Perfluorooctane sulfonate （PFOS） has significant biotoxicity and can disrupt the structure and function of the blood-brain barrier. PFOS exposure can lead to the degradation of tight junction proteins in the blood-brain barrier and damage to astrocytes， resulting in increased permeability of the blood-brain barrier， as well as the activation of multiple signaling pathways， including PI3K/AKT， p38 MAPK， oxidative stress， and calcium signaling pathways. Damage to the blood-brain barrier may trigger various neurological diseases， and PFOS affects the function of the blood-brain barrier through multiple mechanisms， thereby interfering with the normal operation of the central nervous system. This article aims to review the research progress on the signaling pathways related to PFOS-induced blood-brain barrier damage and suggests that future studies could focus on developing more precise in vivo models， utilizing advanced molecular biology techniques to reveal more detailed molecular mechanisms， and exploring the synergistic effects of PFOS with other environmental toxins， in order to provide scientific evidence for the clinical prevention and treatment of PFOS-induced neurological diseases.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To investigate the influencing factors of the course of perioperative prophylactic antibiotics in patients undergoing total hip arthroplasty,and explore management strategies for enhancing perioperative prophylactic medication administration.Methods The clinical data for patients undergoing total hip arthroplasty at Affiliated Hospital of Chengdu University from January,2020 to September,2024 were retrospectively collected.Patients were divided into a 24 h group and a 48-72 h group based on the duration of prophylactic antibacterial therapy.The general characteristics,surgical-related indicators,preoperative and postoperative laboratory test results,and surgical outcome measures between the two groups of patients were compared.Multivariate Logistic regression analysis was performed to identify influencing factors associated with prolonged duration of prophylactic antibacterial therapy.Results A total of 126 patients who underwent total hip arthroplasty were enrolled,including 74 cases in the 24 h group and 52 cases in the 48-72 h group.Univariate analysis results showed that there were statistically significant differences in the following indicators between the two groups:surgical cause,surgical duration,intraoperative blood loss,drainage duration of plasma drainage tubes,preoperative white blood cell count,and preoperative neutrophil count(P<0.05).The results of multivariate Logistic regression analysis showed that the reason for surgery and the duration of plasma drain tube drainage were the influencing factors of antimicrobial treatment course for total hip arthroplasty(P<0.05).The results of receiver operating characteristic curve analysis showed that the prediction model(constructed based on the drainage time of plasma drainage tube)for prophylactic antimicrobial treatment course to 48-72 h was 0.721.When the drainage time of plasma drainage tubes was≥40.56 h,the risk of requiring prophylactic antimicrobial therapy for an extended course of 48-72 h increased significantly.Conclusion The patient's surgical reason and the duration of plasma drain drainage may be related to the prophylactic antimicrobial course of more than 24 hours.Clinical pharmacists may utilize this parameter as a patient-specific characteristic,with the support of information systems,the hierarchical patient management can be implemented,thereby enhancing the effectiveness of medication surveillance and progressively elevating the 24 h discontinuation rate of perioperative prophylactic antibiotics.

OBJECTIVE To investigate the regulatory effect of Rasfonin on SOS1(Son of Seven-less,one of the major guanylate exchange factors)expressions and the underlying mechanism.METHODS① Human cancer cells MCF-7(breast cancer cells,KRASWT wild-type),Calu-1(non-small cell lung cancer,KRASG12C mutation),and UM-UC-3(bladder metastatic cell carcinoma,KRASG12C mutation)were divided into the control group and Rasfonin(1,5,10 and 15 μmol·L-1)treated groups.CCK-8 assay was used to observe the effects of Rasfonin on the proliferation of MCF-7,Calu-1,and UM-UC-3 cells after 24 h of Rasfonin treatment.In addition,these cells were divided into the control group,EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min),and Rasfonin treated groups(pretreated with 5 and 10 μmol·L-1 Rasfonin before 5 min EGF stimulation).Quantitative real-time PCR(real-time fluores-cence PCR)and Western blotting were employed to identify the expression levels of SOS1 mRNA and protein in MCF-7,Calu-1 and UM-UC-3 cells.② The co-expression systems of KRAS and SOS1 were established by transfecting plasmids(KRAS-NC,KRASWT,KRASG12C and SOS1)into 293T cells that were divided into the control group and Rasfonin(1,5 and 10 μmol·L-1)treated group.The dual luciferase reporter gene assay was used to evaluate the effects of Rasfonin on activities of the SOS1 promoter.Moreover,293T cells were divided into the EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min)and Rasfonin treated groups(12 h of treatment with 10 μmol·L-1 Rasfonin before 5 min EGF stimula-tion).Western blotting was performed to determine the role of KRASG12C protein in the inhibition of Rasfonin on SOS1 expression.RESULTS ① Compared with the control group,Rasfonin inhibited the prolifera-tion of Calu-1 and UM-UC-3 cells at concentrations of 5,10 and 15 μmol·L-1(IC50 was 8.22 and 4.94 μmol·L-1).But for MCF-7 cells,only 15 μmol·L-1 Rasfonin could decrease their viability(IC50 was 45.15 μmol·L-1).Compared with the EGF stimulation group,mRNA expressions of SOS1 were increased after Rasfonin treatment of 1 h.mRNA expressions of SOS1 were decreased in Calu-1 cells after 3 h of Rasfonin treatment.These changes also occurred after Rasfonin treatment of 3 h and 6 h in UM-UC-3 cells.Further-more,Rasfonin treatment did not influence SOS1 protein expressions in MCF-7 cells,but can signifi-cantly inhibit SOS1 expression of in UM-UC-3 and Calu-1 cells.② Rasfonin had no significant effects on the activity of SOS1 promoter and its protein level in 293T cells when only SOS1 was expressed,but significantly inhibited its activity and its protein level when SOS1 was co-expressed with KRAS protein.CONCLUSION One of the anti-tumor mechanisms of Rasfonin is to inhibit the activity of SOS1 promoter to decrease mRNA and protein expressions of SOS1 through KRASG12C protein.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To investigate the influencing factors of the course of perioperative prophylactic antibiotics in patients undergoing total hip arthroplasty,and explore management strategies for enhancing perioperative prophylactic medication administration.Methods The clinical data for patients undergoing total hip arthroplasty at Affiliated Hospital of Chengdu University from January,2020 to September,2024 were retrospectively collected.Patients were divided into a 24 h group and a 48-72 h group based on the duration of prophylactic antibacterial therapy.The general characteristics,surgical-related indicators,preoperative and postoperative laboratory test results,and surgical outcome measures between the two groups of patients were compared.Multivariate Logistic regression analysis was performed to identify influencing factors associated with prolonged duration of prophylactic antibacterial therapy.Results A total of 126 patients who underwent total hip arthroplasty were enrolled,including 74 cases in the 24 h group and 52 cases in the 48-72 h group.Univariate analysis results showed that there were statistically significant differences in the following indicators between the two groups:surgical cause,surgical duration,intraoperative blood loss,drainage duration of plasma drainage tubes,preoperative white blood cell count,and preoperative neutrophil count(P<0.05).The results of multivariate Logistic regression analysis showed that the reason for surgery and the duration of plasma drain tube drainage were the influencing factors of antimicrobial treatment course for total hip arthroplasty(P<0.05).The results of receiver operating characteristic curve analysis showed that the prediction model(constructed based on the drainage time of plasma drainage tube)for prophylactic antimicrobial treatment course to 48-72 h was 0.721.When the drainage time of plasma drainage tubes was≥40.56 h,the risk of requiring prophylactic antimicrobial therapy for an extended course of 48-72 h increased significantly.Conclusion The patient's surgical reason and the duration of plasma drain drainage may be related to the prophylactic antimicrobial course of more than 24 hours.Clinical pharmacists may utilize this parameter as a patient-specific characteristic,with the support of information systems,the hierarchical patient management can be implemented,thereby enhancing the effectiveness of medication surveillance and progressively elevating the 24 h discontinuation rate of perioperative prophylactic antibiotics.

OBJECTIVE To investigate the regulatory effect of Rasfonin on SOS1(Son of Seven-less,one of the major guanylate exchange factors)expressions and the underlying mechanism.METHODS① Human cancer cells MCF-7(breast cancer cells,KRASWT wild-type),Calu-1(non-small cell lung cancer,KRASG12C mutation),and UM-UC-3(bladder metastatic cell carcinoma,KRASG12C mutation)were divided into the control group and Rasfonin(1,5,10 and 15 μmol·L-1)treated groups.CCK-8 assay was used to observe the effects of Rasfonin on the proliferation of MCF-7,Calu-1,and UM-UC-3 cells after 24 h of Rasfonin treatment.In addition,these cells were divided into the control group,EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min),and Rasfonin treated groups(pretreated with 5 and 10 μmol·L-1 Rasfonin before 5 min EGF stimulation).Quantitative real-time PCR(real-time fluores-cence PCR)and Western blotting were employed to identify the expression levels of SOS1 mRNA and protein in MCF-7,Calu-1 and UM-UC-3 cells.② The co-expression systems of KRAS and SOS1 were established by transfecting plasmids(KRAS-NC,KRASWT,KRASG12C and SOS1)into 293T cells that were divided into the control group and Rasfonin(1,5 and 10 μmol·L-1)treated group.The dual luciferase reporter gene assay was used to evaluate the effects of Rasfonin on activities of the SOS1 promoter.Moreover,293T cells were divided into the EGF stimulation group(EGF 50 μg·L-1,stimulated for 5 min)and Rasfonin treated groups(12 h of treatment with 10 μmol·L-1 Rasfonin before 5 min EGF stimula-tion).Western blotting was performed to determine the role of KRASG12C protein in the inhibition of Rasfonin on SOS1 expression.RESULTS ① Compared with the control group,Rasfonin inhibited the prolifera-tion of Calu-1 and UM-UC-3 cells at concentrations of 5,10 and 15 μmol·L-1(IC50 was 8.22 and 4.94 μmol·L-1).But for MCF-7 cells,only 15 μmol·L-1 Rasfonin could decrease their viability(IC50 was 45.15 μmol·L-1).Compared with the EGF stimulation group,mRNA expressions of SOS1 were increased after Rasfonin treatment of 1 h.mRNA expressions of SOS1 were decreased in Calu-1 cells after 3 h of Rasfonin treatment.These changes also occurred after Rasfonin treatment of 3 h and 6 h in UM-UC-3 cells.Further-more,Rasfonin treatment did not influence SOS1 protein expressions in MCF-7 cells,but can signifi-cantly inhibit SOS1 expression of in UM-UC-3 and Calu-1 cells.② Rasfonin had no significant effects on the activity of SOS1 promoter and its protein level in 293T cells when only SOS1 was expressed,but significantly inhibited its activity and its protein level when SOS1 was co-expressed with KRAS protein.CONCLUSION One of the anti-tumor mechanisms of Rasfonin is to inhibit the activity of SOS1 promoter to decrease mRNA and protein expressions of SOS1 through KRASG12C protein.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

OBJECTIVE To establish a mouse model of diabetes mellitus(DM)combined with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection to investigate the important pathophysiological changes in the development of DM combined with SARS-CoV-2 infection.METHODS Wild-type(WT)mice and transgenic mice expressing the human angiotensin-converting enzyme 2 receptor driven by the cytokeratin-18 gene promoter(K18-hACE2)were randomly divided into the control group,DM group,SARS-CoV-2 spike protein(S)infection group and DM combined with S protein infection group,with 10 to 12 mice in each group.All the mice were induced by 10 weeks of high-fat diet combined with 40 mg·kg-1 streptozotocin(STZ)for 3 days by ip,except those in the control group or S protein infection group.The control group was given the same volume of 0.1 mol·L-1 sodium citrate buffer.Mice in the S protein infection group and DM+S protein infection group were additionally given 50 μL mixture of 15 μg SARS-CoV-2 spike protein and 1 g·L-1 polyinosinic-polycytidylic acid(poly[I:C])via intranasal drops,while the control group was given an equal volume of sterile water.The glucose tolerance level and pancreatic islet β cell function of mice were evaluated via oral glucose tolerance test at the 6th week of high-fat feeding and 1 week after the administration of STZ by ip.From the 6th week of high-fat feeding to 2 weeks after the administration of STZ,the random blood glucose and fasting blood glucose of mice were measured by a blood glucose meter.Blood samples were taken from subman-dibular veins of 3 mice in each group at 24,48 and 120 h after S protein infection,and lung tissues were taken after euthanization.The pathological changes of lungs of DM mice before and after S protein infection were observed by HE staining.Except for the DM group,blood samples were collected before S protein infection and at 6,24,48,72 and 120 h after infection.The levels of plasma interleukin 1β(IL-1β),IL-2,IL-6,IL-10,IL-17,interferon gamma-induced protein 10(IP-10),interferon γ(IFN-γ),tumor necrosis factor α(TNF-α),monocyte chemotactic protein-1(MCP-1)and granulocyte-colony stimulating factor(G-CSF)were detected by Luminex.The plasma levels of heparan sulfate(HS)were measured by enzyme-linked immunosorbent assay.The levels of cytokines and HS were correlated with the degree of pathological damage by Spearman correlation analysis.RESULTS STZ and high-fat diet could induce DM-like expression in mice,and the random blood glucose(P<0.01)and fasting blood glucose(P<0.05)after 1 week in the hACE2-DM group were significantly higher than in the WT-DM group,and the degree of islet function damage in hACE2-DM mice was significantly higher than that of WT-DM mice(P<0.05).Compared with the DM group,the DM+S group showed more severe pulmonary pathological changes after S protein infection,accompanied by a large number of inflammatory infiltrations and thickening of lung interstitial.Compared with the control group,the levels of pro-inflammatory cytokines G-CSF,IL-6 and IP-10 in the plasma of the WT-S group were significantly increased at 6 h after S pro-tein infection(P<0.01),and those of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 were significantly increased at 24 h after S protein infection(P<0.05).Compared with the control group,the plasma levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,MCP-1,G-CSF and IP-10 in the hACE2-S group were significantly increased at 6 h after S protein infection(P<0.05,P<0.01).IL-17 was significantly increased at 24 h and 6 h after S protein infection in the WT-DM+S group and hACE2-DM+S group,respectively(P<0.01,P<0.05).In the hACE2-DM+S group,IFN-γ and IL-1β were signifi-cantly increased in delay to 48 h(P<0.05,P<0.01),and MCP-1 was significantly increased in delay to 72h(P<0.05).Compared with the control group,the level of HS in the plasma of the WT-S group increased significantly(P<0.05,P<0.01)at 6 h and 24 h after S protein infection,but began to decrease at 48 h.At the same time,compared with the WT-S group,the HS level in the WT-DM+S group was slightly increased at 6 h after infection and decreased at 24 h.Compared with the control group,the HS level in the hACE2-S group was significantly increased at 24 h(P<0.01),as was the case with the WT-S group 24 h,48 h and 120 h after S protein infection.At 6 h,24 h and 48 h after S protein infection,the plasma HS level of the hACE2-DM+S group was significantly increased(P<0.01,P<0.05),and the duration of the increase was longer than in the hACE2-S group.Moreover,the levels of IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS in plasma were positively correlated with the degree of lung dam-age in the DM+S group.CONCLUSION In this study,the mouse model of diabetes combined with SARS-CoV-2 spike protein infection has mimicked part of the pathophysiological features of clinical patients,mainly manifested as blunted immune response and elevated HS levels with longer duration to infection alone.IL-1β,IL-10,MCP-1,IP-10,G-CSF and HS may keep track of the course of disease in patients with diabetes combined with SARS-CoV-2 infection.