Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

[Objective] To analyze the prevalence of human T-lymphocyte leukemia virus (HTLV) among blood donors in Guangzhou from 2016 to 2021, and provide a basis for blood collection and supply management in this region. [Methods] A total of 2 116 951 voluntary blood donors were screened for anti-HTLV by enzyme-linked immunosorbent assay (ELISA) from March 2016 to December 2021 in Guangzhou, and the reactive cases were further confirmed by Western blotting (WB). Qualitative data were analyzed by χ2 with spss19 software. The trend of the total positive rate of HTLV confirmation test by WB from 2016 to 2021 was analyzed with the Joinpoint software, and the annual percent change (APC) was used to determine whether the trend changes were statistically significant. [Results] From March 2016 to December 2021, the total positive rate for anti-HTLV by ELISA among voluntary blood donors in Guangzhou was 0.019 7% (416/ 2116 951), and the WB confirmed positive rate was 0.001 1% (23/2 116 951). The total positive rate of HTLV among individual voluntary blood donors in the six main districts (0.002 12%, 19/895 301) was higher than that among group voluntary blood donors (0.000 32%, 3/951 947) (P<0.05). There was no significant difference in the total positive rate of HTLV confirmation between the six main districts (0.001 19%) and the three non-main districts (0.000 37%) (P>0.05). The trend of the total positive rate of HTLV infection in the six main districts and the Guangzhou area(including the six main districts and three non-main districts) showed no significant increase or decrease. [Conclusion] The prevalence of HTLV among blood donors in Guangzhou remains at a low level.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Background: In the absence of significant pleural effusion, conventional medical thoracoscopy (MT) is often not feasible due to the risk of lung injury. Dry MT mitigates these risks by inducing artificial pneumothorax through needle insufflation or blunt dissection. Although the Veress needle is commonly used by surgeons to create pneumoperitoneum before laparoscopic surgeries, its application in dry MT has not been widely reported in recent times. Methods: We report on a series of 31 patients who underwent dry MT with artificial pneumothorax induction using Veress needle under thoracic ultrasonography (TUS) guidance. A procedure was considered technically successful if it met all the following criteria: successful pneumothorax induction, allowing smooth insertion of the semi-rigid thoracoscope; absence of immediate significant procedural-related complications; and no delayed complications such as persistent air leaks, defined as leakage lasting more than 5 days necessitating extended chest tube placement. Results: Complete pneumothorax induction was achieved in 25 cases, resulting in an 80.6% technical success rate; however, biopsies were successfully performed in all cases. The most frequent histopathological diagnoses were malignancy (n=9, 29.0%), followed by inflammatory pleuritis (n=8, 25.8%) and tuberculosis (n=8, 25.8%). No procedural complications were reported. Conclusion These results indicate that TUS-guided dry MT utilizing a Veress needle is technically feasible and secure when performed by experienced MT practitioners in TUS.

OBJECTIVE: To explore clinical efficacy of percutaneous endoscopic discectomy with a lateral approach and dual-channel method in treating highly free lumbar disc herniation(LDH). METHODS: A retrospective analysis was conducted on 54 patients with highly free LDH who were treated with spinal endoscopic techniques from January 2021 to December 2022. Twenty-seven patients were treated with lateral approach dual-channel(lateral approach dual-channel group), including 16 males and 11 females, with an average age of (54.6±10.5) years old. Twenty-seven patients were treated with unilateral biportal endoscopic (UBE group), including 17 males and 10 females, with an average age of (52.9±12.3) years old. The number of intraoperative fluoroscopy, operation time and hospital stay, as well as visual analogue scale (VAS) and Oswestry diability index (ODI) of low back and leg pain between two patients before operation, 1 day, 1, 3, and 12 months after operation, and the efficacy was evaluated by the modified MacNab criteria at 12 mohths after operation. RESULTS: All patients were successfully completed surgical and were followed up, the time raged from 12 to 22 months with an average of (13.57±4.12) months. There was no statistically significant difference in operation time between two groups (P>0.05). The hospital stay of lateral approach dual-channel group was (3.9±1.1) days, which was shorter than that of UBE group (6.5±1.4) days, the number of intraoperative fluoroscopy in lateral approach dual-channel group was (12.7±2.1) times, which was more than that in UBE group (6.6±1.3) times, the differences were statistically significant (t=5.197, -7.532;P<0.05). VAS and ODI for low back pain at 1 day and 1 month after operation, and VAS for leg pain at 1 day after operation of lateral approach dual-channel group were superior to those of UBE group, and the differences were statistically significant (P<0.05). However, there were no statistically significant differences in VAS and ODI for low back and leg pain between two groups before operation and 3 and 12 months after operation (P>0.05). VAS and ODI of low back and leg pain were significantly improved at each time point before and after operation in both groups, and the difference were statistically significant (P<0.05). At 12 months after operation, according to the modified MacNab criteria, the excellent and good rates of therapeutic effects between lateral approach dual-channel group and UBE group were 92.6% (25/27) and 88.9% (24/27), respectively, and the difference was not statistically significant (χ²=0.22, P>0.05). CONCLUSION For patients with highly free lumbar intervertebral disc protrusion, both of lateral approach dual-channel method and UBE endoscopic surgery are safe and effective. Endoscopic surgery with lateral approach and dual-channel method could be performed under local anesthesia, allowing for the removal of the nucleus pulposus under direct vision. It is simpler, more efficient.
Humans ; Male ; Female ; Intervertebral Disc Displacement/surgery* ; Middle Aged ; Diskectomy, Percutaneous/methods* ; Lumbar Vertebrae/surgery* ; Endoscopy/methods* ; Adult ; Retrospective Studies ; Aged

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Background: In the absence of significant pleural effusion, conventional medical thoracoscopy (MT) is often not feasible due to the risk of lung injury. Dry MT mitigates these risks by inducing artificial pneumothorax through needle insufflation or blunt dissection. Although the Veress needle is commonly used by surgeons to create pneumoperitoneum before laparoscopic surgeries, its application in dry MT has not been widely reported in recent times. Methods: We report on a series of 31 patients who underwent dry MT with artificial pneumothorax induction using Veress needle under thoracic ultrasonography (TUS) guidance. A procedure was considered technically successful if it met all the following criteria: successful pneumothorax induction, allowing smooth insertion of the semi-rigid thoracoscope; absence of immediate significant procedural-related complications; and no delayed complications such as persistent air leaks, defined as leakage lasting more than 5 days necessitating extended chest tube placement. Results: Complete pneumothorax induction was achieved in 25 cases, resulting in an 80.6% technical success rate; however, biopsies were successfully performed in all cases. The most frequent histopathological diagnoses were malignancy (n=9, 29.0%), followed by inflammatory pleuritis (n=8, 25.8%) and tuberculosis (n=8, 25.8%). No procedural complications were reported. Conclusion These results indicate that TUS-guided dry MT utilizing a Veress needle is technically feasible and secure when performed by experienced MT practitioners in TUS.

Background: In the absence of significant pleural effusion, conventional medical thoracoscopy (MT) is often not feasible due to the risk of lung injury. Dry MT mitigates these risks by inducing artificial pneumothorax through needle insufflation or blunt dissection. Although the Veress needle is commonly used by surgeons to create pneumoperitoneum before laparoscopic surgeries, its application in dry MT has not been widely reported in recent times. Methods: We report on a series of 31 patients who underwent dry MT with artificial pneumothorax induction using Veress needle under thoracic ultrasonography (TUS) guidance. A procedure was considered technically successful if it met all the following criteria: successful pneumothorax induction, allowing smooth insertion of the semi-rigid thoracoscope; absence of immediate significant procedural-related complications; and no delayed complications such as persistent air leaks, defined as leakage lasting more than 5 days necessitating extended chest tube placement. Results: Complete pneumothorax induction was achieved in 25 cases, resulting in an 80.6% technical success rate; however, biopsies were successfully performed in all cases. The most frequent histopathological diagnoses were malignancy (n=9, 29.0%), followed by inflammatory pleuritis (n=8, 25.8%) and tuberculosis (n=8, 25.8%). No procedural complications were reported. Conclusion These results indicate that TUS-guided dry MT utilizing a Veress needle is technically feasible and secure when performed by experienced MT practitioners in TUS.

Background: In the absence of significant pleural effusion, conventional medical thoracoscopy (MT) is often not feasible due to the risk of lung injury. Dry MT mitigates these risks by inducing artificial pneumothorax through needle insufflation or blunt dissection. Although the Veress needle is commonly used by surgeons to create pneumoperitoneum before laparoscopic surgeries, its application in dry MT has not been widely reported in recent times. Methods: We report on a series of 31 patients who underwent dry MT with artificial pneumothorax induction using Veress needle under thoracic ultrasonography (TUS) guidance. A procedure was considered technically successful if it met all the following criteria: successful pneumothorax induction, allowing smooth insertion of the semi-rigid thoracoscope; absence of immediate significant procedural-related complications; and no delayed complications such as persistent air leaks, defined as leakage lasting more than 5 days necessitating extended chest tube placement. Results: Complete pneumothorax induction was achieved in 25 cases, resulting in an 80.6% technical success rate; however, biopsies were successfully performed in all cases. The most frequent histopathological diagnoses were malignancy (n=9, 29.0%), followed by inflammatory pleuritis (n=8, 25.8%) and tuberculosis (n=8, 25.8%). No procedural complications were reported. Conclusion These results indicate that TUS-guided dry MT utilizing a Veress needle is technically feasible and secure when performed by experienced MT practitioners in TUS.