Tumor immunotherapy has emerged as the fourth major therapeutic modality, following surgery, radiotherapy, and chemotherapy. Unlike traditional treatments that primarily target tumor cells directly, immunotherapy harnesses the body’s immune system to recognize and eliminate cancer cells. Over the past decade, various immunotherapeutic strategies have been developed, including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T cell therapy, cancer vaccines, and cytokine-based therapies. However, the immunosuppressive tumor microenvironment (TME) poses a significant obstacle to the effectiveness of these treatments. Polyamines—including putrescine, spermidine, and spermine—are polycationic metabolites that often accumulate abnormally in the TME and act as critical immunoregulatory molecules. T cells play a central role in antitumor immunity, yet their function is frequently influenced by immunoregulatory factors within the TME. Elevated polyamine levels in the TME have been implicated in dampening antitumor T cell responses, thereby facilitating tumor immune evasion. Polyamines in the TME originate from both tumor cells and tumor-associated immune cells. Tumor cells often overexpress the oncogene Myc, which drives the upregulation of polyamine biosynthetic enzymes, resulting in excessive intracellular polyamine production. Additionally, M2-polarized tumor-associated macrophages (M2-TAMs) contribute to polyamine accumulation by upregulating arginase-I (Arg-I), an enzyme that catalyzes the conversion of arginine into ornithine—a key precursor in the polyamine biosynthetic pathway. These combined sources lead to sustained polyamine enrichment in the TME, contributing to immune dysfunction and supporting tumor progression. Moreover, polyamines indirectly affect T cell activity by modulating macrophage polarization and directly suppress tumor cell apoptosis, further promoting an immunosuppressive environment. This review highlights the multifaceted roles of polyamines in modulating tumor-infiltrating T cell function, with a particular focus on their influence on CD4+ T cell differentiation,CD8+ T cell cytotoxicity, and immune checkpoint molecule expression. Recent studies suggest that polyamines suppress CD4+ T cell activation and differentiation by modulating the MAPK/ERK signaling pathway. Additionally, polyamines can impair T cell receptor (TCR) signaling and promote immune evasion through the upregulation of PD-L1 expression on tumor cells. These effects collectively contribute to weakened antitumor T cell responses. Polyamine blocking therapy (PBT), which primarily targets polyamine biosynthesis and transport, has emerged as a novel adjunctive immunotherapeutic strategy in cancer treatment. By reducing polyamine levels in the TME, PBT restores T cell effector functions and alleviates immunosuppression. Notably, studies have demonstrated that combining PBT with ICIs produces synergistic antitumor effects and may overcome resistance to ICI monotherapy. Although research has revealed the inhibitory effects of polyamines on T cell immune function, the underlying regulatory mechanisms remain to be fully elucidated. Moreover, due to compensatory mechanisms employed by tumor cells to maintain polyamine homeostasis, multi-targeted approaches may be necessary to achieve safe and effective therapeutic outcomes. Future PBT strategies may benefit from the integration of multi-omics technologies and the development of nanocarrier-based drug delivery systems, which could collectively enhance their specificity, efficacy, and applicability in cancer immunotherapy. This review systematically elucidates the immunomodulatory effects of polyamines on T cell function within the TME and provides theoretical support and novel insights for the advancement of tumor immunotherapeutic strategies.

With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry* ; Calcium Sulfate/chemistry* ; Glycyrrhiza/chemistry* ; Crystallization ; Particle Size ; Medicine, Chinese Traditional ; Rhizome/chemistry*

Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: To construct the inflammation score (IS) and nutrition-immunity score (NIS) for patients with multiple myeloma (MM), and to verify their prognostic stratification effects and significance. METHODS: The clinical data of 129 newly diagnosed MM patients admitted to our hospital from August 2011 to September 2022 were retrospectively analyzed. Univariate and multivariate Cox regression analysis of overall survival (OS) were comducted on clinical parameters, including inflammatory indicators such as red blood cell volume distribution width (RDW) and platelet count (PLT), nutritional-immune indicators such as albumin (ALB), absolute lymphocyte count (ALC), and suppressed immunoglobulin count (S-Ig count). To construct IS and NIS for prognosis, X-tile software and multivariate Cox regression analysis were used to verify the prognostic stratification role and significance of IS and NIS. The time-dependent receiver operating characteristic (ROC) curve, C-index curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical net benefit of IS and NIS in predicting overall survival(OS), and compared to the international staging system (ISS). RESULTS: IS was constructed based on the scores of RDW and PLT, and NIS was constructed based on the scores of ALB, ALC, and S-Ig count. According to X-tile analysis and multivariate Cox regression analysis, IS and NIS can divide the patients into three risk strata respectively: low, medium and high IS and NIS groups. The differences in OS and hazard ratio (HR) between the low, medium, and high strata were statistically significant (P < 0.05). IS and NIS are both independent prognostic predictors for MM. The area under the ROC curve (AUC) and C index of IS and NIS for predicting 1- to 7-year OS were greater than those of ISS, and both were greater than 0.7. The prediction results of IS and NIS for 1-, 3-, and 5-year OS rates were well consistent with the actual observed results. The DCA curves of IS and NIS for predicting 1-, 3-, and 5-year OS were higher than that of ISS in a wide range of threshold probability intervals. CONCLUSION IS and NIS have independent predictive significance for OS in MM patients. Their predictive discrimination, accuracy, and clinical net benefit are higher and better than ISS, and they may have potential application value in MM prognosis.
Humans ; Multiple Myeloma/immunology* ; Prognosis ; Retrospective Studies ; Inflammation ; Male ; Female ; Middle Aged ; ROC Curve ; Aged ; Nutritional Status ; Proportional Hazards Models

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Listeria brainstem encephalitis with myelitis is extremely rare in clinical practice.Since the clinical manifestations are non-specific,MRI is helpful for diagnosis.Positive cerebrospinal fluid culture is considered the gold standard for diagnosis.This article reports a case of an immunocompetent individual with listeria brainstem encephalitis with myelitis,aiming to enhance the awareness of this condition.
Humans ; Brain Stem/pathology* ; Diagnostic Errors ; Encephalitis/complications* ; Encephalomyelitis, Acute Disseminated/diagnosis* ; Listeriosis/complications* ; Myelitis/complications*

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To analyze the influencing factors for the knowledge level,cognition willingness and atti-tude of health care workers(HCWs)towards monkeypox.Methods A cross-sectional survey was conducted,from January to April 2023,700 HCWs were randomly selected from a tertiary hospital in Shanghai.Based on a self-de-signed questionnaire,the survey was conducted anonymously through the online platform"Wenjuanxing".Results A total of 612 questionnaires were collected,581 were valid,with a response rate of 87.43％and an effective rate of 94.93％.The mean score of the questionnaire was(128.80±27.70)points,with a score rate of 58.54％.Multiple linear regression analysis showed that there were statistically significant differences in the knowledge level of mon-keypox among HCWs of different ages,occupations,departments,educational levels,years of working experience,professional titles,initiative cognition on monkeypox,and participation in monkeypox-related lectures organized by the units(all P＜0.05).Conclusion HCWs'cognition on monkeypox is at a moderate level.The training of HC-Ws on monkeypox knowledge should be strengthened to improve the emergency response capabilities during mon-keypox outbreaks.

Objective To explore the independent risk factors for central line-associated bloodstream infection(CLABSI),provide basis for developing intervention measures for infection prevention and control as well as con-ducting targeted treatment.Methods Patients who were diagnosed with CLABSI in a hospital from January 2019 to December 2023 were recruited retrospectively and defined as the infection group.According to 1:4 propensity score matching method,patients who received central venous catheter(CVC)without infection were taken as the control group.With whether CLABSI occurred as the dependent variable,the possible risk factors of the matched two groups as the independent variables,logistic regression analysis was conducted,and independent risk factors for pa-tients developing CLABSI were explored.Results A total of 42 patients in the CLABSI group and 168 patients in the non-CLABSI group were matched.Multivariate logistic regression analysis showed that high score of acute physiology and chronic health evaluation(APACHE)Ⅱ(OR=1.217,95％CI[1.094-1.357],P＜0.001),long duration of central venous catheterization(OR=1.273,95％CI[1.157-1.400],P＜0.001),and femoral venous catheterization(OR=6.846,95％CI[1.511-31.014],P=0.013)were independent risk factors for CLABSI.A total of 118 strains of pathogens were isolated from 42 CLABSI patients,with Gram-negative bacteria being the ma-jority(n=56).Conclusion High score of APACHE Ⅱ,long duration of central venous catheterization,and femo-ral venous catheterization are independent risk factors for CLABSI.The main pathogens are Gram-negative bacilli.Strict prevention and control measures for CLABSI should be implemented to reduce the risk of infection.