Inorganic phosphate (Pi) is an essential nutrient for bacterial growth, metabolism and signal regulation. Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, encounters restricted Pi availability inside host cells. The uptake and utilization of Pi are mainly accomplished by the phosphate-specific transport (Pst) system. The survival and pathogenicity of Mtb rely on its precise sensing and adaptation to the hostile intracellular environment. The Pst system not only mediates bacterial drug resistance, toxin production and invasion, but also regulates virulence expression, membrane vesicle biogenesis and the synthesis of the nucleotide signaling molecule (p)ppGpp via the Pst-SenX3-RegX3 signaling axis, exhibiting typical multifunctional characteristics. As a member of the ATP-binding cassette (ABC) transporter family, the Pst system in Mtb consists of PstS, PstC, PstA, PstB and PhoU-like proteins, with distinct physiological functions for different proteins and their isoforms.This review focuses on the molecular structure and function of key proteins in the Pst system, as well as the molecular mechanisms underlying Pi transport regulation and bacterial drug resistance, providing a reference for further exploring the relationship between this system and drug resistance, as well as the development of novel drugs targeting the Pst system.

Traditional Chinese medicine （TCM） offers a rich theoretical foundation and clinical experience for the prevention and treatment of cardiovascular-kidney-metabolic syndrome（CKM）， demonstrating unique advantage. Building on previous work in managing diabetes， its complications， and chronic kidney disease， our team has proposed a five-phase evolution theory of "constraint， heat， deficiency， stasis， and toxin" as the core pathogenesis. These phases correspond to the pathological progression of constraint of phlegm-dampness， constraint transforming into heat， heat damaging qi and yin， stasis accumulated in the collateral vessels， and toxin induced by deficiency and stasis. In the prevention and treatment of CKM by TCM， it is emphasized to integrate the concept of "treating disease before it arises" with constitution theory， and incorporate the "2-5-8" prevention and treatment strategy， which combines prevention with treatment， tailors interventions to different phases， and employs comprehensive treatment modalities. Our goal is to leverage TCM's holistic advantages in preventing and treating CKM.

Objective The aim of this study is to retrospectively analyze the clinical and imaging characteristics,treatment and prognosis of 13 patients with granulomatous prostatitis(GP),and to provide reference for the diagnosis and treatment for GP.Methods The clinical information of 13 GP patients extracted from electronic medical records including demographic characteristic risk factors,clinical symptoms,laboratory findings,imaging findings(ultrasound,CT,MRI,FDG-PET-CT),treatment and outcomes were analyzed retrospectively from January 2018 to August 2023 at our center.Results The average age of 13 patients with GP was(65.69±6.46)years.And the average score of IPSS was(23.40±5.8).Five patients appeared positive results,of which 11 cases received digital rectal examination.The average level of pre-biopsy tPSA was(23.28±44.94)μg/L with fPSA/tPSA ratio of 0.11±0.05 and PSAD of(0.55±1.07)μg/l/mL.The pre-biopsy mean MRI PI-RADS 2.0 was(4.6±0.6)in this group of patients.Extraprostatic invasion was shown on imaging in 4 patients.The average number of biopsy needles was(19.6±3.9),and the pathological results showed tuber-culous granulomas in 2 cases(15.4％)and non-specific granulomatous inflammation in 11 cases(84.6％).Five patients received local treatment of the prostate after pathological confirmation(PVP in 4 cases,TURP in 1 case),2 patients re-ceived anti-tuberculosis therapy,and 3 cases were given antibiotics.Average follow-up was(20.6±11.2)months,and the average tPSA were(6.94±4.96)μg/L at 3-6 months after biopsy and/or surgery,with no obvious signs of malignancy during the follow-up period.Conclusion GP is the great mimicker of prostate cancer clinically and radiologically.Pros-tate biopsy is the method for confirming the diagnosis.For patients who are considering biopsy-free radical prostatectomy,it is important to consider the possibility of GP.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, which is primarily transmitted through the respiratory tract, and remains one of the diseases with the highest mortality rate of single-pathogen infections globally. The cell wall polysaccharides of M. tuberculosis are critical for maintaining bacterial structure, mediating pathogenesis, and enabling immune evasion. Lipoarabinomannan (LAM), a key polysaccharide component, has revolutionized non-invasive diagnostic technologies as a TB biomarker, while polysaccharide-based vaccines have emerged as innovative strategies for TB prevention. This review systematically examines the composition, subcellular distribution, and functional roles of M. tuberculosis cell wall polysaccharides in bacterial metabolism, drug resistance, and immune regulation. A particular emphasis is placed on recent advancements in LAM-based diagnostics and vaccine development. Future studies should utilize advanced technologies to precisely characterize the structural features of TB polysaccharides and explore their biological functions, providing a foundation for targeted diagnostic and therapeutic innovations. This article aims to provide reference for advancing both basic research and clinical applications related to M. tuberculosis.

OBJECTIVES: To investigate the characteristics of immune cell infiltration in tumor samples from Chinese patients with clear cell renal cell carcinoma (ccRCC) and the correlation of immune cell infiltration with tumor stage and response to immunotherapy. METHODS: Tumor samples and clinicopathological data were collected from 154 ccRCC patients treated in Nanfang Hospital, Southern Medical University from October, 2020 to October, 2023. The immune cell types infiltrating the tumor tissues were identified using immunohistochemistry and immunofluorescence staining, and their correlations with the patients' clinicopathological characteristics were analyzed. Patient-derived tumor tissue fragment models (PDTF) models, constructed using tumor tissues from 22 patients, were treated with PD-1 monoclonal antibody, and T cell activation was detected using flow cytometry to assess the patients' responses to immunotherapy. RESULTS: In Chinese ccRCC patients included in this study, CD8⁺ T cells, CD4⁺ T cells, and CD3⁺ T cells were the most abundant in the tumor tissues. Higher infiltration levels of CD3⁺ T cells (P=0.004), PD-1⁺ T cells (P=0.020), CD68⁺ T cells (P=0.049), CD79⁺ T cells (P=0.049), and Tryptase⁺ cells (P=0.049) were all positively correlated with a larger tumor size (≥5 cm). A higher infiltration level of CD4⁺ T cells was associated with a lower tumor stage. Patients with higher International Society of Urological Pathology (ISUP) grades had higher infiltration levels of CD3⁺ T cells (P=0.023), CD8⁺ T cells (P=0.045), PD-1⁺ T cells (P=0.014), CD20⁺ B cells (P=0.020) and CD79⁺ B cells (P=0.049), and lower levels of Tryptase⁺ cells (P=0.001). Patients with abundant infiltrating immune cells tended to have better responses to immunotherapy. CONCLUSIONS The infiltrating immune cells are heterogeneous in Chinese ccRCC patients, and immune cell infiltration characteristics are closely correlated with clinicopathological parameters of the patients.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; Immunotherapy ; Male ; Lymphocytes, Tumor-Infiltrating/immunology* ; Female ; Middle Aged ; CD8-Positive T-Lymphocytes/immunology* ; Aged ; T-Lymphocytes/immunology* ; Programmed Cell Death 1 Receptor/immunology* ; Adult ; CD4-Positive T-Lymphocytes/immunology* ; Neoplasm Staging

Objective The aim of this study is to retrospectively analyze the clinical and imaging characteristics,treatment and prognosis of 13 patients with granulomatous prostatitis(GP),and to provide reference for the diagnosis and treatment for GP.Methods The clinical information of 13 GP patients extracted from electronic medical records including demographic characteristic risk factors,clinical symptoms,laboratory findings,imaging findings(ultrasound,CT,MRI,FDG-PET-CT),treatment and outcomes were analyzed retrospectively from January 2018 to August 2023 at our center.Results The average age of 13 patients with GP was(65.69±6.46)years.And the average score of IPSS was(23.40±5.8).Five patients appeared positive results,of which 11 cases received digital rectal examination.The average level of pre-biopsy tPSA was(23.28±44.94)μg/L with fPSA/tPSA ratio of 0.11±0.05 and PSAD of(0.55±1.07)μg/l/mL.The pre-biopsy mean MRI PI-RADS 2.0 was(4.6±0.6)in this group of patients.Extraprostatic invasion was shown on imaging in 4 patients.The average number of biopsy needles was(19.6±3.9),and the pathological results showed tuber-culous granulomas in 2 cases(15.4％)and non-specific granulomatous inflammation in 11 cases(84.6％).Five patients received local treatment of the prostate after pathological confirmation(PVP in 4 cases,TURP in 1 case),2 patients re-ceived anti-tuberculosis therapy,and 3 cases were given antibiotics.Average follow-up was(20.6±11.2)months,and the average tPSA were(6.94±4.96)μg/L at 3-6 months after biopsy and/or surgery,with no obvious signs of malignancy during the follow-up period.Conclusion GP is the great mimicker of prostate cancer clinically and radiologically.Pros-tate biopsy is the method for confirming the diagnosis.For patients who are considering biopsy-free radical prostatectomy,it is important to consider the possibility of GP.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Objective To construct YOLOv5x deep learning network model based on SPECT whole body bone scanning,and to observe its value for diagnosing benign and malignant bone lesions.Methods Totally 699 patient who underwent SPECT bone scanning were enrolled,with a total of 5 182 bone lesions,including 3 105 malignant and 2 077 benign lesions.Then 1 121 bone images were divided into training set(n=897),validation set(n=112)or test set(n=112)at the ratio of 8∶1∶1.After augmentation on training set and validation set,the data were inputted to YOLOv5x deep learning network for training to obtain a recognition model.The sensitivity,specificity and accuracy of this model for diagnosing benign and malignant bone lesions were analyzed,and the consistency between its diagnosis results and gold standards was evaluated based on test set.Results The sensitivity,specificity and accuracy of bone scanning YOLOv5x deep learning network model for identifying malignant bone lesions was 95.75％,87.87％and 91.60％,respectively,and for identifying benign bone lesions was 91.62％,94.38％and 93.14％,respectively.The area under the curve(AUC)of this model for identifying bone lesions on bone scanning images was 0.98,for malignant and benign bone lesions was 0.97 and 0.98,respectively.The consistency between the diagnosis results of this model for malignant and benign bone lesions and the gold standards were both good(Kappa=0.83,0.86,both P＜0.05).Conclusion YOLOv5x deep learning network model based on SPECT whole body bone scanning was helpful for diagnosing benign and malignant bone lesions.

Objective:To analyze the whole genome of Omicron variants causing the first local Omicron outbreak in Henan Province and to investigate the mutations in the SARS-CoV-2 genome for source tracing.Methods:Respiratory tract samples from COVID-19 cases in the Omicron outbreak in Henan Province from January 7 to 29, 2022 were subjected to whole-genome sequencing and sequence alignment analysis. Whole-genome identity, variations and evolution of the Omicron variants were analyzed.Results:Through high-throughput sequencing, the whole-genome sequences of SARS-CoV-2 were obtained from 120 cases, which accounted for 25.64% (120/468) of all COVID-19 cases in Anyang during the same period. Compared with the genome of Wuhan reference strain (NC_045512.2), there were 57-59 nucleotide mutation sites in the 120 whole genome sequences, and one or two nucleotide mutation sites were added to the shared 57 nucleotide sites. All of the 120 strains were VOC/Omicron (BA.1.1) variants and shared high homology. The whole-genome sequence obtained from the first case A contained 57 nucleotide mutation sites, while apart from the 57 identical nucleotide mutation sites, one specific mutation site (C1594T) was found in the whole-genome sequence obtained from the first case B, suggesting that the two cases were in the same transmission chain. After comparing with the database of domestic and imported cases by the Chinese Center for Disease Control and Prevention and the Henan Provincial Center for Disease Control and Prevention, it was found that the current outbreak was linked with the same transmission chain as the existing local epidemics in other provinces. Moreover, epidemiological investigation showed that on January 2, case A had come into contact with her cousin and his family who returned from an affected area outside the province.Conclusions:Based on the gene sequencing results and epidemiological investigation, the COVID-19 outbreak in Anyang city, Henan Province was a local epidemic and the source of it was a college student who returned to Anyang city from other province on December 28, 2021. These infections were linked to the same transmission chain as the existing local infection in other provinces.

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
Abietanes ; Acute Lung Injury/drug therapy* ; Animals ; Cytokine Release Syndrome ; Cytokines ; Inflammation/drug therapy* ; Lipopolysaccharides/toxicity* ; Macrophage Activation ; Macrophages ; Mice ; Triacetoneamine-N-Oxyl/pharmacology*