ObjectiveTo analyze the drug resistance and the molecular typing characteristics through pulsed field gel electrophoresis (PFGE) of Campylobacter spp. isolated from patients with infectious diarrhea in Baoshan District of Shanghai, and to provide a basis for Campylobacter spp. prevention and control and clinical medication. MethodsCampylobacter spp. was isolated, cultured and identified from stool samples of diarrheal patients collected from medical institutions at two monitoring sites in Baoshan District from 2019 to 2022. Antimicrobial susceptibility testing for 12 antibiotics was conducted on the isolated Campylobacter jejuni (C. jejuni) and Campylobacter. Coli (C. coli), and molecular typing was performed using PFGE. ResultsA total of 179 strains of Campylobacter spp. were isolated from 1 786 samples of diarrheal patients, with a positive rate of 10.02%. The highest resistance rate of C. jejuni was to ciprofloxacin (98.63%), followed by tetracycline (97.26%) and nalidixic acid (89.73%). C. coli was completely resistant to ciprofloxacin and nalidixic acid (100.00%), followed by tetracycline (90.91%). The multidrug resistance rates of C. jejuni and C. coli were 89.73% and 100.00%, respectively. 142 strains of C. jejuni produced 122 PFGE bands, while 33 strains of C. coli produced 33 PFGE bands, and the distribution of the bands was relatively dispersed. ConclusionFrom 2019 to 2022, the detection rate of Campylobacter in diarrheal patients was relatively high in Baoshan District of Shanghai, the multidrug resistance rate of Campylobacter isolates from diarrheal patients was relatively serious, in addition, the drug resistance pattern was complex, and the PFGE band pattern displayed a polymorphic distribution.

ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Neoantigens exhibit high immunogenic potential and confer a uniqueness to tumor cells, making them ideal targets for personalized cancer immunotherapy. Neoantigens originate from tumor-specific genetic alterations, abnormal viral infections, or other biological mechanisms, including atypical RNA splicing events and post-translational modifications (PTMs). These neoantigens are recognized as foreign by the immune system, eliciting an immune response that largely bypasses conventional mechanisms of central and peripheral tolerance. Advances in next-generation sequencing (NGS), mass spectrometry (MS), and artificial intelligence (AI) have greatly expedited the rapid detection and forecasting of neoantigens, markedly propelling the development of diverse immunotherapeutic strategies, including cancer vaccines, adoptive cell therapy, and antibody treatment. In this review, we comprehensively explore the discovery and characterization of neoantigens and their clinical use within promising immunotherapeutic frameworks. Additionally, we address the current landscape of neoantigen research, the intrinsic challenges of the field, and potential pathways for clinical application in cancer treatment.
Humans ; Neoplasms/therapy* ; Precision Medicine/methods* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; Cancer Vaccines/immunology* ; High-Throughput Nucleotide Sequencing

The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

A 7-year-old girl was admitted to the hospital with rapidly progressive vision loss. Since 1 year of age, she had exhibited developmental delay accompanied by visual impairment and neutropenia. Combined with genetic testing and molecular pathogenicity analysis, she was diagnosed with Cohen syndrome (CS) caused by compound heterozygous variants in VPS13B (c.6940+1G>T and c.2911C>T). The c.6940+1G>T variant resulted in exon 38 skipping, leading to a frameshift and premature termination. Reverse transcription quantitative polymerase chain reaction revealed significantly reduced VPS13B gene expression (P<0.05). Bioinformatic analysis suggested that both variants likely produce truncated proteins. This case highlights that integrating clinical features with molecular pathogenicity assessment (DNA, RNA, and protein analysis) can improve early diagnostic accuracy for CS.
Humans ; Female ; Child ; Vesicular Transport Proteins/genetics* ; Developmental Disabilities/etiology* ; Muscle Hypotonia/etiology* ; Myopia/etiology* ; Heterozygote ; Intellectual Disability/etiology* ; Microcephaly/etiology* ; Obesity/genetics* ; Growth Disorders/etiology* ; Retinal Degeneration/genetics* ; Psychomotor Disorders/genetics* ; Fingers/abnormalities*

OBJECTIVE: This study aims to analyze the influence factors of lower urinary tract symptoms (LUTS) in patients receiving radical prostatectomy for prostate cancer, and to explore effective nursing strategy in order to provide a theoretical basis for improving the postoperative quality of life of patients. METHODS: A retrospective study was conducted on 103 elderly male patients who underwent radical prostatectomy for prostate cancer in the Department of Urology at General Hospital of Eastern Theater Command from August 2022 to August 2024. The patients were categorized into two groups based on whether LUTS occurred. Demographic and clinical characteristics, perioperative parameters, follow-up data, and participation in pelvic floor muscle training were analyzed to identify risk factors associated with postoperative LUTS. RESULTS: The incidence of postoperative LUTS in the patients with LUTS before the operation was significantly higher than that in the patients without LUTS before the operation (68.42% vs 32.61%, P=0.001). Additionally, the use of larger catheters (22F) was closely associated with an increased incidence of postoperative LUTS(P<0.01). Pelvic floor exercises demonstrated a significant protective effect, with patients who engaged in pelvic floor exercises exhibiting a lower incidence of postoperative LUTS (38.60% vs 60.87%, P=0.040). Regression analysis further revealed that pelvic floor exercises was the protective factor for postoperative LUTS (OR=0.215, 95%CI: 0.091－0.508, P<0.01). CONCLUSION Preoperative LUTS and catheter size are significant risk factors for the occurrence of postoperative LUTS following radical prostatectomy. Pelvic floor muscle exercise after surgery has a protective effect. Postoperative personalized nursing interventions are necessary for different patients to achieve optimal recovery outcomes.
Humans ; Male ; Prostatectomy/adverse effects* ; Retrospective Studies ; Lower Urinary Tract Symptoms/nursing* ; Aged ; Risk Factors ; Quality of Life ; Pelvic Floor ; Prostatic Neoplasms/surgery* ; Postoperative Complications/prevention & control* ; Exercise Therapy ; Middle Aged

OBJECTIVE To comprehensively evaluate the quality of adverse drug reaction （ADR） reports in clinical departments or ward （hereinafter referred to as “department”） based on game theory combinatorial weighting-technique for order preference by similarity to ideal solution （TOPSIS）-rank-sum ratio （RSR） method， providing a reference for the further standardization of ADR reporting. METHODS Based on relevant documents and scoring criteria， the ADR report quality evaluation standards previously developed by our team were modified. Using game theory principles， the fusion of subjective and objective weights for each indicator was determined. A game theory combinatorial weighting-TOPSIS-RSR model was developed to evaluate and categorize the quality of raw ADR reports submitted by departments to the pharmacy department at Bozhou Hospital of Anhui Medical University. RESULTS A total of 222 ADR reports from 23 departments were included. The game theory combinatorial weighting method identifies weak points in management， such as ADR symptoms and signs， the description of underlying diseases， timing of ADR， by optimizing the weightings of the indicators. The TOPSIS-RSR method calculates that the mean relative closeness of the departments was 0.401 7， indicating that the overall report quality ranged from moderate to substandard. 20095） Three departments， including neurosurgery， demonstrated medium reporting quality [estinate closeness （Ĉ）i ≥0.506]， while two departments， such as the respiratory department，were rated as unqualified （Ĉi＜0.278）. The remaining departments were all deemed qualified （0.278≤ Ĉi＜0.506）. CONCLUSIONS The developed game theory combinatorial weighting-TOPSIS-RSR method provides an effective approach for the quality evaluation of ADR reports， which not only balances subjective and objective weights but also facilitates comparisons among different departments. There is still room for improvement in the ADR report quality at the hospital.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer. Computational methods have been widely explored and have become increasingly accurate in recent years. However, the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients. We present a novel disentangled synthesis transfer network (DiSyn) for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients. DiSyn uses a domain separation network (DSN) to disentangle drug response related features, employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement. DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets, The Cancer Genome Atlas (TCGA), Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2 (I-SPY2) and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia (NIBR PDXE), achieving competitive performance with the state-of-the-art methods on cancer patients and mice. Furthermore, the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.