Objective: To explore the diagnosis, treatment and prognosis of primary prostatic signet ring cell carcinoma (SRCC), so as to provide reference for the clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on the clinical data of 6 patients with primary prostatic SRCC treated in Nanjing Drum Tower Hospital during Nov.2020 and Sep.2024.The clinical manifestations, imaging features, treatment methods, histological characteristics and prognosis were summarized. Results: The average age of the patients was (72.00±4.28) years.Varying degrees of dysuria occurred in 4 patients. All patients underwent multi-parametric magnetic resonance imaging (mpMRI) examination before surgery, and the results indicated typical prostate cancer.Preoperative biopsies showed high-grade (Gleason 8-10) prostate acinar adenocarcinoma.Postoperative pathological diagnoses were mixed types of prostate acinar adenocarcinoma and SRCC, and no metastasis was found in the pelvic lymph nodes.All patients were followed up for 1 to 46 months after surgery and are currently alive.Robot-assisted laparoscopic radical prostatectomy only was performed in 3 cases; apalutamide and leuprolide/triptorelin was administered after surgery in 2 cases; bicalutamide + goserelin was administered after surgery in 1 case, who developed bladder metastasis of prostate cancer 24 months later, and the serum prostate-specific antigen (PSA) concentration decreased to a safe level (<0.2 ng/mL) after the use of darolutamide with radiotherapy.No recurrence or metastasis was found in the remaining patients. Conclusion: Primary prostatic SRCC is a rare and highly aggressive malignant tumor of the prostate.The diagnosis depends on pathological examinations due to lack of specific imaging features and clinical manifestations.The prognosis is poor, and there is currently no standardized treatment.The combined use of surgery, hormonotherapy and radiotherapy can help improve the survival rate of patients.

OBJECTIVE: To compare the diagnostic accuracy of supraspinatus muscle outlet X-ray film, oblique sagittal multislice helical CT (MSCT), and oblique sagittal MRI in the diagnosis of subacromial impingement syndrome (SIS). METHODS: A retrospective analysis was conducted on the imaging data of 106 patients diagnosed with SIS between January 2023 and December 2024. The cohort consisted of 32 males and 74 females, with ages ranging from 43 to 70 years (mean, 60.19 years). All patients underwent supraspinatus muscle outlet X-ray film, MSCT, and MRI scans, with MSCT further subjected to three-dimensional reconstruction. Two experienced radiologists independently evaluated the acromion morphology in each imaging modality using the Bigliani classification system. Inter-observer reliability was assessed via Kappa statistics. The CT three-dimensional reconstructions were used as the "gold standard". The overall consistency, Kappa values, sensitivity, and specificity of the three imaging modalities were calculated. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was computed. RESULTS: The inter-observer reliability for supraspinatus muscle outlet X-ray film, oblique sagittal MSCT, and oblique sagittal MRI was moderate, with Kappa values of 0.62, 0.63, and 0.55, respectively. When compared to the CT three-dimensional reconstructions as the "gold standard", the overall consistency was 88.7% (94/106), 62.3% (66/106), and 58.5% (62/106), respectively. The supraspinatus muscle outlet X-ray film showed excellent consistency (Kappa=0.77), whereas the consistency of MSCT and MRI was lower (Kappa=0.34 and 0.29, respectively). In terms of diagnostic sensitivity and specificity, the supraspinatus muscle outlet X-ray film outperformed oblique sagittal MSCT and oblique sagittal MRI in distinguishing various acromion types. ROC analysis demonstrated that the AUC for the supraspinatus muscle outlet X-ray film was consistently higher than for oblique sagittal MSCT and oblique sagittal MRI, with the highest diagnostic performance observed for type Ⅲ hooked acromion (AUC=0.939). CONCLUSION Supraspinatus muscle outlet X-ray film provides the highest diagnostic accuracy for acromion classification in SIS patients, particularly in identifying type Ⅲ hooked acromion, which is strongly associated with SIS. Given its superior sensitivity and consistency, it should be considered the primary screening tool. MSCT and MRI serve as valuable supplementary modalities for complex cases and preoperative evaluation.
Humans ; Middle Aged ; Male ; Female ; Shoulder Impingement Syndrome/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Aged ; Adult ; Imaging, Three-Dimensional ; Sensitivity and Specificity ; Tomography, Spiral Computed/methods* ; Multidetector Computed Tomography/methods* ; Reproducibility of Results

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.

(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

OBJECTIVE: To assess the impact of albumin (Alb) administration on the prognosis of patients with acute kidney injury (AKI). METHODS: Clinical data of AKI patients in the intensive care unit (ICU) were retrospectively analyzed from the American Medical Information Mart of Intensive Care-IV (MIMIC-IV), including demographic data, acute physiology score (APS), comorbidities, vital signs, laboratory indicators, treatment status, ICU length of stay, and outcome indicators. The main outcome measure is ICU mortality. AKI patients were divided into Alb infusion group and Alb non infusion group based on whether they received Alb treatment. Multiple imputation was used to process missing data and eliminate variables that missing more than 30%. To ensure the stability of the results, propensity score matching (PSM) and inverse probability weighting (IPW) were used to correct the results. Using Kaplan-Meier survival curve and Cox proportional hazards regression model to evaluate the effect of Alb infusion on ICU survival rate in AKI patients. Perform subgroup analysis based on patient age, gender, and comorbidities to evaluate the prognostic effects of Alb on different patient subgroups. RESULTS: A total of 6 390 AKI patients were included, including 1 721 in the Alb infusion group and 4 669 in the Alb non infusion group. After adjusting for key covariates in the Cox regression model, compared with the Alb non infusion group, patients in the Alb infusion group were significantly younger in age, with APS III score, proportion of vasoactive drugs and continuous renal replacement therapy (CRRT) use, sepsis proportion, heart rate, respiratory frequency, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (Cr), lactic acid (Lac), and arterial partial pressure of carbon dioxide (PaCO₂) levels significantly higher. The proportion of hypertension, myocardial infarction, and congestive heart failure, as well as blood pressure, urine output, platelet count (PLT), and Alb levels were significantly lower. The results of univariate and multivariate Cox regression analysis on the raw data showed that the risk of death in the Alb infusion group was significantly lower than that in the Alb non infusion group [hazard ratio (HR) = 0.69, 95% confidence interval (95%CI) was 0.60-0.80, all P < 0.05]. The results after propensity score matching (PSM) and inverse probability weighting (IPW) processing are consistent with the original data trend (both P < 0.05). The Kaplan-Meier survival curve showed that the cumulative survival rate during ICU stay in the Alb infusion group was significantly higher than that in the Alb non infusion group (24.48% vs. 12.17%, Log-Rank test: χ² = 74.26, P < 0.05). Subgroup analysis shows that Alb infusion has a more significant survival benefit for AKI patients who use vasoactive drugs, have concurrent sepsis, and do not have liver disease. CONCLUSION Albumin infusion can decrease the ICU mortality of AKI patients.
Humans ; Retrospective Studies ; Acute Kidney Injury/mortality* ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units ; Albumins/therapeutic use* ; Proportional Hazards Models ; Adult ; Databases, Factual

Background During urbanization, the passenger load on urban public transport systems continues to increase, exposing bus drivers to a high risk of musculoskeletal disorders (MSDs). This occupational health issue may also potentially compromise public transport safety. Objective To investigate the prevalence of MSDs among bus drivers in a first-tier city and to explore associated influencing factors. Methods A self-administered questionnaire survey was conducted from December 2024 to March 2025 among 1300 bus drivers in a bus company. Data were collected on general demographic information, occupational activities, and MSDs indicators. A total of 1268 valid questionnaires were returned, yielding a response rate of 97.5%. Descriptive statistics were used to analyze the distribution characteristics of MSDs. Pearson χ² tests were employed to examine the association between MSDs prevalence and individual/occupational characteristics. Logistic regression was performed to identify the influencing factors of MSDs. Results The survey revealed that the prevalence of MSDs among the bus drivers was 28.5%, with the highest prevalence in the 41–50 years age group (30.5%). The conditions primarily affected the cervical spine (60.5%) and lumbar spine (61.9%), with some cases involving multiple sites. The logistic regression model indicated that the following factors were associated with a higher risk of MSDs: frequent smoking (OR=1.477), poor or moderate self-reported health status (OR=4.422), 11–20 years of service (OR=1.749), daily cumulative driving time ≥361 min (OR=1.616), frequent whole-body fatigue during driving (OR=2.077), occasional whole-body fatigue during driving (OR=1.873), feeling tense during driving (OR=1.518), fatigue after work (OR=2.485), work-related stress (OR=1.882), and prolonged smartphone use with head-down posture (OR=1.671). Conversely, occasional exercise (OR=0.713)/frequent exercise (OR=0.569), driving intervals ≥21 min per round (OR=0.645), and perceiving the driving seat comfortable (OR=0.429) were associated with a lower risk of MSDs. Conclusion Physical exercise, smoking, years of service, daily cumulative driving time, driving intervals per round, prolonged smartphone use with head-down posture, self-reported health status, and psychological factors such as work-related stress are influencing factors for MSDs among bus drivers. Drivers should increase physical exercise and change unhealthy living habits. Employers should optimize working conditions, arrange reasonable driving schedules, and foster a positive work environment to reduce MSDs prevalence.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*