1.Evaluation of the anticoagulant effect of nafamostat mesylate in continuous veno-venous hemofiltration with different dilution methods for uremic patients
Li SHEN ; Yao ZHANG ; Jun WANG ; Hong ZHU ; Yong QIN ; Yuewu TANG ; Ni DU
China Pharmacy 2026;37(3):350-355
OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate (NM) in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration (CVVH) with different methods (pre- dilution and post-dilution). METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method, with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method, while the post-dilution group adopted the post-dilution replacement method. The coagulation, pressure, and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time (PT), prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), and fibrinogen (FIB) in the peripheral venous blood before the heparin pump and after the filter at 1, 4 and 7 h of CVVH treatment, as well as 20 min after the end of treatment, were compared between the two groups. The single-compartment urea clearance rate (spKt/V), β2-microglobulin (β2-MG) clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs, as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group (P<0.05), while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group (P<0.05). The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h, 4 h, and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group (P<0.001). There were no significant differences in PT, PT- INR, APTT and FIB between the two groups of patients 20 min after the end of treatment (P>0.05). The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group (P<0.001). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding, compared with the pre-dilution treatment method, the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir, a shorter usage time of the filter and pipeline, and a greater impact on extracorporeal coagulation, but has a higher solute clearance rate. Clinically, different dilution methods can be selected according to the different treatment needs of patients.
2.Exploring Anti-inflammatory Synergistic Mechanism of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice Based on Differential Component Tracking Strategy
Hongda XUAN ; Shengnan SHEN ; Linlin LI ; Jingjing LIAO ; Xianyu XU ; Xiaoxia LIU ; Haining LYU ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):228-237
ObjectiveTaking Aurantii Fructus Immaturus juice(AFI)-processed Atractylodis Macrocephalae Rhizoma(AMR) as an example, this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products, investigate the key differential components, evaluate their anti-inflammatory activities, and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry(GC-MS) and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology(NIST)17 database, comparison with retention index(RI) and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine (TCM) spectral library, in conjunction with PubChem and MassBank, characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis(PCA), orthogonal partial least squares-discriminant analysis(OPLS-DA), with variable importance in the projection(VIP) value >1. Components with high log2fold change(FC) among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide(NO) production in a lipopolysaccharide(LPS)-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay(ELISA) was used to detect the effects of the differential components on tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, and monocyte chemotactic protein(MCP)-1 levels, and immunofluorescence(IF) was employed to assess their effects on nuclear transcription factor(NF)-κB p65 translocation, thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR, among which, sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components, 36 compounds were identified, and the main differential components were flavonoids, sesquiterpenoids, and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products, representing compounds directly introduced during processing. Five compounds, including atractylenolide Ⅲ, tangeritin, nobiletin, hesperidin and narirutin, were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L-1 tangerine and narirutin could significantly inhibit LPS-induced NO production(P<0.01) in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7(P<0.05), while narirutin significantly inhibited the levels of TNF-α, IL-1β, MCP-1 and IL-6(P<0.01). IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR, and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.
3.Key Information Research and Modern Clinical Application of Xiaofengsan
Weilu NIU ; Mengjie YANG ; Chengqi LYU ; Cuicui SHEN ; Ningli WANG ; Huangchao JIA ; Liyun WANG ; Xuewei LIU ; Mingsan MIAO ; Xiaomeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):238-249
Employing bibliometric methods and adhering to principles of textual research, this study systematically investigated prescription source, formula name, composition evolution, dose evolution, origin, processing, ancient and modern applications of Xiaofengsan. Xiaofengsan, also known as Renshen Xiaofengsan and Chantui Xiaofengsan, was first recorded in the Taiping Huimin Hejijufang(hereafter referred to as Jufang) of the Southern Song dynasty. The formula composition included Schizonepetae Spica, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoptery Rhizoma et Radix, Bombyx Batryticatus, Saposhnikoviae Radix, Poria, Cicadae Periostracum, Pogostemonis Herba, Ginseng Radix et Rhizoma, Magnoliae Officinalis Cortex and Citri Reticulatae Pericarpium, a total of 12 medicinal materials. In terms of the evolution of formula composition, formulas across dynasties largely aligned with those recorded in Jufang, with only minor variations in application. The results of the formula dosage research indicated that one dose of medication in Jufang corresponded to the following modern dosages:Schizonepetae Spica of 82.6 g, Glycyrrhizae Radix et Rhizoma of 82.6 g, Chuanxiong Rhizoma of 82.6 g, Notoptery Rhizoma et Radix of 82.6 g, Bombyx Batryticatus of 82.6 g, Saposhnikoviae Radix of 82.6 g, Poria of 82.6 g, Cicadae Periostracum of 82.6 g, Pogostemonis Herba of 82.6 g, Ginseng Radix et Rhizoma of 82.6 g, Magnoliae Officinalis Cortex of 20.65 g and Citri Reticulatae Pericarpium of 20.65 g, the origins of all the constituent drugs were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. The results of the investigation into the decoction method indicated that the aforementioned drugs should be finely ground into powder(pass through the No.5 sieve), and 8.26 g was taken for each dose, which was taken with the clear liquid obtained by steeping tea leaves in boiling water for several minutes. This mixture was administered three times daily, 30 min after meals. The ancient functional indications of this formula mainly involved dispelling wind-heat, eliminating pathogenic factors and regulating the middle Jiao. It primarily treated all wind-heat syndromes manifesting as skin diseases, predominantly affecting the upper body, especially the head and face. The diseases involved in modern applications were mostly dermatological diseases, including urticaria, eczema, atopic dermatitis and others. In this paper, by combing the relevant ancient literature, the key information of Xiaofengsan was textual researched, in order to provide reference for the modern application and development of this formula.
4.Efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneu-monia in children
Qingmei ZHU ; Jing WANG ; Lili SHI ; Dongliang YANG ; Jiawei HE ; Jing SHEN ; Jianhua YANG
China Pharmacy 2026;37(4):480-485
OBJECTIVE To investigate the efficacy and safety of omadacycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) in children. METHODS A retrospective study was conducted on children aged 1-18 years old with MUMPP who were hospitalized in the Department of Pediatrics, the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2025. According to the selection of secondary antibiotics after 72 h of initial treatment with macrolides, they were divided into the omadacycline group and the doxycycline group. Based on conventional treatment, children in the omadacycline group were given intravenous infusion of 2.4 mg/kg (once daily) of omadacycline tosylate, while children in the doxycycline group were given oral doxycycline hydrochloride tablets at 2 mg/kg (twice daily). The efficacy and safety were compared between the two groups of pediatric patients. Univariate analysis and multivariate Logistic regression analysis were performed on clinical efficacy, and subgroup analysis along with multiple sensitivity analyses were conducted to verify the robustness of the conclusions. RESULTS A total of 284 children with MUMPP were included in this study, with 142 in the omadacycline group and 142 in the doxycycline group. In terms of efficacy, although the hospitalization time of children in the omadacycline group was longer than that in the doxycycline group ( P <0.05), the lung lesion absorption rate and clinical efficacy were significantly higher or better than those in the doxycycline group ( P <0.05). The results of multivariate Logistic regression analysis showed that medication (OR=5.300, 95%CI: 2.526-11.123), length of hospital stay (OR=1.348, 95%CI: 1.167-1.556), and medication duration (OR=1.422, 95%CI: 1.169-1.729) were influencing factors of clinical efficacy ( P <0.05). The subgroup analysis results showed that the clinical efficacy of omadacycline was significantly better than that of doxycycline in all subgroups ( P <0.05). The results of multiple sensitivity analysis showed that the regression coefficients B of the four models (gradually adjust variables) before and after inverse probability of treatment weighting were significantly greater than 1 ( P <0.05). In terms of safety, there was no statistically significant difference in the inci dence of adverse drug reactions between the two groups of patients ( χ 2 =0.447, P =0.504). CONCLUSIONS In the case of hospitalization and prolonged medication, the efficacy of omadacycline in treating childhood MUMPP is superior to that of doxycycline, and its safety is good.
5.Predicting intraoperative blood transfusion risk in hip fracture patients using explainable machine learning models
Fengting LU ; Xiaoming LI ; Dekui LI ; Xianyuan XIE ; Jiazhong WANG ; Qing YU ; Gan HUANG ; Jun SHEN
Chinese Journal of Blood Transfusion 2026;39(2):196-202
Objective: To investigate the factors influencing intraoperative blood transfusion in patients with hip fractures and to develop a machine learning (ML) model for predicting this risk. Methods: A total of 424 patients with hip fractures who underwent surgical treatment between November 2022 and March 2025 in our hospital were selected. Key feature variables of intraoperative blood transfusion risk were identified using the Boruta algorithm. Four different ML algorithms—support vector machine (SVM), linear discriminant analysis (LDA), mixed discriminant analysis (MDA), and extreme gradient boosting (XGBoost)—were used to develop predictive models for intraoperative blood transfusion risk. The predictive performance of the four ML models were evaluated using accuracy, precision, receiver operating characteristic (ROC) curves, precision-recall curves (PRC), precision-recall gain curves (PRGC), and F1 scores. Shapley additive interpretation (SHAP) was used to interpret the final model. Results: Among the 424 patients, 77(18.2%) received intraoperative blood transfusion. The Boruta algorithm identified albumin (ALB), activated partial thromboplastin time (APTT), types of anesthesia, types of fracture, and hemoglobin (Hb) as key feature variables for predicting intraoperative blood transfusion risk. In model evaluation, the SVM model outperforms the other three models across multiple metrics, including the area under the receiver operating characteristic curve (AUC), recall, recall gain, accuracy, precision, F1 score, and the area under the precision-recall curve (PRC-AUC). The SVM model, interpreted and visualized based on SHAP values, effectively predicted intraoperative blood transfusion risk in patients with hip fracture. A visual online application was developed based on the SVM model (https://pbo-nomogram.shinyapps.io/blood/). Conclusion: Preoperative low ALB and Hb levels, prolonged APTT, general anesthesia, and intertrochanteric fractures are risk factors for intraoperative blood transfusion in hip fracture patients. The risk prediction model for intraoperative blood transfusion constructed based on the SVM algorithm has optimal performance, which provides new ideas and methods for the clinical early identification of hip fracture patients with high transfusion risk and the implementation of targeted interventions.
6.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
7.Study on the safety and efficacy of micro-perfusion device for preserving isolated porcine limbs
Pengkai LI ; Zhaodi MI ; Shen LI ; Man YUAN ; Xiwei PENG ; Jia LÜ ; Sice WANG ; Zhibo JIA ; Xiangyu SONG ; Yixuan ZHU ; Chonghui LI ; Moling XIAO ; Wenjing XU ; Jiang PENG
Organ Transplantation 2026;17(3):422-431
Objective To evaluate the safety and efficacy of a self-developed micro-normothermic machine perfusion (NMP) system (micro-perfusion device) for preserving isolated porcine limbs. Methods Five healthy Landrace pigs were selected, and their left and right forelimbs were randomly divided into the NMP group and static cold storage (SCS) group. The NMP group was perfused with the self-developed micro-perfusion device and polymerized hemoglobin perfusate for 32 hours at normothermia, while the SCS group was preserved at 4 ℃. Hemodynamic parameters such as perfusion pressure and flow were monitored. The pH value, partial pressure of oxygen (PO2), lactic acid (Lac), creatine kinase (CK) and lactate dehydrogenase (LDH) in the perfusate were measured. Hematoxylin-eosin staining was used to assess the muscle tissue structure, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was employed to evaluate muscle cell apoptosis, and immunohistochemistry staining was applied to detect the expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6. A mixed-effects model was used to analyze the effects of time and treatment methods on tissue structure, cell apoptosis and inflammatory factors. Results The device could stably maintain a perfusion pressure of (69±15) mmHg and a flow rate of (117±42) mL/min. The pH value and electrolytes of the perfusate were generally stable, with PO2 maintained at a high level. Lac was maintained at 5.38(3.81, 6.45) mmol/L, while CK and LDH increased over time. After 32 hours of perfusion in the NMP group, both the myocyte spacing and apoptosis rate were better than those in the SCS group. Mixed-effects model analysis showed that there were statistically significant differences in the effects of NMP treatment and SCS treatment on myocyte spacing and apoptosis rate per unit time (both P < 0.05). There were no statistically significant differences in TNF-α and IL-6 between the two groups, and mixed-effects model analysis showed no statistically significant differences in the effects of NMP treatment and SCS treatment on TNF-α and IL-6 per unit time (both P > 0.05). Conclusions The micro-perfusion device used in this study may achieve 32-hour normothermic preservation in a porcine limb amputation model, maintain basic metabolism and ionic homeostasis, reduce muscle structural damage and cell apoptosis without inducing additional inflammatory responses. This technology is expected to significantly extend the time window for replantation of amputated limbs in disaster rescue and long-distance transportation, providing an important technical basis for clinical translation and subsequent replantation research.
8.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
9.Therapeutic effects of carbon monoxide-saturated hemoglobin-loaded oxygen carrier on idiopathic pulmonary fibrosis in mice
Peichen XU ; Shen LI ; Wanjin LI ; Hong WANG ; Jiaxin LIU ; Ye CAO ; Rui ZHONG
Chinese Journal of Blood Transfusion 2026;39(4):478-485
Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.
10.Analysis of ten cases of Acute lymphoblastic leukemia with non-KMT2A::AFF1 transcriptional variant 11q23 rearrangements.
Yuanyuan WANG ; Shuzhen FU ; Yong SHEN ; Qingxia XU
Chinese Journal of Medical Genetics 2026;43(4):265-272
OBJECTIVE:
To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes.
METHODS:
The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342).
RESULTS:
Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months.
CONCLUSION
The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
;
Female
;
Male
;
Myeloid-Lymphoid Leukemia Protein/genetics*
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Histone-Lysine N-Methyltransferase/genetics*
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Adult
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Adolescent
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Chromosomes, Human, Pair 11/genetics*
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Child
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Transcriptional Elongation Factors/genetics*
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Gene Rearrangement
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Oncogene Proteins, Fusion/genetics*
;
Retrospective Studies
;
Young Adult
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Middle Aged
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Prognosis
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Child, Preschool
;
DNA-Binding Proteins/genetics*

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