Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

The concept of'harmony'is the soul of traditional Chinese culture,which has a profound impact on the formation and development of traditional Chinese medicine(TCM).TCM is rooted in traditional Chinese culture,and the mode of thinking in TCM is in line with traditional Chinese culture.Based on the harmony culture,TCM has developed a unique view of health,disease and therapeutics.From the view of the harmony culture and by combining with years of clinical experience in treating dermatosis,Chinese medical master XUAN Guo-Wei has applied the concept of'harmony'in the TCM syndrome differentiation and treatment system in clinic,and has developed the academic thoughts of harmonizing therapy for removing toxins for the diagnosis and treatment of dermatosis.The thoughts of harmonizing therapy for removing toxins includes four aspects,namely harmonizing yin and yang,harmonizing healthy qi and pathogenic qi,harmonizing water and fire(i.e.,clod and hot),and harmonizing the administration of formula and drugs,aiming to remove toxins and expel pathogens and value the harmony.The thoughts of harmonizing therapy for removing toxins will beneficial to the comprehensive understanding of the unique health-disease-therapeutics concept in TCM,and will be helpful for managing the doctor-patient relationship,which is of enlightening significance to the modern clinical practice with TCM.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the factors influencing prognosis in patients with acute myocardial infarction complicated with cardiogenic shock undergoing primary percutaneous coronary intervention(PPCI).Methods Patients with acute myocardial infarction complicated with cardiogenic shock who underwent PPCI at our hospital between January 2015 and December 2019 were enrolled.Clinical baseline characteristics,coronary angiography and PCI-related parameters,and mechanical support information were collected.The patients were followed up for one year and divided into survival and death groups based on their survival status within one year.Differences in various factors between the two groups were compared.Results A total of 40 patients were enrolled,including 26 in the survival group and 14 in the death group.There were no differences in baseline data,diagnosis,risk factors,and comorbidities between the two groups.The survival group had a lower heart rate and higher blood pressure trend at admission compared to the death group.Myocardial enzymes were significantly lower in the survival group compared to the death group(median CK peak:496.00(198.25,2 830.00)U/L vs.3 040.00(405.75,5 626.53)U/L,P=0.003;median CK-MB peak:52.65(31.75,219.50)U/L vs.306.00(27.25,489.63)U/L,P=0.006).When comparing coronary angiography and PCI-related indicators between the two groups,the survival group had a higher rate of complete revascularization compared to the control group(53.85％vs.21.43％,P=0.048).The survival group had a higher proportion of extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)support compared to the control group[38.46％vs.7.14％,P=0.034].Conclusions Survival in patients with acute myocardial infarction complicated with cardiogenic shock undergoing PPCI is associated with lower level of myocardial enzymes,ECMO combined with IABP support and complete revascularization.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Invasive fungal infections threaten the lives and health of humans, especially immunodeficient patients or hospitalized patients with serious underlying diseases, and impose a heavy economic burden on society. The emergence of drug-resistant fungi, the formation of biofilms, and the limits and side effects of existing antifungal drugs increase the difficulty of clinical treatment, and there is an urgent need for the development of novel antifungal drugs. Therefore, based on previous kinase chemical library antifungal activity screening studies, this paper further investigates the activity of anaplastic lymphoma kinase (ALK) inhibitor 3-[5-chloro-2-({2-methoxy-4-[4-(4-methylpiperazin-1-yl)hexahydropyridin-1-yl]phenyl}amino)pyrimidin-4-yl]-1H-indole (HG-14-10-04, HG) against various fungi and elucidates its mechanism of action. The in vitro antifungal activity of HG was evaluated by micro liquid-dilution method, time-killing curve, mycelium formation and biofilm formation assays. The results showed that HG exhibited inhibitory and even fungicidal effects against sensitive and resistant Candida albicans, Candida krusei, Cryptococcus neoformans, Candida tropicalis, Candida glabrata and Candida parapsilosis (MICs = 8-16 μg·mL^-1); HG significantly inhibited the mycelium and biofilm formation, and destroyed the mature biofilm; and it exhibited synergistic antifungal effects with amphotericin B. The antifungal mechanism of HG was investigated by flow cytometry and transmission electron microscopy, etc. Sequencing analysis showed a total of 1 041 differentially expressed genes, of which 666 were up-regulated and 375 were down-regulated. According to the GO functional classification results, the up-regulated genes were mainly involved in ribosome production, oxidation-reduction and other functions, while the down-regulated genes were mainly involved in the synthesis of carbohydrate, glycoproteins, glycolipids and their metabolism, GPI anchor synthesis, and cytoskeleton and other functions. In addition, HG could significantly increase the level of reactive oxygen species (ROS), induce the fungal necrosis, block the cell cycle at the G0/G1 phase, and change the ultrastructure of the fungi, especially the structure of the fungal cell wall. Therefore, the enhanced inhibitory and fungicidal activity of HG may be related to the elevation of ROS, alteration of cellular ultrastructure (especially cell wall structure) and cell cycle arrest at the G0/G1 phase. Further optimization of its structure will provide a basis for the discovery of novel antifungal drugs or lead compounds.

Humans ; Rituximab/therapeutic use* ; Bendamustine Hydrochloride/therapeutic use* ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Lymphoma, B-Cell ; Protein Kinase Inhibitors/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome

End-stage patients experience unbearable pain because of refractory symptoms.Palliative sedation is a form of palliative care which relieves patients' agony by lowering their consciousness.Standard palliative sedation can help patients die with dignity.It is distinct from euthanasia and does not alter the survival of patients.Sufficient palliative care is the premise of palliative sedation.Repeated and detailed clinical evaluation,as well as multidisciplinary involvement,is necessary for the standardized implementation of palliative sedation.Here,we proposed the standard process and specifications of palliative sedation in Peking Union Medical College Hospital.Furthermore,we reported a case of palliative sedation for an advanced cancer patient with refractory delirium and living pain to demonstrate its application in clinical practice.
Humans ; Anesthesia ; Pain ; Hospitals ; Palliative Care ; Universities

Ginsenoside Rg1 is one of the most important saponins in ginseng. It has a wide range of pharmacological activities. It is considered to be a powerful neuroprotective agent. It has neuroprotective effects such as anti-neuroinflammation, anti-oxidative stress, anti-neuronal apoptosis, and enhancing memory. Rg1 shows a good application prospect in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, stroke, and mental diseases such as depression. This paper reviews the research on the neuroprotective mechanism of Rg1 at home and abroad in recent years, in order to provide new research ideas for the clinical treatment of nervous system diseases.