Objective:To investigate the effects and mechanisms of subchronic exposure to pyrethrin on the mice nervous system.Methods:Twenty-four male mice were randomly divided into a control group,low-,medium-,and high-dose groups,and were exposed continuously for 28 days.The control group received corn oil.The general condi-tion of the mice was observed,and the body weight and brain organ coefficient were measured.Neurobehavioral tests were conducted after the exposure period.The histopathological changes of the hippocampus in mice were observed by HE and nissl staining.The activities of lactate dehydrogenase(LDH),superoxide dismutase(SOD),catalase(CAT)and the contents of malondialdehyde(MDA),glutathione(GSH),acetylcholine(ACh)and glutamate(Glu)in brain tissue of mice were detected by biochemical kit.The Western blot was employed to measure the expression levels of kelch-like ech-associated protein 1(Keap1),nuclearfactorerythroid2-relatedfactor2(Nrf2),and heme oxygenase 1(HO-1)in brain tissue of mice.Results:Compared with the control group,the body weight of the mice in the high-dose group decreased,the brain organ coefficient increased,and the neurological function test showed that the mice had reduced autonomic activity,delayed nerve reflex,and impaired sensory and motor function.Histopathology showed that the hippocampal neurons in the middle-and high-dose groups presented with pyknosis,vacuolization,and disordered arrangement of the CA3 area.Biochemical analysis indicated that in the brain tissue of mice,the activity of LDH and the content of MDA were increased in the medium-and high-dose groups,while the activity of CAT and the content of GSH were decreased.The content of Glu was increased and the content of ACh was decreased.The activity of SOD was reduced in the low-,medium-,and high-dose groups.Western blot analysis showed that the expression of HO-1 and Nrf2 protein in the brain tissue of mice in the middle-and high-dose groups was down-regulated,while the expression of Keap1 protein in the high-dose group was up-regulated.Conclusion:Pyrethrin may cause damage to the nervous system by affecting the Keap1/Nrf2/HO-1 signaling pathway and neurotransmitter levels.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

Objective This study examines serum lipid metabolism characteristics in colorectal cancer patients and its diagnostic potential.Methods Serum samples from 57 colorectal cancer patients and 54 healthy controls underwent lipidomic analysis using ultra-high performance liquid chromatography-time-of-flight mass spec-trometry,combined with principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Differential lipids were identified based on criteria of P<0.05,VIP>1,and fold change<0.67 or>1.5.These lipids were further evaluated using receiver operating characteristic(ROC)analysis to identify biomarkers with strong diagnostic value.Results Five classes and 66 differential lipids were identified,with phos-phatidylcholine(PC)and triglyceride(TG)comprising 59.09%.KEGG pathway enrichment indicated involvement in glycerophospholipid and glycerol ester metabolism pathways.ROC analysis identified Sphinganine,MG(19∶0),LysoPC(18∶2),PA(42∶6),PC(36∶5),PC(36∶4),PC(38∶6),and PC(40∶8)as having areas under the curve greater than 0.85.Conclusion The lipid metabolic profile of colorectal cancer(CRC)patients can be systematically analyzed through the efficient enrichment of lipid metabolites in serum using the UPLC-Q/TOF-MS technique,in conjunction with a modified Bligh-Dyer method.The identification of eight specific lipids including Sphinganine,MG(19∶0),LysoPC(18∶2),PA(42∶6),PC(36∶5),PC(36∶4),PC(38∶6),and PC(40∶8)offer novel insights and parameters for differentiating between healthy individuals and those diagnosed with colorec-tal cancer.

Objective:To study the effect of inhibiting heat shock protein 70 ( HSP70) gene expression on the proliferation, invasion and migration of cholangiocarcinoma cells and its mechanism. Methods:Tumor tissues and adjacent normal tissue samples from 23 patients with cholangiocarcinoma who underwent surgery in the Hunan Second People′s Hospital from January 2022 to June 2023 were collected. The mRNA and protein expressions of HSP70 in cholangiocarcinoma tissues, human cholangiocarcinoma cells (HuCC-T1), normal bile duct tissues and human intrahepatic biliary epithelial cells (HIBEpiC) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. HuCC-T1 cells were cultured in vitro, and a HuCC-T1 cell line with stably knocked down HSP70 gene (HuCC-T1-HSP70-KD group) was obtained by screening after infection with shRNA lentivirus. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect the effects of inhibiting HSP70 gene expression on the proliferation, invasion and migration abilities of HuCC-T1 cells. Western blot was used to detect the protein expressions of Toll-like receptor (TLR) 4, phosphorylated extracellular regulated protein kinases 1/2 (p-ERK1/2), ERK1/2, β-catenin, c-myc, Snail and E-cadherin after inhibiting HSP70 gene expression in HuCC-T1 cells. Results:Compared with normal bile duct tissues and HIBEpiC cells, the mRNA and protein expressions of HSP70 in cholangiocarcinoma tissues and HuCC-T1 cells were significantly higher (all P<0.05). After inhibiting HSP70 gene expression in HuCC-T1 cells, the proliferation, invasion and migration abilities of cells in the HuCC-T1-HSP70-KD group were significantly decreased (all P<0.05); the protein expressions of TLR4, p-ERK1/2, β-catenin, c-myc and Snail in the HuCC-T1-HSP70-KD group were significantly decreased, while the protein expression of E-cadherin was significantly increased (all P<0.05). Conclusions:Silencing HSP70 gene expression can significantly inhibit the proliferation, invasion and migration abilities of cholangiocarcinoma cells. The mechanism may be that after the down-regulation of HSP70 gene expression, its activation of downstream TLR4 and MAPK pathways is significantly inhibited, thereby affecting the proliferation, invasion and migration of cholangiocarcinoma cells.

Depression is a severe mental illness. Although existing antidepressant medications have shown efficacy in many patients, a significant proportion show poor responses to current treatments, necessitating the need for novel therapeutic approaches. Photobiomodulation (PBM), an emerging physical therapy, has recently shown promising efficacy in the treatment of depression, as indicated by two systematic reviews, and is characterized by high safety and good tolerability. However, challenges remain in areas such as light delivery techniques and optimization of treatment parameters. This review summarizes the antidepressant mechanisms of PBM, various methods of light transmission, and recent research progress on its application in the treatment of depression. It also discusses issues related to safety, tolerability, and impact of specific parameters, aiming to provide insights and recommendations for future research on PBM as a therapy for depression.

Objective:To explore the application of contrast-enhanced ultrasound in the preoperative evaluation of carotid body tumor (CBT).Methods:The clinical data of 13 CBT patients undergoing contrast enhanced ultrasound test and surgical treatment at Peking Union Medical College Hospital from Nov 2017 to Aug 2021 was retrospectively analyzed.Results:Among the 13 patients, 7 patients had bilateral lesions. 18 tumors were identified by contrast enhanced ultrasound, which showed rich blood supply, with marked enhancement in 13 tumors and moderate enhancement in 5 tumors. The origins of the arterial supply for tumors were identified by contrast enhanced ultrasound. Time-intensity curve analysis showed that the tumors had enhancement characteristics of fast wash in and slow wash out. The mean contrast wash in time was (3.33±1.40) s, the mean peak intensity was (10.41±1.74) dB, and the mean wash out time was (56.47±22.28) s. A total of 13 cases underwent successful surgical removal. Five cases of external carotid artery ligation and 2 cases of internal carotid artery reconstruction were performed during surgery. Postoperative transient neurological injury occurred in 5 cases. There were no cases of cerebral infarction or death in the perioperative period. Mean postoperative follow-up was 14.31 months. Five cases of neurological injury had satisfactory recovery and no other adverse events occurred.Conclusions:Contrast enhanced ultrasound is an effective method of preoperative imaging assessment for CBT, which helps the surgical planning and preoperative preparation.

Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P＜0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P＜0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.

Acute pancreatitis (AP) is a severe inflammatory disease characterized by self-digestion of pancreatic tissue and inflammatory responses. Recent studies have revealed a close connection between gut microbiota and AP. The gut microbiota community, a complex ecosystem composed of trillions of microorganisms, is closely associated with various physiological activities of the host, including metabolic processes, immune system regulation, and intestinal structure maintenance. However, in patients with AP, dysbiosis of the gut microbiota are believed to play a key role in the occurrence and progression of the disease. This dysbiosis not only impairs the integrity of the intestinal barrier, but may also exacerbate inflammatory responses through multiple mechanisms, thereby affecting the severity of the disease and patient' clinical prognosis. This article reviews the mechanisms of action of gut microbiota in AP, explores how gut microbiota dysbiosis affects disease progression, and evaluates current clinical treatment methods to regulate intestinal flora, including probiotic supplementation, fecal microbiota transplantation, antibiotic therapy, and early enteral nutrition. In addition, this article discusses the efficacy and safety of the aforementioned therapeutic approaches, and outlines future research directions, aiming to provide novel perspectives and strategies for the diagnosis, treatment and prognostic evaluation of AP. Through in-depth understanding the interaction between gut microbiota and AP, it is expected that more precise and personalized therapeutic regimens will be developed to improve patients' quality of life and clinical outcomes.
Humans ; Gastrointestinal Microbiome ; Dysbiosis ; Pancreatitis/microbiology* ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use* ; Acute Disease ; Anti-Bacterial Agents/therapeutic use* ; Enteral Nutrition

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*