OBJECTIVE To study the pharmacokinetic characteristics of ciprofol in pregnant and fetal rats， and provide reference for the application of ciprofol in cesarean section. METHODS Eight pregnant rats were selected. A single dose of 2.4 mg/kg of ciprofol was administered via the tail vein. One fetal rat was selected at 2， 4， 8， 12， 16， 25， 35， 45， 60， and 90 minutes respectively after ciprofol administration. Subsequently， whole blood samples were collected simultaneously from both the pregnant rats and fetal rats. HPLC-MS/MS method was used to determine the concentration of ciprofol in the bodies of pregnant and fetal rats. The ratios of fetal-to-maternal blood concentrations （F/M ratios） at each time point were calculated， and the F/M-time curves were plotted. Subsequently， non-compartmental pharmacokinetic parameters were computed using DAS 2.0 software. RESULTS Compared with pregnant rats， cmax， AUC0-90 min and AUC0-∞ of ciprofol in fetal rats were decreased significantly， while MRT was increased significantly （P＜0.05）. The F/M curve of ciprofol initially increased and then decreased， and between 0.16- 0.84， reaching a maximum value of 0.84 at 45 minutes. CONCLUSIONS Ciprofol can penetrate the placental barrier， and there are significant differences in pharmacokinetic parameters between pregnant and fetal rats. Moreover， the exposure level of ciprofol in fetal rats is much lower than that in pregnant rats. Therefore， ciprofol shows promise as an ideal anesthetic agent for cesarean section delivery.

Hepatic ischemia-reperfusion injury （HIRI） is an inevitable major complication during surgical procedures such as liver transplantation and partial hepatectomy， and its prevention and treatment are hotspots and difficulties in clinical practice. This article reviews the mechanism of injury caused by energy metabolism disorders during liver ischemia-reperfusion and related treatment strategies and summarizes the current advances in metabolism-related therapies， in order to provide new ideas for further clarifying the onset mechanism of HIRI and exploring effective clinical prevention and treatment strategies for HIRI.

Background::Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.Methods::Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM 2.5) and/or ozone (O 3) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017. Results::In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O 3 in the total loss from the two pollutants was substantially lower than that of PM 2.5, but it was rapidly growing. The O 3-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM 2.5 and O 3 to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest. Conclusion::The disease burden from O 3 is lower than that of PM 2.5, the O 3-contribution has a significantly increasing trend with the growth of economy and O 3 concentration.

Objective:To explore the effectiveness of the O-AMAS teaching model in clinical teaching for blood purification training nurses.Methods:Convenience sampling was used to select 187 training nurses from the Blood Purification Center of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022 as research subjects. Eighty training nurses enrolled from January to December 2021 were selected as the control group, and 107 training nurses enrolled from January to December 2022 were selected as the experimental group. After three months of intervention, the training nurses' theoretical scores, operational skills assessment scores, and satisfaction were compared between the two groups.Results:The theoretical and operational skills assessment scores of the experimental group were higher than those of the control group ( P<0.05). The satisfaction of the experimental group with the teaching model, teaching effectiveness, completion of theoretical training, guidance on operational skills, and overall teaching was higher than that of the control group ( P<0.05) . Conclusions:The O-AMAS teaching model for clinical teaching can help improve the training effectiveness and satisfaction of blood purification training nurses.

Objective:To investigate the correlation between plasma total α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn), neurofilament light chain(NfL) and subtypes of Parkinson disease(PD).Methods:A total of 62 PD patients admitted to the Department of Neurology, the Affiliated Huai 'an No. 1 People 's Hospital of Nanjing Medical University from September 2021 to January 2023 were selected and scored on the Hoehn-Yahr stage(H-Y), unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ), levodopa equivalent daily dosage(LEDD), mini-mental state examination(MMSE), Parkinson disease quality of life questionnaire(PDQ-39) and activities of daily living(ADL). During the same period, 25 healthy individuals matched in age and sex were enrolled as the control group (HC). Clinical characteristics and blood samples were collected. The plasma levels of α-syn, p-α-syn and NfL were detected by enzyme-linked immunosorbent assay(ELISA). PD patients were divided into tremor dominant type (TD, n=27) and akinetic-rigid dominant type (AR, n=35) based on UPDRS-Ⅲ scores. Multifactorial Logistic regression analysis was performed by SPSS 25.0 software to determine the influencing factors of subtypes of Parkinson disease. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point of plasma NfL between the AR type and the TD type. Results:Plasma α-syn, p-α-syn, NfL levels in the PD group were significantly higher than those of the HC group ( Z=-2.537, -6.580, -7.101, all P<0.05). There were statistically significant differences between the AR type and the TD type in disease duration, H-Y stage, UPDRS-Ⅲ scores, LEDD and MMSE scores ( Z=-2.503, -3.021, -2.025, -2.086, -2.409, all P<0.05). While no significant difference was found in plasma α-syn and p-α-syn levels between the AR type and TD type ( Z=-0.341, -0.085, both P>0.05), the plasma NfL levels were notably higher in the AR type(92.79(16.84, 117.53) pg/mL) compared to the TD type (12.10(6.99, 100.17) pg/mL)( Z=-2.236, P<0.05). Plasma NfL levels were correlated with rigidity scores ( r=0.438, P<0.001), UPDRS-Ⅲ scores ( r=0.337, P<0.05) and motor subtypes ( r=0.286, P<0.05) in PD patients. Multivariate Logistic regression analysis showed that NfL was risk factor for AR( B=0.002, OR=1.002, 95% CI=1.001-1.003, P=0.017). The ROC curve analysis indicated that plasma NfL levels could predict different subtypes of PD with an AUC=0.667, optimal cutoff =26.527. Conclusion:There is a correlation between elevated plasma NfL levels and the occurrence of AR type of PD, suggesting that nerve injury is probably involved in the occurrence and progression of various motor subtypes of PD.

Objective To explore the application and effect of a pulmonary rehabilitation exercise program in patients with moderate to severe COPD based on the Information-Motivation-Behavior Skill(IMB)Model.Methods The convenience sampling method was adopted to select patients with moderate to severe COPD admitted to the department of respiratory and critical care medicine in a tertiary A hospital in Yantai City from October 2021 to February 2022.They were randomly divided into an intervention group(32 cases)and a control group(31 cases).The intervention group was treated with the pulmonary rehabilitation exercise program based on the IMB model on the basis of routine nursing,while the control group was treated with routine nursing.The degree of dyspnea,exercise endurance,quality of life,pulmonary rehabilitation exercise compliance,self-management ability and lung function were compared between the 2 groups before and 6 months after the intervention.Results After intervention,the degree of dyspnea,exercise endurance,quality of life,pulmonary rehabilitation exercise compliance and self-management ability were significantly different between the 2 groups(P＜0.05).There was no statistically significant difference in lung function between the 2 groups after intervention(P＞0.05).Conclusion The pulmonary rehabilitation program based on IMB model can effectively alleviate the symptoms of dyspnea in patients with moderate to severe COPD,improve exercise endurance,improve pulmonary rehabilitation exercise compliance and self-management ability,and improve the patients'quality of life.

Objective:To study the distribution of drug resistance genes and virulence genes in multidrug-resistant Salmonella typhimurium strains.Methods:A total of 96 strains of Salmonella typhimurium were collected，and drug sensitivity tests were performed to evaluate the drug resistance and multidrug-resistance of Salmonella typhimurium.Multidrug-resistant Salmonella typhimurium strains were selected to conducted whole genome sequencing，and the distribution of drug resistance genes and virulence genes in the strain were analyzed.Results:Salmonella typhimurium strains had the highest resistance rates to ampicillin and ampicillin/sulbactam，with 89.58% and 76.04%，respectively.Followed by trimethoprim/sulfamethoxazole，ceftriaxone，and aztreonam，with 47.92%，38.54% and 33.33%，respectively，and low resistance rates to ciprofloxacin and levofloxacin，with 8.33% and 4.17%，respectively.Ninety-six strains were all sensitive to carbapenem antibiotics and piperacillin/tazobactam.Fifty-seven strains（59.38%）of Salmonella typhimurium showed multidrug-resistance.Resistance genes were detected in all 57 multidrug-resistant Salmonella typhimurium strains,with higher carrier rates of 98.25%,77.19%,and 59.65% for aac(6')-Iaa,aadA22,and blaTEM-1B,respectively.The multidrug-resistant Salmonella typhimurium strains had the highest carrier rates for invA，sipA，sseL，and sopB.Conclusion:Multidrug-resistant Salmonella typhimurium strains have a high incidence and a high carrier rate for multiple drug resistance genes and virulence genes.The monitoring and prevention of Salmonella typhimurium should be strengthened in the clinic in order to reduce the spreading epidemic of multidrug-resistant strains.

AIM:To investigate the impact of honokiol(HKL),an activator of silent information regulator 3(SIRT3),on postoperative cognitive dysfunction(POCD)in mice,and to explore the potential mechanisms.METHODS:Ten-month-old male C57/BL6 mice were randomly divided into control(Con)group,surgical(Sur)group and Sur+HKL group(n=10).The mice in Sur+HKL group were intraperitoneally injected with HKL for 7 d before modeling.The mice in Sur and Sur+HKL groups underwent tibial fracture open reduction and internal fixation to establish the POCD model.The assessment of cognitive function was conducted using the open-field test(OFT),novel object recognition test(NORT),Morris water maze test(MWMT),and Y-maze test(YMT).Nissl staining was employed to assess the morphology,struc-ture and vitality of hippocampal and cortical neurons in mice.The protein expression of glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),acyl coenzyme A synthetase long-chain family member 4(ACSL4),SIRT3 and nuclear factor E2-related factor 2(NRF2)in the mouse hippocampus was detected by Western blot,while im-munofluorescence staining was utilized to determine GPX4 level in mouse neurons.RESULTS:No statistically signifi-cant differences were observed among the groups in terms of total distance moved and central zone exploration during the OFT(P>0.05).However,the results from the NORT and YMT indicated that the mice in Sur group exhibited significant-ly lower recognition indexes,reduced alternation rates(P<0.01),and decreased percentages of entries and crossing time into the new arm after side arm blockade(P<0.01),when compared with Con group.Furthermore,the mice in Sur group demonstrated a slower decrease in latency during the learning period of MWMT,while significantly lower latency,fewer crossing number and lower percentage of time in the target quadrant were observed during the testing period of MWMT(P<0.01).The above indicators were obviously enhanced in Sur+HKL group compared with Sur group(P<0.01).The results of Nissl staining indicated lighter neuronal staining in the hippocampal CA1 region and medial prefrontal cortex in Sur group,accompanied by a significant reduction in the number of Nissl-stained positive neurons(P<0.01).Notably,HKL pretreatment demonstrated a significant improvement in neuronal vitality.Analysis of Western blot revealed that compared with Con group,the expression of SIRT3,GPX4,SLC7A11 and NRF2 in Sur group was significantly reduced,while the expression of ACSL4 was significantly increased(P<0.05).However,these alterations were reversed after treatment with HKL(P<0.05).Immunofluorescence staining of hippocampal neurons corroborated the findings from Western blot analy-sis,demonstrating a notable decrease in GPX4 expression in hippocampal neurons of Sur group,which was significantly restored after HKL pretreatment(P<0.01).CONCLUSION:Treatment with HKL attenuates POCD in mice,potentially through its inhibitory effect on hippocampal neuronal ferroptosis.

Background Quartz dust cannot be degraded in the lungs, and inhalation of a large amount of quartz dust in the occupational production process will lead to the occurrence of pulmonary fibrosis, and then develop into silicosis. In recent years, studies have found that exosomes may be involved in the pathogenesis of fibrotic diseases by carrying microribonucleic acid (miRNA), but the mechanism of their actions in silicosis still needs to be studied. Objective To investigate the role of exosome-derived miRNA-21-5p/mothers against decapentaplegic homolog 7 (Smad7) in quartz dust-induced pulmonary fibrosis in rats. Methods Twenty-four healthy male SD rats were randomly divided into four groups (six rats in each group): control 4-week group, control 16-week group, quartz 4-week group, and quartz 16-week group. At the beginning of the experiment, 1 mL of quartz suspension (50 mg·mL⁻¹) and 1 mL of normal saline were injected into the trachea of rats in the quartz group and the control group, respectively, by means of one-time non-exposure intratracheal dust staining. Alveolar lavage was performed at the 4th and 16th weeks after dust staining, the exosomes in lavage solution were extracted by polyethylene glycol (PEG) precipitation, morphological identification was conducted by transmission electron microscopy (TEM), particle size of exosomes was detected by nano-tracking analysis (NTA), and the marker proteins CD9 and CD63 of exosomes were detected by Western blotting (WB). The expression of miRNA-21-5p in exosomes was determined by reverse transcription polymerase chain reaction (RT-PCR). The degree of lung tissue injury and fibrosis was observed by hematoxylin-eosin staining (HE) and Masson staining. The collagen content of lung tissue was detected by hydroxyproline (HYP) method. The expression of Smad7 protein in lung tissue was detected by WB. Results The results of pathological staining showed that compared with the control group, lung inflammatory cell infiltration, alveolar wall thickening, and collagen increase were observed after 4 weeks of dusting, and collagen deposition and silicon nodules appeared after 16 weeks of dusting. Compared with the control group, the expression level of HYP in the lung tissue of the quartz group was increased after 4 weeks and 16 weeks of dust staining (P<0.05). Transmission electron microscopy showed that exosomes were saucer-shaped, and the average particle size of exosomes was 95.8 nm by NTA. Positive expression of exosome marker proteins CD9 and CD81 was found by WB. Compared with the control group, the expression of exosome-derived miRNA-21-5p in alveolar lavage fluid in the quartz group increased in the 4th week and the 16th week (P<0.05), and the expression of Smad7 protein in lung tissue decreased (P<0.05). Conclusion Exosome-derived miRNA-21-5p and Smad7 may be involved in the mechanism of quartz dust-induced pulmonary fibrosis in rats.

OBJECTIVE To compare the metabolomic characteristics of stage T1 papillary thyroid carcinoma(PTC)and nodular goiter(NG),and the relationship between metabolites and lymph node metastasis of PTC.METHODS Serum samples were collected from 60 patients with stage T1 PTC and 30 patients with NG who underwent thyroidectomy at the Department of Otolaryngology Head and Neck Surgery,Civil Aviation General Hospital between September 2021 and April 2022.The PTC group was divided into the N+ group with lymph node metastasis and the N-group without lymph node metastasis according to the presence or absence of lymph node metastasis.The serum metabolites of the N+ and N-groups and the PTC and NG groups were compared and analyzed using an ultra-performance liquid chromatography-mass spectrometry(UPLC-Q-Exactive-MS)coupled platform,and principal component analysis(PCA),partial least squares discriminant analysis(PLS-DA),and orthogonal partial least squares discriminant analysis(OPLS-DA)was performed using SIMCA-P 14.1 software.OPLS-DA modeling,combined with FDR-corrected Mann-Whitney-Wilcoxon test results and metabolite difference multiples in the two groups undergoing comparison,etc.to screen for potential small molecule metabolic markers,and to establish a joint diagnostic model by binary logistic regression analysis.RESULTS There were no significant differential metabolites between the N+ group with lymph node metastasis and the N-group without lymph node metastasis.Seven differential metabolites were found between PCA patients and NG patients,and the five relevant metabolic pathways were the pentose phosphate pathway,pentose and glucuronide interconversion,glycolysis/gluconeogenesis,fructose,and mannose metabolism,and fatty acid biosynthesis.The differential metabolite with an area under the ROC curve>0.9 was D-glyceraldehyde 3-phosphate,and another N-undecanoylglycine,uronic acid,and the area under the ROC curve for three metabolites,N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,was>0.8.CONCLUSION PTC patients differed from NG patients mainly in glucose metabolism and lipid metabolism,and D-glyceraldehyde 3-phosphate could be distinguished from NG patients with the aid of N-undecanoylglycine,uric acid,and triiodothyronine glucuronide,combined with imaging findings.Also,no significant differences in serum metabolites were found in the N+ group compared with the N-group,and the presence or absence of lymph node metastases did not affect serum metabolites in patients with stage T1 PTC.