Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Objective To investigate the distribution characteristics of pathogens causing infections within 90 days after liver transplantation and the influencing factors of infection. Methods Clinical data of 176 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital Affiliated to Capital Medical University from September 2021 to August 2024 were retrospectively analyzed. Patients were divided into the infection group (n=124) and the non-infection group (n=52) based on whether they developed infection within 90 days after transplantation. The distribution characteristics of pathogens in infected patients were analyzed. Univariate and multivariate logistic regression analyses were used to explore the influencing factors of infection. Results Among the 176 liver transplant recipients, 124 cases developed 243 episodes of 518 bacterial, fungal, viral or mycoplasma infections within 90 days after transplantation, with an overall infection rate of 70.5% (124/176). The composition of pathogens was mainly Gram-negative bacteria (38.6%, 200/518), followed by Gram-positive bacteria (32.2%, 167/518) and viruses (15.4%, 80/518), and fungi accounted for 13.1% (68/518). Among Gram-negative bacteria, the main pathogen was Klebsiella pneumoniae (6.8%, 35/518), and among Gram-positive bacteria, the main pathogen was Enterococcus faecalis (8.5%, 44/518). Viruses included Epstein-Barr virus (3.7%, 19/518) and cytomegalovirus (3.7%, 19/518), and fungi were mainly Candida albicans (6.8%, 35/518). The most common infection site among the 243 episodes was pulmonary infection (42.0%, 102/243), followed by abdominal infection (22.6%, 55/243) and bloodstream infection (18.1%, 44/243). The infections mainly occurred within 2 weeks after transplantation (60.9%, 148/243). Multivariate logistic regression analysis indicated that preoperative infection within 2 weeks, a high preoperative model for end-stage liver disease (MELD) score, and preoperative sarcopenia were independent risk factors for infection within 90 days after liver transplantation (all odds ratio>1, P<0.05). After multivariate correction, the levels of CD4⁺T cells and CD8⁺T cells within 90 days after surgery were independently associated with the occurrence of infection. Low levels of CD4⁺T cells and CD8⁺T cells might be related to an increased risk of infection. Conclusions The infection rate after liver transplantation is high, and the pathogens are mainly Gram-negative bacteria. The lungs are the most common infection site. Preoperative MELD score, preoperative sarcopenia and preoperative infection within 2 weeks are independent risk factors for infection within 90 days after liver transplantation. Regular monitoring of immune indicators CD4⁺T cells and CD8⁺T cells levels after transplantation is helpful to reduce the occurrence of post-transplantation infection.

OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

OBJECTIVE To systematically evaluate the correlation between dynamic changes in inflammatory markers during treatment with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） in non-small cell lung cancer （NSCLC） patients and therapeutic efficacy， with the aim of providing evidence-based support for clinical prognosis assessment and treatment strategy adjustment. METHODS Databases including PubMed， Embase， Cochrane Library， CNKI， Wanfang Data， and CBM were searched from the inception to July 20， 2025. Following literature screening， data extraction and quality assessment， descriptive analysis was conducted on the outcomes of included studies. RESULTS A total of eight studies were included to analyze the correlation of 6 inflammatory markers before and after treatment with EGFR-TKIs with therapeutic efficacy. The risk of bias assessment identified six high-quality studies and two moderate-quality studies. Among these studies， seven studies demonstrated that lower levels of neutrophil-to-lymphocyte ratio （NLR）， derived neutrophil-to-lymphocyte ratio （dNLR）， platelet-to-lymphocyte ratio （PLR）， and monocyte-to-lymphocyte ratio （MLR）， higher lymphocyte-to-monocyte ratio （LMR） before treatment， as well as decreased NLR and MLR and increased LMR after treatment were associated with longer median progression-free survival. Five studies indicated that lower levels of NLR， dNLR， PLR， and interleukin-6 （IL-6）， higher LMR before treatment as well as decreased NLR and dNLR and increased LMR were associated with longer median overall survival. Three studies indicated that lower levels of IL-6 were associated with a higher objective response rate， while the association of these markers after treatment remained controversial； another study showed that an early decline in NLR， MLR， and PLR after treatment may be associated with objective response benefit. CONCLUSIONS Lower inflammatory levels during EGFR-TKIs therapy correlate with better therapeutic efficacy in NSCLC patients.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Objective To observe the ultrasonic manifestations of abdominal pregnancy.Methods Ultrasonic and clinical data of 18 pregnant woman with abdominal pregnancy diagnosed by operation and pathology were retrospectively analyzed.Results Among 15 cases in first trimester,no preoperative ultrasonic diagnosis of abdominal pregnancy was obtained.Ultrasound showed no gestational sac in uterine cavity but mass in pelvic cavity,which located in the adnexal region in 8 cases,in the front and the post of uterus each in 2 cases,while in the adnexal region and the front of uterus in 1 case,in the post of the cervix in 1 case,and closed to uterine wall in 1 case,without obvious tubal echo around mass in all 15 cases.There were 2 cases of abdominal pregnancy in the second trimester,which were first diagnosed with ultrasound at 13+6 weeks and 21 weeks,with gestational sac located on the left side of uterus and behind the uterus,respectively.One case of abdominal pregnancy in the third trimester was first diagnosed with ultrasound at 35 4 weeks,with gestational sac located on the right side of uterus.Ultrasonic manifestations of the above three cases all showed gestational sac located outside the uterus without myometrium wrapping around the gestational sac nor placenta implanted in uterus,while echoes of fluid accumulation were detected around fetus.The ultrasonic diagnosis rate of abdominal pregnancy was 16.67％(3/18).Conclusion In the first trimester,if the ectopic pregnancy mass was large or the gestational sac located adjacent to the cervix,anterior or posterior to uterus and on the uterine wall,also no fallopian tube-like echo around the mass,the possibility of abdominal pregnancy should be considered.Ultrasonic manifestations of abdominal pregnancy in the second and third trimester present as gestational sac outside uterine cavity without wrapping uterine muscle layer around,no placenta implantation in uterine cavity,as well as echoes of fluid accumulation around fetus.Transabdominal combined with transvaginal ultrasound could improve diagnostic rate of abdominal pregnancy.

Objective:To analyze the efficacy of endovascular treatment for venous outflow tract obstruction after liver transplantation.Methods:A retrospective analysis was conducted on the data of 7 patients with venous outflow tract obstruction after liver transplantation admitted to Beijing Friendship Hospital, Capital Medical University from November 2020 to December 2024. Among them, there were 5 males and 2 females, with the age of (22.3±8.1) years. The primary diseases included 2 cases of Budd-Chiari syndrome, 1 case of hepatic veno-occlusive disease, 1 case of portal veno-hepatic sinus vascular disease, 1 case of ornithine carbamoyltransferase deficiency, 1 case of primary biliary cirrhosis, and 1 case of autoimmune cirrhosis. Analyze the patient's clinical manifestations, obstruction of venous outflow tract, hemoglobin levels within one week before and one week after the operation, endovascular treatment conditions, and intraoperative complications such as abdominal hemorrhage and vascular injury. Ultrasound was used to measure the depth of ascites and pleural effusion. All patients were followed up immediately after the operation through phone calls or follow-up visits. The clinical symptoms, abdominal vascular ultrasound, enhanced CT and survival status of the patients were followed up.Results:All 7 patients were diagnosed with venous outflow tract obstruction by intraoperative angiography, including 1 cases of inferior vena cava obstruction, 2 cases of hepatic vein obstruction, and 4 cases of vena cava combined with hepatic vein obstruction. A total of 12 endovascular treatments were performed on 7 patients. Among them, 4 patients received balloon dilation and angioplasty once, 1 patient received balloon dilation and angioplasty twice, 1 patient underwent hepatic vein stent implantation after 2 hepatic vein balloon dilation and angioplasty, and 1 patient underwent intrahepatic portosystemic shunt via jugular vein after 2 hepatic vein balloon dilation and angioplasty. The abdominal distensionof the patients were all relieved after the operation, the ascites and pleural effusion decreased, and the edema symptoms of the lower extremities disappeared. There were no intraoperative complications. The preoperative hemoglobin of 7 patients was (113.4±34.0) g/L, and the postoperative hemoglobin was (126.6±34.8) g/L, which increased significantly compared with that before the operation, and the difference was statistically significant ( t=-0.71, P=0.038). Seven patients were followed up for 6 to 24 months, with a median of 12 months. None of them had obvious symptoms including abdominal distension. Abdominal ultrasound and CT indicated that the blood flow of the transplanted liver was unobstructed, and no patient died. Conclusion:Venous outflow tract obstruction after liver transplantation can cause severe symptoms. Endovascular treatment is an effective treatment for venous outflow tract obstruction after liver transplantation.

Objective:To investigate the expression characteristics of Zeste enhancer of Zeste homolog 2 (EZH2) in breast cancer tissue and its influence on tumor progression and prognosis.Methods:Transcriptome data of breast cancer tissue and normal breast tissue adjacent to cancer as well as clinical data of patients were obtained from the cancer genome atlas (TCGA) database, gene expression comprehensive database and European genome phenotype archives database, and the difference of EZH2 expression was analyzed using TIMER 2.0 platform. The survival information of breast cancer patients was obtained from the Kaplan Meier Plotter database, and the overall survival time, relapse free survival time and distant metastasis free survival time of breast cancer patients with low EZH2 expression and high EZH2 expression were compared. Select 14 nude mice were selected and randomly divided into si-EZH2 group and control group, with 7 mice in each group.MCF7 culture suspensions transfected with EZH2 knockdown plasmid and control plasmid were inoculated for corresponding group. The body mass and tumor volume of two groups of nude mice inoculated with MCF7 cells were compared at different times. On the 28th day, the nude mice were euthanized and the tumors were dissected to compare the tumor mass of the two groups of nude mice. The normally distributed quantitative data was represented by xˉ ± s. Two independent sample t-tests were used for comparison between two groups, repeated measures ANOVA was used for comparison of body mass and tumor volume between two groups of nude mice at different times, and Bonferroni test was used for pairwise comparison. The comparison of survival rates was conducted using log rank test. Results:A total of 1085 breast cancer tissues and 291 normal adjacent breast tissues were included in the TCGA database. EZH2 expression in breast cancer tissues was higher than that in normal adjacent breast tissues ( P<0.05). In the Kaplan Meier Plotter database, the total survival time, relapse free survival time, and distant metastasis free survival time of breast cancer patients in the EZH2 overexpression group were shorter than those in the EZH2 low expression group ( P=0.013, <0.001, <0.001). After 7 days of inoculation with MCF7 culture suspension, significant subcutaneous tumors were observed on the left back of both groups of nude mice. On the first day, there were no statistically significant difference in body mass between the two groups of nude mice ( P>0.05); On day 7, 13, 19, 25, and 28, the body mass and tumor volume of both groups of nude mice gradually increased (nude mouse body mass: within group F=29.31, P<0.001, between groups F=234.32, P<0.001, Finteraction=16.83, P<0.001; Tumor volume: within group F=34.00, P<0.001, between groups F=193.17, P<0.001, Finteraction=35.61, P<0.001). And the body mass of the siEZH2 group nude mice was higher than that of control group (all P<0.05). On days 19, 25, and 28, tumor the volume of the siEZH2 group nude mice was smaller than that of control group (all P<0.05). On the 28th day, the mass of tumors dissected in the siEZH2 group of nude mice was lower than that in the control group [(0.30±0.07) g vs. (0.61±0.14) g, t=5.16, P<0.001]。 Conclusions:EZH2 is highly expressed in breast cancer tissues and is significantly associated with poor prognosis. Knockdown of EZH2 can significantly inhibit the proliferation and tumor formation of breast cancer cells.

Objective:To evaluate the factors influencing test failure after resampling in non-invasive prenatal testing (NIPT) and to explore its impact on pregnancy outcomes.Methods:The information of pregnant women who failed to undergo NIPT for the first time and resampled for testing in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to January 2022 were collected and retrospectively analyzed. According to the results of resampled NIPT, the pregnant women were divided into the failure group (170 cases) and the success group(485 cases), and the general clinical data and pregnancy outcomes of the two groups were compared.Results:(1) A total of 88 928 pregnant women underwent NIPT in Beijing Obstetrics and Gynecology Hospital during the study period, of which 1 299 (1.461%, 1 299/88 928) failed in the first NIPT. Among the 1 299 pregnant women who failed in the first NIPT, 720 were resampled for testing. Finally, 655 pregnant women who met the inclusion criteria and had complete clinical information and perinatal outcomes were collected. The success rate of resampling was 74.0% (485/655). Compared with the success group, the pregnant women in the failure group had a later gestational age at resampling, a higher pre-pregnancy body mass index (BMI) and a higher fetal fraction, and the differences were statistically significant (all P<0.001). (2) Among the 485 pregnant women in the success group, 130 cases (26.8%, 130/485) were detected with chromosome aneuploidy. Among the 170 pregnant women in the failure group, 8 cases had abnormal amniocentesis, 2 cases had abnormal maternal serum screening of aneuploidy in the second trimester, 3 cases had abnormal ultrasound anomaly removal, and 157 cases had no abnormality. (3) The incidence of fetal or neonatal malformation in the failure group was significantly higher than that in the success group [11.2% (19/170) vs 5.8% (28/485), P=0.019], but after adjusting for age and pre-pregnancy BMI, fetal or neonatal malformation was not associated with the success of resampling ( RR=0.675, 95% CI: 0.346-1.319; P=0.250). The incidences of gestational diabetes mellitus and hypertensive disorders in pregnancy in the failure group were significantly higher than those in the success group (all P<0.05), but after adjusting for age and pre-pregnancy BMI, only the incidence of gestational diabetes mellitus in the failure group was higher ( RR=0.630, 95% CI: 0.426-0.932; P=0.021). Conclusions:For pregnant women who failed the initial NIPT, the success of the resampling test is associated with pre-pregnancy BMI and the gestational week at the time of resampling. Those who failed the resampling test are more likely to develop gestational diabetes mellitus. When providing genetic counseling for pregnant women who failed the initial NIPT, it is important to consider the successful rate of resampling testing. The risk of chromosomal abnormalities should be comprehensively considered to develop further screening strategies.

Inflammaging is a process of cellular dysfunction associated with chronic inflammation, which plays a significant role in the onset and progression of liver diseases. Research on its mechanisms has become a hotspot. In viral hepatitis, inflammaging primarily involve oxidative stress, cell apoptosis and necrosis, as well as gut microbiota dysbiosis. In non-alcoholic fatty liver disease, inflammaging is more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, gut microbiota dysbiosis, and abnormalities in NAD⁺ metabolism. In liver tumors, inflammaging is characterized by weakening of tumor suppressive mechanisms, remodeling of the liver microenvironment, metabolic reprogramming, and enhanced immune evasion. Therapeutic strategies targeting inflammaging have been developing recently, and antioxidant therapy, metabolic disorder improvement, and immunotherapy are emerging as important interventions for liver diseases. This review focuses on the mechanisms of inflammaging in liver diseases, aiming to provide novel insights for the prevention and treatment of liver diseases.
Humans ; Liver Diseases/pathology* ; Inflammation ; Oxidative Stress ; Non-alcoholic Fatty Liver Disease ; Liver Neoplasms ; Gastrointestinal Microbiome