[Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world].

Objective: To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) . Methods: From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis. Results: ①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five naïve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions: There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

Heralded Three-Photon Entanglement from a Single-Photon Source on a Photonic Chip.

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

[Study on the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogelin post-traumatic osteoarthritis].

Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.

[Notch1 inhibits the mechanistic role of STING signaling to regulate hepatocyte lipophagy in nonalcoholic steatohepatitis].

Objective: To study the mechanistic role of myeloid-specific Notch1 knockout inhibiting STING signaling to regulate hepatocyte lipophagy. Methods: A mouse model of nonalcoholic steatohepatitis (NASH) was established using a high-fat diet (HFD) and mouse bone marrow-derived macrophages (BMMs). Primary hepatocytes were isolated to construct a co-culture system. Twelve Notch1(FL/FL) mice were randomly divided into two groups: the Notch1(FL/FL) + normal diet (NCD) and the Notch1(FL/FL) + HFD group. Further, 12 Notch1(M-KO) mice were randomly divided into two groups: Notch1(M-KO) + NCD, and Notch1(M-KO) + HFD group.Serum alanine aminotransferase (sALT), total cholesterol (TC) and triglyceride (TG) were collected from mice serum samples. Liver tissue samples were collected for H&E staining, immunofluorescence (IF), Western blot and qRT-PCR. Tumor necrosis factor (TNF)-α was detected in the supernatant by enzyme-linked immunosorbent assay (ELISA). The comparison of inter group data was conducted using a t-test. Results: The mouse NASH model, mouse BMMs co-culture system, and primary hepatocytes were successfully constructed. Compared with the Notch1(FL/FL) + HFD group, the Notch1(M-KO) + HFD group showed a significant increase in serum ALT [(250.02 ± 58.21) U/L vs (370.70 ± 54.57) U/L, t = 3.705, P = 0.004], TG [(29.90 ± 3.54) mg/g vs (43.83 ± 8.56) mg/g, t = 3.685, P = 0.004], and TC [(33.70 ± 8.43) mg/g vs (90.53 ± 12.53) mg/g, t = 9.917, P < 0.001]. HE staining of liver tissue showed remarkable balloon-like alterations in liver cells, while IF staining demonstrated increased macrophage infiltration (t = 7.346, P < 0.001). Compared with the hepatocyte group co-cultured with Notch1(FL/FL) BMMs, the BODIPY probe showed a significant increase in lipid droplet (LDs) deposition in liver cells in the Notch1(M-KO) group (t = 3.835, P < 0.001). The co-localization of lysosomal associated membrane protein 1 (LAMP1), LDs (t = 7.103, P < 0.001), microtubule-associated protein light chain 3 (LC3) -II/LC3-I (t = 5.0, P = 0.007), and autophagy associated gene 12 (Atg12) (t = 28.36, P < 0.001) had decreased expression, while P-62 had increased expression (t = 3.253, P = 0.03), indicating a decrease in autophagic flow. Additionally, LC3 and LDs colocalization decreased (t = 5.24, P = 0.0003), indicating reduced lipophagy. Compared with the Notch1(FL/FL) group, the Notch1(M-KO) BMMS mouse group showed an increase in the expression of p-STING (t = 5.318, P = 0.006), p-TANK1 binding kinase 1 (TKB1) (t = 6.467, P = 0.002), p-interferon regulatory factor 3 (IRF3) (t = 14.61, P < 0.001), and p-P65 (t = 12.7, P = 0.002) protein, accompanied by mRNA expression of the inflammatory mediators interferon (IFN)-ß (t = 7.978, P < 0.001), TNFα (t = 8.496, P = 0.001), interleukin-1 ß (IL-1 ß) (t = 4.7, P < 0.001), and CXCL-10 (t = 4.428, P = 0.001). The STING gene was knocked out in the BMMs Notch1(M-KO) mice using CRISPR/Cas9. Compared with the CRISPR-Control group, the expression of P-TKB1 (t = 2.909, P = 0.044), p-IRF3 (t = 10.96, P < 0.001), p-IRF3 (t = 10.96, P < 0.001), and p-P65 (t = 7.091, P = 0.002) proteins was lower in the STING-KO BMMs group. The release of TNF-α in the supernatant was decreased (732.3 ± 129.35 pg/ml vs. 398.17 ± 47.15 pg/ml, t = 4.204, P = 0.014). However, in hepatocytes co-cultured with STING-KO BMMs, LC3-II/LC3-I (t = 7.546, P = 0.001) increased, p-62 (t = 10.96, P < 0.001) expression decreased, autophagic flow increased, and the colocalization of LC3 and LDs increased, lipophagy increased, and LDs deposition decreased. Conclusion: Myeloid-specific Notch1 knockout can activate macrophages STING signaling, increase the expression of inflammatory mediator genes, inhibit the occurrence of autophagy flow and lipophagy in hepatocyte cells, and aggravate LDs deposition and NASH progression.

[Prognostic factors for non-small cell lung cancer patients with central nervous system metastasis with positive driver genes].

Objective: To investigate the prognostic factors of patients with central nervous system (CNS) metastatic non-small cell lung cancer (NSCLC) with positive driver genes. Methods: The clinical data of 103 patients with CNS metastatic NSCLC admitted to Beijing Tongren Hospital from January 2016 to December 2020 were retrospectively analyzed, and the patients were divided into positive driver gene group (patients with driver genes mutation and receiving corresponding targeted therapy) and negative driver gene group. Cox univariate and multivariate regression analyses were performed to identify the factors affecting patients' prognosis, and the receiver operating characteristic curve (ROC) was used to compare the predictive ability of 4 scoring systems [recursive partitioning analysis (RPA) classes, diagnosis-specific graded prognostic assessment (DS-GPA) index, basic score for brain metastasesn (BS-BM) and (lung-molecular graded prognostic assessment (lung-mol GPA)]on patients' prognosis. Results: Among the 103 patients, 48 were males and 55 were females, and aged (64.6±9.7) years old. The median survival time of the 103 patients was 24.0 (95%CI: 20.0-28.0) months, the median survival time of the 59 patients in the positive driver gene group was 33.0 (95%CI: 23.4-42.6) months, the median survival time of the 44 patients in the negative driver gene group was 17.0 (95%CI: 14.4-19.6) months, and the difference was statistically significant (χ2=24.69, P<0.001). The results of Cox multivariate analysis showed that the negative driver genes (HR=3.788, 95%CI: 1.951-7.301, P=0.001), Karnofsky performance status (KPS) score<70 (HR=2.613, 95%CI: 1.185-5.761, P=0.017) and neutrophil-to-lymphocyte ratio (NLR)>3.22 (HR=2.714, 95%CI: 1.157-6.365, P=0.022) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC. KPS score<70 (HR=3.719, 95%CI: 1.165-11.876, P=0.027) and no radiotherapy (HR=2.032, 95%CI: 1.033-11.364, P=0.041) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC with positive driver genes. ROC curve analysis showed that the area under curve (AUC) value of lung-mol GPA was the highest among the 4 scoring systems (AUC=0.843, 95%CI: 0.731-0.956, P<0.001), and the AUC value of the lung-mol GPA combined scoring system (AUC=0.904, 95%CI: 0.816-0.991, P<0.001) was higher than lung-mol GPA. Conclusions: A low KPS score and no cranial radiation therapy are independent risk factors for the prognosis of patients with CNS metastatic NSCLC with positive driver genes; the lung-mol GPA joint scoring system is more conducive to the prognostic assessment of patients with CNS metastatic NSCLC with positive driver genes.

[Antimicrobial resistance and plasmid-mediated colistin resistance mechanism of diarrheagenic Escherichia coli recovered from foods in parts of China in 2020].

Objective: To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods: For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results: Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion: An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.

[Evaluation of the clinical manifestations of COVID-19 in patients with aplastic anemia undergoing immunosuppressive therapy: a prospective cohort study (NICHE)].

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.

[Progress in research of economic evaluation of non-pharmaceutical interventions for COVID-19 prevention and control].

Objective: To understand the research progresses of economic evaluation of non-pharmaceutical interventions (NPIs) both at home and abroad, and provide reference for economic evaluation of NPIs using real-world data in China. Methods: The literature retrieval was conducted by searching Chinese and English databases to indude papers about economic evaluation of NPIs and integrated NPIs published from January, 2020 to December, 2021, and the results were analyzed comprehensively. Results: A total of 30 Chinese and English literatures about economic evaluation of NPIs for COVID-19 prevention and control were included; including 7 papers about nucleic acid and testing and screening, 6 papers about individual prevention and protection measures, 12 papers about integrated implementation of individual prevention and protection, social distancing, nucleic acid or antigen testing, community screening and symptom screening, as well as close contact tracing and isolation/quarantine, and 5 papers about contain strategies, such as lockdown. This study found that personal protection, social distancing, and testing-tracing-isolation measures were cost-effective; however, different combinations of NPIs might lead to different results. Moreover, the cost of lockdown was high, which might cause huge economic burden. Conclusions: Most NPIs are cost-effective except lockdown, while the cost-effectiveness of the integrations of NPIs at different levels and in different scenarios needs to be further evaluated. It is necessary to carry out economic evaluation of integrated NPIs and the combination of NPIs with other interventions, such as vaccination and medication, based on real-world settings in China.

[Progress in research of genomic epidemiology of pathogenic fungi].

Genomic epidemiology, based on whole-genome sequencing technology and bioinformatics analysis, can make up for the shortcomings of traditional molecular typing methods and provide a novel insight for the genetic evolution and transmission of pathogenic fungi. The combination of genetic information and epidemiological methods of pathogenic fungi can predict fungi transmission routes and risks, and provide a theoretical basis for the development of public health strategies for fungi infection prevention and control. This paper summarizes the development of molecular epidemiology and genomic epidemiology, as well as the application of genomic epidemiology methods in the analyses of genetic relationship, origin, evolution, drug resistance, virulence, and genome-wide association of pathogenic fungi, and discusses the development of pathogenic fungi genomic epidemiology.

[Value of hypoxic burden in evaluating the impairments of organ systems in obstructive sleep apnea].

Obstructive sleep apnea (OSA) is a common sleep-disordered-breathing with decreased or even suspended ventilation due to upper airway obstruction, which is characterized by intermittent hypoxia and sleep fragmentation. OSA can damage a variety of organ systems, especially the cardiovascular system, seriously affecting the quality of life of patients. Therefore, more attention is paid to the precise assessment of the impairments of the organ systems caused by OSA and the evaluation of indicators, in order to carry out preventive measures as soon as possible. However, due to the limitations of traditional indicators such as apnea-hypopnea index (AHI) in assessing the severity of disease, it is necessary to explore other alternative indicators to obtain multi-dimensional characteristics of OSA. A promising parameter, hypoxic burden (HB) can better quantify the severity of OSA and capture the disease load of OSA. This review mainly focused on the basic concept, main features, calculating method of HB and its clinical significance in predicting the adverse consequences of OSA, aiming at a better management of patients with OSA.

[Progress in research of economic evaluation of COVID-19 vaccination strategies].

Objective: To understand the research progresses of economic evaluation of COVID-19 vaccination strategies both at home and abroad, and provide reference for the economic evaluation of COVID-19 vaccination strategies using real word data in China. Methods: Literature retrieval was conducted for related papers published from January, 2020 to December, 2021 in Chinese and English databases, including the economic evaluation of COVID-19 vaccination, and the results of the related literatures were narratively integrated. Results: A total of 16 English literatures (including 3 reviews) were included, and it was found that the COVID-19 vaccination was cost-effective or cost-saving regardless of the vaccine types, while the cost-effectiveness in different population and under different vaccination dose strategies varied due to vaccine efficacy, vaccine price, duration of natural immunity, duration of vaccination campaign, vaccine supply, and vaccination pace. Conclusions: China lacks suitable evidences of economic evaluation of COVID-19 vaccination strategies based on real-world data in the context of long-term epidemic. Therefore, further researches of suitable strategies of booster COVID-19 vaccination are needed.

[Study on the etiological characteristics and prevention and control of adult community-acquired pneumonia in hospitalized patients in a hospital in Beijing from 2015 to 2019].

Objective: To explore the distribution characteristics of pathogens in adult patients with community-acquired pneumonia (CAP) and to provide basis for the diagnosis, treatment, prevention of CAP. Methods: 1 446 inpatients with CAP were prospectively enrolled in a third-class hospital in Beijing in recent 5 years (from January 2015 to December 2019). Respiratory tract samples were collected for smear, culture, nucleic acid, antigen and antibody detection to identify the pathogen of CAP. Mann-Whitney U test was used for continuous variables and χ2 test or Fisher's exact test was used for categorical data for statistical analysis. Results: Among the 1 446 patients, 822 (56.85%) patients were infected with a single pathogen, 231 (15.98%) patients were infected with multiple pathogens, and 393 (27.18%) patients were not clear about the pathogen. Influenza virus is the first pathogen of CAP (20.95%, 303/1 446), mainly H1N1 (8.51%, 123/1 446), followed by mycoplasma pneumoniae (7.19%, 104/1 446), Mycobacterium tuberculosis (5.33%, 77/1 446) and Streptococcus pneumoniae (5.05%, 73/1 446). The outbreak of H1N1 occurred from December 2018 to February 2019, and the epidemic of mycoplasma pneumoniae pneumonia was monitored from August to November 2019. Patients under 65 years old had high detection rates of Mycoplasma pneumoniae (14.41% vs. 2.41%, χ²=74.712,P<0.001), Streptococcus pneumoniae (8.16% vs. 2.99%, χ²=18.156, P<0.001), rhinovirus (6.08% vs. 3.56%, χ²=5.025, P<0.025), Chlamydia pneumoniae (5.90% vs. 1.15%, χ²=26.542, P<0.001) and adenovirus (3.13% vs. 0.92%, χ²=9.547, P=0.002). The severe disease rate of CAP was 14.66% (212/1 446), and the average mortality rate was 3.66% (53/1 446). The severe illness rate and mortality rate of bacterial-viral co-infection were 28.97% (31/107) and 19.63% (21/107), respectively. Conclusions: Influenza virus is the primary pathogen of adult CAP. Outbreaks of Mycoplasma pneumoniae and H1N1 were detected in 2018 and 2019, respectively. The remission rate and mortality rate of virus-bacteria co-infection were significantly higher than those of single pathogen infection. Accurate etiological basis not only plays a role in clinical diagnosis and treatment, but also provides important data support for prevention and early warning.

[Analysis on academic quality and influence of Chinese Journal of Epidemiology, 2006-2019].

Objective: In recent years, the editorial board and editorial department of Chinese Journal of Epidemiology have taken a series of measures to further improve the academic quality and influence of the journal. This study analyzed the citation index of Chinese Journal of Epidemiology from 2006 to 2019, and evaluated the academic quality and influence of the journal. Methods: The total citation frequency, impact factor, annual index and other citation rate etc. of Chinese Journal of Epidemiology were extracted from Chinese S&T Journal Citation Report, 2006-2019 (Expanded Edition) and Chinese S&T Journal Citation Report, 2006-2019 (Natural Science) for the analysis on academic quality and influence of the journal. Results: From 2006 to 2019, there were 241-406 articles published in Chinese Journal of Epidemiology per year. The literature selection rate over the years ranged from 66% to 100%. The total expanded citation frequency of Chinese Journal of Epidemiology increased from 3 365 in 2006 to 7 817 in 2019, and the total core citation frequency increased from 1 875 in 2006 to 5 055 in 2019 with slight fluctuation. The expanded impact factor increased from 1.566 in 2006 to 2.799 in 2019. The core impact factor increased from 0.904 in 2006 to 1.842 in 2019. The expanded annual index rose from 0.224 in 2006 to 0.741 in 2019. The core annual index rose from 0.170 in 2006 to 0.602 in 2019. Conclusion: The academic quality and influence of Chinese Journal of Epidemiology has been improved gradually and its ability to focus on hot spots and report new academic achievement has been further strengthened in recent years.

[A real-world study of 176 cases with aplastic anemia treated in outpatient].

Objective: To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting. Methods: The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed. Results: The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion: In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.

[Clinical characteristics of viral pneumonia in patients with chronic obstructive pulmonary disease].

Objective: To study the clinical and etiological characteristics of viral pneumonia in patients with chronic obstructive pulmonary disease(VP-COPD), and to identify the risk factors associated with poor prognosis. Methods: From August 1, 2017 to August 1, 2019, totally 235 patients in a general hospital in Beijing were prospectively enrolled in this research, and all patients were diagnosed with viral pneumonia by imaging and etiology. The patients were divided into VP-COPD group(n=60) and VP-nCOPD(viral pneumonia in non-COPD patients) group(n=175). Pathogen detection and clinical characteristics were compared between the two groups.Finally, the binomial logistic regression was used to explore the risk factors associated with severe VP-COPD. Results: Compared with the VP-nCOPD group, the VP-COPD group was older(76.5 vs 66.0 years, P=0.001), and the CURB-65 score(2 vs 1, P= 0.001) and the PSI score(111 vs 85, P<0.001) were higher at admission. Pseudomonas aeruginosa(χ²= 10.308, P= 0.001) and Staphylococcus aureus(χ²= 5.953, P=0.028) were the most common co-infection bacteria. In the VP-COPD group type Ⅱ respiratory failure was more common(23.3% vs 6.8%, P<0.001), the number of severely ill patients was larger(48.3% vs 30.3%, P=0.011), the length of hospital stay was longer(13 vs 8, P<0.001), and the mortality rate during hospitalization was higher(18.3% vs 7.4%, P=0.016) in the VP-nCOPD group. Multivariate analysis showed that the level of blood glucose(OR: 1.73, 95%CI: 1.22-2.44, P= 0.002) and pleural effusion(OR: 133.12, 95%CI: 7.57-2 340.36, P=0.001) were risk factors for severe VP-COPD patients. Conclusion: Viral pneumonia in patients with COPD tended to develop into severe cases and had a poor prognosis.

[The study on the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis].

Objective: To explore the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis (CWP) , the relationship of extracellular histones in plasma with pulmonary fibrosis caused by coal mine dust was analyzed, and the stimulating effect of extracellular histones on fibroblast proliferation was studied. Methods: In May 2019, a total of 220 coal mine dust exposure workers (including coal miners and CWP patients) who visited the occupational disease outpatient department of Peking University Third Hospital from 2012 to 2015 were enrolled in the study. According to the classification of small opacity profusion (SOP) in chest radiograph for pneumoconiosis diagnosis (category 0, 1, 2, 3) , 61 coal miners were in category 0 SOP, 65 coal miners were in category 1 SOP, 56 coal miners were in category 2 SOP and 38 coal miners were in category 3 SOP. The plasma levels of extracellular histone H4 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. The stimulating effects of CWP patients' plasma and calf thymus histones (CTHs) on fibroblast and the antagonizing effect of anti-H4 antibody were investigated by fibroblast proliferation experiment in vitro. Results: Among the study subjects, there were 195 males (88.6%, 195/220) and 25 females (11.4%, 25/220) , age (55.1±7.2) years, coal mine dust exposure time (16.3±4.4) years. The plasma concentrations of histone H4 in the coal miners with category 0, 1, 2 and 3 SOP were (3.92±1.75) 、(9.84±4.17) 、(14.35±5.52) and (17.83±7.69) µg/ml, respectively. There were significant differences among the four groups (P<0.01) . The plasma level of histone H4 was positively correlated with the plasma level of PDGF in the coal miners (r=0.769, P<0.01) . Compared with healthy control plasma group, the cell proliferation percentages of patients' plasma group (272%±87%) and CTH group (283%±84%) were significantly increased (P<0.05) . Compared with patients' plasma group, the cell proliferation percentage of patients' plasma+anti-H4 antibody group (185%±66%) was significantly decreased (P<0.05) . Compared with CTH group, the cell proliferation percentage of CTH+anti-H4 antibody group (167%±59%) was significantly decreased (P<0.05) . Conclusion: Extracellular histones in plasma are associated with pulmonary fibrosis in patients with CWP. Studies in vitro have shown that extracellular histones can promote proliferation of pulmonary fibroblasts. It is suggested that extracellular histones can be important biomarkers for pulmonary fibrosis caused by coal mine dust.

Upregulated miR-101 inhibits acute kidney injury-chronic kidney disease transition by regulating epithelial-mesenchymal transition.

Acute kidney injury (AKI) is an independent risk factor for chronic kidney disease (CKD). However, the role and mechanism of microRNA (miRNA, miR) in AKI-CKD transition are elusive. In this study, a murine model of renal ischemia/reperfusion was established to investigate the repairing effect and mechanism of miR-101a-3p on renal injury. The pathological damage of renal tissue was observed by hematoxylin and eosin and Masson staining. The levels of miR-101, profibrotic cytokines, and epithelial-mesenchymal transition (EMT) markers were analyzed using Western blotting, real-time polymerase chain reaction, and/or immunofluorescence. MiR-101 overexpression caused the downregulation of α-smooth muscle actin, collagen-1, and vimentin, as well as upregulation of E-cadherin, thereby alleviating the degree of renal tissue damage. MiR-101 overexpression mitigated hypoxic HK-2 cell damage. Collagen, type X, alpha 1 and transforming growth factor ß receptor 1 levels were downregulated in hypoxic cells transfected with miR-101 mimic. Our study indicates that miR-101 is an anti-EMT miRNA, which provides a novel therapeutic strategy for AKI-CKD transition.

[Activation of lung endothelial cells by extracellular histone in mice with acute respiratory distress syndrome].

Objective: To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) . Methods: The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model. Results: The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells. Conclusion: Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.

Effects of Sca-1(+) bone marrow mesenchymal stem cells on lung ischemia-reperfusion injury.

This study aimed to explore the effect of Sca-1+ bone marrow stromal stem cells (BMSCs) on lung ischemia reperfusion injury in mice. Five healthy Sprague-Dawley rats were selected to isolate and purify their Sca-1+ BMSCs using a Sca-1+ magnetic sorting kit in conjunction with whole bone marrow culture. In addition, 21 male C57BL/6J mice were divided into 3 groups (7 mice in each group), namely sham group (group A), I/R group (group B) and BMSCs group (group C). A pulmonary ischemia reperfusion injury model was established by ligating the left pulmonary portal vessel for 60 min and reperfusion for 240 min, after which the right pulmonary portal vessel was blocked to measure arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Subsequently, the mice were sacrificed to determine their superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the lung tissue. The histological changes were observed by light microscopy, while an enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in plasma expressions of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the mice. In addition, plasma expressions of TNF-α and B-cell lymphoma-2 (bcl-2) in the mice were detected by immunohistochemistry, while the apoptosis of transplanted lung cells was detected by a TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Compared with group A, group B showed a decreased level of PaO2 and SOD activity but an increased level of MDA content and MPO activity (P less than 0.01), indicating that group B had significant ischemia reperfusion injury compared to group A. In conclusion, BMSCs significantly reduced lung ischemia-reperfusion injury and improved lung function through their anti-oxidation, anti-inflammatory and anti-apoptosis properties.