BACKGROUND:According to existing clinical studies,vertebroplasty treatment with both the external pedicle approach and the pedicle approach can improve the pain and quality of life of patients with spinal compression fractures.Compared with the pedicle approach,the external pedicle approach has a freer puncture angle,and good bone cement dispersion effect can be obtained by adjusting the puncture angle. OBJECTIVE:To compare the impact of vertebroplasty through individualized unilateral external pedicle approach and bilateral pedicle approach on the treatment of spinal compression fractures by quantifying the dispersion effect of bone cement. METHODS:A total of 80 patients with thoracolumbar compression fracture were divided into two groups by random number table method.The bilateral pedicle group(n=40)underwent vertebroplasty through a bilateral pedicle approach,while the unilateral external pedicle group(n=40)underwent individualized vertebroplasty through a unilateral external pedicle approach.Anteroposterior and lateral X-rays of the affected vertebrae from two groups of patients were photographed to assess effect and type of bone cement dispersion within 3 days after surgery.Visual analog scale score,tenderness threshold around fracture,and Oswestry dysfunction index were assessed before,1,7 days,and 1 month after surgery. RESULTS AND CONCLUSION:(1)Dispersion effect of bone cement in unilateral external pedicle group was better than that in bilateral pedicle group(P<0.001),and the amount of bone cement perfusion was higher than that in bilateral pedicle group(P<0.001).In the bilateral pedicle group,the bone cement dispersion types were mainly concentrated in type Ⅰ and type Ⅲ,while in the unilateral external pedicle group,the bone cement dispersion types were mainly concentrated in type I and type Ⅱ,and there was a significant difference in bone cement dispersion types between the two groups(P<0.001).(2)Postoperative visual analog scale scores and Oswestry disability index of both groups were lower than those before surgery(P<0.001),and postoperative tenderness threshold around fracture showed a trend of decreasing first and then increasing.At the same time point after treatment,there were no significant differences in visual analog scale score,Oswestry disability index,and tenderness threshold around fracture between the two groups(P>0.05).(3)The results indicate that individualized vertebroplasty via unilateral external pedicle approach can achieve better bone cement dispersion,and the treatment effect is consistent with the vertebroplasty via classical bilateral pedicle approach.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Objective To investigate the effects of remimazolam(REM)on cerebral ischemia-reperfusion injury(CIRI)rats and the AMP-activated protein kinase(AMPK)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods One hundred rats were selected to construct the CIRI rat model(Mod)and stochastically separated into a Mod group,low,medium,and high dose remifentanil groups(REM-L,REM-M,REM-H),and high dose remifentanil+pathway inhibitor Compound C group(REM-H+Compound C),with 20 rats in each group.Another 20 healthy rats were included as the control(Ctrl)group.All rats were subjected to neurobehavioral scoring.The water content,infarct area,and oxidative stress indicators of brain tissue were detected.The morphology and apoptosis of brain tissue were observed by HE and TUNEL staining.Western blotting was applied to detect protein expression related to the AMPK/NLRP3 signaling pathway.Results Compared with the Mod group,with the increase of REM dose,the movement disorders in rats were alleviated,the overall structure of brain tissue gradually recovered,pathological damage was reduced,the area of cerebral infarction,brain water content,and apoptosis rate of brain tissue cells decreased,reactive oxygen species(ROS)level,malondialdehyde(MDA)content,and NLRP3 and Caspase-1 protein expression levels decreased,superoxide dismutase the(SOD)content and AMPK protein expression level increased(P＜0.05).Compared with the REM-H group,the REM-H+Compound C group showed aggravated motor disorders,and more severe pathological damage to brain tissue,the area of cerebral infarction,cerebral water content and apoptosis rate of brain tissue cells increased,the ROS level,MDA content and the protein expression of NLRP3 and Caspase-1 increased,while the content of SOD and the protein expression decreased(P＜0.05).Conclusion Remimazolam can enhance the antioxidant function of the body,reduce brain cell apoptosis,alleviate brain tissue injury,and thus have a certain protective effect on ischemia-reperfusion brain injury in rats,the mechanism of which may be related to the activation of the AMPK/NLRP3 signaling pathway.

Objective To investigate the prognosis of patients with negative sentinel lymph nodes(SLN)after neoadjuvant chemotherapy(NAC)for breast cancer who are exempt from axillary lymph node dissection(ALND)and evaluate its safety in clinical treatment.Methods Clinical data of 2,163 patients initially diagnosed with breast cancer and having negative SLNs after NAC were se-lected from the SEER database from 2018 to 2021.Among them,373 patients underwent only SLN biopsy(SLNB group),and 1,790 patients underwent ALND(ALND group).Propensity score matching(PSM)was used to control for confounding factors,and the Kaplan-Meier method was em-ployed to analyze the overall survival rate.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing the exemption from ALND in patients with negative SLNs after NAC for breast cancer.Results Before PSM,significant differences were observed be-tween the two groups in terms of clinical tumor stage,molecular subtype,estrogen receptor(ER)sta-tus,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER-2)status,efficacy of NAC,and breast surgery method(P＜0.05).After PSM,363 patients were included in each group.Univariate Cox regression analysis after PSM revealed that age,clinical tumor stage,and ER status were associated with overall survival(OS)of patients(P＜0.05).There was no sig-nificant difference in OS between patients who underwent SLNB and those who underwent ALND(P＞0.05).Multivariate Cox regression analysis indicated that age and clinical tumor stage were independent factors influencing OS in patients with negative SLNs after NAC.Survival curve analysis after PSM showed no statistically significant difference in overall survival rate between the SLNB and ALND groups(P=0.278).Conclusion Exemption from ALND in patients with negative SLNs af-ter NAC is feasible and does not affect the overall survival rate of patients.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective To investigate the association of endometrial thickness(EMT)with obstetric and neonatal outcomes of monoparous pregnancy in fresh cleavage embryos transfer.Methods A total of 1 845 patients of monoparous pregnancy after fresh cleavage embryos transfer cycles from Jan 2016 to Mar 2022 at Shanghai First Maternity and Infant Hospital,Tongji Universtiy were analyzed retrospectively.Patients were categorized into three groups by EMT on transferation day:≤8 mm(group A),8-14 mm(group B)and≥14 mm(group C).The primary outcomes were preterm birth(PTB),birth weight and birth weight z-score,small-for-gestation age,large-for-gestation age,very low birth weight,low birth weight and macrosomia.The second outcomes were pregnancy and perinatal complications.The relationship between EMT and adverse neonatal outcomes was estimated by Logistic regression analysis.Results The rate of ectopic pregnancy was increased significantly in group A.No significant differences were found among the three groups in gestation age,birth weight,birth weight z-score,PTB,small for gestation age,large for gestation age,low birth weight,very low birth weight and macrosomia.Compared with group B,the odds of adverse neonatal outcomes did not show significant differences before and after adjustment in both group A and group C by Logistic regression analysis.Conclusion Thinner EMT in fresh cleavage embryos transfer is associated with higher rate of ectopic pregnancy,while it is not independently associated with adverse perinatal outcomes.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Osteosarcoma is the most common primary malignant bone tumor,typically treated with a combination of surgery and chemotherapy in clinical practice.However,the increasing prevalence of chemotherapy resistance poses a significant challenge.Chemotherapy resistance can lead to a sharp decline in patients'survival rates.Traditional Chinese medicine,known for its low cost,wide-ranging efficacy,and diverse varieties,has attracted significant attention from researchers.Their attempts to investigate the sensitizing effect of extracted ingredients on osteosarcoma chemoresistance both in vitro and in vivo have yielded promising results.This review has summarized the studies of single traditional Chinese medicine ingredients on reversing osteosarcoma chemoresistance by the mechanisms of chemoresistance,and found that the current research of the clinical mechanism of traditional Chinese medicine ingredients in reversing osteosarcoma chemoresistance is still lacking,indicating significant potential for future development.Utilizing the theory of herbal medicine properties as the theoretical basis for ingredient development may provide novel strategies for the development of new therapeutic approaches.