Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective:To investigate the behavioral, electroencephalographic, and cognitive functional differences in drug-resistant epileptic rat models of cognitive impairment prepared by intraperitoneal injection of lithium chloride-pilocarpine followed by intracranial injection of pilocarpine or carbamylcholine.Methods:One hundred and sixty adult male SD rats were randomly divided into normal control group ( n=10), lithium chloride-pilocarpine group (establishing epileptic rat models by intraperitoneal injection of lithium chloride-pilocarpine, n=50), pilocarpine-pilocarpine group (intracranial injection of pilocarpine after intraperitoneal injection of lithium chloride-pilocarpine, n=50)and pilocarpine-carbamylcholine group (intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine, n=50). Frequency and duration of spontaneously recurrent seizures (SRSs) were observed by video monitoring system, and 2 weeks after that, phenobarbital and phenytoin sodium were injected intraperitoneally to screen drug-resistant models. Frequency and amplitude of the epileptic waves in EEG were recorded by BL-420 Bio-signal Acquisition and Processing System. Novel object recognition experiment was used to detect the novel exploration, Y-maze free exploration experiment and new and different arm experiment were used to detect the spatial recognition and memory ability, and Morris water maze experiment was used to detect the spatial memory ability. Results:(1) Twenty-four rats (48.00%) survived in the lithium chloride-pilocarpine group, 25 (78.00%) in the pilocarpine-pilocarpine group, and 21 (65.62%) in the pilocarpine-carbamylcholine group; and ultimately 7, 9, and 8 drug-resistant epileptic rat models were identified, respectively; frequency and duration of SRSs in the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group were significantly higher/longer than those in the lithium chloride-pilocarpine group ( P<0.05). (2) The pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly higher amplitude of the epileptic waves in EEG compared with the lithium chloride-pilocarpine group ( P<0.05); the frequency of the epileptic waves in EEG increased gradually in the lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group ( P<0.05). (3) Discrimination index, accuracy, ratio of distance traveled in novel arm to total distance, and time of novel arm entries gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). (4) Compared with the normal control group, the pilocarpine-pilocarpine group and pilocarpine-carbamylcholine group had significantly decreased frequency in crossing the original platform ( P<0.05); compared with the normal control group, lithium-pilocarpine chloride group and pilocarpine-pilocarpine group, the pilocarpine-carbamylcholine group had statistically shorter distance of target quadrant activity ( P<0.05); number of entries in the target quadrant gradually decreased in the normal control group, lithium chloride-pilocarpine group, pilocarpine-pilocarpine group, and pilocarpine-carbamylcholine group, with significant differences ( P<0.05). Conclusion:Drug-resistant epileptic rat models established by intracranial injection of carbamylcholine after intraperitoneal injection of lithium chloride-pilocarpine have high survival rate, high SRSs rate, and severe cognitive impairment, which is suitable for studying drug-resistant epilepsy combined with cognitive impairment.

Severe traumatic brain injury (sTBI) has a high mortality and disability rate, making it a difficult issue and hot topic in neurosurgery. Controlled decompression is an important technique in the treatment of sTBI combined with intracranial hypertension, which can reduce the ischemia-reperfusion injury to the nervous tissue and intracranial vessel and can significantly lower the incidence of complications related to decompressive craniectomy. However, the effects of the controlled decompression technique have been affected by different understandings of the technique and nonstandard surgical procedures in clinical practice. For this purpose, the authors discussed the concept of controlled decompression technique, its indications and the key problems during operation so as to standardize the surgical procedures and improve the therapeutic effects of controlled decompression technique in the treatment of sTBI.

Objective To investigate the role and mechanism of exosomes derived from mesenchymal stem cells in hyperbaric oxygen caused pulmonary oxygen toxicity.Methods Mice were divided into the control group that was exposed to normal air,and hyperbaric oxygen exposure groups treated with phosphate buffer saline(PBS)or exosomes,respectively.PBS and exosome treatment were given one day prior to exposure.Mice were subjected to 0.23 MPa pure oxygen for 8 hours.The lung wet-dry ratio,inflammation,exudation and pathological injury were analyzed,while cell death and antioxidant related molecules were detected.Results Pretreatment with exosome significantly attenuated lung injury caused by hyperbaric oxygen exposure by decreasing the lung wet-dry ratio,inflammation,and cell apoptosis.Conclusion Prophylactic administration of exosomes derived from mesenchymal stem cells can alleviate hyperbaric oxygen induced pulmonary oxygen poisoning by attenuating cell death and inflammation.

Objective:To explore the application value of ventricular intracranial pressure monitoring (V-ICPM) in the treatment of unilateral temporal lobe cerebral contusion.Methods:A retrospective cohort study was conducted to analyze the clinical data of 295 patients with unilateral temporal lobe cerebral contusion admitted to 904th Hospital of PLA Joint Support Force from January 2014 to August 2021, including 172 males and 123 females; aged 14-78 years [(46.3±14.7)years]. V-ICPM was used in 136 patients (V-ICPM group), who received surgical or non-surgical treatment according to the monitoring, while not in 159 patients (non-V-ICPM group), who received routine surgery or non-surgical treatment. The two groups were compared in terms of the rates of intracranial hematoma clearance by craniotomy, decompressive craniectomy (DC) and dehydration and osmotic therapy during hospitalization, use time of 20% mass fraction of mannitol and 30 g/L hypertonic salt, displacement rate of brain midline structure of head CT≥10 mm after discharge, rate of intracranial infection, hydrocephalus and epilepsy, and Glasgow Outcome Scale (GOS) at 6 months after discharge.Results:All patients were followed up for 6-12 months [(8.9±2.1)months]. During hospitalization, the rate of intracranial hematoma clearance by craniotomy and the rate of DC in V-ICPM group were 35.3% (48/136) and 8.1% (11/136), lower than 47.2% (75/159) and 22.0% (35/159) in non-V-ICPM group ( P<0.05 or 0.01). There was no significant difference between the two groups in the rate of dehydration and osmotic therapy or the use time of mannitol (all P>0.05). The use time of hypertonic salt in V-ICPM group was (7.2±2.5)days, more than (4.1±1.8)days in non-V-ICPM group ( P<0.05). After discharge, the displacement rate of brain midline structure of head CT in V-ICPM group was 29.4% (40/136), lower than 42.8% (68/159) in non-V-ICPM group ( P<0.05). There was no significant difference between the two groups in the rate of intracranial infection, hydrocephalus and epilepsy (all P>0.05). Six months after discharge, the good rate of GOS in V-ICPM group was 91.2% (124/136), significantly better than 81.8% (130/159) in non-V-ICPM group ( P<0.05). Conclusion:For unilateral temporal lobe cerebral contusion, V-ICPM is associated with reduced rate of craniotomy exploration and DC, decreased incidence of complications and improved prognosis of the patients in spite of longer use time of hypertonic salt.

Purpose To investigate the clinicopathological and molecular genetic features of oncocytic carcinoma of the thy-roid(OCA).Methods The clinicopathological and immuno-histochemical data of 25 patients with oncocytic carcinoma of the thyroid were retrospectively reviewed.Genetic features were determined by fluorescence quantitative PCR.Results The male to female ratio of the 25 patients was 1 ∶ 1.8,and the aver-age age was 49 years.The tumor was confined to the thyroid gland.Of the 22 cases with a single nodule,5 cases were ill-de-marcated and 3 cases were multiple nodular lesions.The average size was 2.7 centimeter in diameter.Cytologically,the tumor cells were arranged in detached clusters with abundant eosino-philic and granular cytoplasm and hyperchromatic nuclei with prominent nucleoli.Histologically,the oncocytic tumor cells mainly arranged in trabecular and solid architecture.Capsular,blood and lymphoid vascular invasion could be observed in a cer-tain extent.Among 25 cases of OCA,8 cases were minimally in-vasive,14 cases were encapsulated angio-invasive and 3 cases were widely invasive.Positive immunoreaction with TTF-1,thy-roglobulin and CD56 supported the thyroid epithelial origination of the tumour.One recurrent case was found to have cervical lymph node metastasis,and another case was presented with bone metastasis,which was determined to harbor TERT promoter mu-tation(C228T)in each case.Different point mutation of RAS gene was determined in 2 cases(8%),respectively.Conclu-sion Oncocytic carcinoma of the thyroid shows typical eosino-philic and granular cytoplasm,immunohistochemical staining is helpful in differential diagnosis with other oncocytic lesions.It lacks BRAF-like mutation.Low frequency of RAS mutations could be found.Rare TERT promoter mutation has significant mutation with clinical behavior of OCA.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective: To describe the status quo of overweight and obesity among children aged 3 to 5 in Beijing and Tokyo, and to explore its relationship with lifestyle. Methods: Using the method of cluster stratified random sampling, a sample of 444 children aged 3-5 years from Beijing and Tokyo were selected in Oct. and Nov. of 2019. Height, weight and lifestyle were measured. Overweight and obesity among children in the two cities and its relationship with lifestyle were compared and analyzed. Results: Average level of BMI, rate of overweight and obesity of children in Beijing(25.28%) were higher than those in Tokyo( 18.44 %). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with physical activity before breakfast( χ 2=29.14, 31.18, P <0.05). There were significant differences in overweight and obesity rates between children in Beijing and Tokyo with different snack frequency after dinner( χ 2=24.72, 21.93, P <0.05). Logistic regression analysis further showed that children s lack of physical activity before breakfast in Beijing is positively related to overweight and obesity( OR= 1.45, 95%CI =1.10-2.68). Beijing children who often eat snacks after supper ( OR=2.56, 95%CI =1.44-3.57,) and sometimes eat snacks were positively correlated with the occurrence of overweight or obesity ( OR=1.72, 95%CI =1.21-2.72). Conclusion The prevalence of overweight and obesity among preschool children in Beijing is higher than that in Tokyo. Potential risk factors for overweight and obesity among infants in Beijing include lack of physical activity before breakfast and frequent snacking after dinner.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.