The current treatment of glioma is facing drug resistance,which limits the efficacy of traditional chemotherapy drugs.This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound(KZL204)against glioma.Through the Cell Counting Kit-8(CCK-8)assay,we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells,with a 48-hour half-maximal inhibitory concentration(IC50)of 3.63±0.38 μmol/L,which is significantly better than the positive control drug temozolomide(TMZ)(IC50 value of 81.67±5.49 μmol/L).Additionally,flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase.At the same time,the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells.Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204,of which 1 320 were upregulated,and 1 115 were downregulated.KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways.Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets,with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes.Quantitative real-time PCR(RT-qPCR)experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1,CSF1,CXCL5,BCL3,and the upregulating effects on genes like FOS,LT A,PTGS2,MAP2K3.Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins,including the upregulation of Bax,cleaved Caspase-3 protein,and the downregulation ofAKT,Bcl-2,Caspase-3,and Caspase-8 protein expression.In summary,KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways,demonstrating its potential as a candidate drug against drug-resistant glioma.

Objective To study the anti-inflammatory and analgesic effects of Ski protein overexpression on writing in mice induced by acetic acid.Methods Eight-week-old male ICR mice were administered 0.7%acetic acid solution(0.1 mL/10 g)to induce a writhing reaction.The mice were divided into sham,acetic acid,acetic acid+ibuprofen,acetic acid+ad-EGFP,acetic acid+ad-ski-1,acetic acid+ad-ski-2,and acetic acid+sulfasalazine groups(n=10 mice per group).The time to the first appearance of twisting and the number of twists within 15 min were recorded.Small intestine tissues were removed to identify the effect of adenovirus transfection and to detect protein expression levels of pro-inflammatory factors and pain biomarkers and protein expression of nuclear factor(NF)-κB p65 and its binding with Ski protein.Results Ski protein was successfully overexpressed in small intestine after intraperitoneal injection of Ad-ski adenovirus.Overexpressed Ski protein delayed the start and decreased the frequency of writhing,comparable to ibuprofen(P＞0.05).Groups in which ski protein was overexpressed showed significantly inhibited protein expression of pro-inflammatory factors and pain biomarkers compared with the acetic acid group(P＜0.05).Moreover,NF-κB p65 formed complexes with Ski.Conclusions Overexpression of Ski protein has anti-inflammatory and analgesic effects on acetic acid-induced inflammatory pain by inhibiting the expression of inflammatory factors and pain biomarkers,via regulation of the NF-κB signaling pathway.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

Objective:To preliminarily evaluate the effects and analyze the influencing factors of continuous renal replacement therapy (CRRT) in severe burn patients complicated with acute kidney injury (AKI).Methods:This study was a retrospective case series study. From January 2010 to December 2020, 79 severe burn patients complicated with AKI who received CRRT and met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University). The general data (the same below) of all patients were collected, including gender, age, body mass index, burn area, burn index, cause of injury, whether combined with inhalation injury, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score on admission, admission time after burn, and time of AKI after admission. The total efficacy of CRRT, including overall effective rate, complete effective rate, partial effective rate, ineffective rate, and deterioration rate, creatinine, urea, cystatin C, and fluid overload rate before and after treatment, in-hospital mortality, predictive mortality based on Baux scoring model, the most common cause of death, and length of hospital stay were recorded. According to the effect of CRRT, the patients were divided into effective group (42 patients) and ineffective group (37 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, etiology of AKI, AKI stage before CRRT initiation, CRRT mode, anticoagulant type, and in-hospital mortality were compared between the two groups of patients. The independent influencing factors for CRRT in severe burn patients complicated with AKI were screened. According to the etiology of AKI, the patients were divided into prerenal group (22 patients) and renal group (57 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, and total efficacy of CRRT (except for the most common cause of death) were compared between the two groups of patients.Results:Among the 79 patients, 73 cases were male and 6 cases were female, with age of (46±14) years, body mass index of (24.0±2.9) kg/m 2, total burn area of (69±26)% total body surface area (TBSA), full-thickness burn area of (44±25)%TBSA, and burn index of 57 (36, 76). There were 36 cases of flame burns, 19 cases of electrical burns, 16 cases of hydrothermal burns, 6 cases of explosive burns, and 2 cases of chemical burns. Thirty-nine patients were complicated with inhalation injury. The APACHE Ⅱ score was 16 (12, 18) and the SOFA score was 11 (5, 13) on admission. The patients were admitted to the hospital on 0 (0, 2) d after burn, and AKI occurred on 0 (0, 6) d after admission. The overall effective rate of CRRT was 53.16% (42/79), the complete effective rate was 30.38% (24/79), the partial effective rate was 22.78% (18/79), the ineffective rate was 31.65% (25/79), and the deterioration rate was 15.19% (12/79). The creatinine and urea of patients after treatment were significantly lower than those before treatment (with Z values of -3.26 and -2.54, respectively, P<0.05); there were no statistically significant differences in the cystatin C and fluid overload rate of patients before and after treatment ( P>0.05). The in-hospital mortality of patients was 17.72% (14/79), and the predictive mortality based on Baux scoring model was 75.10% (18.94%, 91.84%). The most common cause of death was multiple organ failure, and the length of hospital stay was 39.43 (11.52, 110.58) d. There were statistically significant differences in the full-thickness burn area, the duration of CRRT, and etiology of AKI of patients between effective group and ineffective group (with Z values of -1.99 and -2.90, respectively, χ2=5.58, P<0.05). There were no statistically significant differences in the other indicators ( P>0.05). The etiology of AKI and full-thickness burn area were the independent influencing factors for CRRT in severe burn patients complicated with AKI (with odds ratios of 4.21 and 1.03, respectively, 95% confidence intervals of 1.20-14.80 and 1.00-1.05, respectively, P<0.05). There were statistically significant differences in the cause of injury, overall effective rate of CRRT, total burn area, burn index, admission time after burn, time of AKI after admission, the time to initiate CRRT after the occurrence of AKI, and predictive mortality based on Baux score model of patients between prerenal group and renal group (with χ2 values of 12.59 and 5.58, respectively, Z values of 2.46, 2.43, -2.43, -4.03, -3.01, and -2.31, respectively, P<0.05). Before treatment, urea and cystatin C of patients in renal group were significantly higher than those in prerenal group (with Z values of -2.98 and -2.77, respectively, P<0.05), and the liquid overload rate was significantly lower than that in prerenal group ( Z=-2.99, P<0.05); after treatment, the cystatin C of patients in renal group was significantly higher than that in prerenal group ( Z=-2.08, P<0.05); there were no statistically significant differences in the other indicators ( P>0.05). Conclusions:CRRT can significantly improve renal function, avoid fluid overload, and alleviate renal injury in severe burn patients complicated with AKI. Prerenal AKI is the main independent influencing factor leading to ineffective CRRT.

Objective To carry out rigid-body inverse dynamics modelling and analysis of a self-designed 6RSS parallel bio-inspired masticatory robot.Methods Firstly,the functions of kinematic variables including translational/rotational velocities and accelerations were derived for rigid-body inverse dynamics modelling.Secondly,the rigid-body inverse dynamics model was established with the Newton-Euler's law.Finally,the chewing motion trajectories of the oral health volunteers were tracked and numerical calculations were carried out in the case where the robot was subjected to a chewing reaction force.Results Numerical calculations showed that the driving torque and the constraint force of the robot peaked when the chewing reaction force was at its maximum.Conclusion The external force has a large impact on the inverse dynamics of the robot,and theoretical references are provided for the motion control and optimal design of the robot.[Chinese Medical Equipment Journal,2024,45(3):16-22]

Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects(VSD)in offspring.Methods A case-control study was conducted,recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants.A questionnaire survey collected data on maternal exposures,and blood samples were analyzed for genetic polymorphisms.Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD.Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake.Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD(P<0.05).The GC and CC genotypes at rs3768139,AG and GG at rs1050993,AT and TT at rs4659743,GG at rs3768142,and GT and TT at rs3820571 were associated with a decreased risk of VSD(P<0.05).The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD(P<0.05).Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring.Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period,suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Objective:To analyze the clinical characteristics, prognosis and gene mutation in patients with dilated cardiomyopathy (DCM) in Keshan disease area of Sichuan Province, and to explore the risk factors for all-cause death in DCM patients.Methods:In June 2016, 55 DCM patients diagnosed at the local disease prevention and control center through clinical manifestations, electrocardiogram examination, and echocardiography were selected as the survey subjects in Mianning County, Liangshan Yi Autonomous Prefecture, and Renhe District, Panzhihua City, Keshan disease areas of Sichuan Province. Baseline clinical data were analyzed and long-term follow-up was conducted. The follow-up period ended June 15, 2021, with the endpoint of all-cause death. Univariate Cox regression was used to analyze the influencing factors of all-cause death in patients, and Kaplan-Meier (K-M) survival curve was used to analyze the survival time of patients. At the same time, peripheral venous blood was collected from 27 DCM patients. After separating white blood cells, DNA was extracted, and whole exome sequencing was performed to screen potential pathogenic genes.Results:Among the 55 DCM patients, 40 were males and 15 were females. The age was (54.09 ± 12.38) years old. The heart function classification of New York Heart Association (NYHA) was mainly grade Ⅱ and Ⅲ, accounting for 94.55% (52/55). The follow-up time for 55 DCM patients was (7.02 ± 2.96) years, and 17 patients experienced all-cause death, accounting for 30.91% (17/55), including 15 males and 2 females. Compared with the survival group, the death group had a lower incidence of syncope (χ 2 = 6.57, P = 0.010), but higher rates of bilateral lower limb edema (χ 2 = 6.43, P = 0.017), pulmonary congestion (χ 2 = 7.61, P = 0.006), intraventricular conduction block (χ 2 = 6.41, P = 0.011), and angiotensin-converting enzyme inhibitor (ACEI) use (χ 2 = 6.57, P = 0.010), as well as increased left ventricular diameter ( t = 2.36, P = 0.022). Univariate Cox regression analysis showed that bilateral lower limb edema [hazard ratio ( HR) = 4.61, P = 0.042] and intraventricular conduction block ( HR = 3.20, P = 0.019) were risk factors for all-cause death of DCM patients. The results of K-M survival curve analysis showed that patients with bilateral lower limb edema and intraventricular conduction block had higher all-cause death rates (log-rank χ 2 = 5.02, 6.24, P = 0.025, 0.012). Whole exome sequencing results showed that 4 patients were detected to carry pathogenic or suspected pathogenic gene mutations, with a positive rate of 14.81% (4/27), involving three genes: β-myosin heavy chain 7 (MYH7), calreticulin 3 (CALR3), and gelsolin (GSN). Conclusions:The all-cause death rate of DCM patients in the Keshan disease area of Sichuan Province is relatively high. Dead patients are prone to bilateral lower limb edema, pulmonary congestion, and intraventricular conduction block, as well as increased left ventricular diameter. Bilateral lower limb edema and intraventricular conduction block are independent predictive risk factors for all-cause death in DCM patients. MYH7, CALR3 and GSN are involved in the pathogenesis of DCM.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

The intervention and prevention of perioperative hypothermia is not only reflected in the technical level, but also reveals the important role of humanistic care in the whole intervention work. If perioperative patients have hypothermia, it is likely to cause a series of complications such as postoperative shivering, which seriously threatens the life safety of patients. Prevention and intervention was based on a comprehensive understanding of the causes and hazards of hypothermia, especially the impact on the lives of the elderly. Effective supervision was implemented in the whole process of operation, such as dynamic monitoring of vital signs including body temperature, followed by room temperature regulation, body temperature protection and preoperative and postoperative psychological nursing. At this time, the sense of responsibility, good humanistic care of medical staff are of positive significance to effectively prevent and reduce the probability of perioperative hypothermia and accelerate the postoperative rehabilitation of patients.

Objective To understand the epidemiological characteristics and genotype distribution of enterovirus (EV) in influenza-negative influenza-like illness (ILI) cases in Chongqing, and to provide a scientific basis for EV prevention and control. Methods Throat swab samples of influenza-negative ILI cases were collected from surveillance sites. The samples were detected for EV using real-time RT-PCR. The VP4 regions of positive samples were amplified and sequenced for genotyping. Results A total of 3 960 influenza-negative ILI samples were collected from January to December 2021, and 316 (7.98%) of them were EV-positive. EV could be detected in influenza-negative ILI cases in Chongqing all year round. The months with high EV-positive rates were January (11.60%), April (10.56%), May (11.79%), June (12.62%), and July (10.33%). There was a statistically significant difference in the detection rate of EV in ILI cases in different regions, gender, and age groups (χ²=29.647，χ²=4.192，χ²=69.176，P<0.05). A total of 213 EV-positive cases were successfully genotyped, including 17 genotypes of EV-A, EV-B, and EV-C and 5 genotypes of HRV-B. The dominant genotypes were CV-A4 (32.86%), CV-A2 (23.00%), CA-6 (12.21%), and CA-10 (11.74%). EV-D and novel EV were not identified in this study. Conclusion EV is an important pathogen in ILI cases in Chongqing. The prevalence of EV in ILI cases in Chongqing has typical regional, seasonal and population characteristics. Prevention and control should be carried out in Chongqing according to the epidemic characteristics of EV.