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.

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Objective To investigate the effects and molecular mechanism of β-asarone(β-As)on renal cell carcinoma(RCC).Methods Human RCC 786-O and 769-P cells were used in in vitro experiments,and murine RCC Renca cells were used in in vivo experiments.MTT,wound healing assay and Transwell assay were used to evaluate cell migration and invasion.Western blot was used to detect changes in protein levels during autophagy and epithelial-mesenchymal transition(EMT).Xenograft models of Balb/c mice were used to detect the anti-tumor effect of β-As in vivo.Results β-As inhibited cell growth in a concentration-dependent manner;upregulated the expression of E-cadherin,but down-regulated the expressions of N-cadherin and Vimentin;inhibited cell proliferation,migration and invasion.β-As upregulated the expression of LC3 and p-AMPK,downregulated the expressions of p-mTOR and p-S6K in a concentration-dependent manner,but had no effects on the expressions of AMPK and mTOR.β-As inhibited the proliferation of RCC cells in vivo.Conclusion β-As inhibits the proliferation,migration,invasion and EMT of RCC cells through the autophagy-dependent AMPK/mTOR signaling pathway,which may provide new ideas for the treatment of RCC,especially advanced RCC.

The identification of the components absorbed in serum of platycosides in total saponins fraction of Platycodonis Radix is great significance, but there are still great challenges. In this study, 8 types of 44 primordial components from Platycodon saponins were firstly identified using the ultra-performance liquid chromatography-linear ion trap electrostatic field orbitrap high resolution mass spectrometry (UPLC-LTQ-Orbitrap-MS) equipped with the software of Compound Discoverer 3.2 and Trace finder 2.1. Then, the platycosides and their deglycosylated metabolites were used as the template molecules to construct the intestinal microbiota mediated method to identify the primary components and the prototypes in serum. As results, 57 components originating from 44 prototypes of platycosides were identified from drug-containing plasma. Those compounds consist of 12 prototypes of platycosides and 45 metabolites, while the prototypes in serum are also deglycosylated metabolites of other platycosides. The results showed that the intestinal microbiota mediated method could be applied to identify the metabolites of platycosides in total saponins fraction of Platycodonis Radix; and reveal the potential existing forms of prototypes of platycosides in plasma; In addition, it could clearly illustrate the one to many and many to one network of the prototypes and metabolites of platycosides. All animal protocols were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (No.JZLLSC-202100322).

Objective To investigate and compare the median effect-site concentration(Ce50)of sufentanil combined with propofol or ciprofol blunting cardiovascular responses to tracheal intubation in eld-erly patients.Methods Sixty-six elderly patients were selected for extracranial-intracranial cerebral revas-cularization for general anesthesia with tracheal intubation,32 males and 34 females,aged ≥ 65 years,BMI 20-30 kg/m2.Patients were randomly divided into two groups:1.5 mg/kg propofol group(group P)and 0.3 mg/kg ciprofol group(group C),33 patients in each group.Sufentanil was target controlled infused with the initial dose of 0.30 μg/kg,then propofol 1.5 mg/kg or ciprofol 0.30 mg/kg injected slowly after reaching the effect-site concentration.After the lose of consciousness and BIS score less than or equal to six-ty,rocuronium 0.60 mg/kg was administrated,and underwent endotracheal intubation after the TOF value monitored by muscle relaxation drops to zero.Dixon's up and down sequential method was used to determined the target concentration of sufentanil.A positive response was defined as a 20％increase in HR or SBP exceeding the baseline within 2 minutes after tracheal intubation,otherwise,it was considered a neg-ative response.According to the Dixon's sequential method,the ratio of adjacent dosed was 1.2 and if the patient had a positive response,the dose of next patient was moved up one gradient,otherwise,the dose would be reduced.The trail was terminated when the seventh crossover point was observed.When a positive response turned to a negative response,it was called a crossover point.HR,SBP,DBP and BIS were recor-ded before induction of anesthesia(T0),before tracheal intubation(T1),1 minutes after tracheal intubation(T2),3 minutes after tracheal intubation(T3)and 5 minutes after tracheal intubation(T4).Dixon-Mood's half effective quantity sequential calculation formula was used to calculate the Ce50 and 95％confidence interval(CI).Results Compared with group P,SBP was significantly increased at T1,BIS was significantly decreased at T2-T4 in group C(P＜0.05).The Ce50 and 95％CI of sufentanil inhibiting cardiovascular response to tracheal intubation were 0.253 ng/ml(95％CI 0.215-0.297 ng/ml)in group P and 0.241 ng/ml(95％CI 0.209-0.279 ng/ml)in group C.There was no significant difference in Ce50 between the two groups.Conclusion When combined with propofol 1.5 mg/kg during anesthesia induction,the Ce50 of sufentanil inhibiting cardiovascular response to tracheal intubation in elderly patients was 0.253 ng/ml(95％CI 0.215-0.297 ng/ml).While combined with cirprofol 0.30 mg/kg,Ce50 of sufentanil was 0.241 ng/ml(95％CI 0.209-0.279 ng/ml).

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.
Animals ; Mice ; Interleukin-17/metabolism* ; Intercellular Adhesion Molecule-1 ; Imiquimod/adverse effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Ligands ; Psoriasis/chemically induced* ; Keratinocytes ; Inflammation/drug therapy* ; Chemokines/metabolism* ; Interferon-gamma/metabolism* ; Disease Models, Animal ; Mice, Inbred BALB C

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.
Humans ; Child ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Tuberculosis, Pulmonary/drug therapy* ; Tuberculosis ; China/epidemiology*