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 investigate the effect of SerpinA5 on the malignant biological behavior of esophageal squamous cell carcinoma (ESCC) and its molecular mechanism. Methods The expression levels of the SerpinA5 gene in various tumors and adjacent normal tissues were analyzed by using the TIMER2.0 database. The expression levels of SerpinA5 in the ESCC cell line and esophageal epithelial cells were detected through Western blot analysis. Stably transfected KYSE150 cell line with overexpression of SerpinA5 was constructed through lentiviral transfection, and overexpression efficiency was detected via Western blot analysis. The effects of SerpinA5 overexpression on the proliferation, apoptosis, migration, and invasion of ESCC cells were detected by employing the CCK8, plate cloning, flow cytometry, wound healing, and Transwell invasion assays. The nude mice subcutaneous xenograft model with SerpinA5 overexpression was constructed. Tumor growth was observed, and tumor volume and mass were measured. The cell proliferation level of the subcutaneous xenograft tumors in nude mice was detected via immunohistochemistry (IHC). Coimmunoprecipitation (Co-IP) was employed to determine the interaction between SerpinA5 and Fn. Western blot analysis was applied to detect the expression levels of proteins (Fn, Integrin-β1, FAK, and p-FAK) related to the Fn/Integrin-β1 signaling pathway in transplanted tumors. Results SerpinA5 was expressed at low levels in ESCC tissues and cell lines. In ESCC cells, SerpinA5 overexpression can considerably inhibit cell proliferation, migration, and invasion and promote cell apoptosis. In the subcutaneous xenograft experiment on nude mice, the tumor volume and weight of the SerpinA5 overexpression group were lower than those of the negative control group. IHC results demonstrated that SerpinA5 overexpression significantly inhibited the proliferation of ESCC cells in tumor tissues. Co-IP confirmed the interaction between SerpinA5 and Fn. Western blot analysis results showed that the expression levels of Fn, Integrin-β1, and p-FAK in the Fn/Integrin-β1 signaling pathway of ESCC cells in the subcutaneous xenograft tumors of nude mice significantly decreased after SerpinA5 overexpression. Conclusion Serpin A5 may inhibit proliferation, migration, and invasion and promote apoptosis of ESCC cells by regulating the Fn/Integrin-β1 signaling pathway.

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 clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Objective:To clarify the changes in incidence and mortality of various cancers based on analysis on registration data of malignant tumor incidence and mortality from Dehui City and Yanji City in Jilin Province.Methods:The incidence and mortality data of malignant tumors from 2009 to 2016 in Dehui City and Yanji City in Jilin Province,were collected from the Chinese Cancer Registry Annual Report published by the National Cancer Center.The number of cases,deaths,crude incidence rate,crude mortality rate,age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and annual percentage change(APC)of the malignant tumors were analyzed by cancer sites and genders.Results:From 2009 to 2016,the CIR of malignant tumors in Dehui City(APC=1.2%,P=0.019)and Yanji City(APC=3.6%,P=0.058)showed an increasing trend.After standard population age adjustment,the ASIR in males in Dehui City showed a significant decline(APC=-5.7%,P=0.021),while the ASIR in females exhibited an overall downward trend,but the difference was not significant(APC=-2.2%,P=0.111).In Yanji City,the ASIR in males(APC=-1.4%,P=0.535)and females(APC=0.0%,P=0.988)showed no significant changes.The CMR of malignant tumors in Dehui City(APC=1.9%,P=0.001)and Yanji City(APC=5.9%,P=0.001)showed a continuous upward trend.After age-standardization,the ASMR in males(APC=-3.1%,P=0.100)and females(APC=-4.2%,P=0.053)in Dehui City,as well as in males(APC=-1.3%,P=0.438)in Yanji City,showed a slight downward trend.Although the ASMR in females in Yanji City showed a slight increase,the difference was not statistically significant(APC=0.5%,P=0.838).In 2016,the most common malignant tumor in terms of both incidence and mortality in Dehui City was lung cancer,with a CIR of 60.76/100 000 and a CMR of 46.96/100 000.In Yanji City,the most common malignant tumor was liver cancer,with a CIR of 49.04/100 000 and a CMR of 51.09/100 000.Conclusion:Lung cancer,liver cancer,and gastric cancer are the major malignant tumors threatening residents in Dehui City,Yanji City,and even the entire Jilin Province,and should be prioritized in cancer prevention and control efforts.Early diagnosis and treatment should be strengthened.

The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Objective To observe the clinical efficacy of autologous hair follicle stem cell transplantation for hair restoration in patients with alopecia. Methods Ten patients with alopecia, including five with androgenic alopecia and five with seborrheic alopecia, were selected from November 2022 to May 2023. They were treated with autologous hair follicle stem cell transplantation. Data before treatment were used as the control group, and data after treatment were used as the study group. Follow-up was conducted for 3 to 8 months. The FPF scoring system was designed to collect data and evaluate the treatment effect. Results Nine patients had an improvement score of ≥7 points, and one patient had an improvement score of 2 points, with a treatment excellence rate of 90% (9/10). Compared with the total score of (2.81±0.92) points in the control group, the total score of the study group was (9.00±2.21) points, and the difference was statistically significant (P < 0.001). Conclusion Autologous hair follicle stem cell transplantation for hair restoration is safe and effective, and has a broad range of indications.

Objective:To evaluate the relationship between the mechanism by which aucubin improved attention deficit hyperactivity disorder (ADHD) induced by maternal exposure to S-ketamine and GABAergic neurons in the habenular nucleus of offspring mice.Methods:SPF healthy C57BL/6 wild-type pregnant mice were used in this study, and an ADHD model in offspring mice was established by intraperitoneally injecting S-ketamine in the middle and late pregnancy. Twenty-four offspring of pregnant mice exposed to S-ketamine were divided into 2 groups ( n=12 each) at 14 days after birth using a random number table method: ADHD + normal saline group (AN group) and ADHD + aucubin group (AA group). Twenty-four offspring of pregnant mice exposed to normal saline were divided into 2 groups ( n=12 each) at 14 days after birth by a random number table method: control + normal saline group (CN group) and control + aucubin group (CA group). Aucubin 40 mg/kg was intraperitoneally injected once a day for 7 consecutive days in CA group and AA group, and the equal volume of normal saline was given instead in CN group and AN group. At 14 days after birth, the 16-channel microfilament array electrode was placed in the habenular nucleus, and the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was recorded when the mice buried beads in the marble burying test. At 21 days after birth (after the end of peritoneal administration), the impulsive and stereotypical behaviors of offspring mice were evaluated by elevated zero maze and marble burying test, respectively, and then the expression of glutamate decarboxylase 2 (GAD2) in habenular nucleus was detected by the immunofluorescence method. Results:Compared with CN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly increased, the expression of GAD2 was down-regulated, the time spent in the open arm was prolonged, the number of entries into the open arm and the number of buried beads were increased in AN group ( P<0.05), and no statistically significant differences were found in the above indexes in CA group ( P>0.05). Compared with AN group, the ratio of excitatory neurons to inhibitory neurons in the habenular nucleus was significantly decreased, the expression of GAD2 was up-regulated, the time spent in the open arm was shortened, and the number of entries into the open arm and the number of buried beads were decreased in AA group ( P<0.05). Conclusions:The mechanism by which aucubin alleviates prenatal S-ketamine exposure-induced ADHD may be related to increasing the number of GABAergic neurons in the habenular nucleus of offspring mice.

The timely treatment of dental caries and pulp disease in primary teeth holds significant importance for maintaining children's oral health.Direct pulp capping(DPC)is a vital pulp treatment that involves covering the ex-posed pulp with bioactive materials to promote dentin bridge formation.DPC is commonly used in primary teeth with vi-tal pulp and mechanical pulp exposure not exceeding 1 mm.DPC offers advantages such as minimal invasiveness,com-fort,simplicity of operation and short chair-side time,making it suitable for pediatric dental clinical practice.Early stud-ies suggested negative treatment outcomes for DPC in primary teeth with carious pulp exposure.Over the years,there have been advancements in materials and technology demonstrating positive outcomes in the clinical research of prima-ry teeth with deep caries.However,due to the limited quality of related studies,DPC has not been widely recommended for the treatment of primary teeth with carious pulp exposure,and its widespread use needs further support by more high-quality evidence-based medical research.The success rate of DPC in primary teeth is influenced by factors including pulp status,clinical operations(such as isolation and caries removal),pulp capping material,cavity type,tooth position,coronal sealing,and dental fear.In clinical operation,dentists should accurately assess pulp status and minimize bacte-rial contamination.Mineral trioxide aggregate(MTA)is a DPC agent with relatively sufficient evidence and good thera-peutic effects,and the crown should be tightly sealed after pulp capping.Additionally,the effects of novel biocompati-ble materials such as iRoot BP Plus used in DPC of primary teeth,and the influence of other factors like hemostatic methods on the prognosis of affected teeth,need further exploration.