Animal model research on spleen and stomach diseases in traditional Chinese medicine （TCM） is of great significance for elucidating the nature of diseases and syndromes and for revealing the mechanisms of action of Chinese herbal medicinals. At present， studies on classical TCM syndrome models of spleen and stomach diseases mainly focus on spleen deficiency syndrome， liver constraint syndrome， and damp-heat syndrome. Model construction is mostly based on the etiological and pathophysiological characteristics of syndrome， and model evaluation primarily involves macroscopic manifestations and physicochemical indicators. This paper summarizes the current research status of animal models integrating disease and syndrome for seven common spleen and stomach diseases， including chronic gastritis and gastric precancerous lesions， gastroesophageal reflux disease， functional dyspepsia， inflammatory bowel disease， irritable bowel syndrome， functional constipation， and functional diarrhea. The modeling methods and characteristics of disease-syndrome combined animal models for each disease are analyzed. It is proposed that future research on disease-syndrome integration in spleen and stomach diseases should move toward syste-matic， precise， and integrative development， and that interdisciplinary and cross-disciplinary research approaches should be adopted to enhance the predictive value and application efficiency of disease-syndrome combined animal models.

The introduction of immunotherapy has changed the traditional paradigms in cancer treatment and has demonstrated substantial clinical benefits across various malignancies. However, this progress is accompanied with emerging challenges, such as immune evasion and low response rates to immunotherapy. As an immunomodulatory molecule, zymogen granule protein 16 (ZG16) plays a crucial role in immunotherapy by inhibiting the binding of programmed death 1 (PD-1) to its ligand PD-L1, preventing immune evasion and restoring the immune system's ability to recognize and eliminate tumor cells. ZG16 is downregulated in multiple gastrointestinal tumors, and its regulatory mechanisms vary depending on the tumor type. ZG16 expression is closely associated with patient prognosis, and it has been identified as a favorable prognostic marker in colorectal cancer. This article provides a systematic overview of the structural characteristics, expression regulation mechanisms, and antitumor immune functions of ZG16.

Objective:To investigate the association between anti-rituximab antibodies (ARA) and relapse after rituximab (RTX) therapy in children with frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS).Methods:A retrospective cohort study was conducted. Clinical and laboratory data were collected from 48 FRNS or SDNS children treated with RTX in the Department of Pediatrics, General Hospital of Eastern Theater Command, between April 2024 and October 2024. Data included RTX dosing frequency, relapse events, peripheral CD20? B-cell counts, and ARA levels. With a 6-month observation period after the last RTX therapy, the children were divided into an ARA-positive group and an ARA-negative group based on ARA test results. Chi-square test, independent sample t-test, or Mann-Whitney U test were used to compare relapse rates and laboratory indicators between the two groups. The predictive value of ARA levels for relapse was evaluated using univariate receiver operating characteristic (ROC) curve analysis. Results:Among the 48 children (36 males, 12 females), the age of disease onset was 3.5 (2.0, 6.0) years, the ages at the first and last RTX treatments were 7.0 (5.0, 12.0) years and 9.5 (7.0, 13.0) years, respectively. The overall ARA positive rate was 29% (14/48). The relapse rate in the ARA-positive group was significantly higher than that in the negative group ( P<0.05). The ARA level was 0.01 (0.01, 5.88) μg/L, and all 12 children with ARA levels >5.88 μg/L relapsed. ROC curve analysis showed that ARA levels predicted relapse after RTX treatment in FRNS or SDNS children with an area under the curve (AUC) of 0.73, sensitivity of 0.50, specificity of 1.00, and an optimal cut-off value of 5.02 μg/L. All children received single-dose RTX therapy, with no significant difference in treatment frequency between the two groups ( P>0.05). At 3 months after the last rituximab therapy, CD20? B cell counts were significantly higher in the ARA-positive group ( P<0.05). During follow-up, 15% (7/48) of the children experienced infusion-related adverse reactions, with no significant difference in incidence between the two groups ( P>0.05). Conclusion:ARA is significantly associated with relapse in FRNS or SDNS children after RTX therapy.

Objective:To investigate the therapeutic effect and potential mechanism of Nepetoidin B on rheumatoid arthritis (RA).Methods:DBA/1 mice were divided into four groups using the random number method, namely the control group, model group, methotrexate group, and Nepetoidin B group. The collagen-induced arthritis (CIA) model was prepared. Mice were treated from day 21th to day 60th. Arthritis symptoms were evaluated every three days during treatment. At the end of treatment, pathological changes of joint tissue were observed through HE staining. Serum IL-17, IL-6, MDA, and NO levels were measured using ELISA and biochemical colorimetric assays. The Nrf2/HO1 pathway in joint tissues was detected using western blot. A group of CIA mice was treated with Nepetoidin B, followed by an Nrf2 inhibitor to validate the mechanism. One-way analysis of variance was used to compare between multiple groups with homogeneity of variance, pairwise comparison using LSD- t test. Results:The study found that mice treated with methotrexate and Nepetoidin B exhibited a significant reduction in arthritis scores(CIA+Meth group 5.2±1.3, CIA+NepB group 6.8±1.2 vs. CIA group 11.0±1.7, t=6.69, P=0.004; t=5.00, P=0.009), and joint histopathology compared to the CIA mice(CIA+Meth group 1.5±1.0, CIA+NepB group 2.2±0.8 vs. CIA group 4.0±0.9, t=4.44, P<0.001; t=3.84, P=0.005). Additionally, there was a significant decrease in serum IL-17[CIA+Meth group(257±69)ng/ml, CIA+NepB group (279±103)ng/ml vs. CIA group(414±71)ng/ml, t=3.86, P=0.006; t=2.63, P=0.020], IL-6[CIA+Meth group(32±6)ng/ml, CIA+NepB group (44±5)ng/ml vs. CIA group(56±11)ng/ml, t=4.69, P<0.001; t=2.48, P=0.040) ,MDA [CIA+Meth group(22±4)μmol/L, CIA+NepB group(22±8)μmol/L vs. CIA group(34±11)μmol/L, t=2.77, P=0.038; t=2.29, P=0.049]and NO[ CIA+Meth group(37±12)μmol/L, CIA+NepB group(37±11)μmol/L vs. CIA group(56±12)μmol/L, t=2.71, P=0.040; t=2.90, P=0.035] levels, and a significant elevation in the Nrf2( 0.263±0.021, 0.273±0.022 vs. 0.221±0.034, t=3.18, P=0.044; t=2.70, P=0.049)/HO1 (0.524±0.021, 0.501±0.014 vs. 0.453±0.033, t=3.95, P=0.006; t=3.41, P=0.032) pathway in methotrexate and Nepetoidin B treated group. It was also observed that Nrf2 inhibitors could counteract the treatment effects of Nepetoidin B on arthritis (1.8±0.8 vs. 3.2±0.8, t=3.07, P=0.024). Conclusion:Nepetoidin B has the ability to inhibit oxidative stress by activating the Nrf2/HO1 pathway, which alleviates collagen-induced arthritis in mice.

OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To explore the immunophenotypic characteristics of bone marrow granulocytes (G) and their clinical significance in patients with multiple myeloma (MM). METHODS: The granulocyte immunophenotypes of bone marrow in 70 MM patients (MM group) and 40 anemia patients (control group) were detected by flow cytometry, and its correlation with clinical characteristics was further analyzed. Univariate and multivariate regression analysis were used to screen factors that affected prognosis. RESULTS: The CD56⁺G%, CD13⁺G%, CD22⁺G% and CD117⁺G% in MM group were higher than those in the control group (all P <0.05). CD56⁺G% and CD117⁺G% in CR⁺VGPR group were significantly lower than those in PR+MR+PD group (both P <0.05). The CD10⁺G% in RISS Ⅲ stage and Ca²⁺ ≥2.65 mmol/L groups were increased (both P <0.05). The CD56⁺G% in elevated lactate dehydrogenase, β₂-microglobulin≥5.5 mg/L and hemoglobin <85 g/L groups were increased (all P <0.05), while the CD117⁺G% in high-risk cytogenetic positive group was decreased (P <0.05). The expression rate of CD molecules on granulocytes was divided into low (L) and high (H) groups according to the median value. The overall survival (OS) of the LCD56⁺G%, LCD13⁺G% and LCD22⁺G% groups was significantly prolonged (all P <0.05). CD13⁺G% and CD22⁺G% were independent risk factors for OS in MM patients (HR=0.443, 0.410, both P <0.05). CONCLUSION The CD56⁺G%, CD10⁺G% and CD117⁺G% are closely correlated with clinical features in MM patients, while CD13⁺G% and CD22⁺G% are closely correlated with prognosis. Detection of CD molecules expression on granulocytes may be used to evaluate prognosis and guide treatment.
Humans ; Multiple Myeloma/immunology* ; Granulocytes/immunology* ; Prognosis ; Immunophenotyping ; Male ; Bone Marrow ; Female ; Flow Cytometry ; Middle Aged ; Aged ; Clinical Relevance

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant

OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent

Objective To analyze the effect of topical recombinant human acidic fibroblast growth factor(rh-aFGF)on wound healing in burn and scald patients.Methods A total of 240 burn pa-tients were selected as the study subjects and divided into observation group and control group,with 120 cases in each group.The control group was treated with compound polymyxin B ointment,while the observation group received rh-aFGF combined with compound polymyxin B ointment.The wound healing time,wound healing rate,positive detection rate of wound pathogens and wound inflammatory response were compared between the two groups after treatment.Results After 28 days of medication,the wound healing time of patients in the observation group was significantly shorter,and the wound healing rate was significantly higher than that in the control group(P＜0.05).The detection rate of pathogens in the burn wounds of the observation group was significantly lower than that of the control group at 7,14,21,and 28 days after treatment(P＜0.05).There was a statistically significant differ-ence in wound inflammatory response between the two groups(P＜0.05).Conclusion The rh-aFGF is effective in treatment of burn and scald wound,and it is conductive to promoting wound healing,shortening healing time,and reducing wound inflammatory responses.

In vitro erythrocyte manufacturing technology offers a novel solution for transfusion therapy,en-suring sustainable blood supply,reducing dependence on donors,and minimizing the risk of infectious disease transmission.This review summarizes recent advancements in in vitro erythrocyte production,including techniques for generating red blood cells(RBC)from various cell sources,with a focus on the cultivation and development of immortalized erythroid cell lines.The importance of enhancing enucleation efficiency and ensuring the safety of immortalized erythroid cells is emphasized.Additionally,the potential and challenges in clinical translation are discussed,aiming to provide new insights for future sustainable RBC supply and therapeutic applications.