Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the inhibitory effect of lycium barbarum polysaccharide(LBP)on apoptosis of Schwann cells(SCs)and its related mechanisms.Methods:The autophagy model was prepared by starvation treatment of RSC96 cells for 12 h,and the expressions of autophagy related proteins LC3 and p62 were detected by Western Blot.Cell Counting Kit-8(CCK-8)kits were used to detect the optimal concentration of LBP.RSC96 cells were randomly divided into Control group,Starvation group and Starvation+LBP group.The expressions of autophagy associated pro-teins(LC3,p62)and myelin associated proteins(p75NTR,PMP22,S100β)were detected by Western Blot or immu-nofluorescence staining.Annexin V/PI fluorescence staining was used to detect apoptosis of the cells.The cell cycle was analyzed by flow cytometry.Western Blot analysis of phosphorylation levels of pathway proteins Erk1/2 and Akt.Results:CCK8 results showed that the viability of damaged RSC96 cells was the best when LBP was 300 μg/ml.Com-pared with Control group,LC3-Ⅱ/LC3-I levels in Starvation group were significantly increased(P＜0.05).Compared with Starvation group,the proportion of apoptotic and necrotic cells in Starvation+LBP group was significantly de-creased,and the proportion of cells in S and G2/M stages was increased.The expression levels of LC3-Ⅱ,p75NTR,PMP22 and S100β were increased,while the expression levels of autophagy substrate protein p62 were decreased.In-creased expression of pathway protein p-Erk1/2(P＜0.05),while the expression of p-Akt protein decreased slightly.Conclusion:LBP can inhibit the apoptosis of SCs and promote the expression of myelin-related proteins by enhancing autophagy,which is related to the activation of Erk1/2 and/or the inhibition of Akt.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective:To explore the therapeutic law of moxibustion in Professor Zhou Meisheng's medical manuscripts for epidemic hemorrhagic fever (EHF) based on data mining and knowledge map technology.Methods:The manuscript data of Professor Zhou Meisheng's moxibustion treatment of EHFwere collected from Infectious Diseases Department of Dangshan County People's Hospital from December 16, 1985 to December 25, 1987. Graphpad Grism 8.0 software was used for descriptive analysis. PHP 5.4 program code was used for association rule analysis. SPSS Statistics 26.0 was used for clustering analysis. Neo4j Community 3.5.25 database was used to analyze the syndrome-weight graph.Results:205 prescriptions were included. There were 21 symptoms with frequency>40, in which the frequency of aversion to cold, fever, rash and irritability was 100%. The main types of moxibustion methods used in the treatment included moxibustion frame fumigation moxibustion, Wanying acupoint moxibustion pen moxibustion, and fire needle instead of moxibustion. There were 29 acupoints with a frequency of >25, including Zhongwan (CV12), Shenshu (BL23) and Mingmen (DU4), etc. Association rules showed that Sanyinjiao (SP6)-Zhongwan (CV12)-Feishu (BL13)-Shenshu (BL23)-Zhiyang (DU9) had the highest correlation. Six effective clustering combinations of moxibustion for EHF were summarized by clustering analysis. The weight graph can obtained the first 30 relationships with high correlation of target syndromes.Conclusions:Professor Zhou applied the idea of "moxibustion for heat syndrome" to the treatment of EHF, and took the method of "acupoint selection according to symptoms" as the main acupoint selection idea for moxibustion treatment of EHF. In clinical practice, moxibustion combined with auxiliary operation of TCM is often used to treat EHF, which can achieve good results.

Nurses not only focus on nursing fees,but also participate in other medical fees,which is an important part of the hospital's medical services for patients.For the main resource consumption-labor cost in medical service project cost accounting,the labor cost of doctors(including medical and technical staff)and nurses is the most important part,but the labor cost accounting of nurses has not been paid enough attention for a long time.From the perspective of management accounting and the integration of industry and finance,it analyzes the characteristics of nurses'labor cost and accounting,and studies and discusses some problems of medical service project cost accounting based on nurses'labor cost,hoping to provide references for hospitals to carry out nurses'labor cost accounting in medical service projects more scientifically and reasonably.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribo-somopathy genes have also been found to be intimately associated with cancer development.The cor-relation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Objective To investigate the effect of type 2 diabetes mellitus(T2DM)on the expression of human leukocyte antigen-DR(HLA-DR)on the peripheral blood monocytes in patients with sepsis.Methods From March 2021 to February 2022,65 cases of sepsis with T2DM(sepsis with T2DM group),67 cases of sepsis without T2DM(sepsis group),and 60 cases of T2DM patients(T2DM group)admitted to Beijing Chaoyang Hospital of Capital Medical University were selected as the research objects.A total of 45 healthy volunteers who underwent physical examination during the same period were enrolled as the healthy control group.Gender,age,past medical history,glycated hemoglobin(HbA1c),blood glucose at admission,white blood cell count(WBC),lymphocyte count(LYM),hypersensitivity C-reactive protein(hs-CRP)and major infection sites were collected,sequential organ failure assessment(SOFA)score was performed within 24 hours after admission.The levels of HLA-DR+CD14+ in peripheral blood were detected by flow cytometry,expressed as a percentage and mean fluorescence intensity(MFI).The patients were followed up for 28 days.The effect of T2DM on the prognosis of sepsis patients at 28 days was observed,and the difference of HLA-DR+CD14+ levels between the survivor group and the non-survivor group was compared.Results The percentage and MFI of HLA-DR+CD14+ expressions in T2DM group were significantly lower than those in the healthy control group[the percentage of HLA-DR+CD14+ expression:87.72%(76.18%,93.64%)vs.94.86%(92.91%,95.70%),HLA-DR+CD14+ MFI:10.80(8.45,14.45)vs.12.40(1.45,15.28)],the sepsis with T2DM group and sepsis group were further reduced than those in healthy control group and T2DM group[the percentage of HLA-DR+CD14+ expression:70.78%(42.22%,84.73%),68.95%(44.95%,87.00%)vs.94.86%(92.91%,95.70%),87.72%(76.18%,93.64%),MFI of HLA-DR+CD14+:5.50(3.81,9.20),5.29(3.35,9.59)vs.12.40(1.45,15.28),10.80(8.45,14.45),all P<0.05].There was no significant difference in the percentage and MFI of HLA-DR+CD14+ expressions,SOFA score,and 28-day mortality between sepsis group and sepsis with T2DM group(P>0.05).The age of the non-survivor group of sepsis patients with and without T2DM was significantly higher than that of the survivor group[years:sepsis group was 68(60,74)vs.61(52,69),sepsis with T2DM group was 66(64,73)vs.60(53,68),both P<0.05],and SOFA score was significantly higher than that of the survivor group[sepsis group:14(11,16)vs.8(5,11),sepsis with T2DM group:12(9,16)vs.8(6,11),both P<0.05],the percentage of HLA-DR+CD14+ and HLA-DR+CD14+ MFI in the non-survivor group were significantly lower than those in the survivor group[the percentage of HLA-DR+CD14+was 44.94%(28.01%,64.45%)vs.77.14%(47.41%,88.35%)in sepsis group and 40.68%(34.83%,66.64%)vs.73.46%(58.44%,85.31%)in sepsis with T2DM group,the MFI of HLA-DR+CD14+ was 3.92(2.30,5.44)vs.7.07(3.39,10.55)in sepsis group and 3.90(3.34,6.04)vs.6.81(4.41,9.32)in sepsis with T2DM group,all P<0.05].Correlation analysis showed that the percentage of HLA-DR+CD14+ in T2DM group,sepsis group,and sepsis with T2DM group was negatively correlated with hs-CRP(r values were-0.448,-0.628 and-0.457,all P<0.001),MFI was also negatively associated with hs-CRP(rvalues were-0.289,-0.540,-0.323,all P<0.05).The percentage of HLA-DR+CD14+ in sepsis group and sepsis with T2DM group was negatively correlated with SOFA score(r values were-0.520 and-0.558,all P<0.001),and MFI was also negatively correlated with SOFA score(r values were-0.327 and-0.482,all P<0.01).Conclusion The levels of HLA-DR+CD14+ decreased in both T2DM and sepsis patients,however,there was no further decrease in those patients with sepsis who also had T2DM.

【Objective】 To investigate the feasibility and safety of semiconductor blue laser in the treatment of non-muscle invasive bladder cancer (NMIBC) in the day surgery model. 【Methods】 The clinical data of 22 NMIBC patients (average age 55.8 years and tumor size 1.4 cm) who underwent outpatient screening and accepted blue laser ambulatory surgery in our hospital during Jun.2022 and Sep.2022 were retrospectively analyzed. On the day of admission, transurethral resection of cancer was performed using blue laser en bloc enucleation. On the day of surgery or in the morning of next day, bladder irrigation was stopped, the catheter was removed, and patients were discharged. The baseline data, pre-hospital waiting time, operation time, length of hospital stay, hemoglobin decrease, complications and management, follow-up, medical costs, and patients’ satisfaction rate were recorded. 【Results】 The pre-hospital waiting time was 2 to 7 days, average (4.1±1.3)days. The operation time was 29 to 50 minutes, average (40.8±5.5)minutes. The length of hospital stay was 0.6 to 1.2 days, average (0.9±0.2)days. Hemoglobin decrease was 1 g/L to 8 g/L, average (3.8±1.8)g/L. The catheter was indwelt for 0.5 to 1 day, average (0.7±0.1)day. The medical costs were 13 790 to 16 811 Yuan, average (14 941.5±690.2) Yuan. Patients’ satisfaction rate was 100.0%. Mild intraoperative and postoperative complications occurred in 2 cases. One patient developed symptoms of cystitis which disappeared after 2 days of oral antibiotic cefixime, and another patient developed bladder spasm which was relieved after oral solifenacin succinate tablets. No adverse events such as obturator nerve reflex or bladder perforation occurred. After removal of the catheter, no urinary retention was observed. 【Conclusion】 This study was the first to apply blue laser ambulatory surgery in the treatment of bladder cancer, confirming that it is a safe, feasible, economical and efficient model for selected patients, which can be promoted in suitable hospitals.

Objective:To develop the Nurse Managers Negative Leadership Behavior Scale and test its reliability and validity.Methods:This study is a cross-sectional study. The Nurse Managers Negative Leadership Behavior Scale item pool was formed through literature review and semi-structured interviews. A total of 28 nursing management experts from Hubei Province, Beijing, Guangdong Province and other places were selected for expert consultation to form the first draft of the scale. The scale was further revised through pre-experiment and item analysis. In May 2022, 300 nurses from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were selected by convenient sampling for a questionnaire survey to test the reliability and validity of the scale. A total of 300 questionnaires were distributed, and 265 valid questionnaires were recovered, with an effective recovery rate of 88.33%. One week after the survey, 20 nurses were randomly selected to re-issue the questionnaire for the retest reliability test of the scale.Results:Totally, 19 experts completed two rounds of expert consultation, with expert authority coefficient of 0.880, Kendall harmony coefficient of 0.160 and 0.130 ( P<0.05) . Exploratory factor analysis extracted six factors, including neglect of needs, personal attack, right satisfaction, unpredictable behavior, slack work and improper supervision, and the cumulative variance interpretation rate was 75.125%. The confirmatory factor analysis showed that the model fitted well and the factor structure was stable. The Nurse Managers Negative Leadership Behavior Scale included six dimensions and 36 items. The total Cronbach's α coefficient of the scale was 0.880, the split-half reliability coefficient was 0.895, and the retest reliability coefficient was 0.876. The content validity index of the scale was 0.930, and the content validity index of each item was 0.800 to 1.000. Conclusions:The Nurse Managers Negative Leadership Behavior Scale has good reliability and validity, and can be used to evaluate the negative leadership behavior of head nurses in China.