1.Mechanism Exploration of Doxorubicin and Sepsis Induced Myocardial Injury: Differences and Convergences
Tao ZHANG ; Zihan NAN ; Lixia LIU ; Jiaqi LIU ; Xiukai CHEN ; Xiaoting WANG ; Suwen SU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):23-32
Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.
2.Explainable Machine Learning Model for Predicting Prognosis in Patients with Malignant Tumors Complicated by Acute Respiratory Failure: Based on the eICU Collaborative Research Database in the United States
Zihan NAN ; Linan HAN ; Suwei LI ; Ziyi ZHU ; Qinqin ZHU ; Yan DUAN ; Xiaoting WANG ; Lixia LIU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):98-108
To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework. Clinical data of patients with malignant tumors and ARF were extracted from the eICU Collaborative Research Database in the United States, including demographic characteristics, comorbidities, vital signs, laboratory test indicators, and major interventions within the first 24 hours after ICU admission.The study outcome was ICU death.Enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3.Predictor variables were selected using least absolute shrinkage and selection operator (LASSO) regression.Five machine learning algorithms-extreme gradient boosting (XGBoost), support vector machine (SVM), Logistic regression, multilayer perceptron (MLP), and C5.0 Decision Tree-were employed to construct predictive models.Model performance was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and other metrics.The optimal model was further interpreted using the Shapley additive explanations (SHAP) algorithm. A total of 3196 patients with malignant tumors complicated by ARF were included.The training set comprised 2, 261 patients and the validation set 935 patients; 683 patients died during ICU stay, while 2513 survived.LASSO regression ultimately selected 12 variables closely associated with patient ICU outcomes, including sepsis comorbidity, use of vasoactive drugs, and within the first 24 hours after ICU admission: minimum mean arterial pressure, maximum heart rate, maximum respiratory rate, minimum oxygen saturation, minimum serum bicarbonate, minimum blood urea nitrogen, maximum white blood cell count, maximum mean corpuscular volume, maximum serum potassium, and maximum blood glucose.After model evaluation, the XGBoost model demonstrated the best performance.The AUCs for predicting ICU mortality risk in the training and validation sets were 0.940 and 0.763, respectively; accuracy was 88.3% and 81.2%;sensitivity was 98.5% and 95.9%.Its predictive performance also remained optimal in sensitivity analyses.SHAP analysis indicated that the top five variables contributing to the model's predictions were minimum oxygen saturation, minimum serum bicarbonate, minimum mean arterial pressure, use of vasoactive drugs, and maximum white blood cell count. This study successfully developed a mortality risk prediction model for ICU patients with malignant tumors complicated by ARF based on a large-scale dataset and performed explainability analysis.The model aids clinicians in early identification of high-risk patients and implementing individualized interventions.
3.Clinical comprehensive evaluation of 16 commonly used kinds of enteral nutrition preparations in Hebei province
Zhihan ZHANG ; Yue CHENG ; Lamei XU ; Qingsong LI ; Yuan GAO ; Congxin LI ; Shuqing GAO
China Pharmacy 2026;37(3):281-287
OBJECTIVE To comprehensively evaluate the 16 commonly used kinds of enteral nutrition preparations in Hebei province, aiming to provide a reference for the selection of drugs in medical institutions and clinical drug decision-making. METHODS Based on the Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions (the Second Edition), evaluation evidence was collected, and the included drugs were scored and evaluated from four dimensions of pharmaceutical characteristics, clinical characteristics, economy and other attributes. RESULTS & CONCLUSIONS The scores for Enteral nutritional emulsion (TPF-T), Enteral nutritional emulsion (TPF-D), Enteral nutritional emulsion (TPF), Enteral nutritional emulsion (TPF-HE), Enteral nutritional emulsion (TP), Enteral nutritional emulsion (SP), Enteral nutritional suspension (TPF) (1.5 kcal/mL, 1 kcal=4.184 kJ), Enteral nutritional suspension (TPF) (1.0 kcal/mL), Intact protein enteral nutrition (powder), Enteral nutritional suspension (TPF-DM), Enteral nutritional suspension (TPF-MCT), Enteral nutritional suspension (SP), Short- peptide enteral nutrition, Enteral nutritional powder (TP), Enteral nutritional suspension (TPF-D) and Enteral nutritional suspension (TPF-FOS) were 82.9, 84.1, 84.1, 86.1, 78.4, 79.1, 82.6, 82.3, 82.4, 80.2, 83.0, 82.4, 82.1, 85.7, 76.0, 82.4 points, respectively. All medications scored above 70 points. In practice, appropriate drugs can be selected according to clinical requirements and patient needs.
4.Impact of X-ray irradiation on stored platelets and their mitochondrial function
Na WANG ; Ning AN ; Xiaoying WANG ; Dongyan YANG ; Xiaole ZHANG ; Yajuan WANG ; Jie CHEN ; Xingbin HU ; Chen CHEN
Chinese Journal of Blood Transfusion 2026;39(1):16-23
Objective: To investigate the effects of clinical routine X-ray irradiation dose (average irradiation dose: 29.7±0.54 Gy) on the function, apoptosis, activation state and mitochondrial function of platelets during in vitro storage, so as to provide experimental evidence for optimizing platelet irradiation strategies. Methods: A paired experimental design was adopted. Platelets were collected from 12 healthy donors, and each sample was equally divided into the irradiated group and the control group (non-irradiated). All samples were stored for 5 days under standard platelet preservation conditions (22±2℃, continuous oscillation). Flow cytometry was used to detect platelet count, apoptosis rate (Annexin V+ positive rate), activation markers (CD62P, PAC-1, CD42b) and reactive oxygen species (ROS) level. Meanwhile, mitochondrial-specific probes were used to evaluate changes in mitochondrial count, membrane potential and adenosine triphosphate (ATP) content. Additionally, transmission electron microscopy (TEM) was employed to observe the ultrastructure of platelets, with a focus on mitochondrial morphology, platelet membrane integrity and granule distribution. Results: Within 5 days of storage, the platelet count was (841±89.16)×10
/L in the irradiated group and (824.5±92.88)×10
/L in the control group, with no statistically significant difference between the two groups (P=0.54). The apoptosis rate was (4.94±1.39) % in the irradiated group and (5.50±0.83) % in the control group, showing no significant difference (P=0.31). For activation indicators, the CD62P expression rate was (24.32±7.57) % in the irradiated group versus (25.21±8.13) % in the control group (P=0.43). The PAC-1 positive rates were (12.15±4.43) % and (11.75±3.40) % in the irradiated group and control group, respectively (P=0.44). The CD42b expression rates were (12.14±4.43) % and (11.75±3.4) % in the two groups, respectively (P=0.47). The ROS levels were (31.98±8.1) % and (30.64±5.89) % in the two groups, respectively (P=0.45). No significant differences were found in the above indicators. For mitochondrial function indicators, the mitochondrial count was (55.88±11.49) % in the irradiated group and (53.5±7.24) % in the control group (P=0.57). The ATP contents were (42.45±5.29) % and (41.58±9.50) % in the irradiated group and control group, respectively (P=0.77). The relative membrane potential values were (59.53±10.89) % and (57.49±6.54) % in the two groups, respectively (P=0.47). No significant difference were observed on the mitochondrial function-related indicators. TEM further confirmed that the ultrastructure of platelets in the irradiation group was intact, the mitochondrial morphology was normal, and no pathological changes such as swelling or vacuolization were observed. Conclusion: This study evaluated the impact of conventional-dose X-ray irradiation on platelet storage quality, confirming that this dose does not significant impair platelet count, apoptosis rate, activation status, or mitochondrial function. This finding provides important experimental evidence for the clinical promotion of X-ray irradiation technology and suggests its potential as a safe alternative to γ irradiation. Future studies could further expand the sample size and extend the observation period to verify the effects of X-ray irradiation on long-term platelet storage and post-transfusion in vivo survival rate.
5.Predictive value of aqueous humor stromal cell-derived factor-1 and epithelial neutrophil-activating peptide-78 levels for visual impairment following vitrectomy in patients with diabetic retinopathy
Man XU ; Jiamin ZHENG ; Wenjin ZHONG
International Eye Science 2026;26(3):493-498
AIM:To investigate the predictive value of aqueous humor stromal cell-derived factor-1(SDF-1)and epithelial neutrophil-activating peptide-78(ENA78)for visual impairment following vitrectomy in patients with diabetic retinopathy(DR).METHODS: Patients with DR who underwent vitrectomy in the ophthalmology department of our hospital from March 2022 to March 2024 were enrolled as study group. According to the results of uncorrected visual acuity examination during the 1-year follow-up after surgery, they were further divided into visual impairment group and good visual acuity group. In addition, patients with cataracts who were treated in our hospital during the same period were recruited as control group. The levels of SDF-1 and ENA78 in aqueous humor were detected by enzyme-linked immunosorbent assay(ELISA). Pearson correlation analysis was used to evaluate the correlation of indicators. Multivariate Logistic regression analysis was performed to identify the influencing factors of postoperative visual impairment in DR patients. Relative risk analysis was conducted to assess the impact of different aqueous humor SDF-1 and ENA78 levels on postoperative visual impairment in DR patients. Receiver operating characteristic(ROC)curve analysis was applied to determine the predictive value of aqueous humor SDF-1 and ENA78 levels for postoperative visual impairment in DR patients.RESULTS: Totally 156 cases(156 eyes)were enrolled in the study group, including 87 males and 69 females, with a mean age of 60.65±8.91 years old; and 91 cases(91 eyes)were enrolled in the control group, including 53 males and 38 females, with a mean age of 58.72±8.43 years old. The levels of SDF-1 and ENA78 in aqueous humor of the study group were significantly higher than those of the control group(P<0.001). According to the results of uncorrected visual acuity during the 1-year follow-up after surgery, the study group was further divided into the visual impairment group(n=49)and the good visual acuity group(n=107), including 28 males and 21 females in the visual impairment group, with a mean age of 63.73±7.41 years, and 59 males and 48 females in the good visual acuity group, with a mean age of 59.24±8.47 years. The age and glycated hemoglobin(HbA1c)levels of the visual impairment group were higher than those of the good visual acuity group(all P<0.05). Compared with the good visual acuity group, the levels of SDF-1 and ENA78 in aqueous humor of the visual impairment group were significantly elevated(all P<0.05). A positive correlation was found in the study group between the levels of SDF-1, ENA78 in aqueous humor and HbA1c(r=0.314, 0.362, all P<0.05). Elevated levels of aqueous humor SDF-1(OR=2.936, 95% CI: 1.628-5.296)and ENA78(OR=3.092, 95% CI: 1.738-5.502)were identified as risk factors for postoperative visual impairment in DR patients(all P<0.05). High levels of SDF-1 and ENA78 increased the risk of postoperative visual impairment by 1.958-fold and 2.030-fold compared with the low-level groups, respectively; the area under the curve(AUC)of combined detection of aqueous humor SDF-1 and ENA78 for predicting postoperative visual impairment in DR patients was 0.936, which was superior to the predictive value of SDF-1 or ENA78 alone(Zcombination-SDF-1=2.850, Zcombination-ENA78=2.445, all P<0.05).CONCLUSION: Elevated levels of aqueous humor SDF-1 and ENA78 are risk factors for postoperative visual impairment in DR patients, and the combined detection of SDF-1 and ENA78 has high clinical application value for predicting postoperative visual impairment in DR patients.
6.The Role of Histone Lactylation in Diseases and Intervention by Traditional Chinese Medicine
Xin ZHANG ; Jie DU ; Zhao-Huan LI ; Feng GAO
Progress in Biochemistry and Biophysics 2026;53(4):887-904
Histone lactylation is a recently identified post-translational modification, wherein lactate mediates the enzymatic addition of lactyl groups to lysine residues on histones. Since its discovery, extensive research has demonstrated that histone lactylation is widely present in human tissues and plays a pivotal role in regulating the transcription of specific genes. Subsequent studies have further established this modification as a widespread epigenetic mark with significant physiological implications. With advancing research, accumulating evidence confirms that lactylation at distinct histone sites elicits diverse biological effects—such as promoting cell proliferation, driving inflammatory responses, and enhancing fibrosis—all of which profoundly influence disease progression and serve as key drivers of disease onset and development. Conversely, inhibiting histone lactylation can alter disease outcomes, positioning histone lactylation as a promising therapeutic target. Moreover, studies have revealed crosstalk between histone lactylation and other post-translational modifications, such as acetylation and methylation, which collectively regulate disease progression. Notably, lactylation occurs not only on histones but also on non-histone proteins. Histone lactylation activates specific gene transcription and reshapes metabolic epigenetics, while non-histone lactylation directly modulates enzyme activity, signal transduction, and protein stability. These two facets form a synergistic network through shared lactate pools, common modifying enzyme systems, and pathway crosstalk, thereby constructing a multi-dimensional regulatory framework—namely, the “histone lactylation-metabolism hub-non-histone lactylation” axis. This architecture bridges metabolism and epigenetics, and deciphering its topological structure may provide novel targets for precise intervention in diseases driven by lactate-mediated signaling hijacking. Traditional Chinese medicine (TCM), grounded in clinical practice, has been shown to regulate histone lactylation by modulating lactate metabolism and lactylation-related enzymes, thereby influencing disease progression. Moreover, certain TCM formulations exhibit potential as alternative therapies for drug-resistant diseases, underscoring the significance of further exploring TCM-mediated regulation of histone lactylation in future therapeutic strategies. This review aims to elucidate the mechanisms underlying histone lactylation, systematically delineate the associations between site-specific histone lactylation and various diseases, present a comprehensive landscape of the “lactate-histone lactylation and functional protein lactylation” axis, and summarize the mechanistic basis and research advances in TCM-mediated regulation of histone lactylation for disease treatment. Additionally, we discuss current challenges in histone lactylation research and propose future directions, ultimately aiming to deepen understanding and broaden perspectives on the roles and therapeutic potential of histone lactylation in disease.
7.Evaluation and decision-making for liver transplantation in acute-on-chronic liver failure: Evolution, integration, and challenges
Journal of Clinical Hepatology 2026;42(3):535-540
Acute-on-chronic liver failure (ACLF) is a syndrome of acute liver function decompensation in patients with chronic liver disease and is characterized by a high short-term mortality rate. Liver transplantation is an effective radical treatment method for ACLF and can significantly improve the survival rate of patients. However, in the context of a shortage of donor organs globally, how to achieve a balance between saving lives and avoiding futile transplantation while optimizing organ utilization is a critical challenge in clinical decision-making. This article systematically reviews the evolution of the evaluation and decision-making system for liver transplantation in ACLF patients and points out s that the core of this system has shifted from relying solely on the MELD score to a model based on multidimensional prognostic assessment, dynamic evaluation, and multidisciplinary collaboration. In the future, the integration of Eastern and Western criteria, the application of artificial intelligence for precise prediction, and the establishment of a more equitable priority and allocation system will be the key directions for development in this field.
8.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.
9.Effects of ω-3 polyunsaturated fatty acid combined with clomiphene on clinical efficacy,pregnancy and safety in patients with polycystic ovary syndrome
Hailing HU ; Qiongjiao ZHOU ; Dan XIE ; Yu CAI
China Pharmacy 2026;37(9):1190-1194
OBJECTIVE To investigate the effects of ω-3 polyunsaturated fatty acid (ω-3PUFA) combined with clomiphene on clinical efficacy, pregnancy and safety in patients with polycystic ovary syndrome (PCOS). METHODS A retrospective analysis was performed on the clinical data of 112 PCOS patients who received treatment in Dept. of Obstetrics and Gynecology of Hunan Prevention and Treatment Institute for Occupational Diseases from January 2022 to December 2023. According to the different treatment regimens, the patients were divided into single-drug group (60 cases) and drug-combination group (52 cases). Single-drug group was given clomiphene orally, and drug-combination group was given clomiphene+ω-3PUFA. Clinical efficacy, pregnancy status and the occurrence of adverse drug reaction (ADR) as well as ovarian function and oxidative stress indexes before and after treatment were compared between 2 groups. RESULTS The overall response rate (90.38% vs. 71.67%), ovulation rate (84.62% vs. 61.67%), and pregnancy rate (51.92% vs. 26.67%) were all markedly higher in drug combination group than single drug group ( P <0.05). Before treatment, there was no statistical significance in ovarian function and oxidative stress indexes between 2 groups ( P >0.05). Compared with before treatment, serum anti-Müllerian hormone levels, inhibin B concentr ations, and the number of cystic follicles in 2 groups were decreased significantly after 12 weeks of treatment ( P <0.05). The endometrial thickness increased significantly ( P <0.05), while the serum levels of malondialdehyde and advanced oxidation protein products decreased significantly ( P <0.05); the activities of serum superoxide dismutase and glutathione peroxidase increased significantly ( P <0.05); the improvement of drug combination group was significantly better than single drug group ( P <0.05). The ovarian volumes in both groups were significantly smaller after treatment compared to before treatment ( P <0.05), but there was no statistically significant difference between the two groups ( P >0.05). There was no significant difference in the overall incidence of ADR between the two groups during the treatment ( P >0.05). CONCLUSIONS The combination of ω-3PUFA and clomiphene has a definite therapeutic effect on PCOS, which can effectively reduce the body’s oxidative stress response, improve ovarian function, and increase ovulation and pregnancy rates.
10.Fabrication and evaluation of an inositol hexaphosphate-zinc hydrogel with dual capabilities of self-mineralization and osteoinduction
LIU Mingyi ; MIAO Xiaoyu ; CAI Yunfan ; WANG Yan ; SUN Xiaotang ; KANG Jingrui ; ZHAO Yao ; NIU Lina
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(1):29-40
Objective:
To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials.
Methods:
The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group
Results:
The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group.
Conclusion
The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.


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