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.

Background Heavy metals may play an important role in environmental risk factors associated disorders of activities of daily living (ADL) in older adults. Objective To investigate the associations between plasma levels of six heavy metals (zinc, arsenic, cadmium, lead, manganese, and copper) and ADL disorders in older adults. Methods A cross-sectional survey was conducted from 2018 to 2019 among 1412 rural elderly people in Gongcheng Yao Autonomous County, Guangxi Zhuang Autonomous Region. The plasma metal concentrations were detected by inductively coupled plasma mass spectrometry (ICP-MS), and subsequently classified into three groups (T1-T3) based on tertiles, with the T1 group as the reference. The samples were assessed for ADL disorders using the ADL scale. Logistic regression and restricted cubic spline model (RCS) were used to estimate the odds ratio (OR) and 95% confidence interval (CI) to assess the associations between heavy metals and the prevalence of reporting ADL disorders. Results The mean age of the study population was (68.52 ± 5.92) years, 825 (58.4%) female and 587 (41.6%) male. Of these, 372 (26.34%) subjects reported ADL disorders, and most of them were female (74.30%). The results of logistic regression showed that the participants in the cadmium T2 group (0.15-0.25 µg·L⁻¹) had a higher risk of ADL disorders compared to the T1 group (≤0.15 μg·L⁻¹) (OR=1.552, 95%CI: 1.086, 2.134). After stratification by sex, the relative risk of ADL disorders was lower in the plasma copper T3 group (>1019.58 µg·L⁻¹) compared to the T1 group (≤868.12 μg·L⁻¹) in men (OR=0.481, 95%CI: 0.232, 0.998). The relative risk of ADL disorders was higher in the plasma cadmium T2 group (0.15-0.25 µg·L⁻¹) compared to the T1 group (≤0.15 μg·L⁻¹) in women (OR=1.758, 95%CI: 1.182, 2.616). The RCS results showed that the risk of ADL disorders in men was nonlinearly associated with copper (P_nonlinear=0.011, P_overall<0.05). Conclusion High levels of cadmium are positively associated with the risk of reporting ADL disorders, while high levels of copper are negatively associated with the risk of reporting ADL disorders in men.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Myogenous temporomandibular disorder(M-TMD)is one of the main subtypes of temporomandibular dis-order(TMD)and typically manifests as masticatory myofascial pain;the incidence of TMD has been increasing annually in recent years.Botulinum toxin type A(BTX-A)is a potent neurotoxin produced by Clostridium botulinum.BTX-A in-hibits the release of acetylcholine from the presynaptic membrane,thereby blocking neuromuscular junction signaling.The noncosmetic application of BTX-A in the oral and maxillofacial regions is a prominent research topic.In recent years,an increasing number of studies have focused on the application of BTX-A in the treatment of M-TMD.The re-sults of a literature review revealed that an appropriate dose(10-50 U unilaterally)of BTX-A administered in a single in-jection into the masticatory muscles can effectively treat myalgia over a period of 3-6 months.Common adverse effects,such as masticatory weakness and facial paralysis,are transient and can be avoided by standardized injection tech-niques.However,there is a lack of standardized guidelines for injection techniques in clinical practice.

[Objective]To explore the role of estrogen and estrogen receptor (ER) in the pathogenesis and regulation of non-invasive fungal rhinosinusitis (NIFR).[Methods]Totally 60 patients with NIFS who met the inclusion criteria in Fuzhou Second General Hospital from November 2020 to November 2023 were selected as the NIFS group,while 30 healthy volunteers were recruited as the blank control group. Samples of each group were collected. The number of eosinophils and mast cells in each group were detected by HE staining;ER expression was detected by immunohistochemistry and immunofluorescence;mRNA expression levels of NF-κB,IKK and MASPIN were detected by qPCR;and protein expression levels of NF-κB,IKK and MASPIN were detected by immunohistochemistry and Western blot.[Results]In the NIFS group,the counts of eosinophils and mast cells were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01 and P<0.05,respectively). The Estrogen Receptor (ER) score in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.05). Additionally,the average high-density value in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.01). The expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01,P<0.05,and P<0.01,respectively). The mRNA expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased,respectively,compared with those in the control group (P<0.01). Furthermore,the protein expression levels of NF-κB,IKK,and MASPIN in the NIFS group were increased,respectively,and the inter-group differences are statistically significant (P<0.01,P<0.01,and P<0.05,respectively).[Conclusion]Our results show that the significant increase in the number of eosinophils and mast cells,and in the expression levels of ER,NF-κB,IKK and MASPIN may indicate a significant increase in eosinophil and mast cell infiltration in ER positive patients,and suggest the involvement of estrogen and its receptors in the pathogenesis of NIFS.

OBJECTIVE To investigate the inhibitory effect and mechanism of 5,6-dimethylxanthe-none-4-acetic acid(DMXAA)on metastasis of Lewis lung cancer(LLC)in mice.METHODS The inhibi-tory effect of DMXAA on tumor metastasis was analyzed via an LLC xenograft tumor model and LLC metastatic tumor model.The mice of LLC xenograft tumor model were randomly divided into three groups:model group(physiological saline containing 1%DMSO,ip,once every two days),model+suni-tinib group(30 mg·kg-1,ip,once every two days),and model+DMXAA group(25 mg·kg-1,ip,once).Tumor volume and body mass were measured once every two days after administration.Two and five days after administration,tumor mass was measured by sacrificing the mice,followed by immunofluores-cence staining of tumor tissues.Platelet/endothelial cell adhesion molecule-1(CD31)and α-smooth muscle actin(α-SMA)were used to analyze the vascular structure of tumor tissues.The tumor hypoxia level was detected using the hypoxia probe pimonidazole staining.The mice of LLC metastatic tumor model were randomly divided into three groups:model group(physiological saline containing 1%DMSO,ip,twice a week),model+sunitinib group(60 mg·kg-1,ip,twice a week),and model+DMXAA group(25 mg·kg-1,ip,once).At the Two and five weeks after administration,the in vivo tumor growth and metastasis were observed and quantified using a small animal live imaging system.RESULTS Compared with the model group,the tumor volume and mass of the model+sunitinib group and model+ DMXAA group were significantly reduced(P<0.05,P<0.01),and DMXAA took effect faster and more significantly than sunitinib.At the same time,compared with the model group,the body mass in the model+sunitinib group decreased significantly(P<0.05),but there was no significant difference in body mass the model+DMXAA group.Compared with the model group,model+sunitinib had no effect on tumor metastasis,but model+DMXAA significantly reduced tumor metastasis two weeks after administration(P<0.01).Compared with the model group,the coverage rate of α-SMA/CD31 in the model+sunitinib group and model+DMXAA group increased significantly(P<0.05).Compared with the model group,there was no significant change in the tumor hypoxia area in the model+sunitinib group,but this in the model+DMXAA group decreased significantly(P<0.01).CONCLUSION DMXAA significantly inhibits the growth and metastasis of LLC in mice,and its mechanism may be related to its improvement of tumor vascular normalization and hyposic microenvironments.

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.

Macrophage-capping protein(CapG)is a member of the gelsolin superfamily.It is a universal multifunctional actin binding protein in the body and highly expressed in breast cancer,bladder cancer,prostate cancer and other types of cancer,which can promote the metastasis and invasion of cancer cells.This article reviews the structure,function,related signal pathways and roles of CapG in tumor invasiveness.

OBJECTIVE To study the effects of SR9009 and LXH0225,nuclear receptor subfamily 1 group D member(REV-ERB)agonists,on mood disorders and cognitive impairment in over-training mice.METHODS Male C57BL/6J mice were randomly divided into the normal control,over-training model,model+fluoxetine(15 mg?kg-1),model+SR9009(100 mg?kg-1)and model+LXH0225(50 mg?kg-1)groups.Mice in the normal control group were ip given15%cremophor without extra stress while those in other groups were ip given 15%cremophor or different drugs respectively 30 min before daily forced swimming stress.When stressed,mice were forced to swim in 19-21℃water for 20 min per day for 18 d.After that,locomotor activity was assessed.Rotarod test and weight-loaded swimming test were performed to measure physical strength,while open field test and stair-climbing test were performed to measure anxiety-like behavior.Tail suspension test and forced swimming test were used to measure depression-like behavior while novel object recognition test and Y maze test were conducted to measure recogni-tion function.ELISA was used to measure serum corticosterone contents.RESULTS Compared with the normal control group,the locomotor activity of mice in the model group was significantly increased(P<0.01).There were anxiety-like behaviors with a significant increase in the number of times of stair-climb-ing and rearing(P<0.01).Depression-like behaviors were observed with a significant increase immobile time in forced swimming test(P<0.01).Cognitive impairment was manifested as decreased accuracy of Y-maze spontaneous alternation response(P<0.01).The corticosterone content was significantly elevated(P<0.01)in forced swimming mice.Compared with the model group,the accuracy of Y-maze spontaneous alternations was higher(P<0.01)and the content of serum corticosterone was lower(P<0.01)in the model+fluoxetine group.The immobile time was shorter(P<0.01),the spontaneous alternation response of Y maze was was less accurate(P<0.05)and serum corticosterone content was lower(P<0.01)in the model+SR9009 group than in the model group.The latency to fall off the rotarod was longer(P<0.05),the immobile time was shorter(P<0.01)and the content of serum corticosterone was lower(P<0.01)in the model+LXH0225 group compared with the model group.CONCLUSION The REV-ERBs agonists SR9009 and LXH0225 may protect against forced swimming over-training induced mood disorders and cognitive impairment.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.