The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective:To investigate the effects of psychosocial factors on early puberty and its sex specific differences.Methods:Bengbu Yuhui Longitudinal Study of Children Development Cohort, consisting of 1 162 students in grades 1-3 (524 girls) and their parents, was established in April 2021 in Bengbu, Anhui Province. The parents were surveyed by questionnaire to collect the information about their children's 56 items of psychosocial factor exposures, including 5 dimensions: major life events, early life adversity, interpersonal/relational conflict, family economic status and daily life troubles. Pubertal growth and physical examinations were conducted by trained professionals at baseline, the 1 st (May 2022), 2 nd (October 2022), 3 rd (May 2023), and 4 th (October 2023) follow-up surveys. In this study, the pubertal development status data were from the 4 th follow-up examination. Fianally, the valid data on pubertal development of 1 105 children were obtained, including the data from 510 girls (46.15%). Multinomial logistic regression model was used to analyze the association between psychosocial factors and early puberty, and the final predictors of early puberty were explored by using four models [least absolute shrinkage and selection operator (LASSO), multiple logistic regression, ridge regression, and Bayesian]. Results:The detection rates of early puberty in boys and girls were 13.60% and 16.30%, respectively. The median of intra-group absolute correlation of psychosocial factor exposure (0.042-0.066) was generally higher than that of inter-group among girls (0.031-0.059), while no similar diference was found among boys. LASSO model showed that moving house, being raised by someone other than parents, sexual abuse, peer conflict, high monthly household income, and high exposure to electronics on school days were predictors of early puberty in girls, while moving house and high monthly household income were the predictors of early puberty in girls in all four models (LASSO, multiple logistic regression, ridge regression, and Bayesian). Among boys, only a transient loss from family was a predictor of early puberty.Conclusion:Early puberty in children can be predicted by psychosocial factors, and there are gender-specific differences.

Objective:To investigate the application of pedicled or perforator flaps transfer in the stage Ⅰ tissue defect repair after vulvar cancer surgery.Methods:From January 2005 to December 2023, 20 patients with vulvar cancer who underwent extensive episiectomy or extended episiectomy±inguinal lymph node resection+vulvar defect flap transfer were collected in Huanxing Cancer Hospital of Chaoyang District and Cancer Hospital and Peking Union Medical College, Chinese Academy of Medical Sciences. The survival status, appearance structure, sexual function satisfaction, tumor recurrence, and survival were analyzed.Results:(1) The median age of the 20 patients was 59 years (ranged: 29-73 years). There were 14 patients with recurrence and 6 patients with initial treatment. Pathological types: 14 cases of squamous cell carcinoma, 4 cases of Paget′s disease, 1 case of malignant melanoma, 1 case of adenoid cystic carcinoma (salivary gland type carcinoma). (2) Among the 20 patients, 6 cases underwent extensive episiotomy and 14 underwent extended episiotomy (1 of them underwent extensive excision of inguinal masses). Simultaneous inguinal lymphadenectomy (or dissection) were performed in 11 cases, including 7 cases of bilateral inguinal lymph node resection (or dissection) and 4 cases of unilateral inguinal lymph node resection (or dissection). Flap source: pedicled flap in 12 cases, perforator flap in 8 cases. All the 20 patients were removed at 10-14 days after operation, and all of them survived with rosy skin color and good elasticity. Seventeen cases of transferred flaps healed at stage Ⅰ, 2 cases healed at about 6 weeks due to incision leakage, and 1 case healed at 6 weeks after incision infection debridement. Six months after the operation, 2 cases felt that the pubic mound was thick and swollen. The other 18 cases showed vulva fullness and elasticity, no displacement of urethral opening, no deviation of urethra during urination, no stenosis of vaginal opening, no vulvar scar pain. In addition to 1 unmarried 29-year-old patient and 6 patients over 65 years old who had no sexual life before and after surgery, the other 13 patients had normal sexual life after surgery. (3) The follow-up period were 6 to 100 months, and 9 cases (45%, 9/20) relapsed during the follow-up period. There were 5 deaths (25%, 5/20), who were due to recurrence of vulvar cancer. The 5-year survival rate of 20 patients was 75%, including 83% in 6 patients with initial treatment and 71% in 14 patients with recurrence and reoperation.Conclusions:The combination of flap transfer for episioplasty with vulvar cancer surgery does not affect the wound healing. Because the external structure of the vulva is repaired, it could effectively improve the local wound healing ability and improve the organ function, and has good clinical application value.

Objective:To evaluate the value of preoperative triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio in predicting postoperative delirium (POD) following internal fixation for lower limb fracture in geriatric patients.Methods:In this retrospective case-control study, the medical records of patients, aged ≥ 65 yr, with American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, who underwent internal fixation for lower limb fracture under general anesthesia or spinal-epidural anes-thesia at Hebei General Hospital from January 2023 to July 2024, with the postoperative length of hospital stay of at least 3 days, were collected. The baseline characteristics, preoperative length of hospital stay, parameters of the last preoperative laboratory tests, type of surgery, anesthesia method, duration of surgery and anesthesia, and intraoperative hypotension and fluid intake and output were collected, and the ratio of TG to HDL-C was calculated. Patients were stratified into POD group and non-POD group based on whether POD developed. The logistic regression was carried out to identify influencing factors for POD. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive accuracy of preoperative TG/HDL-C ratio in predicting POD.Results:A total of 234 patients were finally included, of whom 30 developed POD, with an incidence of 12.8%. The results of multivariate logistic regression indicated that the elevated preoperative TG/HDL-C ratio, increased WBC count and a history of cerebrovascular disease were independent risk factors for POD, and the increased albumin concentration was an independent protective factor for POD ( P<0.05). The area under the curve of preoperative TG/HDL-C ratio in predicting POD was 0.758, with a specificity of 0.809 and sensitivity of 0.633, and the optimal cut-off value was 3.285 ( P<0.001). Conclusions:Elevated preoperative TG/HDL-C ratio is an independent risk factor for POD and may have a certain predictive value for POD in geriatric patients undergoing internal fixation for lower limb fracture.