Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Effectiveness of Acupoint Application in Patients with Pharyngeal Pain: Evidence from CHUNBO, A Prospective Real-World Study / 中国结合医学杂志

OBJECTIVE@#To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application.@*METHODS@#Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching (PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain (within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events.@*RESULTS@#Of 7,699 enrolled participants, 6,693 (86.9%) received acupoint application and 1,450 (21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group (AG) and non-application group (NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG (P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG (logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41-1.63). The median age of effective cases was 4 years, mainly 3-6 years old (40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG (P<0.05). The commonly used acupoints for the effective cases were Tiantu (RN 22), Shenque (RN 8) and Dazhui (DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently (support 84.39%). A total of 1,324 (17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs between goups (P<0.05). All AEs reported were the first grade, and the average regression days of AEs was 2.8 days.@*CONCLUSIONS@#Acupoint application in patients with pharyngeal pain resulted in improved effective rate and shortened duration, especially children aged 3-6 years old, and those with tonsil diseases. Acupoint of RN 22, RN 8 and DU 14, Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae were the most commonly used herbs in the treatment of pharyngeal pain.

Influences of aerobic exercise associated with the pharmacological treatment of copd / Influências do exercício aeróbico associado ao tratamento farmacológico da dpoc / Influencias del ejercicio aeróbico asociado al tratamiento farmacológico de la epoc

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is a type of inflammatory respiratory system disease characterized by chronic airflow limitation. Aerobic exercise training is believed to influence the drug treatment of this disease positively. Objective: Study the impact of complementary aerobic exercise intervention on pharmacological treatment in patients with COPD. Methods: In a controlled experiment, 40 volunteers under pharmacological treatment for COPD were selected and equally divided into two groups. The experimental group was treated with aerobic exercise training and drug treatment, while the control group was treated with regular drug treatment only. The exercise protocol lasted 60 minutes daily for a total period of eight weeks. Borg scale, oxygen saturation, and six-minute walk test among other markers were checked before and after the intervention. Results: According to the data obtained from the experiment, the peak oxygen consumption of aerobic exercise combined with the drug group was from 1,205.42±293.74ml/min to 1,301.84±293.91ml/min, peak ventilation started at 37.85±11.67L/min to 48.81±13.11L/min. However, the variations in the control group were not significant. Conclusion: Aerobic exercise associated with pharmacological intervention positively influenced the treatment of patients with COPD. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A doença pulmonar obstrutiva crônica (DPOC) é um tipo de doença inflamatória do sistema respiratório caracterizada pela limitação crônica do fluxo de ar. Acredita-se que o treinamento com exercícios aeróbicos possa influenciar positivamente no tratamento medicamentoso dessa enfermidade. Objetivo: Estudar os impactos da intervenção complementar com exercícios aeróbicos sobre o tratamento farmacológico em portadores de DPOC. Métodos: Através de um experimento controlado, 40 voluntários sob tratamento farmacológico para DPOC foram selecionados e igualmente divididos em dois grupos. O grupo experimental foi tratado com treinamento de exercício aeróbico combinado com o tratamento medicamentoso, enquanto o grupo controle foi tratado apenas com o tratamento medicamentoso regular. O protocolo de exercícios teve duração de 60 minutos diários, num período total de oito semanas. A escala de Borg, saturação de oxigênio, teste de caminhada de seis minutos entre outros marcadores foram verificados antes e após a intervenção. Resultados: De acordo com os dados obtidos do experimento, o pico de consumo de oxigênio do exercício aeróbico combinado com o grupo de fármacos foi de 1.205,42±293,74ml/min para 1.301,84±293,91ml/min, pico de ventilação iniciou em 37,85±11,67L/min para 48,81±13,11L/min. Porém as variações no grupo controle não foram significativas. Conclusão: O exercício aeróbico associado à intervenção farmacológica representou uma influência positiva no tratamento dos pacientes portadores de DPOC. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La enfermedad pulmonar obstructiva crónica (EPOC) es un tipo de enfermedad inflamatoria del sistema respiratorio caracterizada por la limitación crónica del flujo aéreo. Se cree que el entrenamiento con ejercicios aeróbicos puede influir positivamente en el tratamiento farmacológico de esta enfermedad. Objetivo: Estudiar el impacto de la intervención complementaria con ejercicios aeróbicos sobre el tratamiento farmacológico en pacientes con EPOC. Métodos: Mediante un experimento controlado, se seleccionaron 40 voluntarios bajo tratamiento farmacológico para la EPOC y se dividieron equitativamente en dos grupos. El grupo experimental fue tratado con entrenamiento de ejercicio aeróbico combinado con tratamiento farmacológico, mientras que el grupo de control fue tratado únicamente con tratamiento farmacológico regular. El protocolo de ejercicio duró 60 minutos diarios durante un período total de ocho semanas. Se comprobaron la escala de Borg, la saturación de oxígeno y la prueba de la marcha de seis minutos, entre otros marcadores, antes y después de la intervención. Resultados: Según los datos obtenidos del experimento, el consumo máximo de oxígeno del grupo de ejercicio aeróbico combinado con fármaco fue de 1.205,42±293,74ml/min a 1.301,84±293,91ml/min, la ventilación máxima comenzó en 37,85±11,67L/min a 48,81±13,11L/min. Sin embargo, las variaciones en el grupo de control no fueron significativas. Conclusión: El ejercicio aeróbico asociado a la intervención farmacológica tuvo una influencia positiva en el tratamiento de los pacientes con EPOC. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Current status and progress on the application of ventricular assist device / 器官移植

At present, heart transplantation is the most effective treatment for end-stage heart failure. Nevertheless, the shortage of donors is becoming an increasingly severe challenge. In recent years, rapid development of mechanical circulatory support technologies has provided multiple therapeutic options for patients with end-stage heart failure. As an important mechanical circulatory support device, ventricular assist device (VAD) are divided into durable VAD (dVAD) and temporary VAD (tVAD) according to the duration of assistance. dVAD shows application potential in bridging heart transplantation, destination therapy and bridge to decision. With technological progress and experience accumulation in clinical application, VAD is evolving towards the direction of more biocompatible, lighter, more bionic and intelligent. In this article, the development of VAD, application status at home and abroad and the overall application of VAD in our hospital were reviewed, aiming to provide reference for promoting the clinical application of VAD in China.

Isonlosinine induces autophagy of PC9 cells by ERK signaling pathway in lung cancer / 中国临床药理学与治疗学

AIM: To investigate the effects of isonlosinine on proliferation, invasion, migration and autophagy of PC9 cells in non-small cell lung cancer (NSCLC), and to explore its possible molecular mechanism. METHODS: The effect of Isoliensinine on the proliferation of PC9 cells were measured by CCK-8 assay, and the IC50 value of PC9 cells was calculated. Wound healing and transwell experiments were used to study the effect of Isoliensinine on migration and invasion of PC9 cells in vitro, respectively. The formation of autophagosome was observed with acridine orange staining under fluorescence microscope. The expression levels of LC3, pERK and ERK in the PC9 cells were determined by western blot. RESULTS: Isonlosinine significantly inhibited the proliferation of PC9 cells. IC50 of isonlosinine (24 h) for the PC9 cells was 34.11 µmol / L. Isonlosinine significantly inhibited cell migration and invasion of PC9 cells. The results of acridine orange fluorescent staining showed that the number of the intracellular acid dye follicular bright red fluorescence in PC9 cells was significantly increased after isonlosinine treatment, while the autophagic lysosomes were rarely observed in control group. The expression of LC3-II in PC9 cells was significantly enhanced after isonlosinine treatment. Furthermore, molecular mechanism study showed that isonlosinine could activate the expression level of p-ERK. CONCLUSION: Isoliensinine significantly inhibits the proliferation, migration and invasion, and induces autophagy of PC9 cells, which may be correlated with the activation of ERK signaling pathway.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Efficacy analysis of anti-thymocyte globulin regimens with different timing strategies for matched sibling donor hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/μl vs 852 cells/μl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.

nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story / 神经科学通报·英文版

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Characteristics of plasma Epstein-Barr virus DNA in children with primary infection / 中华儿科杂志

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

Clinical effect of laparoscopy for the treatment of biliary stricture after biliary dilatation operation / 中华外科杂志

Objective: To investigate the safety and effect of laparoscopy for the treatment of biliary stricture after the biliary dilatation operation. Methods: The clinical data of 78 patients,including 27 males and 51 females aged (48.6±14.2)years(range:17 to 76 years),who presented biliary stricture after biliary dilatation operation from January 2017 to June 2021 in the Department of Minimally Invasive Hepatobiliary Surgery,Hunan Provincial People's Hospital,were retrospectively collected,with 38 cases in the laparoscopy group and 40 cases in the laparotomy group. Of the 78 patients,there were 67 cases of cholangiojejunostomy stricture and 11 cases of stricture of the high intrahepatic bile duct. Statistical methods such as t-test and χ2 test were carried out to compare perioperative clinical data and follow-up information between the two groups. Results: Less intraoperative blood loss((102.6±76.4)ml vs. (162.5±105.9) ml, t=-2.874,P=0.005),shorter postoperative stay length of stay((10.5±3.7)days vs. (14.5±6.4)days, t=-3.379,P=0.001) and shorter waiting time for postoperative anal exhaust((2.0±0.6)days vs. (2.5±0.9)days, t=-2.827,P=0.006) were found in the laparoscopy group than that in the laparotomy group,with statistically significant differences. While there was no statistically difference in the operative time((252.8±54.7)minutes vs. (257.4±68.6)minutes,t=-0.331,P=0.742). Postoperative review and follow-up did not show statistically significant differences between the two groups in the residual stone rate(5.3%(2/38) vs. 5.0%(2/40)) and the incidence of recurrent biliary stricture(5.3%(2/38) vs. 7.5%(3/40))(both P>0.05). Conclusion: Laparoscopy may be safe and effective in the treatment of biliary stricture after the biliary dilatation operation,with less trauma,faster recovery compared to laparotomy.

Basic principles,methods and evaluation of minimally invasive treatment for infected pancreatic necrosis / 中华外科杂志

Infected pancreatic necrosis(IPN) is the main surgical indication of acute pancreatitis. Minimally invasive debridement has become the mainstream surgical strategy of IPN,and it is only preserved for IPN patients who are not response for adequate non-surgical treatment. Transluminal or retroperitoneal drainage is preferred,and appropriate debridement can be performed. At present,it is reported that video assisted transluminal,trans-abdominal and retroperitoneal approaches can effectively control IPN infection. However,in terms of reducing pancreatic leakage and other complications,surgical and endoscopic transgastric debridement may be the future direction in the treatment of IPN.

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs / 中华肿瘤杂志

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.

Isobaric tags for relative and absolute quantitation quantitative proteomics research of human lens epithelial cells after ultraviolet-B irradiation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of protein expressions in human lens epithelial cells(SRA01/04)undergoing oxidative damage, hoping to provide new protein target for the pathogenesis of age-related cataract(ARC).METHODS: SRA01/04 cells were divided into experimental group and control group. In the experimental group, cells were irradiated with ultraviolet-B(UVB)for 10min to establish the model of oxidative damage, whereas cells in the control group were untreated. Protein expression profile from the two groups was sequenced by isobaric tags for relative and absolute quantitation(iTRAQ). The filtering criteria that fold change &#x0026;#x003E;1.2 and p&#x0026;#x003C;0.05 was used to determine the differentially expressed proteins(DEPs). Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)database were utilized for functional enrichment analysis of the top 50 DEPs with either up-regulated or down-regulated significance. Furthermore, Pathway commons software was used to establish the protein-protein interaction(PPI)network.RESULTS: Overall, 552 DEPs were screened out. A total of 176 DEPs were up-regulated in the experimental group compared with the control group, including HMGB1 and USP1, while 376 DEPs were down-regulated, including POLR2A and POLR2B. GO and KEGG enrichment analysis indicated that the top 50 DEPs with up-regulated or down-regulated significance were involved in various crucial biological processes and signaling pathways. PPI network revealed that oxidative damage repair(ODR)-related proteins might play a key role in UVB-induced oxidative damage.CONCLUSIONS: The expressions of multiple proteins, especially ODR-related proteins, can be altered in SRA01/04 cells via UVB irradiation. These findings may provide cellular-related insights into the pathogenesis of ARC and into proteins or pathways associated with therapeutic targets.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Key Prediction Genes of Nasopharyngeal Carcinoma:Screening Based on Systematic Bioinformatics and Validation by Cell Experiments / 中国医学科学院学报

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.

A Campylobacteriosis Outbreak Caused by One Asymptomatic Food Handler Carrier / 生物医学与环境科学（英文）

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.

A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry / 中华医学杂志(英文版)

BACKGROUND@#The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.@*METHODS@#The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.@*RESULTS@#A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.@*CONCLUSION@#The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03916432.

Clinical Efficacy of Chinese Medicine Combined with Indirect Moxibustion Plaster on COVID-19 Patients During Recovery Period Based on COVID-19 Diagnosis and Treatment Protocol（Tenth Edition） / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Chinese medicine combined with indirect moxibustion plaster on corona virus disease 2019 （COVID-19） patients during recovery period. MethodNinety patients of COVID-19 during the recovery period were randomly divided into a Chinese medicine group， an indirect moxibustion plaster group， and a combination group，with 30 cases in each group. According to the 10th edition of COVID-19 Diagnosis and Treatment Protocol，patients in the Chinese medicine group received oral Chinese medicine based on syndrome differentiation，one dose per day， twice a day. Patients in the indirect moxibustion plaster group were treated with indirect moxibustion plaster at Zusanli （ST 36）， Pishu （BL 20）， Dazhui （GV 14）， Feishu （BL 13）， Kongzui （LU 6）， and Tiantu （CV 22），once a day，40 min each time. Patients in the combination group were treated with Chinese medicine combined with indirect moxibustion plaster. Treatment lasted two weeks. Before and after treatment，the traditional Chinese medicine （TCM） symptom score，pulmonary computed tomography （CT） score，St. George's Respiratory Questionnaire （SGRQ） score，blood routine indexes ［white blood cell count （WBC），neutrophil count （NEUT），and lymphocyte count （LYM）］， and inflammatory indexes ［C-reactive protein （CRP），serum ferritin， and interleukin-6 （IL-6）］ were observed in the three groups. The clinical efficacy was evaluated. ResultAfter treatment，the scores of TCM symptoms，pulmonary CT， and SGRQ，CRP，IL-6，and ferritin in the three groups decreased（P<0.05），while WBC and LYM increased（P<0.05）， but there was no significant difference in NEUT. The above indexes in the combination group were better than those in the other two groups（P<0.05）. After treatment， the cured and markedly effective rate was 76.7% （23/30） in the combination group， 50.0% （15/30） in the Chinese medicine group， and 46.7% （14/30） in the indirect moxibustion plaster group. The cured and markedly effective rate of the combination group was significantly higher than that of the Chinese medicine group （χ2=4.593， P<0.05） and the indirect moxibustion plaster group （χ2=5.711， P<0.05）. The total effective rate was 96.7 % （29/30） in the combination group， 93.3% （28/30） in the Chinese medicine group， and 86.7% （26/30） in the indirect moxibustion plaster group. The total effective rate of the combination group was higher than that of the Chinese medicine group and the indirect moxibustion plaster group， but the differences were not statistically significant. ConclusionChinese medicine combined with indirect moxibustion plaster can effectively improve the clinical symptoms，promote pulmonary inflammation，blood routine indexes， and inflammatory indexes， and improve the quality of life of COVID-19 patients during the recovery period，which is more advantageous than Chinese medicine alone or indirect moxibustion plaster.

Research Progress of Allogeneic Hematopoietic Stem Sell Trans-plantation in the Treatment of Adult Hemophagocytic Lympho-histiocytosis --Review / 中国实验血液学杂志

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory clinical syndrome of uncontrolled immune response which results in hypercytokinemia due to underlying primary or secondary immune defect. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only cure therapy for primary HLH and recurrent/refractory hemophagocytic lymphohistiocytosis. Compared with children HLH, adult HLH is a much more heterogeneous syndrome requiring a more individualized protocol depending on the underlying trigger, disease severity and genetic background. At present, there remain controversies in various aspects including indications of haematopoietic cell transplantation (HCT), conditioning regimen, efficacy and prognosis. This article will review the recent advances of allo-HSCT in the treatment of adult HLH based on the above issues.