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.

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

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*

ObjectiveTo determine the prevalence and determinants of Mycobacterium tuberculosis latent infection among primary and secondary school students in Cixi City, Zhejiang Province, so as to provide references for the prevention and control of tuberculosis in school settings. MethodsInterferon-γ release assay (IGRA) testing was performed to fourth-grade primary school students , as well as to those grade 7 and grade 10 students of the academic year 2024‒2025 in Cixi City. Individuals tested positive for IGRA were subsequently subjected to chest X-ray examination and sputum tests (including three smear microscopy examinations and one mycobaterial culture), and epidemiological investigations were carried out for confirmed cases. Infection rates were compared across student categories by χ² tests, while factors influencing infection were analysed through multivariate logistic regression. ResultsA total of 36 214 students completed tuberculosis screening, with an infection rate of 0.72% (260/36 214). The tuberculosis infection rates among fourth-grade primary school students, non boarding grade 7 students, boarding grade 7 students, grade 10 students of senior high school and of vocational high school were 0.68% (89/13 139), 0.75% (86/11 501), 0.51% (13/2 553), 0.76% (52/6 819), and 0.91% (20/2 202), respectively. Multivariate logistic regression analyses indicated that students with a history of close contact with tuberculosis patients (OR=21.435, P<0.001) had a higher risk of tuberculosis infection, students with a geographic origin outside Zhejiang Province (OR=1.485, P=0.002) had a higher risk of infection than those within Zhejiang Province. Furthermore, students from ethnic minority classes (OR=4.232, P<0.001) might be high-risk groups for tuberculosis infection in high school settings. One IGRA-positive student was confirmed as bacteriologically positive pulmonary tuberculosis by liquid culture of sputum collected one month later. ConclusionSchools should prioritize tuberculosis screening. Students with a history of close contact, those with a geographic origin outside Zhejiang Province, and those enrolled in minority classes should be taken as priority targets for future tuberculosis screening programmes. A tracking and follow-up system must be established for IGRA-positive students to prevent persistent transmission of Mycobacterium tuberculosis within the school settings.

Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2％response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.

Background::Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods::This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Na?ve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.Results::The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. Conclusions::Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Osteoarthritis(OA)is the most common degenerative disease in clinical practice.Joint pain is the main manifestation of OA,and in severe cases,it can lead to joint deformity.The main pathological changes include destruction of articular cartilage,synovitis,thickening of subchondral bone,bone redundancy,degeneration of articular ligaments,and enlargement of articular periosteum.Clinicopathological changes and pain degrees in OA patients vary from person to person,and treatment options vary from person to person.Clinically,non-steroidal anti-inflammatory drugs are used to treat the pain of OA patients now,but the effect is not ideal,and long-term use of these drugs will bring obvious toxic and side effects.Traditional Chinese medicine obtains good results in relieving the pain of OA patients.Therefore,this paper reviews the research on traditional Chinese medicine treatment and pain mechanisms of OA,with a view to providing ideas and references for clinical relief of pain in OA patients.