.Moreover,the activity,proliferation,migration,invasion and in vivo tumorigenesis abilities of ESCC cells were significantly reduced after knocking down circ_0071653,and this effect could be reversed by downregulating the expression of miR-197-3p.Con-clusions Circ_0071653 promotes the malignant pro-gression of ESCC through targeted regulation of miR-197-3p.