ObjectiveTo construct and evaluate various machine learning models for predicting the risk of chronic obstructive pulmonary disease （COPD） in individuals， thereby providing data support for early screening and intervention. MethodsA total of 823 subjects were selected for this study， comprising 142 individuals in the high-risk group for COPD and 681 individuals in the low-risk group. Data collected included demographic characteristics， smoking history， symptoms （such as cough and shortness of breath）， and scores from the Chronic obstructive pulmonary disease screening questionnaire. Four machine learning algorithms—Logistic regression， random forest， support vector machine， and XGBoost—were utilized to construct risk prediction models. The performance of these models was assessed using 5-fold cross-validation， with evaluation metrics including accuracy， precision， recall， F1-score， area under the receiver operating characteristic curve （AUC）， and average precision （AP）. Furthermore， a feature importance analysis was performed. ResultsThe Logistic Regression model exhibited superior performance， achieving an AUC of 0.982 and an AP of 0.939. This was closely followed by the Random Forest model， which recorded an AUC of 0.975 and an AP of 0.890. Feature importance analysis revealed that smoking history， symptoms of shortness of breath， and body weight were significant predictors. All models demonstrated robust performance in identifying low-risk populations； however， variations were observed in their efficacy in identifying high-risk populations. ConclusionMachine learning models have proven effective in identifying individuals at high risk for COPD. Among these， the Logistic regression model exhibits the best overall performance， efficiently identifying high-risk populations and serving as a valuable clinical auxiliary screening tool. Various models， each with distinct performance characteristics， are suited to different clinical screening scenarios， thereby offering targeted decision-making support for the establishment of a hierarchical and intelligent COPD screening pathway.

Objective To evaluate the characteristics, related therapeutic regimens, risk factors of cardiovascular adverse events (CVAEs) and prognosis in the current therapy of newly diagnosed multiple myeloma (NDMM) patients in China. Methods A retrospective observational study was performed on patients with NDMM treated at Zhongshan Hospital, Fudan University, from January 2013 to October 2021. The propensity score matching at a ratio of 1∶1 was employed to balance baseline confounders between the therapeutic group and the control group, and CVAEs incidences were compared between the corresponding groups. Independent risk factors for CVAEs were identified through Fine-Gray competing risk regression model. Kaplan-Meier survival curves and log-rank tests were used to assess overall survival and progression-free survival of patients. Results A total of 829 patients with NDMM were analyzed, with a median of 33.1 months of follow-up for survivors. CVAEs occurred in 65 patients (7.8%) during first-line treatment, and a total of 74 events were recorded, with 52.7% grade 3 or greater in severity. Arrhythmia (particularly atrial fibrillation), thrombotic event (TE), and heart failure were the most common types. The median time from treatment to the first occurrence of CVAEs was 26 days, while the medium occurrence time of TE was later than the other events (76 d vs 19 d, P＝0.003). The exposure to immunomodulatory drugs was related to a higher incidence of TEs, whereas other therapeutic regimens, including bortezomib, didn’t show the effect of cardiovascular toxicity. Results of multivariate analysis showed that Eastern Cooperative Oncology Group performance status ＞2, symptomatic heart diseases within three months before treatment, and estimated glomerular filtration rate≤50 mL·min⁻¹·(1.73 m²)⁻¹ were independent risk factors for CVAEs. Compared with patients without CVAE, patients who experienced CVAEs had significantly inferior progression-free survival and overall survival, and higher cardiovascular mortality (P＜0.001). Conclusions The incidence of CVAE is relatively high during first-line treatment in NDMM patients, and the prognosis of CVAE patients is poor. The risk of CVAE is significantly increased in patients with underlying cardiovascular diseases.

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

With the widespread useof immune checkpoint inhibitors(ICIs)in the treatment of various solid tumors,immune-related adverse events have attracted increasing clinical attention.Although ICI-associated myocarditis is rare,it typically has an insidious onset,progresses rapidly,and carries a high mortality rate,making it one of the most severe complications of ICI therapy.Early recognition and management remain challenging due to the absence of standardized diagnostic and therapeutic guidelines.ICI-associated myocarditis is characterized by the following features,with symptom onset commonly occurring within weeks of initiating ICI therapy.Its clinical manifestations are often non-specific and can be misdiagnosed as coronary artery disease or viral myocarditis.Prompt administration of high-dose corticosteroids combined with immunosuppressants,cardiac rhythm and functional support,is crucial for effective management.Although numerous stud-ies highlight the importance of early detection and multidisciplinary collaboration,there is still no consensus on standardized treatment pro-tocols.This report describes a case of acute ICI-associated myocarditis with ovarian cancer who developed symptoms after receiving com-bined apalutamide and toripalimab therapy.The patient responded well to corticosteroid pulse therapy,second-line immunosuppressants,and intensive care support.Due to recurrent ventricular arrhythmias,an implantable cardioverter defibrillator was placed,and cardiac func-tion remained stable during follow-up.Through this case and a review of the relevant literature,we discuss the clinical features,compre-hensive treatment strategies,and long-term management approaches for ICI-associated myocarditis,aiming to raise clinical awareness,pro-mote standardized multidisciplinary team collaboration,and ultimately improve patient outcomes.

Objective:To explore the genetic testing outcomes of a fetal family with Thyroid secretion disorder type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.Methods:One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.(2021)GSFY(65)].Results:The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c. 413dupA(p.Tyr138*) frameshift mutation in exon 4 and c. 573G>A(p.Trp191*) nonsense mutation in exon 5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+ PM2_Supporting+ PM3) and likely pathogenic variant (PVS1+ PM2_Supporting), respectively. And the nonsense mutation c. 6972C>A(p.Tyr2264*) was detected in exon 46 of the NF1 in the fetus, inherited from the mother. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A(p.Tyr2264*) was classified as pathogenic variant (PVS1+ PS4_Supporting+ PP4+ PM2_Supporting). Conclusion:The mutations in the DUOXA2 gene c. 413dupA(p.Tyr138*) and c. 573G>A(p.Trp191*), and the NF1 gene c. 6972C>A(p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c. 573G>A(p.Trp191*) enriches the spectrum of pathogenic gene variations.

BACKGROUND:Ferroptosis is a programmed cell death mode regulated by iron dependent lipid peroxidation,closely related to the occurrence,development,and outcome of ischemic brain injury.With the continuous deepening of research on ferroptosis in recent years,it has been found that Chinese herbal compounds and monomers can regulate ferroptosis by reducing iron overload,reducing the production of reactive oxygen species,and regulating lipid synthesis,to alleviate cerebral ischemic injury and promote neurological function recovery.OBJECTIVE:To explore the relationship between ferroptosis and ischemic brain injury,and the mechanism by which traditional Chinese medicine regulates ferroptosis in the treatment of ischemic brain injury.METHODS:Literature on ferroptosis and ischemic brain injury and the regulatory mechanism of traditional Chinese medicine published from January 2018 to May 2024 was searched in CNKI and PubMed databases.The search terms were"iron death,ischemic stroke,brain injury,reactive oxygen species,lipid metabolism,traditional Chinese medicine formulas,terpenes,flavonoids,phenols,alkaloids,phthalides"in Chinese and English,respectively.Irrelevant,duplicated or outdated literature was excluded.A total of 1 526 relevant literature were retrieved,and 87 articles were ultimately included.RESULTS AND CONCLUSION:Numerous experimental studies have confirmed that ferroptosis plays an important role in ischemic brain injury.Chinese medicine prescriptions can regulate ferroptosis through various approaches,for examples:total saponins of Panax notoginseng can regulate iron metabolism and inhibit lipid peroxidation;carvacrol inhibits neuronal ferroptosis by increasing glutathione peroxidase 4 expression;Chinese herbal compounds and monomeric active ingredients can regulate ferroptosis-related pathways,such as glutathione/glutathione peroxidase 4(GPX4),nuclear factor E2-related factor 2(Nrf2)/hemoglobin oxygenase 1(HO-1),ferric death inhibitory protein 1(FSP1)/CoQ10 and guanosine triphosphate cyclohydrolase 1(GCH1)/tetrahydrobiopterin(BH4),to reduce neuronal damage and death,and exert neuroprotective effects.

BACKGROUND:Research has shown that endoplasmic reticulum stress-induced autophagy of neurons in the ischemic penumbra is a key link in cerebral ischemia-reperfusion injury.Autophagy mediated by the dissociation and activation of endoplasmic reticulum transmembrane proteins PERK,IRE1 α,ATF6,and GRP78/BIP plays an important role in neuronal outcomes.Traditional Chinese medicine can regulate endoplasmic reticulum stress-autophagy,reduce neuronal damage or death,and exert neuroprotective effects.OBJECTIVE:To explore the role of endoplasmic reticulum stress-autophagy in cerebral ischemia-reperfusion injury and the research progress in the regulatory mechanisms of traditional Chinese medicine.METHODS:A literature retrieval was conducted in CNKI and PubMed for relevant literature related to endoplasmic reticulum stress,autophagy,cerebral ischemia-reperfusion injury,and regulation by traditional Chinese Medicine published from January 2015 to May 2024.The search terms were"cerebral ischemia-reperfusion injury,ischemic stroke,brain injury,endoplasmic reticulum stress,autophagy,traditional Chinese medicine,compounds,signaling pathways,saponins,polyphenols,alkaloids"in Chinese and English,respectively.Any literature that is inconsistent with the research content,outdated,or duplicated was excluded.A total of 1197 relevant literature were retrieved,and 71 articles were ultimately included.RESULTS AND CONCLUSION:(1)Numerous studies have suggested that endoplasmic reticulum stress-autophagy is closely related with cerebral ischemia-reperfusion injury.(2)The active ingredients and compound formulas of traditional Chinese medicine monomers can regulate the expression of endoplasmic reticulum stress-autophagy related proteins,alleviate neuronal damage,and exert neuroprotective effects by regulating signal pathways such as PERK-eIF2α-ATF4,IRE1α-ASK1-JNK,and IRE1α-XBP.

Mitochondrial autophagy is an important mechanism for maintaining cellular homeostasis,closely related to the occurrence and development of cerebral ischemic injury,and is an important way of neuronal death.In recent years,a large number of experimental studies have confirmed that traditional Chinese medicine has a significant effect on treating cerebral ischemic injury.Its advantages of multi-target,multi pathway,low toxicity and high efficiency have become an important component of the treatment of cerebral ischemic injury.Traditional Chinese medicine formulas and monomeric active ingredients such as Xiaoxuming decoction,Zishen Huoxue formula,flavonoids,alkaloids,etc.can regulate mitochondrial autophagy related signaling pathways and targets,inhibit neuronal autophagic death,alleviate pathological damage to brain tissue,and exert neuroprotective effects.This article analyzes the molecular mechanism of traditional Chinese medicine regulating mitochondrial autophagy in the treatment of cerebral ischemic injury from four aspects:an overview of mitochondrial autophagy,related signaling pathways,its relationship with cerebral ischemic injury,and the regulatory effects of traditional Chinese medicine.The aim is to provide ideas and references for future basic research and clinical treatment.

OBJECTIVE: To explore the genetic testing outcomes of a fetal family with Thyroid dyshormonogenesis type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations. METHODS: One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.（2021）GSFY（65）]. RESULTS: The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c.413dupA (p.Tyr138*) frameshift mutation in exon4 and c.573G>A (p.Trp191*) nonsense mutation in exon5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+PM2_Supporting+PM3) and likely pathogenic variant (PVS1+PM2_Supporting), respectively. And the nonsense mutation c.6972C>A (p.Tyr2264*) was detected in exon46 of the NF1 in the fetus, inherited from the mother maternal grandfather. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A (p.Tyr2264 *) was classified as pathogenic variant (PVS1+PS4_Supporting+PP4+PM2_Supporting). CONCLUSION The mutations in the DUOXA2 gene c.413dupA (p.Tyr138*) and c.573G>A (p.Trp191*), and the NF1 gene c.6972C>A (p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c.573G>A (p.Trp191*) enriches the spectrum of pathogenic gene variations.
Humans ; Female ; Pedigree ; Pregnancy ; Neurofibromatosis 1/complications* ; Male ; Genetic Testing ; Adult ; Thyroid Dysgenesis/genetics* ; Fetus ; Exome Sequencing ; Mutation

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.