OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

OBJECTIVE: To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation. METHODS: The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups. RESULTS: The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups. CONCLUSION Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.
Child ; Child, Preschool ; Graft vs Host Disease/complications* ; Hematopoietic Stem Cell Transplantation ; Humans ; Quality of Life ; Retrospective Studies ; Thalassemia/therapy* ; beta-Thalassemia/therapy*

ObjectiveTo study the clinical efficacy of dapagliflozin combined with Shexiang Baoxinwan （SXBXW） in the treatment of acute heart failure with reduced ejection fraction （HFrEF） and syndrome of Qi deficiency and blood stasis. MethodA total of 176 patients hospitalized due to acute HFrEF （syndrome of Qi deficiency and blood stasis） were selected and randomized into control group， SXBXW group， dapagliflozin group， and SXBXW + dapagliflozin group （the latter three groups were called the intervention groups）. The New York Heart Association （NYHA） class， 6-minute walk test （6MWT） score， Kansas City Cardiomyopathy Questionnaire （KCCQ） score， traditional Chinese medicine （TCM） syndrome score， N-terminal pro-brain natriuretic peptide （NT-proBNP）， soluble suppression of tumorigenicity 2 （sST2）， interleukin-6 （IL-6）， and hypersensitive C-reactive protein （hs-CRP） of the patients were evaluated and measured at the time of admission， 1 week after treatment， and 2 weeks of treatment. Furthermore， the hospital stay， in-hospital mortality， and 30-day re-admission rate were recorded. Statistical analysis was performed to evaluate the efficacy of each group. ResultAfter 1 week of treatment， the SXBXW group exhibited superior NYHA class， KCCQ score， TCM syndrome score and curative effect， IL-6， and hs-CRP to the control group （P<0.05， P<0.01）. After 2 weeks of treatment， the SXBXW group showed superior TCM syndrome score， TCM curative effect， and hs-CRP （P<0.05， P<0.01） to the control group. The dapagliflozin group was superior to the control group in terms of TCM syndrome score， NT-proBNP， and sST2 （P<0.05， P<0.01） after 1 week of treatment and in terms of NYHA class， KCCQ score， NT-proBNP， sST2， and hospital stay （P<0.05， P<0.01） after 2 weeks of treatment. The SXBXW + dapagliflozin group exhibited better efficacy than the control group in terms of NYHA class， 6MWT score， KCCQ score， TCM syndrome score and curative effect， NT-proBNP， sST2， IL-6， and hs-CRP （P=0.014） after 1 week of treatment and in terms of NYHA class， KCCQ score， TCM syndrome score and curative effect， NT-proBNP， sST2， IL-6， hs-CRP， and hospital stay （P<0.01） after 2 weeks of treatment. ConclusionSXBXW and dapagliflozin have good therapeutic effect on acute HFrEF and syndrome of Qi deficiency and blood stasis， and their combination demonstrated better therapeutic effect， with good safety and tolerability.

Connexin (Cx), a multigene-encoded transmembrane protein family, forms either gap junctions ( GJ) or hemichannels (HC) to mediate intercellular communication in plasma mem¬brane between adjacent cells or interacts with proteins by its car- boxyl terminal in the cytoplasm to participate in the process of tumor cell proliferation, apoptosis, necrosis, invasion, metasta¬sis, drug resistance and stem cell characteristics.However, mi- slocalization of Cx in cytoplasm or nucleus often occurs in many tumors, and involved in the occurrence and development of tumors.Subcellular localization of Cx is affected by post-transla- tional modifications, including phosphorylation, ubiquitination, and acetylation.In this paper the classification and function of Cx, the relationship between subcellular localization of Cx and tumorigenesis and the regulation of post-translational modifica¬tion on Cx are reviewed in order to provide new ideas for the study of Cx as a potential target for cancer therapy.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. METHODS: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. RESULTS: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. CONCLUSIONS Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.
COVID-19 ; China/epidemiology* ; Cities ; Humans ; SARS-CoV-2

PURPOSE: The purpose of this study was to evaluate the long-term clinical outcome and toxicity of induction chemotherapy (IC) followed by concomitant chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC). MATERIALS AND METHODS: A total of 194 locoregionally advanced nasopharyngeal carcinoma patients youngerthan 21 years who received CCRT with or without IC before were included in the study population. Overall survival (OS) rate, progression-free survival (PFS) rate, locoregional recurrence-free survival (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified and compared between two groups. RESULTS: One hundred and thiry of 194 patients received IC+CCRT. Patients who were younger and with more advanced TNM stage were more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition of IC before CCRT failed to improve survival significantly. The matched analysis identified 43 well-balanced patients in both two groups. With a median follow-up of 51.5 months, no differences were found between the IC+CCRT group and the CCRT group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355), LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition of IC was associated with increased rates of grade 3 to 4 neutropenia. CONCLUSION: This study failed to demonstrate that adding IC before CCRT could provide a significant additional survival benefit for LACANPC patients. Further investigations are warranted.
Adolescent* ; Chemoradiotherapy* ; Child* ; Cohort Studies* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Induction Chemotherapy* ; Methods ; Neutropenia ; Radiotherapy

Scopolin (SC-1), scopoletin (SC-2) and isofraxidin (IS-1) are the main active constituents in Chimonanthi Radix. However, the in vivo metabolism of SC-1, SC-2 and IS-1 have not been comprehensively clarified. In this study, the in vivo metabolic profiles of these three coumarins in the rat plasma, urine and feces were analyzed. Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) method was applied to characterize the prototypes and metabolites of SC-1, SC-2 and IS-1 in rat feces, urine, and plasma after intravenous administration. A total of 11 metabolites of the three parent compounds were tentatively identified. The main metabolic pathways were analyzed by identification of metabolites, and it was found that these three coumarins underwent multiple in vivo metabolic reactions including glucuronidation, sulfonation, isomerism and reduction. In this study, the analysis of metabolites of three coumarins basically demonstrated their in vivo metabolic process, providing basis for the further pharmacokinetics and pharmacological evaluations of SC-1, SC-2 and IS-1.
Animals ; Calycanthaceae ; chemistry ; Chromatography, High Pressure Liquid ; Coumarins ; metabolism ; pharmacokinetics ; Drugs, Chinese Herbal ; metabolism ; pharmacokinetics ; Rats ; Tandem Mass Spectrometry

Objective: To study the effect of levocarnitine (L-CN) on tissue inhibitor of metalloproteinase-1 (TIMP-1) and intercellular adhesion molecule-1 (ICAM-1) expression of rats with coronary heart disease and evaluate the protective effect of L-CN on myocardial cells. Methods: High-fat diet feeding and intraperitoneal injection of pituitrin was performed on rats in model group and CHD Model of rats was built. Rats with successful model-building were selected and divided into L-CN group and Ctrl group randomly. Rats in L-CN group were given L-CN treatment, with intraperitoneal injection of 200 mg·kg