Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

Objective To investigate the effect of dexmedetomidine(Dex)on neural injury in rats with kainic acid(KA)-induced epilepsy and its possible mechanism.Methods Rats were ran-domly divided into Sham group,model group,Dex low-dose(Dex-L)group,Dex high-dose(Dex-H)group,and Dex-H+recombinant high mobility group box 1(rHMGB1)group using a random number table method,with 10 rats in each group.Except for the Sham group,epilepsy modeling was per-formed in the other groups.The seizure conditions of rats in each group were observed.The Morris water maze test was used to assess the spatial learning and memory abilities(latency,time spent in the target quadrant,and the number of platform crossings)of the rats.Enzyme-linked immunosorbent assay(ELISA)was employed to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-18(IL-18),and γ-aminobutyric acid(GABA)in the hippocampal tissue of the rats.Nissl staining was used to observe the morphological changes in the hippocampal tissue.The TUNEL method was applied to detect the apoptosis rate of hippocampal neurons.Western blotting was used to measure the expression levels of proteins related to the high mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)/nuclear factor κB(NF-κB)pathway.Results Compared with the Sham group,the model group had higher seizure scores and hippocampal neuronal apoptosis rates,elevated levels of TNF-α,IL-18,IL-6,and cleaved caspase-3,HMGB1,RAGE,and phos-phorylated(p)-NF-κB/NF-κB proteins in the hippocampal tissue,prolonged seizure duration and latency,decreased hippocampal neuronal numbers and platform crossings,shortened time spent in the target quadrant,and reduced GABA levels,with statistically significant differences(P＜0.05).Compared with the model group,the Dex-L and Dex-H groups had lower seizure scores and hipp-ocampal neuronal apoptosis rates,reduced levels of TNF-α,IL-18,IL-6,and cleaved-caspase-3,HMGB1,RAGE,and p-NF-κB/NF-κB proteins in the hippocampal tissue,shortened seizure dura-tion and latency,increased hippocampal neuronal numbers and platform crossings,prolonged time spent in the target quadrant,and elevated GABA levels,with statistically significant differences(P＜0.05).The rHMGB1 could weaken the ameliorative effect of Dex on neural injury in KA-in-duced epileptic rats.Conclusion Dex can alleviate inflammatory responses,oxidative stress,and neuronal apoptosisin KA-induced epileptic rats,and improve neurological function,possibly by in-hibiting the HMGB1/RAGE/NF-κB pathway.

Objective: To investigate the role and mechanism of PGC-1 α-mediated mitochondrial biosynthesis in AMP-activated protein kinase (AMPK) agonist anti-hepatic ischemia-reperfusion injury (HIRI) ． Methods : SD rats were randomly divided into Control group，HIRI group，HIRI + AICAR group，HIRI + SR-18292 group and HIRI + AICAR + SR-18292 group，with 8 rats in each group．The rats were intraperitoneally injected with AICAR (500 mg / kg) or SR-18292 (32 mg / kg) before operation，and then the HIRI model was established by non-invasive vascular clamp clamping method．The samples were taken 24 hours after reperfusion．The contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and the levels of malondialdehyde (MDA) ，superoxide dis- mutase (SOD) and adenosine triphosphate (ATP) in liver tissue were detected．HE staining was used to observe the pathological changes of liver tissue．The level of reactive oxygen species (ROS) and the changes of mitochondri- al membrane potential in liver tissue were detected by fluorescence probe．The copy number of mitochondrial DNA (mtDNA) and the mitochondrial biosynthesis-related genes PGC-1 α, NRF1，TFAM，UQCRC2 and other mRNA ex- pression levels were detected by qRT-PCR. Western blot was used to detect the protein expression levels of AMPKα, p-AMPKα , mTOR , p-mTOR , PGC-1α and TFAM in liver tissue． Results : Compared with the control group，the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI group increased，while the levels of SOD and ATP decreased ( all P ＜0. 05) ．At the same time，the mtDNA copy number，mitochondrial membrane potential and the mRNA expression levels of PGC-1α , NRF1，TFAM，and UQCRC2 in liver tissues de- creased，and the protein ratio of p-AMPKα/AMPKα and the protein expression levels of PGC-1α and TFAM de- creased．The ratio of p-mTOR/ mTOR protein increased (both P＜0. 05) ．Compared with HIRI group，the levels of ALT and AST in serum and MDA and ROS in liver tissue of rats in HIRI + AICAR group decreased，while the levels of SOD and ATP increased ( all P ＜0. 05) ．At the same time，the mtDNA copy number，mitochondrial membrane potential and the mRNA expression levels of PGC-1α , NRF1，TFAM，and UQCRC2 in liver tissue increased，and the protein ratio of p-AMPKα/AMPKα and the protein expression levels of PGC-1α and TFAM increased．The ratio of p-mTOR/ mTOR protein decreased (both P＜0. 05) ．However，combined with SR-18292 intervention，the protective effect of AICAR on liver tissue of HIRI rats was significantly reversed． Conclusion PGC-1α mediated mitochondri- al biosynthesis is involved in the regulation of AMPK agonist-mediated protective effect of HIRI，and its mechanism may be related to the activation of AMPK/ mTOR signaling pathway．

Objective To evaluate the correlation between positive end-expiratory pressure (PEEP) level and postoperative pulmonary complications (PPCs) in patients undergoing thoracoscopic lung surgery. Methods The clinical data of patients who underwent elective thoracoscopic lung surgery at West China Hospital of Sichuan University from January 2022 to June 2023 were retrospectively analyzed. Patients were divided into 2 groups according to intraoperative PEEP levels: a PEEP 5 cm H2O group and a PEEP 10 cm H2O group. The incidence of PPCs in the two groups after matching was compared using a nearest neighbor matching method with a ratio of 1∶1, setting the clamp value as 0.02. Results A total of 538 patients were screened, and after propensity score-matching, a total of 229 pairs (458 patients) were matched, with an average age of 53.9 years and 69.4% (318/458) females. A total of 118 (25.8%) patients had PPCs during hospitalization after surgery, including 60 (26.2%) patients in the PEEP 5 cm H2O group and 58 (25.3%) patients in the PEEP 10 cm H2O group, with no statistically significant difference between the two groups [OR=0.997, 95%CI (0.495, 1.926), P=0.915]. Multivariate logistic regression analysis showed that PEEP was not an independent risk factor for PPCs [OR=0.920, 95%CI (0.587, 1.441), P=0.715]. Conclusion For patients undergoing thoracoscopic lung surgery, intraoperative PEEP (5 cm H2O or 10 cm H2O) is not associated with the risk of PPCs during hospitalization after surgery, which needs to be further verified by prospective, large-sample randomized controlled studies.

OBJECTIVE To establish a method to detect the blood concentration of ibrutinib and apply it to the clinic. METHODS Using zanubrutinib as internal standard， the concentration of ibrutinib was detected by high performance liquid chromatography （HPLC） after plasma samples were processed by solid-phase extraction. The separation was performed on an Agilent 5 TC-C18（2） column with acetonitrile-0.5% potassium dihydrogen phosphate solution （43∶57， V/V） as the mobile phase at a flow rate of 1 mL/min， a detection wavelength of 260 nm， a column temperature of 40 ℃ ， a sample size of 20 μL， and a run time of 25 min. The concentration of ibrutinib was measured in the plasma of 9 patients with non-Hodgkin’s lymphoma 2 h after drug administration on the 30th day by the above method. RESULTS The linear range of the assayed mass concentration of ibrutinib was 10-500 ng/mL （R 2＝0.998 9）， the lower limit of quantification was 10 ng/mL， and the RSDs of the intra-batch and inter-batch precision tests were not higher than 12.77%. The recoveries of the extraction were 74.80% and 97.70%， with both RSDs＜2.90%， and the RSDs of the stability tests were not higher than 7.10%. The peak plasma concentrations of 9 patients were 15.341-279.628 ng/mL. CONCLUSIONS The established HPLC method is simple and rapid， and can be used for the determination of ibrutinib concentration in plasma samples.

Objective:To identify the risk factors for postoperative pulmonary complications (PPCs) after thoracoscopic lung resection and evaluate the predictive value for the development of PPCs.Methods:The perioperative data of patients, aged≥18 yr, of American Society of Anesthesiologists (ASA) physical statusⅠ-Ⅲ, were obtained through the electronic medical record system.The blood routine within 24 h after surgery was recorded, and systemic immune-inflammation index (SII) was calculated.According to the development of PPCs, the patients were divided into non-PPCs group and PPCs group.Multivariate logistic regression analysis was used to analyze the variables of which P values were less than 0.05 to identify the risk factors for PPCs, and the receiver operating characteristic curve was drawn to evaluate the predictive value of risk factors. Results:A total of 699 patients were enrolled in this study, including 620 patients in non-PPCs group and 79 patients in PPCs group.The results of logistic regression analysis found that body mass index ≥25 kg/m 2, ASA physical status Ⅲ, lung segmental resection, resection of lobes or above, multi-port thoracoscopic surgery and increased postoperative SII were the risk factors for PPCs ( P<0.05 or 0.01). The AUC (95% confidence interval) of postoperative SII in predicting PPCs was 0.636 (0.599-0.671) ( P<0.05), the cut-off value of SII in predicting PPCs was set at 1 052.3, and the sensitivity and specificity were 68.4% and 57.3%, respectively. Conclusions:Body mass index ≥25 kg/m 2, ASA physical status Ⅲ, lung segmental resection, resection of lobes or above, multi-port thoracoscopic surgery and increased postoperative SII are the risk factors for PPCs.Postoperative SII can predict the occurrence of PPCs to a certain extent in the patients undergoing thoracoscopic lung resection.

Objective:To investigate the value of CT findings of childhood hepatoblastoma (HB) in predicting preoperative tumor risk stratification.Methods:Totally 46 children with HB confirmed by surgery and pathology were retrospectively enrolled from October 2010 to October 2019 in Shenzhen Children′s Hospital and Xuzhou Children′s Hospital. The preoperative abdominal plain CT and three-phasic contrast-enhanced CT with complete clinical files were evaluated. According to the clinical risk stratification established by the multidisciplinary diagnosis and treatment consensus for children with HB, the HB children were divided into high-risk group and non-high-risk group with 16 and 30 cases respectively. The maximum diameter of tumor, relative tumor volume index, cystic change or necrosis, bleeding, calcification, fibrous septations, tumor rupture, liver capsule retraction and subcapsular effusion were evaluated. Enhancement percentage and enhancement index on arterial, venous and delayed phases of each tumor were measured and calculated. Pearson′s χ 2 test or Fisher′s exact test were used to compare the differences in gender and lesion morphological characteristics between the high-risk group and the non-high-risk group. Two independent sample t test or Mann-Whitney U test were used to compare the differences in age, gestational age, birth weight, α-fetoprotein, platelets, maximum diameter of tumor, relative tumor volume index and CT parameters of the lesion between the two groups. Statistically significant features were included in the binary logistic regression analysis and independent predictors related to high-risk group were obtained. The ROC curve was used to determine the critical value of the high-risk group. Results:There were statistically significant differences in age, maximum diameter of tumor, relative tumor volume index and tumor rupture between the high-risk group and the non-high-risk group (all P<0.05). The logistic regression analysis showed that the maximum diameter of tumor (OR=1.906, P=0.004) and tumor rupture (OR=16.558, P=0.005) were risk factors of the high-risk group. Based on ROC curve, the optimum cut-off point of maximum diameter of tumor to predict high-risk group was 10.5 cm. Tumor rupture, maximum diameter of tumor and maximum diameter of tumor combined with tumor rupture for predicting the incidence of high-risk group resulted in the area under the curve of 0.744, 0.807 and 0.879, respectively. The sensitivity and specificity of maximum diameter of tumor combined with tumor rupture were 75.0% and 96.7%, respectively. Conclusion:The age of onset in high-risk group is relatively older. The maximum diameter of tumor greater than 10.5 cm accompanied by tumor rupture can be regarded as a high-risk sign.

Objective To discuss the image characteristics of enlarged prostatic utricle in children.Methods 13 children with enlarged prostatic utricle were retrospectively analyzed,6 of whom checked by voiding cystic urethrography (VCUG),5 of whom by MRI,2 of whom by both VCUG and MRI.Results 8 cases with VCUG showed round-like or long circle utricle filled with contrast media located in the rear posterior urethra.Among them,3 cases showed the tubiform between utricle and posterior urethra.The other 5 cases displayed overlap between utricle and urethra,and there was no tubiform between utricle and posterior urethra.7 cases with MRI showed oblong cyst at the right rear middle of the bladder that showed low signal with T1 weighted image and high signal with T2 weighted image,crossing the center of prostate gland.Among them,5 cases showed the communication between oblong cyst and posterior urethra.Also,among them,5 cases were associated with the orchitis,epididymis phlogistic,scrotal phlogistic,and 1 case showed the right renal agenesis.Conclusion The VCUG and MRI are helpful to check enlarged prostatic utricle in children.They have different advantages in different aspect.

Objective:To assess the changing trends in Gleason score (GS)of Chinese prostate carci-noma (PCa)from January 1995 to December 2014.Methods:In the study,875 patients admitted to hospital from January 1995 to December 2004 (1995 -2004)and from January 2005 to December 2014 (2005 -2014)were divided into two groups.The mean levels and proportions of GS,primary and se-condary grades were studied.The patients were divided into four groups according to age: <60,60 -69,70 -79 and ≥80 years.Types of specimen included needle biopsy (NB),transurethral resection of the prostate (TURP)and radical prostatectomy (RP).Histological types were made up by acinar carci-noma and other types (including atrophic,pseudohyperplastic,foam,signet ring cell and ductal carcino-ma,and so on).The total prostate-specific antigen (tPSA)involved groups of <20.0 μg/L and ≥20.0 μg/L.We observed the mean levels and proportions of GS in age,types of specimen,histological types and total prostate-specific antigen in different periods,and used SPSS 17.0 software for statistical analysis.Results:Compared with 1995 -2004,the mean levels of GS,primary and secondary grades decreased 0.32 (P =0.003),0.19 (P =0.001)and 0.12 (P =0.016)in 2005 -2014,respectively. The proportions of ≤6 in GS increased 10.9% (P =0.003),and ≥8 decreased 14.0% (P <0.001). The difference of GS 7 was not statistically significant.In the primary grade,the ratio of grades≤3 in-creased 12.8% (P =0.001 ),and grade 4 decreased 7.4% (P =0.037),grade 5 decreased 5.5%(P =0.007).The ratio of secondary grades≤3 increased 7.6% (P =0.037).The difference of grades 4 and 5 was not statistically significant.Conclusion:GS in Chinese patients with PCa showed a down-ward trend,which is one of the notable features in the past 20 years in China.The types of specimen and age are important factors in GS,while the histological types and tPSA have less impact on the GS.

Reduced responsiveness to reward stimuli is a central feature of major depressive disorder (MDD). Study on the changes of neural substrates and behavior contributes to understand the mechanism of MDD. Functional magnetic resonance imaging (fMRI) has the unique advantage of investigating reward processing, which is of importance in the brain imaging study. The progresses of event-related fMRI (ER-fMRI) in field of rewarding stimuli in major depressive disorder were reviewed in this article.