To explore the inhibitory effect of ginkgolide B (GB) on MH7A human fibroblast-like synoviocytes (FLS) and its potential mechanism. Firstly, 20 μg/L tumor necrosis factor-α (TNF-α) was pretreated with MH7A to establish a cell model of arthritis. After incubation of MH7A cells with various concentrations of GB, CCK-8 assay, Transwell assay, and flow cytometry (FCM) were separately used to detect cell viability, cell invasion, and cell apoptosis rate and cell cycle; Real-time quantitative PCR and Western blot assay were performed to detect the apoptosis- and cycle-related gene transcriptions and protein expressions, respectively. The results showed that compared with the control group, GB dose- and time-dependently suppressed cell viability to a greater extent; GB significantly reduced cell invasive ability and increased cell apoptosis rate and proportion of G0/G1 phase in MH7A cells, along with increased transcription levels of Bcl-2-associated X protein (Bax) and p21 mRNA and decreased transcription levels of Bcl-2, myeloid cell leukemia 1(Mcl-1), protein kinase B (PKB; AKT), IP3K, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) mRNA; GB remarkably increased expression levels of Bax, p21, and cleaved-Caspase 3 protein and decreased expression levels of Bcl-2, Mcl-1, p-AKT, p-PI3K, Cyclin D1, and CDK4 protein, with decreased ratios of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax. In conclusion, GB blocks the G1-to-S cell cycle transition, suppresses cell viability and cell invasion and induces cell apoptosis of MH7A human RA-FLS via suppressing the PI3K/AKT signaling pathway.

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

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Incomplete debridement of chronic osteomyelitis is the main factor leading to recurrence. For the treatment of chronic osteomyelitis, the complete elimination of the source of infection is the key to preventing recurrence. This process includes not only the complete removal of infected lesions, dead bone, accreted scar tissue and granulation tissue, but also the elimination of dead space and improved local blood circulation. In these steps, debridement is a core procedure, and judging the scope of debridement is the premise of whether it could be completely debridement. This article systematically reviewed the application of different imaging techniques in evaluating the scope of chronic osteomyelitis infection, and discusses its future development trend. Although traditional plain X-ray film could preliminarily indicate osteomyelitis, it is difficult to determine the infection scope. CT scan has the function of accurate anatomic localization, which is important for preoperative assessment of the scope of bone infection, but the recognition of soft tissue information is limited. MRI, with its high sensitivity, clearly distinguishes between infected bone and soft tissue, which plays an important role in the evaluation of soft tissue infection, but may overestimate the extent of bone infection. Nuclide techniques such as 18F-FDG PET/CT and SPECT/CT show great potential for accurately assessing the extent of infection before surgery. In the future, by optimizing the combination of different imaging technologies, combining clinical symptoms, intraoperative conditions and pathological results, and developing an image analysis platform based on artificial intelligence, it will be able to more accurately assess the scope of infection, provide more effective and personalized treatment plans for patients with chronic osteomyelitis, enhance treatment effects, and significantly improve quality of life of patients.
Humans ; Osteomyelitis/diagnosis* ; Chronic Disease ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed

OBJECTIVE: To summarize the early clinical results and safety of Stand-alone OLIF application of lumbar lesions, and explored its surgical indications. METHODS: Total of 92 cases of lumbar spine lesions treated with Stand-alone OLIF at two medical centers from October 2014 to December 2018 were retrospectively analyzed, including 30 males and 62 females with an average age of (61.20±12.94) years old ranged from 32 to 83 years old. There were 20 cases of lumbar spinal stenosis, 15 cases of lumbar disc degeneration, 11 cases of lumbar degenerative spondylolisthesis, 6 cases of discogenic low back pain, 7 cases of giant lumbar disc herniation, 13 cases of primary lumbar discitis, 6 cases of adjacent vertebral disease after lumbar internal fixation surgery, and 14 cases of degenerative lumbar scoliosis. Pre-operative dual energy X-ray bone density examination 31 cases' T-values ranged from -1 to -2.4, 8 cases' T-values ranged from -2.5 to -3.5, and the rest had normal bone density. The number of fusion segments: 68 cases of single segment, 9 cases of two segment, 12 cases of three segment , and 3 cases of four segment. Fusion site:L_1,2 1 case, L_2,3 4 cases, L_3,4 10 cases, L_4,5 53 cases, L_2,3-L_3,4 3 cases, L_3,4-L_4,5 6 cases, L_1,2L_2,3L_3,4 1 case, L_1,2L_3,4L_4,5 1 case, L_2,3L_3,4L_4,5 10 cases, L_1,2L_2,3L_3,4L_4,5 3 cases. The clinical results and imaging results of this group of cases were observed, as well as the complications. RESULTS: The surgical time ranged from 40 to 140 minutes with an average of (60.92±27.40) minutes. The intraoperative bleeding volume was 20 to 720 ml with an average of (68.22±141.60) ml. The patients had a follow-up period of 6 to 84 months with an average of (38.50±12.75) months. The height of the intervertebral space recovered from (9.23±1.94) mm in preoperative to (12.68±2.01) mm in postoperative, and (9.11±1.72) mm at the last follow-up, there was a statistically significant difference(F=6.641, P=0.008);there was also a statistically significant difference between the postoperative and preoperative height of the intervertebral space(t=9.27, P<0.000 1);and there was also a statistically significant difference (t=10.06, P<0.000 1) between the last follow-up and postoperative height of the intervertebral space. At the last follow-up, cage subsidence grading was as follows:level 0 in 69 cases (76 segments), levelⅠin 17 cases (43 segments), level Ⅱin 5 cases (14 segments), and level Ⅲ in 1 case (1 segment);according to the number of segments, normal subsidence accounts for 56.72%, abnormal subsidence accounts for 43.28%. Bone mineral desity of normal subsidence groups was -0.50±0.07 whinch was better than that the abnormal subsidence groups -2.10±0.43, and the difference was statistically significant(χ²=2.275, P=0.014). As well as there was a statistically significant difference in the patient's VAS of backache from (6.28±2.11) in preoperative to (1.48±0.59) in last follow-up(t=8.56, P<0.05). The ODI recovered from (36.30±7.52)% before surgery to (10.20±2.50)% at the last follow-up, with a statistically significant difference (t=7.79, P<0.000 1). Complications involved 4 cases of intraoperative vascular injury, 21 cases of endplate injury, and 4 cases of combined vertebral fractures. The incision skin has no necrosis or infection. There were 4 cases of left sympathetic chain injury, 4 cases of transient left hip flexion weakness, 2 cases of left thigh anterolateral numbness with quadriceps femoris weakness, and 1 case of incomplete intestinal obstruction;8 cases were treated with posterior pedicle screw fixation due to fusion cage settlement accompanied by stubborn lower back pain, and 6 cases were treated with fusion cage settlement and lateral displacement. According to the actual number of cases, there were 38 complications, with an incidence rate of 41.3%. CONCLUSION The application of Stand alone OLIF in lumbar spine disease fusion has achieved good early results, with obvious clinical advantages, but also there are high probability of complications. It is recommended to choose carefully. It is necessary to continuously summarize and gradually clarify and complete the surgical indications and specific case selection criteria.
Humans ; Male ; Female ; Middle Aged ; Spinal Fusion/methods* ; Lumbar Vertebrae/injuries* ; Aged ; Adult ; Retrospective Studies ; Aged, 80 and over

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Nutritional support therapy is one of the extremely important treatment methods for patients in the intensive care unit. Timely and effective nutritional support regimens can improve patients' immune function, reduce complications, and optimize clinical outcomes. Energy expenditure is influenced by multiple factors, including patients' baseline characteristics (such as physical condition, gender, age) and dynamic changes in indicators (such as body temperature, nutritional support regimens, and therapeutic interventions). The currently recognized "gold standard" for accurately assessing energy metabolism in clinical practice is the indirect calorimetry system, also known as the metabolic cart. This device monitors carbon dioxide production and oxygen consumption in real time and uses specific algorithms to estimate the metabolic proportions of the three major nutrients (carbohydrates, fats, and proteins) in energy expenditure. An appropriate nutrient ratio helps maintain the balance between supply and demand in the body's nutritional metabolism. In the management of critically ill patients, the application of the metabolic cart enables personalized nutritional therapy, avoiding over- or under-supply of energy and optimizing the use of medical resources. Furthermore, with real-time, quantitative data support from the energy metabolism monitoring system, clinicians can develop more precise nutritional intervention strategies, thereby improving patient prognosis. This article provides a systematic review of the technical features of the metabolic cart and its application value in various critical care scenarios, aiming to offer a reference for indirect calorimetry in clinical practice.
Humans ; Critical Illness/therapy* ; Nutritional Support ; Energy Metabolism ; Calorimetry, Indirect