Case of Extensively Drug-Resistant Shigella sonnei Infection, United States.

We report extensively drug-resistant (XDR) Shigella sonnei infection in an immunocompromised patient in Texas, USA. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify XDR Shigella, but whole-genome sequencing accurately characterized the strain. First-line antimicrobials are not effective against emerging XDR Shigella. Fosfomycin, carbapenems, and tigecycline are potential alternatives.

Investigation on the emulsification mechanism in aqueous enzymatic extraction of edible oil from Schizochytrium sp.

BACKGROUND: The interaction between emulsified substances and lipids generates an emulsification system during the extraction of microalgae edible oil by aqueous enzymatic method. This study aimed to resolve the dynamics of interfacial protein adsorption during the extraction of microalgae oil at different enzymatic times and the effect on the stability of the interfacial membrane formed by the proteins based on interfacial effects. RESULTS: At 1.5 h of enzymatic hydrolysis, the molecular weights of the proteins/peptides were all below 35 kD. In addition, the protein-peptide structure was loose, with the lowest number of disulfide bonds, peak surface hydrophobicity, the highest number of residues, and disordered lipid acyl arrangement. At the same time, the physical stability of the emulsion was the lowest, and the interfacial membrane rupture was distinct. On excessive enzymatic hydrolysis (at 3.0 h), a more uniform interfacial membrane was re-formed on the lipid surface. CONCLUSION: Protein is the main emulsifying substance in the emulsification system. The addition of protease affects the stability of the interfacial membrane formed by proteins. In addition, sufficient enzymatic hydrolysis (1.5 h) inhibited emulsification, while excessive enzymatic hydrolysis (3.0 h) promoted emulsification. © 2023 Society of Chemical Industry.

The measurement of critical quality attributes of Tongren niuhuang qingxin pills based on MIF-HEMT biosensor technology / 药学学报

There is still a serious challenge of the measurement of critical quality attributes (CQAs) related to clinical efficacy for Chinese materia medica manufacturing. To overcome this challenge, an integrated strategy of biosensor and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was proposed using Tongren niuhuang qingxin pills as a trial. Firstly, an original biosensor was created using a semiconductor chip material high electron mobility transistor (HEMT) as the transducer and the macrophage migration inhibitory factor (MIF) as the identification element. By this MIF-HEMT biosensor, the efficacy on stoke of different components from Tongren niuhuang qingxin pills was measured. It was clear that all three components of Tongren niuhuang qingxin pills had strong therapeutic effects on stroke, especially the section A, the KD of which reached to 8.722×10-10 g·mL-1. Furthermore, MIF-HEMT biosensor integrated UPLC-MS/MS was introduced to identify the efficacy CQAs of different components of Tongren niuhuang qingxin pills. As a result, 19 potential CQAs, such as albiforin, paeoniflorin, and prim-O-glucosylcimifugin, were measured as the efficacy CQAs of Tongren niuhuang qingxin pills on stroke treatment by MIF. These results provided vital measurement techniques and methodological guidance for the CQAs study of Tongren niuhuang qingxin pills intervention in MIF-induced stroke treatment. This also provided an essential guideline for the efficient utilization and quality control measurement of high-quality classical recipes.

Identification of taste critical quality attribute and formulation optimization of Xiaoer Qingrening Granules based on electronic tongue and human senses / 药学学报

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

Post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy on post-stroke dysphagia treated with four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation.@*METHODS@#Sixty patients with post-stroke dysphagia were randomly divided into an observation group and a control group, with 30 cases in each group. The neuromuscular electrical stimulation was adopted in the control group. Besides the treatment as the control group, in the observation group, the four-step acupuncture therapy for opening orifices and benefiting throat was supplemented. Step 1: the three areas of scalp acupuncture on the affected side were stimulated. Step 2: pricking method was operated on the posterior pharyngeal wall. Step 3: bleeding technique was operated at Jinjin (EX-HN 12) and Yuye (EX-HN 13). Step 4: deep insertion of needle was operated at three-pharynx points. The needles were retained for 30 min at the three areas of scalp acupuncture and the three-pharynx points. The intervention of each group was delivered once daily, 6 times a week, at the interval of 1 day. One course of treatment was 1 week and 4 successive courses were required. The rating of Kubota water swallow test, the score of standardized swallowing assessment (SSA) and the rating of Rosenbek penetration- aspiration scale (PAS) were observed before and after treatment in patients of the two groups. The incidence of clinical complications and clinical efficacy were compared between the two groups.@*RESULTS@#Compared with those before treatment, the rating of Kubota water swallow test, the scores of SSA and the rating of PAS of patients in the two groups were decreased after treatment (P<0.01), and the values of the observation group were lower than those of the control group after treatment (P<0.05). The incidence of clinical complications in the observation group was 13.3% (4/30), lower than 36.7% (11/30) in the control group (P<0.05). The total effective rate in the observation group was 93.3% (28/30), which was better than 70.0% (21/30) in the control group (P<0.05).@*CONCLUSION@#The four-step acupuncture therapy for opening orifices and benefiting throat combined with neuromuscular electrical stimulation can improve the swallowing function of patients with post-stroke dysphagia and reduce the incidence of clinical complications.

Gold microneedling radio-frequency treatment for depression scar of facial acne: a meta-analysis / 中华医学美学美容杂志

Objective:To evaluate the efficacy and safety of gold micrhenedle radiofrequency and other photoelectric methods in the treatment of facial acne depression scar by using a meta-analysis.Methods:From January 2015 to August 2022, gold microneedles and radio frequence for treatment of facial acne depression scar of randomized controlled trial were retrieved from CNKI, Wanfang Database, VIP, China Biomedical Literature Service System, PubMed database, Cochrane Library and Embase database, including 12 papers. There were 6 Chinese and 6 English literatures, with a sample size of 612 cases.Results:Gold microneedling radio-frequency showed better efficacy in the treatment of facial acne depression scar ( P<0.05). After subgroup analysis, the effective rate in the observation group was higher than that in the control group after 4 treatments, and the difference was statistically significant ( P<0.05). Clinical acne scarring assessment scale, pain score and recovery time had statistically significant difference ( P<0.05). Conclusions:Gold microneedling radiofrequency alone or in collaboration with other photoelectricity in the treatment of acne depression scar has short rest period, slight pain, and obvious improvement of scar effect. However, the improvement effect on icicle depression scar is limited.

Clinical characteristics among 67 cases of botulism in Xinjiang Uygur Autonomous Region, China / 中华神经科杂志

Objective:To investigate epidemiological and clinical characteristics of botulism, and the adverse events among those received botulinum antitoxin treatment.Methods:Patients with discharge diagnosis as botulism in the Second Affiliated Hospital of Xinjiang Medical University were enrolled between 2017 and 2021. The epidemiological and clinical characteristics were evaluated. Infection and mechanical ventilation as in-hospital outcomes according to baseline characteristics were analyzed. Patients with and without the interested outcomes were compared. The adverse outcomes among those received botulinum antitoxin treatment were investigated. Those with and without the adverse outcomes were also compared.Results:Sixty-seven cases of botulism were enrolled, and most cases got sick between January and March (32/67, 47.8%); among them 62 cases were Han ethnicity (92.5%); prevalence was highest in Aksu region (15/67, 22.4%); commonly seen symptoms and signs included fatigue (58/67, 86.6%), dysphagia (48/67, 71.6%), dizziness (42/67, 62.7%), ptosis (42/67, 62.7%), blurred vision (41/67, 61.2%), and limb weakness (35/67, 52.2%). Compared with patients without in-hospital infection ( n=52), patients with in-hospital infection ( n=15) were more likely to have severe botulism (0/52 vs 5/15, χ 2=19.79, P<0.001), diplopia (16/52, 30.8% vs 11/15, χ 2=8.77, P=0.003), dysarthria (17/52, 32.7% vs 11/15, χ 2=7.91, P=0.005), consciousness disorder (1/52, 1.9% vs 4/15, χ 2=10.32, P=0.008). Compared with patients without mechanical ventilation (62/67, 92.5%), patients with mechanical ventilation (5/67, 7.5%) were more likely to have severe botulism (5/5 vs 0/62, χ 2=41.17, P<0.001), and consciousness disorder (4/5 vs 1/62, 1.6%, χ 2=29.58, P<0.001). Among 67 cases of botulism, 19 cases (28.4%) had adverse events after receiving antitoxin treatment, with an average of 6.5 days from the antitoxin treatment beginning to the adverse event onset; among the 19 cases, 18 cases (94.7%) had rash. Age, sex, and severity did not differ between the groups with ( n=19) and without adverse events ( n=48) after receiving antitoxin treatment. Conclusions:Fatigue, dysphagia, dizziness, ptosis were the most frequent symptoms and signs in the botulism in Xinjiang Uygur Autonomous Region, China. Infection was a commonly seen complication of botulism, and proactive prevention and close monitoring were needed. Adverse events after receiving antitoxin were prevalent, and might not be associated with age, sex, and severity of botulism.

Liraglutide inhibits high glucose-induced cardiomyocyte hypertrophy via modulating autophagy and Na / 中国药理学通报

Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

Effect of Buyang Huanwu Decoction on cerebral ischemia-reperfusion injury in rats by regulating autophagy through PI3K/AKT pathway / 中国药理学通报

Aim To explore the effect of Buyang Huanwu Decoction on cerebral ischemia-reperfusion injury in rats by regulating autophagy through PI3K/AKT pathway. Methods The rats were randomly divided into five groups(n=10): sham operation group(Sham), model group(Model), Buyang Huanwu Decoction group(BYHWD), PI3K inhibitor group(LY294002)and Vehicle group(Vehicle). Except Sham group, the other groups were treated with 2h ischemia and 72 h reperfusion for modeling. The Zea Longa score was used to assess the neurological defects, HE was used to observe brain injury in the ischemic penumbra(IP), immunofluorescence was employed to detect LC3, and Western blot was used to detect pathway and autophagy marker proteins. Results Compared BYHWD group with model group, the neurological score of rats decreased, cerebral infarction volume decreased, the pathological lesions of brain IP were relieved, PI3K and p-AKT/AKT expression increased, and LC3Ⅱ/ decreased and p62 increased(P<0.05). The regulatory effect of BYHWD was weakened by LY294002(P<0.05). Conclusion Buyang Huanwu Decoction alleviates cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT pathway to inhibit autophagy.

Study on the relationship between secondhand smoke exposure and dyslipidemia in adult residents in Beijing / 中华流行病学杂志

Objective: To understand the relationship between secondhand smoke exposure and dyslipidemia among adults in Beijing and to provide a scientific basis for relevant intervention. Methods: Data were from Beijing Adult Non-communicable and Chronic Diseases and Risk Factors Surveillance Program in 2017. A total of 13 240 respondents were selected by multistage cluster stratified sampling method. The monitoring contents include a questionnaire survey, physical measurement, collection of fasting venous blood, and determination of related biochemical indicators. SPSS 20.0 software was used for the chi-square test and multivariate logistic regression analysis. Results: The prevalence of total dyslipidemia (39.27%), hypertriglyceridemia (22.61%), and high LDL-C (6.03%) were the highest among those exposed to daily secondhand smoke. Among the male respondents, the prevalence of total dyslipidemia (44.42%) and hypertriglyceridemia (26.12%) were the highest among those exposed to secondhand smoke daily. Multivariate logistic regression analysis after adjustment for confounding factors showed that compared with no exposure to secondhand smoke, the population with an average exposure frequency of 1-3 days per week had the highest risk of total dyslipidemia (OR=1.276, 95%CI: 1.023-1.591). Among the patients with hypertriglyceridemia, those exposed to secondhand smoke daily had the highest risk (OR=1.356, 95%CI: 1.107-1.661). Among the male respondents, those exposed to secondhand smoke for 1-3 days per week had a higher risk of total dyslipidemia (OR=1.366, 95%CI: 1.019-1.831), and the highest risk of hypertriglyceridemia (OR=1.377, 95%CI: 1.058-1.793). There was no significant correlation between the frequency of secondhand smoke exposure and the risk of dyslipidemia among female respondents. Conclusions: Secondhand smoke exposure in Beijing adults, especially men, will increase the risk of total dyslipidemia, especially hyperlipidemia. Improving personal health awareness and minimizing or avoiding exposure to secondhand smoke is necessary.

Study on the relationship between indexes of different abnormal weight and dyslipidemia in adults in Beijing City / 中华预防医学杂志

Objective: To analyze the relationship and consistency between indexes of different abnormal weight and dyslipidemia in adults in Beijing City. Methods: From August to December of 2017, 4 975 residents aged 18 to 79 years old in 5 districts of Beijing were randomly selected as subjects by using a multi-stage stratified cluster sampling method. Questionnaire, physical examination and laboratory tests were conducted. The prevalence of overweight/obesity, high body fat rate, central obesity, and high waist-to-height ratio was calculated. Partial correlation was used to analyze the correlation of blood lipid with body mass index (BMI), body fat rate, waist circumference and waist-height ratio. Logistic regression analysis for complex sampling was used to analyze the relationship between indexes of different abnormal weight and dyslipidemia after controlling for relevant risk factors, including age, sex, smoking status, drinking, insufficiency intake of vegetable and fruit, physical inactivity. Kappa value was computed to analyze the consistency between indexes of different abnormal weight. Results: The weighted prevalence of dyslipidemia was 30.48%, and it was higher in men than that in women (40.16% vs. 20.52%, P<0.01). The weighted rate of overweight/obesity, high body fat rate, central obesity, and high waist-to-height ratio was 56.65%, 47.52%, 42.48% and 59.45%, respectively. BMI, body fat rate, waist circumference and waist-to-height ratio were positively correlated with the level of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and negatively correlated with high-density lipoprotein cholesterol. Logistic regression analysis for complex sampling showed that the high body fat rate (OR=1.67, 95%CI: 1.35-2.07), overweight/obesity (OR=1.65, 95%CI: 1.26-2.14) and high waist-to-height ratio (OR=1.46, 95%CI: 1.09-1.96) were associated with dyslipidemias. Kappa values of high body fat rate with overweight/obesity, high waist-to-height ratio and central obesity were 0.65, 0.53 and 0.58, respectively (P<0.05). Conclusion: In 2017, the prevalence of dyslipidemia in adults in Beijing City is high, especially in men. Overweight/obesity, high body fat rate and high waist-to-height ratio are associated with dyslipidemia. The high body fat rate is most associated with dyslipidemia.

Leishmaniasis and Heart.

As one of the neglected tropical diseases, leishmaniasis is defined as a parasitic communicable disease that is most prevalent in tropical and subtropical regions, affecting especially populations living in poverty. It has a profound negative impact on developing economies. It represents a group of heterogeneous syndromes with a wide spectrum of severity ranging from self-resolving cutaneous injuries to disseminated visceral compromise. Visceral leishmaniasis represents its most severe form, can affect almost all organs, and can have fatal consequences, especially in immunosuppressed patients. Cardiac involvement seems to be rare but has not been deeply studied. Consequently, there are no clear recommendations for the screening of cardiac manifestations in these patients. However, cardiovascular complications could be potentially lethal. In addition, there are valuable reports on the potential cardiotoxicity caused by drugs used in the treatment of this condition, so knowledge of its side effects could have important implications. This article is a part of the "Neglected Tropical Diseases and other Infectious Diseases affecting the Heart" project (the NET-Heart Project); its purpose is to review all the information available regarding cardiac implications of this disease and its treatment and to add knowledge to this field of study, focusing on the barriers for diagnosis and treatment, and how to adopt strategies to overcome them.

Como una de las enfermedades tropicales desatendidas (ETD), la leishmaniasis se define como una enfermedad parasitaria transmisible y muy prevalente en regiones tropicales-subtropicales afectando especialmente a poblaciones que viven en la pobreza. Tiene un profundo impacto negativo en las economías en vías de desarrollo. Representa un grupo heterogéneo de síndromes clínicos con un amplio espectro de severidad que va desde lesiones cutáneas que resuelven espontáneamente hasta compromiso visceral diseminado. La leishmaniasis visceral representa su forma más grave, puede afectar a casi todos los órganos del ser humano y suele tener consecuencias fatales, especialmente en pacientes inmunosuprimidos. La afectación cardíaca parece ser rara, pero nunca se ha estudiado en profundidad. En consecuencia, no existen recomendaciones claras para el cribado de las manifestaciones cardíacas en estos pacientes; sin embargo, las complicaciones cardiovasculares pueden ser potencialmente letales. Además, existen publicaciones sobre la potencial cardiotoxicidad provocada por los fármacos utilizados en el tratamiento de esta afección, por lo que el conocimiento de sus efectos secundarios podría tener importantes implicancias. Como parte del proyecto "Neglected Tropical Diseases and other Infectious Diseases affecting the Heart" (Proyecto NET-Heart), el propósito de este artículo es revisar toda la información disponible sobre el compromiso cardiovascular de esta enfermedad y su tratamiento y agregar conocimientos a este campo de estudio, centrándose en las barreras para el diagnóstico y tratamiento y cómo adoptar estrategias para superarlas.

Mechanism of gubenfangxiaoyin drinking in the treatment of infantile asthma prevention by network pharmacology and molecular docking / 中国药理学通报

Aim To explore the mechanism of pediatric asthma based on network pharmacology and molecular docking technology. Methods Through TCMSP database, the chemical information and the targets of TCM chemical components and pediatric asthma targets in PubChem, SwissTargetPrediction and GeneCards were collected, and the intersection gene, namely the target gene of pediatric asthma was used. The “Drug-active ingredient-target” map was plotted with the Cytosacape 3.7.2 software. Protein interaction network maps were constructed based on the String database and analyzed by Cytoscape 3.7.2. GO and KEGG pathway analysis of acting targets using the Metascape database and bubbles were plotted on the Omicshare platform. Results A total of 238 active components and 11 corresponding 697 main targets were selected, 1 052 pediatric asthma disease target targets and 242 common targets were selected. Enrichment analysis found that common targets were primarily involved in biological processes such as MAPK cascade regulation and inflammatory response, as well as calcium signaling pathway, cAMP signaling pathway, AGE-RAGE signaling pathway, cGMP-PKG signaling pathway, etc. Molecular docking results showed that the active components of Astragalus(5'hydroxyiso-muronulatol-2',5'-di-O-Glucoside)docked well with the SRC, TP53, and IL-6 targets. We proved that anti-resistant drinking could down-regulate the expression of IL-6, SRC and TP53. Conclusions Gubenfangxiaoyin drinking may be involved in the regulation of the STAT3, SRC, AKT1, TP53, TNF, MAPK3, TP53,TNF,MAPK3 and IL6 and other targets, involved in the regulation of calcium-CAMP signaling pathway in childhood asthma, AGE-RAGE signaling pathway, cGMP-PKG signaling pathway, reduce the MAPK cascade, inflammatory response, etc, and play a role in the prevention and treatment of asthma.

Buyang huanwu decoction attenuates cerebral ischemia-reperfusion injury in rats by regulating autophagy through AMPK/mTOR/ULKl signaling pathway / 中国药理学通报

Aim To explore the mechanism of Buyang huanwu decoction attenuating cerebral ischemia-reper- fusion injury in rats by regulating autophagv through AMPK/mTOR/ULKl signaling pathway.Methods Left eerebral ischemia model in rats was established by modified thread ocelusion method, then the rats in each group were given medieine onee every 24 hours for 3 times.After 72 hours of reperfusion, the nerve injury and the changes of cerebral infarction volume were observed; the morphology, number and apoptosis of nerve cells were observed by Nissl staining and TUNEL staining; the expression of autophagy protein and AMPK/mTOR/LJLKl autophagy signaling pathway related proteins were detected by Western blot.Results Buyang huanwu decoction could improve the neurological deficit of rats, reduce the volume of cere bral infarction and neuronal apoptosis, reduce the pathological injury of brain tissues, inhibit the phosphorylation activation of AMPK, relieve the inhibition of AMPK on downstream mTOR and LJLK1 , promote the phosphorylation activation of both, and inhibit autophagy.AMPK agonist metformin increased the level of autophagy and reversed the protective effect of Buyang huanwu decoction on cerebral ischemia-reperfusion injury in rats.Conclusion Buyang huanwu decoction mediates AMPK/mTOR/ULKl autophagy signaling pathway to play a neuroprotective effect on cerebral is- chemia-reperfusion injury in rats.

Liraglutide attenuates myocardial inflammation and oxidative stress injury in diabetes rats via modulating AMPK/mTOR autophagy signalling / 中国药理学通报

Aim To investigate the effeets of liraglutide ( LRG) on myocardial injury in type 2 diabetes melli- tus (T2DM) rats and its mechanisms.Methods For¬ty male SD rats were alloeated into eontrol group, T2DM group, LRG group, and LRG + AMPK inhibitor Compound C group (LRG + CC ).Four weeks later blood glucose and blood lipids of T2DM rats were measured.The eardiae function was measured by echo¬cardiography.The activities of superoxide dismutase (SOD ) , glutathione ( GSH ) and the malondialdehyde (MDA) eontent were assessed with corresponding rea¬gent kits.Cardiomyoeyte apoptosis was analyzed by TXJNEL staining.The expressions of inflammation, oxi-dative stress, apoptosis, autophagy, and AMPK/ mTOR signaling related proteins were deteeted by Western blot.Results Treatment with LRG alleviated hyperglycemia and hyperlipidemia, and improved heart function markers in T2DM rats.LRG inhibited inflam¬mation, oxidative stress and apoptosis and restored au- tophagy in T2DM rats by decreasing the expression of IL-6, TNF-a, IL-lp, N0X2, N0X4, cleaved caspase-3, Bax, p-mTOR/mTOR and the MDA con¬tent , and increasing the expression of Bcl-2, Atg5, Beclin-1 , LC3-II/LC3-I, p-AMPK/AMPK and the ac¬tivities of SOD and GSH.However, these effects were largely abolished by the AMPK inhibitor Compound C.Conclusions LRG exerts a protective role against dia¬betes-induced myocardial injury by ameliorating in-flammation, oxidative stress and apoptosis via the AMPK/mTOR autophagy signaling.

Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction / 中国结合医学杂志

OBJECTIVE@#To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways.@*METHODS@#Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis.@*RESULTS@#The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1.@*CONCLUSION@#LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.

Significance of Lymphocyte-to-Monocyte Ratio and Corrected Levels of Serum Calcium as Prognostic Markers in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the significance of peripheral blood lymphocyte to monocyte ratio (LMR) and corrected levels of serum calcium (cCa) as prognostic markers for the newly diagnosed multiple myeloma (MM) patients.@*METHODS@#The clinical data of 114 newly diagnosed MM patients in the Second Affiliated Hospital of Kunming Medical University from January 2013 to March 2020 were retrospectively analyzed. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value, and the patients were divided into high LMR group and low LMR group (LMR≥3.35 and LMR < 3.35). Moreover, the patients were divided into four groups according to initial diagnosis LMR and LMR after four courses of treatment (LMR4): Group A (LMR≥3.35, LMR4≥3.35), Group B (LMR≥3.35, LMR4 < 3.35), Group C (LMR < 3.35, LMR4≥3.35), and group D (LMR < 3.35, LMR4 < 3.35). The simple prognosis model was established by combined with LMR and cCa, the patients were divided into Group a (no risk factor), group b (1 risk factor) and Group c (2 risk factors). Independent sample T-test, Pearson Chi-square test or Mann-Whitney U test were used to evaluate the differences between various parameters, and Kaplan-Meier method and Cox regression were used for survival analysis.@*RESULTS@#The median follow-up time was 13.05（0.1-72.5）months. Survival analysis showed that the patients with low LMR predicted poor prognosis, the overall survival (OS) time of the patients with low LMR was significantly shorter (17 vs 50.5 months, P=0.006) than the patients with high LMR, the difference was also significant between group A and Group D (56.5 vs 30.5 months, P=0.043). The OS of the patients was also significantly shorter in the high cCa group (≥2.75 mmol/L) compared with normal group (8.5 vs 34 months, P=0.006). Multivariate survival analysis showed that LMR < 3.35 (P=0.028) and cCa≥2.75 mmol/L (P=0.036) were the independent risk factors affecting prognosis of MM patients. The comparison of risk factors showed that the median OS of Group a, b and c was 50, 20, and 8.5 months, respectively. The prognosis of the patients without risk factors was better than that of patients with 1-2 risk factors (Group a vs Group b, P < 0.0001; Group a vs Group c, P=0.002).@*CONCLUSION@#LMR and cCa are the independent risk factors affecting the prognosis of newly diagnosed MM patients, and the development of a simple prognosis system combining them can quickly identify the prognosis of newly diagnosed MM patients.

Detection of NPM1 Mutation in Acute Myeloid Leukemia by Droplet Digital PCR and Its Clinical Application Value / 中国实验血液学杂志

OBJECTIVE@#To establish the droplet digital PCR (ddPCR) assay for the detection of NPM1 type A mutation in patients with acute myeloid leukemia (AML), and to evaluate its specificity, sensitivity and its value in clinical application.@*METHODS@#NPM1 mutant and wildtype plasmids were used to verify the performance of ddPCR. Both ddPCR and Sanger sequencing were used to detect the bone marrow samples of 87 AML patients, which were confirmed by next generation sequencing (NGS). Moreover, NPM1 mutation burden was dynamically monitored in five patients by ddPCR.@*RESULTS@#The limit of blank (LOB) of ddPCR established for NPM1 mutation detection was 1.1 copies/μl, and the limit of detection (LOD) was 2.43 copies/μl, which had good linearity. Among the 87 newly diagnosed AML patients, ddPCR identified seventeen cases positive for NPM1 mutation (19.5%)， which was consistent with Sanger sequencing. NGS confirmed 12 positive cases, including 8 of type A mutations, 2 of type D mutations, and 2 of rare type mutations. The results of dynamic monitoring of NPM1 mutation burden in 5 patients showed that the NPM1 mutation burden decreased obviously even close to 0, when patients achieve complete remission after chemotherapy. However, the mutation burden was increased again at the time of relapse.@*CONCLUSION@#In this study, we established a ddPCR method for detection of NPM1 mutation with good sensitivity and repeatability, which can be used for screening NPM1 mutation in newly diagnosed AML patients and for minimal residual disease monitoring after remission in positive AML patients to guide treatment.

Clinicopathological features of very well-differentiated adenocarcinoma of the stomach / 中华病理学杂志

Objective: To investigate the clinicopathological features of very well-differentiated adenocarcinoma (VWDA) of the stomach. Methods: The clinicopathological data of 12 cases of VWDA of the stomach were collected retrospectively at the People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from January 2013 to May 2021. The histological characteristics and immunophenotypes were observed and analyzed with review of current literature. Results: There were 8 males and 4 females with a median age of 63 years (range 47 to 80 years). The tumor involved in the upper part of the stomach in 6 cases, the middle part in 2 cases, and the lower part in 4 cases. The median diameter of the tumors was 17 mm (range 5-65 mm). The tumor cells were similar to absorbent cells, Paneth cells, foveolar epithelial cells, and goblet cells. The cells were arranged in a single layer, and the nuclei were slightly enlarged and located at the base. The nuclei were fusiform to slightly irregular, with loss of nuclear polarity. Early tubular VWDA was found in 9 cases, and the tumor glands were similar to intestinal metaplasia. In two cases the tumors infiltrated into the submucosa. The lesions in the mucosa and submucosa showed the glands with cystic expansion, bending, branching, spiky and abortive growth pattern. One case of early papillary tubular VWDA was confined to the mucosal layer and composed of foveolar-type epithelial cells. There were two cases of advanced papillary tubular VWDA, which consisted of foveolar-type epithelial, pyloric glands, or mucinous neck cells and were associated with intra-lymphatic cancer embolus and lymph node metastases. Background mucosal atrophy and intestinal metaplasia were observed in all cases. Immunohistochemical staining showed intestinal type VWDA in 1 case, mixed gastrointestinal type VWDA in 9 cases, and gastric type VWDA in 2 cases. The Ki-67 proliferation index of 8 cases limited to the mucosa was 40%-70%, 2 cases of infiltration into the submucosa and 2 cases of advanced carcinoma was 10%-25%. All the tumors showed a wild type of p53 protein expression pattern and negative HER2. Adenocarcinoma or high-grade dysplasia was diagnosed on preoperative biopsy in 5 cases, and chronic atrophic gastritis with intestinal metaplasia in 7 cases. The median follow-up time was 28 months (range 12-72 months). No recurrence was found in the 10 patients with early cancer. Of the two patients with advanced carcinoma, one patient had lung metastases and the other died. Conclusions: Gastric VWDA is a rare low-grade malignancy with structural features of highly differentiated adenocarcinoma and extremely low cytological atypia. The diagnostic value of structural abnormality is significantly greater than cytological atypia. The invasive growth of irregular glands in the deep mucosa and submucosa is reliable evidence for diagnosis. The diagnosis of intramucosal VWDA is challenging and very difficult in some biopsy specimens.

Current status of regular exercise and influencing factors in 18-64 year old labor force population in Beijing / 中华流行病学杂志

Objective: To understand the regular exercise status and influencing factors in 18-64 year-old labor force population in Beijing, and provide evidences for behavioral intervention. Methods: Data were collected from Beijing Adult Non-communicable and Chronic Diseases and Risk Factors Surveillance Program from August to December, 2017. The stratified cluster sampling method was used to select 13 240 survey subjects throughout the city. The valid sample size included in this study were 11 604 persons aged 18 to 64 years. Questionnaire was used to collection the information about basic demographic characteristics, chronic disease history and physical activity prevalence of the study subjects. The body height and weight were measured by standard methods. Fasting venous blood samples were collected for the detection of fasting blood glucose, blood lipids and other biochemical indicators. Software SPSS 20.0 was used fort complex sampling sample weighting and data analysis. Results: The proportions of the study subjects who did regular exercise and never had leisure-time activity in 18-64 year-old labor force population in Beijing were 23.74% (95%CI: 21.51%-26.12%) and 64.34% (95%CI: 61.66%-66.94%) respectively; The average daily physical activity time was 23.44 min (95%CI: 21.16-25.71), and the total daily sedentary behavior time was 6.96 hours (95%CI: 6.80-7.13). With the increase of age, the proportions of the study subjects who did regular exercise and never had leisure-time activity increased (P=0.006, P<0.001). With the increase of educational level, the proportion of those who did regular exercise increased (P<0.001), and the proportion of those who never had leisure-time activity decreased (P<0.001); the higher the level of physical activity, the higher the regular exercise proportion (P<0.001); the proportions of employed people who did regular exercise was lower than those in unemployed people (P<0.001); the proportions of women never had leisure-time activity was higher than those in men (P=0.024). The results of multivariate analysis showed that older age and higher education level were positive factors for regular exercise (35- years old: OR=0.653, 95%CI: 0.530-0.804, P<0.001; 50-64 years old: OR=0.695, 95%CI: 0.560-0.864, P=0.001; high school/technical secondary school/technical School: OR=0.679, 95%CI: 0.593-0.777, P<0.001; college graduation: OR=0.478, 95%CI: 0.387-0.590, P<0.001; bachelor degree and above: OR=0.435, 95%CI: 0.347-0.546, P<0.001), while employment (OR=1.631, 95%CI: 1.330-2.000, P<0.001) and married/cohabitation (OR=1.340, 95%CI: 1.093-1.644, P=0.038) were negative factors for regular exercise. Conclusions: The rate of regular exercise in 18-64 year-old labor force population in Beijing needs to be improved. Older age and high educational level were positive factors for regular exercise, while being married and employed were negative factors for it.