Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice and has the features of high incidence rate, poor prognosis, and high mortality rate, and its incidence rate and mortality rate rank among the top malignant tumors in the world. High heterogeneity of HCC affects the evolution and therapeutic response of HCC. Since most HCC patients are in the advanced stage at the time of diagnosis, systemic treatment has become the main treatment option. In recent years, remarkable achievements have been made in molecular targeted therapy and immunotherapy for HCC, and the latest NCCN guidelines for the systemic treatment of HCC show that sorafenib, lenvatinib, and atezolizumab combined with bevacizumab are recommended as the first-line treatment of HCC, and regorafenib, cabozantinib, nivolumab, pembrolizumab, and ramucirumab are the second-line treatment options for HCC. In the era of precision medicine, how to select the optimal individualized systemic treatment regimen is the key problem in the systemic treatment of HCC. This article reviews the advances in the systemic treatment of HCC in the era of precision medicine and discusses the development direction of HCC treatment in the future.

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.

Objective To investigate the efficacy and influence factors of uterine artery embolization (UAE)in treatment of intractable postpartum hemorrhage (PPH).Methods 126 patients with intractable PPH were treated by UAE in our hospital.We analyzed the influence factors of failed UAE treatments according to the amount of bleeding,the stability of hemodynamics,with disseminated intravascular coagulation(DIC)or not and active extravasation detected in angiography.Results In 126 intractable PPH patients,13 cases (10.3%) failed to stop bleeding after UAE and the other 113 cases (89.7%)successfully got hemostasis.Logistic regression analysis showed that DIC was a significant factor in failed UAE group (P=0.033,OR 0.107,95%CI 0.014-0.835).Conclusion UAE is an effective method of treating intractable PPH.DIC may be the main cause of the failure of UAE in treatment of intractable PPH.

Aim Toinvestigatetheeffectofhigh,me-dium and low doses of Mahuang decoction on the re-lease amount of rat hippocampal neural transmitter (Glu,Gly,Asp,GABA),then compare Mahuang de-contion with ephedra alkaloids and ephedra.Methods Ratswererandomlydividedinto6groupsandgiven orally with Mahuang decoction of high dose (calculated by ephedra 4 g·kg-1 ),medium dose (calculated by ephedra 2 g·kg-1 ),low dose (calculated by ephedra 1 g · kg-1 ),ephedra (calculated by ephedra 2 g · kg-1 ),ephedra alkaloids (ephedrine 7 mg · kg-1 , pseudoephedrine 2. 4 mg · kg-1 , methylephedrine 1. 12 mg · kg-1 )and blank control group.Samples were obtained from the hippocampus of conscious rat by microdialysis sampling technique.The content of ami-no acid neurotransmitters in dialysates was detected u-sing the established HPLC-ECD with OPA pre-column derivationmethod.Results Fouraminoacidneuro-transmitters could be well separated in 28 min.High, medium and low doses of Mahuang decoction,ephedra and ephedra alkaloids significantly increased the con-tent of these four amino acid neurotransmitters,com-pared with blank control group (P<0. 05 ).Ephedra alkaloids significantly reduced the levels of inhibitoryamino acid neurotransmitters GABA and Gly in 90 min,compared with the medium dose of Mahuang de-coction.Excitatory neurotransmitters of ASP and Glu in hippocampus showed the trend of increase first and then decrease after oral administration of Mahuang de-coction and ephedra. The levels of Glu and Asp reached peaks from 90 min to 120 min after treatment with Mahuang decoction,and also increased along with dose increase of Mahuang decoction.In comparison with the medium dose of Mahuang decoction group,the level of Glu reached peak at 90 min and 150 min in ephedra alkaloids group and ephedra group respective-ly,and the content of Glu significantly increased at peaktime.Conclusions Increasedcontentofexcita-tory amino acid neurotransmitters (Asp and Glu ) shows positive correlation with the dose of Mahuang de-coction.Other components in Mahuang decoction in-hibits the up-regulation effect of ephedra and ephedra alkaloids on Glu,and promotes the up-regulation effect of ephedra alkaloids on GABA and Gly.

OBJECTIVE:To explore basic technology for synthesis of active ingredients of Ophiocordyceps xuefengensis,and provide necessary technical support for comprehensive development of O. xuefengensis sourse. METHODS:Submerged fermenta-tion method was used to cultivate the mycelium,achieving efficient synthesis of active ingredients by controlling medium composi-tion and cultivation conditions. Using the bacteria as starting strain,the effects of different carbon sources (sucrose,glucose and soluble starch),different nitrogen sources (peptone,yeast extract powder,yeast extract,sodium nitrate,potassium nitrate and urea),different vitamin B(vitamin B1 and vitamin B complex)and different initial pH(pH was set at 4,5,6,7,8 and 9,re-spectively)on mycelial growth,extracellular and intracellular polysaccharide synthesis,cordycepin synthesis and intracellular triter-penoid synthesis were investigated to screen the optimal medium composition. RESULTS:The optimal carbon source,nitrogen source,vitamin B and initial pH were sucrose,yeast extract powder,vitamin B1 and 8,respectively. High biomass and metabolite accumulation levels can be obtained when carbon source was sucrose,nitrogen source was yeast extract powder,adding 0.1 g/L vi-tamin B1 with initial pH of 8. CONCLUSIONS:O. xuefengensis can efficiently accumulate metabolites,and achieve the optimiza-tion of strain cell growth and synthesis of active metabolite by optimizing and controlling the fermentation process.

A 10-year and 9-month-old female patient presented with skin rashes all over the body,fever and superficial lymphadenectasis for 18 days after an intravenous drip of fosfomycin.Skin examination showed generalized swollen erythema all over the body,whose surfaces were covered with a large number of sticky furfuraceous grey-white scales.Laboratory examination revealed markedly increased levels of alanine aminotransferase and aspartate aminotransferase,as well as an increased number of eosinophils.Histopathological examination of skin lesions showed infiltration of scattered lymphocytes in the superficial dermis,as well as around skin appendages.Immunohistochemical study demonstrated that the infiltrating lymphocytes mainly included T lymphocytes,and no atypical cells were observed.The patient was diagnosed with druginduced hypersensitivity syndrome.After the treatment with intravenous glucocorticoids,immunoglobulin and oral cyclosporine,favorable therapeutic effects were achieved.

Objective To evaluate effects of propranolol on the proliferation and apoptosis of in vitro cultured hemangioma endothelial cells (HemEC),and to explore their molecular mechanisms.Methods Hemangioma tissues were resected from 7 children with proliferative hemangioma,and used for in vitro culture of HemEC.Meanwhile,cultured human umbilical vein endothelial cells (HUVEC) served as controls.The 2 kinds of cells were treated with propranolol at different concentrations of 0,25,50,75,100,125 and 150 μmol/L for 24,48 and 72 hours separately.Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate cellular proliferative activity,and flow cytometry to determine the apoptosis rate.Some cultured HemEC were divided into 2 groups to be treated with 100 μmol/L propranolol-containing culture medium (propranolol group) and culture medium alone (blank control group),respectively,for 18 hours.Total RNA in the 2 groups was extracted separately.Differentially expressed genes in HemEC between the above 2 groups were identified by DNA microarray technology,and verified by real-time quantitative PCR.Results The treatment with 25 μmol/L propranolol for 24 and 48 hours caused a slight proliferation of HemEC (P ＜ 0.05).The survival rate of HemEC was decreased after the treatment with propranolol at the concentration of ≥ 100 μmol/L for more than 24 hours,while the proliferation of HUVEC was inhibited by the treatment with propranolol at the concentration of ≥ 100 μ mol/L for more than 48 hours.During 24-72 hours of treatment with 100-150 μmol/L propranolol,the survival rates of HemEC were significantly lower than those of HUVEC (P ＜ 0.05).After the treatment with 100-150 μmol/L propranolol,the apoptosis rate of HemEC gradually increased with the increase in treatment duration and concentrations of propranolol (all P ＜ 0.05).Compared with the blank control group,186 differentially expressed genes (＞ 1.5-fold changes) were screened out by DNA microarray technology,including 128 upregulated genes and 58 down-regulated genes.Real-time quantitative PCR showed that the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) and fatty acid binding protein 3 (FABP3) in the propranolol group were (9.88 ± 2.19) and (21.90 ± 8.18) times that in the blank control group respectively (t =7.028,4.427 respectively,P ＜ 0.05).Conclusions Propranolol at high concentrations can inhibit the proliferation of HemEC and HUVEC,and its inhibitory effect on HemEC is stronger than that on HUVEC.The inhibitory effect of propranolol on HemEC may be related to the inhibition of HemEC proliferation and promotion of HemEC apoptosis.

Objective To compare the effect of nursing students acting as social volunteers to participate in gerontological nursing practice teaching with traditional practice teaching mode, and promote the reform of teaching mode in nursing practice. Methods Students of two classes from department of nursing, medical college of Wuhan University of Science and Technology were selected as research objects. In class one nursing students acted as social volunteers to participate in gerontological nursing practice teaching (the experimental group), In class two nursing students took practice in geriatric wards according to traditional practice mode(the control group). The practice effect was compared between two groups. Results The average final grade of the experimental group was 86.50, and 78.51 in the control group. Ridit analysis revealed that, setting class one as the experimental group, R=0.796 8,95% confidence interval was 0.715 1-0.878 4, in the control group, R =0.500 0. The investigation showed that the experimental group and the control group were different in moral elevation aspect, teaching level, capability improving aspect and employment promotion aspect, the difference was significant (P<0.01). Conclusions The mode of nursing students acting as social volunteers to participate in gerontological nursing practice teaching has advantage over traditional practice teaching, and it can gain satisfying teaching effect.