Study on the stability and H+ permeable membrane properties of polymersomes / 药学实践杂志

Objective To prepare polymersomes (PSs) by block copolymers，evaluate their membrane structural stability，investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

Blood and synovial tissue metabolomics of rheumatoid arthritis rats treated with less polar ginsenosides / 中华风湿病学杂志

Objective:The therapeutic effect of less polar ginsenosides on rats with rheumatoid arthritis was studied, and the metabolic pathway that produce anti-inflammatory effect of less polar ginsenosides was identified.Methods:Rats were randomly divided into the control group, the model group, methotrexate treatment group, and high dose, medium dose, and low dose less polar ginsenosides groups. After 30 days of oral administration, less polar ginsenosides reduced the disease activity significantly in rats with rheumatoid arthritis. Blood and ankle synovial tissue metabolisms were measured by ultra performance liquid chromatography (UPLC) tandem mass spectrometry (MS) to explore the mechanism of less polar ginsenosides.The resulting data were subjected to principal component analysis and orthogonal partial least squares discriminant analysis(OPLS-DA).Results:Compared with the model group, erythrocyte sedimentation rate and RF decreased significantly in the high dose of less polar ginsenosides ( P<0.01). Metabolomics showed that R2X and R2Y of serum OPLS-DA were 0.626 and 0.904 respectively. The R2X and R2Y of synovial OPLS-DA were 0.429 and 0.689 respectively. Major differential metabolites were identified in the model group of rats, including arachidonic acid, valine, linoleic acid, and guanine nucleoside, etc. The main differential metabolites were identified in rats in the high dose group of less polar ginsenosides, including linoleic acid, betaine, eicosapentaenoic acid, alanine, methionine sulfoxide, isoleucine, etc. Conclusion:The metabolic spectrum has shown that inflammation is associated with linoleic acid metabolism, valine, leucine and isoleucine degradation, arachidonic acid metabolism. Less polar ginsenosides regulatethe linolenic acid metabolism, methionine metabolism and glucose alanine cycle.

Impact of lead oxide nanoparticle exposure on the polarization of microglia cells in mouse hippocampus / 中国职业医学

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Construction of albumin nanoparticles loading PROTAC and its inhibition effect on NAD+ in glioma cells / 药学实践杂志

Objective To prepare and optimize the formulation of Albumin nanoparticles loading PROTAC molecule and observe the inhibition effect of nanoparticles on the proliferation and NAD+ metabolism of glioma cells. Methods Albumin nanoparticles loading NPT-B2 were prepared and characterized with a thermal driving method, and the prescription was optimized. An HPLC method was established to determine the content of NPT-B2. The proliferation inhibition of NPT-B2 and B2-BSA-NPs on U251 cells were investigated by the CCK8 method, and the degradation effects of NPT-B2 and B2-BSA-NPs on NAMPT in glioma cells were investigated by western blotting. Results The HPLC method was stable, with good linearity, precision, and recovery rate. The nanoparticles had a particle size of about 55.48 nm, a potential of about −12.9 mV, an encapsulation rate of about 94.74%, and a drug loading amount of about 8.61%. The IC50 of NPT-B2 on glioma cells was 61.16 nmol/L, which had a degradation effect on NAMPT. The IC50 of B2-BSA-NPs on glioma was 41.21 nmol/L, which had a very significant degradation effect on NAMPT. Conclusion Albumin nanoparticles loading PROTAC molecules were constructed. The prescription was optimized to improve the drug encapsulation rate, and the low water solubility of PROTAC molecule was improved, which had a significant inhibitory effect on the proliferation and NAD+ energy metabolism of glioma cells.

Effect of Dahuang Lingxian prescription on the scf/c-kit signaling pathway in gallbladder interstitial cells of Cajal in a guinea pig model of cholesterol gallstone / 临床肝胆病杂志

Objective To investigate the expression levels of scf and c-kit under the regulation of Dahuang Lingxian prescription and the possible mechanism of its effect on gallbladder dynamics, and to provide a theoretical basis for Dahuang Lingxian prescription in preventing the development and recurrence of cholesterol gallstone. Methods A total of 45 specific pathogen-free healthy male guinea pigs were randomly divided into normal group, model group, and traditional Chinese medicine (TCM) group. The guinea pigs in the normal group were fed with normal diet, and those in the model group and the TCM group were fed with high-fat lithogenic diet. After 8 weeks of feeding, 5 guinea pigs were randomly selected from each group, and successful modeling was determined if gallstone was observed with the naked eye in more than 4 guinea pigs. After successful modeling, the guinea pigs in the TCM group were given Dahuang Lingxian prescription by gavage, and those in the model group were given an equal volume of normal saline by gavage. After 8 consecutive weeks of administration by gavage, gallbladder tissue samples were collected, and HE staining was used to observe the pathological changes of gallbladder tissue; Western blot was used to measure the expression level of tumor necrosis factor-α (TNF-α) in gallbladder tissue; immunohistochemistry was used to measure the protein expression levels of scf and c-kit in gallbladder smooth muscle tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference multiple comparison method was used for further comparison between two groups. Results HE staining showed marked inflammation of gallbladder tissue in the model group, and compared with the model group, the TCM group had a significantly lower degree of inflammation. Western blot showed that the model group had the highest expression level of TNF-α in gallbladder tissue, followed by the TCM group and the normal group ( P < 0.05); immunohistochemistry showed that compared with the model group, the normal group and the TCM group had significantly higher protein expression levels of scf and c-kit in gallbladder smooth muscle tissue ( P < 0.05). Conclusion Dahuang Lingxian prescription can enhance the dynamic function of the gallbladder, possibly by upregulating the scf/c-kit signaling pathway in interstitial cells of Cajal in gallbladder.

Application and mechanism of nanomedicine and nanomaterials in antibacterial infection therapy / 药学学报

Antibacterial therapy is a global health issue. The antibiotic resistance is becoming an increasingly serious threat, which caused by misuse and overuse of antibacterial agents combined with the emergence of new resistance mechanism. The resulting infection treatment risk and incidence of the spread of disease, severe cases and deaths are increased in different degrees. With the extensive application of biomaterials and nanotechnology to biomedicine, extensive research has been conducted on antibacterial infection. With the specific physicochemical properties like optical, electric and magnetic and high penetration, inorganic nanomaterials can produce natural antibacterial effect. Nanomedicine can be designed to allow controlled drug release and targeting effect, thus demonstrated better antibacterial efficiency. In this review, the mechanism of antibacterial resistance is described, and the antibacterial infection research on inorganic nanomaterials, as well as nano-drug delivery system including liposomes, nanoparticles, dendrimers and biomimetic nanocarriers are summarized. Nanomaterials and nanotechnology offer promising strategies for the development of new agents that can improve efficacy on antibacterial infections and overcome antibiotic resistance potentially.

Establishment of duplex TaqMan RT-PCR method for detection of Entamoeba histolytica and Giardia lamblia in fecal sample / 中国热带医学

@#Abstract: Objective To establish the duplex TaqMan RT-PCR method for detection of Entamoeba histolytica and Giardia lamblia in fecal samples. Methods Primer pairs and probes for Entamoeba histolytica and Giardia lamblia were designed and duplex TaqMan RT-PCR amplification system was constructed. PCR products were inserted into the pUC57 plasmid, and the lower limit of detection of the method was determined. Clinical stool samples were tested in order to evaluated the efficacy of the method. Results The detection limits of duplex TaqMan RT-PCR were 31.6 copies/μL for Entamoeba histolytica and 32 copies/μL for Giardia lamblia, respectively. Of the total of 212 clinical stool samples tested, all 3 samples with E. histolytica-positive patients by microscopy were positive by PCR, while 1 from 209 samples with E. histolytica-negative patients by microscopy were positive by PCR, and the remaining samples were negative. For Giardia lamblia, all 8 samples positive by microscopy were positive by PCR, and 1 from 204 sample with a microscopy-negative patient was positive by PCR, and the remaining samples were negative. The amplification product sequencing and blast analysis were used to confirm that the amplified sequence in the specimen of a patient with negative microscopy but positive PCR belongs to the targeted pathogen, supported by clinical symptoms and laboratory test results. PCR results for other diarrhea-causing pathogens were negative, indicating no cross-reactivity. Conclusions The dual TaqMan RT-PCR method developed in this study can not only detect microscopy-positive samples of Entamoeba histolytica and Giardia lamblia but also can detect samples that were missed by microscopy, with higher sensitivity than the microscopy method. Further, this detection method does not cross-react with other diarrhea-causing pathogens, including cross-react with other diarrhea-causing pathogens including Iodamoeba butschlii, Blastocystis hominis, Plesiomonas, Aeromonas, Salmonella, Shigella, Sphaerozoum fuscum, and Entamoeba hartmani, thus has a good specificity.

Research progress on biomarkers of pseudoexfoliative glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Pseudoexfoliative glaucoma(PEXG)is an eye disease that seriously endangers vision. It is more invasive than primary open-angle glaucoma(POAG), with more serious damage to the optic nerve, worse prognosis and higher resistance to treatment. Early diagnosis of PEXG can help to treat the disease in time and delay the progress of the disease, so it is important to determine appropriate biomarkers. In recent years, more and more people have begun to study the biomarkers of PEXG, hoping to understand the pathogenesis of the disease, find out the potential early diagnosis and treatment targets of PEXG, and provide some help to the disease through the research of genomics, transcriptomics, proteomics, metabolomics and lipomics markers. This article will review the progress of biomarkers of PEXG in recent years, some biomarkers may provide new ideas for early diagnosis of PEXG in the future.

Identification and verification of α-11 giardin-interacting protein / 中国血吸虫病防治杂志

Objective To identify and verify the interacting protein of α-11 giardin, so as provide the experimental evidence for studies on the α-11 giardin function. Methods The yeast two-hybrid cDNA library of the Giardia lambia C2 strain and the bait plasmid of α-11 giardin were constructed. All proteins interacting with α-11 giardin were screened using the yeast two-hybrid system. α-11 giardin and all screened potential interacting protein genes were constructed into pBiFc-Vc-155 and pBiFc-Vn-173 plasmids, and co-transfected into the breast cancer cell line MDA-MB-231. The interactions between α-11 giardin and interacting proteins were verified using bimolecular fluorescence complementation (BiFC). Results The yeast two-hybrid G. lambia cDNA library which was quantified at 2.715 × 107 colony-forming units (CFU) and the bait plasmid containing α-11 giardin gene without an autoactivation activity were constructed. Following two-round positive screening with the yeast two-hybrid system, two potential proteins interacting with α-11 giardin were screened, including eukaryotic translation initiation factor 5A (EIF5A), calmodulin-dependent protein kinase (CAMKL) and nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH), hypothetical protein 1 (GL50803_95880), hypothetical protein 2 (GL50803_87261) and a protein from Giardia canis virus. The α-11 giardin and EIF5A genes were transfected into the pBiFc-Vc-155 and pBiFc-Vn-173 plasmids using BiFC, and the recombinant plasmids pBiFc-Vc-155-α-11 and pBiFc-Vn-173-EIF5A were co-tranfected into MDA-MB-231 cells, which displayed green fluorescence under a microscope, indicating the interaction between α-11 giardin and EIF5A protein in cells. Conclusion The yeast two-hybrid cDNA library of the G. lambia C2 strain has been successfully constructed, and six potential protein interacting with α-11 giardin have been identified, including EIF5A that interacts with α-11 giardin in cells.

Progress on exosomes in the diagnosis and treatment of disease and drug delivery system / 药学实践杂志

As a type of extracellular vesicles, exosomes are released by living cells and contain diverse bioactive molecules, including nucleic acids, proteins, lipids and metabolites. They play an important role in various physiological and pathological processes by a special intercellular communication medium. As endogenous vesicles, exosomes also have the advantages of systemic circulation stability, good biocompatibility and specific targeting of tissues and cells, as well as they are promising candidates for drug delivery system. The production mechanism of exosomes describe was summarized, the methods of extraction and separation the application and mechanism of exosomes in immune and inflammation-related diseases, cardiovascular system diseases, nervous system diseases, tumors, etc. were reviewed. The engineering modifications of exosomes in high targeting properties based on the drug delivery were overviewed. Exosomes support the diagnosis and prognostic assessment of multiple diseases, which have broad application prospects as a very potential safe and specific endogenous nano-drug carrier.

Clinical characteristics and risk factors for early-onset necrotizing enterocolitis in preterm infants with very/extremely low birth weight / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW).@*METHODS@#A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis.@*RESULTS@#Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05).@*CONCLUSIONS@#VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.

Progress in preparation and application of biomimetic nano carriers for cell membrane / 药学实践杂志

Nanocarriers prepared from organic or inorganic materials are widely used in drug targeting system and diagnosis and treatment of disease. However, there are some problems, such as poor targeting, short circulation time in vivo and improvement in the biocompatibility. Biomimetic nanocarriers has carried out research on the issues, which based on different kinds of cell membrane for the nanocarriers modification, endogenous biofilm improving the biocompatibility of carriers in vivo, more accurate targeting, and even producing immunotherapeutic effect. The principle, method, targeting mechanism and therapeutic effect of biomimetic nano carrier technology of cell membrane have been reviewed in this paper, which provide a new direction for the research of new drug delivery system.

Preparation and anti-Vibrio vulnificus hemolysin A of macrophage membrane hybrid liposome / 药学实践杂志

Objective To prepare a biomimetic nano carrier macrophage membrane hybrid liposome by heterozygous macrophage membrane and liposome, which could be used for the clearance and toxicity inhibition of Vibrio vulnificus hemolysin A (VvhA). Methods Macrophage membrane was extracted and hybridized with liposome by thin-film evaporation combined extrusion method. The hybridized liposome of macrophage membrane was constructed and characterized. The in vitro detoxification ability of the hybridized vector was evaluated by hemolysis test and cytotoxicity test. The detoxification ability of the vector was evaluated by mouse skin infection model. Results Anti toxoid studies in vivo and in vitro showed that the anti-hemolysis rate of macrophage membrane heterozygous liposomes in vitro reached 97.03%, which could effectively inhibit the skin ulceration in subcutaneous infected mice and make the survival rate of abdominal infected mice reach 80%. Conclusion The constructed macrophage membrane hybrid liposome had high detoxification ability, which could provide a potential solution and research basis for the prevention and treatment of Vibrio vulnificus infection.

Evaluation of Inspection Efficiency of Diatom Artificial Intelligence Search System Based on Scanning Electron Microscope / 法医学杂志

OBJECTIVES@#To explore the application values of diatom artificial intelligence (AI) search system in the diagnosis of drowning.@*METHODS@#The liver and kidney tissues of 12 drowned corpses were taken and were performed with the diatom test, the view images were obtained by scanning electron microscopy (SEM). Diatom detection and forensic expert manual identification were carried out under the thresholds of 0.5, 0.7 and 0.9 of the diatom AI search system, respectively. Diatom recall rate, precision rate and image exclusion rate were used to detect and compare the efficiency of diatom AI search system.@*RESULTS@#There was no statistical difference between the number of diatoms detected in the target marked by the diatom AI search system and the number of diatoms identified manually (P>0.05); the recall rates of the diatom AI search system were statistically different under different thresholds (P<0.05); the precision rates of the diatom AI system were statistically different under different thresholds(P<0.05), and the highest precision rate was 53.15%; the image exclusion rates of the diatom AI search system were statistically different under different thresholds (P<0.05), and the highest image exclusion rate was 99.72%. For the same sample, the time taken by the diatom AI search system to identify diatoms was only 1/7 of that of manual identification.@*CONCLUSIONS@#Diatom AI search system has a good application prospect in drowning cases. Its automatic diatom search ability is equal to that of experienced forensic experts, and it can greatly reduce the workload of manual observation of images.

Quality of life and influencing factors of postoperative accelerated rehabilitation of esophageal cancer patients / 中华肿瘤杂志

Objective: To explore the quality of life and its influencing factors of enhanced recovery after surgery (ERAS) of esophageal cancer patients. Methods: The quality of life of 134 esophageal cancer patients was assessed using the quality of life assessment scale (EORTC QLQ-C30) developed by the European Cancer Research and Treatment Organization. Student's t test, One-way ANOVA and multiple linear regression statistical methods were used to analyze the effects of sociodemographic and clinical characteristics on patients' quality of life. Results: The overall score of quality of life (74.00) was lower than that of the general population (75.30). However, the scores of emotion and cognition in function dimension (93.97 and 95.77) were better than those of the general population (82.80 and 86.50). The results of fatigue, pain, insomnia and constipation in symptom dimension (14.18, 10.94, 11.69 and 5.72) were better than those of the general population (28.80, 20.50, 20.40 and 10.70). The pathological stage, body mass index and dietary were independent influencing factors for the quality of life of patients with esophageal cancer (P<0.05). Conclusions: ERAS can partially improve the quality of life of esophageal cancer patients. More attention should be paid to the esophageal cancer patients after surgery and take targeted measures to improve their quality of life.

Clinical practice of double lumen cannula for veno-venous extracorporeal membrane oxygenation in adults / 中华危重病急救医学

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life support technique for patients with severe respiratory failure. In the past, single lumen cannula was mostly used to constract the vascular pathway of extracorporeal membrane oxygenation. Compared with single-lumen cannula, double lumen cannula (DLC) can reduce recirculation fraction, reduce complications such as infection and bleeding, and facilitate patient's rehabilitation. DLC requires accurate positioning of the catheter. It has been gradually applied in China. This paper will review the key points related to the use of DLC, such as the insertion, position, and complications, etc. to provide guidance for clinical application practice.

Predictive value of left ventricular ejection fraction for the occurrence of postoperative myocardial infarction after coronary endarterectomy in patients with diffuse coronary artery disease / 中华心血管病杂志

Objective: To investigate the predictive value of ejection fraction for the postoperative myocardial infarction after coronary endarterectomy (CE) in patients with diffuse coronary artery disease (DCAD). Methods: Patients who underwent cardiac artery bypass graft (CABG) surgery and CE in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2020 were enrolled in this prospective observational study. Baseline features including age, sex and echocardiography parameters were obtained. Left ventricular ejection fraction(EF) was measured by echocardiography. The patients were divided into postoperative myocardial infarction (PMI) group and non-PMI group according to PMI occurrence. Linear regression analysis, logistic regression model, and receiver operating characteristic(ROC) curve were used to analyze the correlation between left ventricular ejection fraction and PMI and the influencing factors. Results: A total of 120 patients were enrolled in the study. There were 32 patients (27%) in the PMI group (male 27(84%), age (62±8)), inferior myocardial infarction occurred in 24 (75%) patients. There were 88 patients (73%) in the non-PMI group (male 70(80%), age (62±8)). EF (55% (49%, 64%) vs. 62% (55%, 67%), P=0.01) was significantly lower in the PMI group than in the non-PMI group. Perioperative TNI, IABP use and length of hospitalization were significantly higher in the PMI group than in the non-PMI group. Multivariate logistic regression showed that lower EF was an independent risk factor of PMI (OR=0.93, 95%CI: 0.89-0.98, P=0.01) after adjusting age, sex and body mass index. ROC curve analysis showed that EF<60% could sufficiently predict the occurrence of PMI (AUC= 0.67, sensitivity 64%, specificity 69%, P=0.01). Linear regression analysis showed that left ventricular end-diastolic diameter (OR=-0.52, 95%CI:-1.13-0.60, P<0.001), graft flow in left anterior descending (OR=-0.20, 95%CI:-0.15-0.01, P=0.02) and history of diabetes (OR=-0.28, 95%CI:-8.25-1.85, P=0.002) were negatively correlated with preoperative EF value. Conclusion: Lower preoperative EF is an independent risk factor for PMI after CABG and CE in DCAD patients, closely related to the left ventricular end-diastolic diameter, graft flow in left anterior descending artery and diabetes mellitus.

The role of FGF21 in inhibition of heart failure with empagliflozin and related mechanisms / 药学学报

The aim of this study is to investigate the role of fibroblast growth factor 21 (FGF21) in empagliflozin (EMP) in treatment of heart failure and the related mechanisms. FGF21 knockout (FGF21 KO) and littermate wild-type (WT) mice induced by doxorubicin (Dox) were used to establish heart failure mouse model in vivo. The experiment process and animal welfare follow the regulations of Animal Ethics Committee of Hefei University of Technology strictly. The results suggest that Dox (5 mg·kg-1) induced typical heart failure symptoms in both WT and FGF21 KO mice. In WT mice, EMP (10 mg·kg-1) significantly improved Dox-induced cardiac atrophy, decreased myocardial systolic function, decreased left ventricular ejection fraction and shortened fraction; EMP treatment also significantly inhibited the increase of Dox-induced cardiotoxicity indexes (aspartate amino transferase, creatine kinase, hydroxybutyrate dehydrogenase, lactate dehydrogenase) in mice. Dox induced cardiac fibrosis, inflammation and oxidative stress were also significantly improved by EMP. However, in FGF21 KO mice, the therapeutic effects of EMP on heart failure was significantly inhibited. The results suggest that the function of EMP in treating heart failure partly depends on the presence of FGF21, and the mechanism may be related to the effect of FGF21 on improving fibrosis, inflammation and oxidative stress.

Role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats / 中华麻醉学杂志

Objective:To evaluate the role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats.Methods:Thirty-two SPF healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 360-380 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), surgery group (group S), surgery + dimethyl sulfoxide (DMSO) group (group SD), and surgery + SR9009 group (group SS). Exploratory laparotomy was performed under sevoflurane anesthesia in S, SD and SS groups.Normal saline containing 0.1% DMSO was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group SD, and REV-ERBα agonist SR9009 (in normal saline containing 0.1% DMSO) was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group S+ SR9009.Morris water maze test was performed at 1 and 3 days after operation.Rats were sacrificed at 1 h after the end of Morris water maze test on day 3 after surgery, and the hippocampal tissues were obtained for determination of the expression of REV-ERBα, Brain and Muscle ARNT-Like 1 (BMAL1) protein, synaptophysin (SYN), postsynaptic density (PSD)-95 protein and N-methyl-D-aspartate receptor 2B subunit (GRIN2B) (by Western blot) and microscopic examination of the morphology of hippocampal neurons and Nissl bodies (by Nissl staining), and the viable neurons were counted. Results:Compared with group C, the percentage of time of staying at the target quadrant was significantly decreased, and the number of crossing platform was reduced on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα, BMAL1, PSD95, SYN and GRIN2B was down-regulated, and the number of viable neurons was decreased in group S and group SD ( P<0.05). Compared with group S and group SD, the percentage of time of staying at the target quadrant and the number of crossing platform were significantly increased on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα and PSD95 was up-regulated, the number of viable neurons was increased ( P<0.05), and no significant change was found in the expression of BMAL1, SYN and GRIN2B in group SS ( P>0.05). There was no significant difference in the indexes mentioned above between group S and group SD ( P>0.05). Conclusions:Activation of REV-ERBα can improve postoperative cognitive dysfunction, and the mechanism may be related to up-regulation of PSD95 expression in hippocampus and reduction of neuronal damage in rats.

A multicenter prospective randomized controlled study on the timing of laparoscopic cholecystectomy after percutaneous transhepatic gallbladder drainage for grade Ⅱ-Ⅲ acute cholecystitis / 中华肝胆外科杂志

Objective:To study the optimal timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD) for grade Ⅱ-Ⅲ acute cholecystitis.Methods:A multicenter, single blind and randomized controlled study was conducted at Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai Pudong Hospital, and Shanghai Minhang District Central Hospital from October 2018 to September 2021. Patients who underwent LC after PTGBD were divided 1∶1 into the early group and the late group. LC was performed 4-6 weeks after PTGBD in the early group and 7-8 weeks after PTGBD in the late group. Gender, age, AC grade, complications after PTGBD, body mass index, complications before LC, operation time of LC, intraoperative bleeding, total treatment cost, conversion rate to open surgery and complications after LC were compared between the two groups. The 36-Item Short Form Health Survey (SF-36) before and after LC was also compared.Results:Of 248 patients who were eligible for the study, there were 52 males and 196 females, with ages ranging from 18 to 89 years, and mean ±s.d. of (52.5 ± 20.2) years. There were 126 patients in the early group and 122 patients in the late group. There were no significant differences in gender, age, AC grade, body mass index and complications before LC between the two groups (all P>0.05). The preoperative score of SF-36 in the early group was significantly better than that in late group, and the complications of PTGBD in the late group were significantly higher than the early group (both P<0.05). The operation time and total treatment cost of the early group were significantly less than those of the late group (37.2±12.8 min vs. 48.5±19.7 min, 20 856±2 136 yuan vs. 2 2207±2 049 yuan) (both P<0.05). The intraoperative bleeding volume of LC in the early group was [ M( Q1, Q3)] 40 (40, 60) ml and the late group was [ M( Q1, Q3)] 35 (25, 40) ml. The difference was also significant ( P<0.05). There was no significant differences in the conversion rates to open surgery, complications and SF-36 scores after LC between the two groups (all P>0.05). Conclusion:LC should be performed 4-6 weeks after PTGBD for grade Ⅱ-Ⅲ acute cholecystitis. Although the amount of intraoperative bleeding was higher, the operation time was shorter, the burden on patients was reduced and there was more rapid recovery.