Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

OBJECTIVE To formulate the Hazardous Drug List in China， and provide a scientific basis for standardizing the management of hazardous drugs， preventing and controlling occupational exposure risks in medical institutions at all levels in China. METHODS Under the joint organization of the Intravenous Medication Admixture Management Professional Committee of the Chinese Pharmaceutical Association and the National Medical Quality Control Center for Pharmaceutical Management， based on literature research and international hazardous drug lists and their development procedures， the scope of hazardous drug selection， selection principles， and evidence confirmation criteria were determined through expert panel seminars and expert questionnaire survey method （Delphi method）. Chemical drugs， biological agents， and Chinese patent medicines marketed in China that met the selecti on principles were screened to form the Chinese Expert Consensus on the Hazardous Drug List . RESULTS Five principles for selecting hazardous drugs were established （including protective labeling in package inserts， carcinogenicity， reproductive toxicity， genotoxicity， and organ toxicity at low doses）， along with the corresponding evidence confirmation criteria. The Hazardous Drug List containing 210 drugs was formulated， covering anti-tumor drugs， endocrine system drugs， nervous system drugs， immunomodulators， anti-infective drugs， cardiovascular system drugs， hematological system drugs， urinary system drugs， obstetrics and gynecology drugs， dermatological drugs and other categories. Compared with international hazardous drug lists， 25 newly included hazardous drugs were added， including 15 anti-tumor drugs， 6 Chinese patent medicines and 4 biological agents. In addition， 88 Chinese patent medicines that may have potential occupational exposure risks are listed in the appendix for reference by medical institutions in management. CONCLUSIONS The development of this consensus closely aligns with the actual clinical drug use in China， with a scientific and rigorous methodology， and can serve as a reference for medical institutions at all levels to standardize the management of hazardous drugs and prevent and control occupational exposure risks.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Objective To investigate the effect of salvianolic acid B(Sal B)on high glucose(HG)induced necrotic apoptosis of retinal pigment epithelial cells(RPE)by regulating the receptor-interacting protein kinase 1(RIP1)/RIP3/mixed lineage kinase domain like protein(MLKL)signaling pathway.Methods RPE cells ARPE-19 were used as the research object and separated into control(Con)group,HG group,L-Sal B group,M-Sal B group,H-Sal B group,pcDNA3.1-NC group,and pcDNA3.1-RIP1 group.The qRT-PCR method was applied to detect the expression of RIP1,RIP3,and MLKL in ARPE-19 cells in each group.CCK8 was applied to detect ARPE-19 cell survival rate.Flow cytometry was applied to detect cell apoptosis.DCFH-DA fluorescent probe was applied to detect reactive oxygen species(ROS)level.ELISA was applied to detect the expression of tumor necrosis factor-α(TNF-α),interleukin(IL-1β),and IL-6.Western blot was applied to detect the expression of RIP1,RIP3,and MLKL proteins.Results The cell survival rate was lower in the HG group than in the Con group(P<0.05).The cell apoptosis rate,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL were higher in the HG group than in the Con group(P<0.05).The cell survival rates were higher,while the cell apoptosis rates,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL were lower in the L-Sal B,M-Sal B,and H-Sal B groups than in the HG group(P<0.05).The cell survival rates increased successively(P<0.05),while the cell apoptosis rates,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL decreased successively in the L-Sal B,M-Sal B,and H-Sal B groups(P<0.05).The cell survival rate was lower(P<0.05),while the cell apoptosis rate,the proportion of ROS-positive cells,TNF-α,IL-1β,IL-6,and the mRNA and protein expressions of RIP1,RIP3,and MLKL were higher in the pcDNA3.1-RIP1 group than in the H-Sal B and pcDNA3.1-NC groups(P<0.05).Conclusions Sal B may inhibit the necrotic apoptosis of RPE cells induced by HG by suppressing the RIP1/RIP3/MLKL signaling pathway.

Aim To investigate the effects of tran-scription factor FoxO1 on acute kidney injury(AKI)induced by ischemic reperfusion injury(IRI)and to explore the underlying mechanisms.Methods Male C57BL/6 mice were randomly divided into four groups:Sham,IRI,FoxO1 inducible cell-specific knockout(FoxO1 icKO),and IRI+FoxO1 icKO.Tamoxifen(25 mg·kg-1)was intraperitoneally injec-ted to specifically knock out FoxO1 in mouse macro-phages,and a unilateral renal IRI model was estab-lished.The levels of serum creatinine(Scr),blood u-rea nitrogen(BUN),Fe2+,malondialdehyde(MDA),reactive oxygen species(ROS),and reduced glutathi-one(GSH)in renal tissues were detected.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in renal tissues.Quantitative polymer-ase chain reaction(qPCR)was used to detect the mR-NA levels of inflammatory factors such as IL-1β and MCP1 in renal tissues.Western blot was used to detect the expression levels of apoptosis and ferroptosis-relat-ed proteins.Results Compared with the control group,the levels of Scr and BUN in the IRI group were significantly upregulated,the infiltration of inflammato-ry factors IL-1β,TNF-α and MCP1 increased,the pro-tein expressions of Bax/Bc12,cleaved-caspase-3/caspase-3,cytochrome C,and FTH1 in renal tissues were significantly enhanced,while the expression of GPX4 decreased.In addition,the levels of Fe2+,MDA and ROS in the renal cortex of the IRI group signifi-cantly increased,and the level of GSH markedly de-creased(P＜0.05).Compared with the IRI group,the levels of Scr and BUN in the FoxO1 icKO group were significantly reduced,the infiltration of inflammatory factors was alleviated,the expression of apoptosis-relat-ed proteins in renal tissue decreased,the expression level of ferroptosis protein GPX4 increased,and the ex-pression of FTH1 decreased.The levels of Fe2+,MDA and ROS in the renal cortex decreased,and the level of GSH significantly increased(P＜0.05).Conclusion Inducing the specific knockout of FoxO1 in macro-phages can alleviate AKI induced by IRI,and its mech-anism may be related to the inhibition of ferroptosis caused by IRI by FoxO1.

Objective To analyze the impact of the National Centralized Drug Procurement Policy(hereinafter referred to as the"centralized procurement policy")on the utilization of breast cancer treatment drugs in a specialized cancer hospital.Methods The defined daily dose(DDD)method was used to compare the daily drug cost(DDC),drug utilization frequency(DDDs),and affordability of letrozole,anastrozole,and capecitabine before and after the implementation of the centralized pro-curement policy in a tertiary specialized cancer hospital in Guangzhou.Results and Conclusion After the policy implementa-tion,the DDC of all three drugs decreased.The out-of-pocket DDC for the selected drugs remained stable or decreased,while the out-of-pocket DDC for both originator drugs and generic drugs increased,with a more pronounced increase for originator drugs.The proportion of DDDs for the selected drugs increased post-policy.The centralized procurement policy not only reduced the prices of selected drugs but also drove down the prices of generic and originator drugs.It is recommended to further expand the scope of centralized procurement for anticancer drugs and the types of cancers covered,as well as to establish a transitional mech-anism for medical insurance payment standards.

BACKGROUND:Radiotherapy for head and neck tumors can easily cause xerostomia,seriously affecting the quality of life of patients.In recent years,engineered stem cells and their paracrine factors have shown therapeutic potential in the repair of salivary gland injury.However,there is currently no experimental study on the application of amniotic mesenchymal stem cell-derived exosome in radiation-induced salivary gland injury.OBJECTIVE:To preliminarily explore the repair effect of exosome derived from human amniotic mesenchymal stem cells on radiation-induced submandibular gland injury.METHODS:H uman amniotic mesenchymal stem cell exosomes were extracted and identified by ultrafiltration and ultracentrifugation.SD rats were randomly divided into a control group,a radiation injury group,and a radiation injury+exosome group.An in vitro model of radiation-induced submandibular gland injury was constructed using the submandibular gland tissue of SD rats irradiated with 18 Gy of radiation.One day after radiation modeling,exosome derived from human amniotic mesenchymal stem cells was injected into the submandibular gland in situ.Samples are taken at 1,3,7,and 14 days to detect the resting salivary flow rate.The structure of the submandibular gland tissue was observed by hematoxylin-eosin staining.The expression of glycogen particles in the submandibular gland tissue was observed by Periodic Acid-Schiff staining.Fibrosis in the submandibular gland tissue was observed by Masson staining.The secretion of salivary amylase was detected by enzyme-linked immunosorbent assay.The expression of aquaporin and tight junction proteins in submandibular gland tissue was observed by immunofluorescence staining.Real-time fluorescence quantitative PCR was used to detect the relative expression levels of aquaporins and salivary amylase mRNA in submandibular gland tissue.TUNEL assay was used to detect the apoptosis rate of submandibular gland tissues in each group.RESULTS AND CONCLUSION:After radiomodeling,compared with the radiation injury group,(1)hematoxylin-eosin staining observed that the submandibular gland tissue structure in the radiation injury+exosome group was restored,the nucleoli increased,the number of acinus increased,and the acinar atrophy improved.(2)Glycogen staining observed that the number and density of positive zymogen granules in the acinar cytoplasm of the radiation injury+exosome group gradually increased.(3)Masson staining results observed that the number and density of positive collagen fibers in the interstitium and around the ducts in the radiation injury+exosome group gradually decreased,the degree of fibrosis decreased,and the collagen deposition decreased.(4)The salivary flow rate in the radiation injury+exosome group increased(P＜0.05).The fluorescence intensity of aquaporin-5 was enhanced(P＜0.05)and the gene expression was significantly enhanced(P＜0.01).The fluorescence distribution of tight junction protein 4 was weakened and the fluorescence intensity decreased(P＜0.05,P＜0.01).The content of salivary amylase increased(P＜0.05)and gene expression were significantly increased(P＜0.01).The number of positive apoptotic cells decreased(P＜0.05,P＜0.01).It is indicated that local injection of exosome derived from human amniotic mesenchymal stem cells could improve the pathological morphology of submandibular gland tissue,promote saliva flow rate and amylase expression,and may play a functional repair role in radioactive submandibular gland injury by inhibiting acinar apoptosis.

This study was aimed at preliminarily investigating the genetic and antimicrobial resistance characteristics of Salmonella Alachua isolates through whole-genome analyses.Five Salmonella Alachua isolates from various sources(both hu-man and non-human)were collected and identified.Phenotype and serotype verification,antimicrobial susceptibility testing,and whole-genome sequencing were performed.Virulence genes,antimicrobial resistance genes,and plasmid replicons were predicted according to globally available Salmonella Alachua genomic data.A phylogenetic tree was constructed to explore the genetic background.The first report of Salmonella Alachua in China emerged in Shanghai in 2015,and patients presented pri-marily with diarrhea.The isolates have been found predominantly in the eastern and southern coastal regions.Among the five i-solates analyzed,four belonged to sequence type(ST)2061,and one belonged to ST1298.All isolates were susceptible to most commonly used clinical antibiotics.Whole-genome analyses revealed that two ST2061 strains carried the blaKPC-2 gene,and one ST1298 strain carried the fosA7 gene.Phylogenetic analysis of global Salmonella Alachua populations indicated that the ST2061 clone belonged to the C1 clade,which was closely related to strains from the UK,whereas the ST1298 clone was found in the C4 clade,a globally disseminated fosA 7-positive lineage.This study provides initial insights into the genetic and antimi-crobial resistance characteristics of Salmonella Alachua in China,highlighting the presence of strains carrying blaKPC-2 and fo-sA7 genes.These findings may provide a reference for future large-scale molecular epidemiological surveillance and source-trac-ing efforts,and they underscore the importance of enhanced resistance monitoring for Salmonella Alachua.

Objective:To explore the value of serum P-selectin,Interleukin-18(IL-18),and Homocysteine(Hcy)levels in predicting the adverse outcomes of interventional therapy in elderly patients with deep vein thrombosis(DVT)in the lower extremities.Methods:A total of 165 elderly patients with DVT from January 2020 to August 2023 were se-lected.All patients underwent transcatheter intervention thrombolysis therapy.Patients were divided into good outcome group and poor outcome group according to the clinical treatment outcome.Serum P-selectin,IL-18,and Hcy levels were compared between the two groups.The correlation between serum P-selectin,IL-18,and Hcy levels and disease indicators,as well as the outcomes of interventional therapy was analyzed.The predictive value of serum P-selectin,IL-18,and Hcy levels for the outcomes of interventional therapy was evaluated.Results:The total effective rate of catheter-based interventional thrombolysis in 165 patients was 81.82%(135/165).The patients with good outcomes were included in the good outcome group,and the patients with poor outcomes were included in the poor outcome group.The difference in circumference between the affected side and the healthy side of the thigh and the difference in circumference between the affected side and the healthy side of the calf in the poor outcome group were greater than those in the good outcome group(P<0.05).The levels of serum P-selectin,IL-18,and Hcy in the poor outcome group were higher than those in the good outcome group(P<0.05).The levels of serum P-selectin,IL-18,and Hcy were posi-tively correlated with the difference in circumference between the affected and healthy thighs and the difference in cir-cumference between the affected and healthy calves,and negatively correlated with the outcome of interventional therapy(P<0.05).Before and after correcting other factors,serum P-selectin,IL-18,and Hcy were all independent risk factors for the outcome of interventional therapy in elderly patients with DVT(P<0.05).The area under the curve(AUC)of serum P-selectin,IL-18,and Hcy for predicting the outcome of interventional therapy for elderly DVT was 0.789(95%CI:0.718-0.848),0.812(95%CI:0.744-0.868),and 0.792(95%CI:0.722-0.851),respectively.The cutoff values were 44.21 ng/mL,185.73 ng/L,and 23.60 μmol/L,with sensitivities of 70.00%,70.00%,and 80.00%,and specificities of 82.22%,82.96%,and 68.15%,respectively.The AUC of the combined prediction of the outcomes of interventional therapy for elderly DVT was 0.935(95%CI:0.886-0.967),with a cutoff value of 44.08 ng/mL,185.16 ng/L,and 23.37 μmol/L for the three variables,with a sensitivity of 86.67%and a specificity of 88.15%.This was significantly better than the individual prediction values of the three variables(Z=5.817,4.753,5.206,all P<0.001).Conclusion:Serum P-selectin,IL-18,and Hcy are significantly correlated with disease indicators and interventional treatment outcomes in el-derly patients with DVT,and can effectively predict the outcome of interventional treatment,with a high combined pre-dictive value.

Objective To understand the nursing practice of prone position ventilation for patients with moderate to severe acute respiratory distress syndrome(ARDS)in intensive care unit(ICU)in Shandong province,so as to provide basis for standardizing the nursing practice process of prone position ventilation and carrying out training for hospitals.Methods A self-made questionnaire was used,and convenience sampling was adopted.From September 15th to November 5th,2023,ICU nurses were selected from various hospital levels in Shandong province to investigate the obstructive factors of prone ventilation implementation,the weak links in nursing practice and status,and the occurrence of complications.Results A total of 1 188 questionnaires were collected,of which 991 were valid.92.8%(920/991)of nurses had performed prone position ventilation.The biggest obstacle to the implementation of prone position ventilation was the complexity of patient treatments and multiple devices involved[74.6%(686/920)].Regarding the status of training,90.5%(897/991)of nurses had received training on prone position ventilation and 77.0%(763/991)of nurses felt that training was needed.As for pre-operation assessment,more than 80.0%of nurses evaluated patients'vital signs,airway and secretions and so on,among which the evaluation awareness of analgesia was the worst[81.6%(751/920)].As for the main points of implementation,only 14.0%(129/920)of nurses chose the opposite side of the most important pipeline as the turning direction;48.6%(447/920)of nurses chose the anti-Trendelenburg position;36.3%(334/920)of nurses chose to ventilate≥12 hours.Facial edema[81.7%(752/920)],skin pressure injury[78.9%(726/920)]and eye complication[75.8%(697/920)]were the top 3 most frequent complications.Conclusions ICU nurses'prone position ventilation practices were generally line with the nursing team standard for prone position of adult mechanically ventilated patients and the best evidence recommendation,and needs to be further standardized in aspects of turning direction,position management,ventilation duration,and enteral nutrition management.It is recommended that nursing managers at all levels of hospitals further improve the quality of nursing practice of prone position ventilation according to relevant evidence-based evidence and the actual situation of hospitals.