Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Feasibility analysis of puncture robot technology for the application of acupuncture robot / 中国针灸

The difficulties such as how to accurately locate acupoints and safely insert needles are presented in acupuncture robot. The puncture robot with high technological similarity to acupuncture robot is getting mature, and a large number of human trials and animal experiments have been conducted for the development of puncture robot. Through comparing the similarities and differences between puncture robot and acupuncture robot in the aspects of through-skin puncture, needle insertion and needle removal, the valuable technology of puncture robot is analyzed for the development of acupuncture robot, and the crucial direction of technology migration is determined. ①Integrating the mechanical feedback and medical imaging technology and utilizing the multi-modal perception to achieve the safety of acupuncture operation. ②Emphasizing the integration of the existing designs of chest puncture robot to realize the acupuncture operation with inhalation and exhalation involved. ③Focusing on the development of relevant technology of automatic needle removal through conducting the actual scenario of treatment with acupuncture robot in patients under non-anaesthetic condition.

Review of Research on Volunteer Action Ethics in Public Health Emergencies / 中国医学伦理学

【Objective:】 To summarize the research status, problems and countermeasures of ethical issues related to volunteer action in public health emergencies by reviewing relevant literature. 【Methods:】 Using four keywords: public health emergencies, volunteers, ethics, and research, this paper searched the Chinese and English databases for the literature published from December 2006 to December 2021 (15 years in total) on "ethical research on volunteer action in public health emergencies". After searching, it was found that there were not many related papers. A total of 31 papers were retrieved, and only 23 papers were selected. 【Results:】 The ethical problems faced by volunteers in public health emergencies were complex and diverse, and the individual ethical behavior of volunteers was affected by many factors. The strategies to solve the relevant ethical issues were not yet perfect. 【Conclusions:】 The ethical issues related to volunteer actions in public health emergencies needed to be further studied.

The epidemic situation and influencing factors of plague in the foci of Meriones unguiculatus in Inner Mongolia Plateau / 中华地方病学杂志

Objective:To analyze the epidemic situation of plague among animals in the foci of Meriones unguiculatus in Inner Mongolia Plateau, and to find out key influencing factors affecting the epidemic of the plague, and to provide theoretical basis for the prediction, early warning and risk assessment of the plague. Methods:The monitoring data including gerbils density, gerbils body flea index, plague epidemic intensity, etc., as well as environmental data including temperature, precipitation and El Ni?o activity (Southern Oscillation Index, SOI) from 19 banners (counties, cities and districts) in Ulanqab Plateau area, the foci of Meriones unguiculatus in Inner Mongolia Plateau were selected. The methods of correlation analysis, structural equation model and rank correlation were used to analyze the epidemic and key influencing factors of plague among animals in the foci. Results:The plague epidemic cycle in the foci of Meriones unguiculatus in Inner Mongolia Plateau was 5 to 10 years. The correlation analysis results showed that all the factors had influence on each other. Structural equation model screened out that the main influencing factors of plague epidemic were SOI, gerbils density and temperature. SOI had a negative effect on plague epidemic intensity (-0.022) and temperature (-0.029), while gerbils density had a positive effect on plague epidemic intensity (0.014), and temperature had a negative effect on plague epidemic intensity (-0.065). In rank correlation, when the gerbils density was at a high value, the probability of high plague epidemic intensity in that year was 4/9; when SOI was at a low value, the probability was 5/9; when the temperature was at a low value, the probability was 5/9. When the plague epidemic intensity was at a high value in that year, the probability of the plague epidemic intensity being high in the following year was 5/8; when the gerbils density was at a high value in that year, the probability was 4/9; when SOI was at a low value in that year, the probability was 4/9. Conclusion:Climate and biological factors can affect prevalence of plague, and countermeasures should be taken in advance to prevent plague outbreaks when El Ni?o phenomenon, low temperature, high density of gerbils, and high previous-year prevalence of plague appear.

Erianin inhibits oral cancer cell growth, migration, and invasion via the Nrf2/HO-1/ GPX4 pathway

Objective: To evaluate the effect of erianin on the viability, migration, and invasion of KB cells and elucidate its underlying mechanisms. Methods: Cell Counting Kit-8, colony formation, wound healing, and Transwell assays were used to determine the proliferation, migration, and invasion of oral cancer KB cells. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels were determined. Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions. Additionally, the expressions of ferroptosis-related proteins, NF-E2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting assays. Results: Erianin induced ferroptosis and inhibited the proliferation, migration, and invasion of KB cells. Moreover, erianin decreased GSH level, increased MDA level, elevated intracellular ROS and Fe

Clinical Efficacy of Modified Sanxiaoyin in Treatment of Mild or Moderate COVID-19 Patients： Based on Retrospective Analysis / 中国实验方剂学杂志

ObjectiveTo retrospectively analyze the clinical data of 52 patients with coronavirus disease-2019 （COVID-19） and explore the clinical efficacy of modified Sanxiaoyin on mild/moderate COVID-19 patients. MethodThe propensity score matching method was used to collect the clinical data of mild or moderate COVID-19 patients enrolled in the designated hospital of the Second Hospital of Jingzhou from December 2019 to May 2020. A total of 26 eligible patients who were treated with modified Sanxiaoyin were included in the observation group， and the 26 patients treated with conventional method were the regarded as the control. The disappearance of clinical symptoms， disappearance time of main symptoms， efficacy on traditional Chinese medicine （TCM） symptoms， hospitalization duration， laboratory test indicators， and CT imaging changes in the two groups were compared. ResultThe general data in the two groups were insignificantly different and thus they were comparable. After 7 days of treatment， the disappearance rate of fever， cough， fatigue， dry throat， anorexia， poor mental state， and poor sleep quality in the observation group was higher than that in the control group （P<0.05）， and the difference in the disappearance rate of expectoration and chest distress was insignificant. For the cases with the disappearance of symptoms， the main symptoms （fever， cough， fatigue， dry throat， anorexia， chest distress） disappeared earlier in the observation group than in the control group （P<0.01）. After 7 days of treatment， the scores of the TCM symptom scale of both groups decreased （P<0.01）， and the decrease of the observation group was larger that of the control group （P<0.01）. All patients in the two groups were cured and discharged. The average hospitalization duration in the observation group ［（12.79±2.68） d］ was shorter than that in the control group ［（15.27±3.11） d］ （P<0.01）. The effective rate in the observation group （92.31%， 24/26） was higher than that in the control group （76.92%， 20/26） . After 7 days of treatment， the lymphocyte （LYM） count increased （P<0.05）， and white blood cell （WBC） count and neutrophil （NEUT） count decreased insignificantly in the two groups. Moreover， levels of C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， and procalcitonin （PCT） reduced in the two groups after treatment （P<0.01） and the reduction in the observation group was larger than that in the control group （P<0.01）. Through 7 days of treatment， the total effective rate on pulmonary shadow in the observation group （90.00%， 18/20） was higher than that in the control group （77.27%， 17/22） （P>0.05） and the improvement of lung shadow in the observation group was better than that in the control group （P<0.01）. ConclusionModified Sanxiaoyin can significantly alleviate fever， cough， fatigue， anorexia， chest distress， poor sleep quality， and other symptoms of patients with mild or moderate COVID-19， improve biochemical indicators， and promote the recovery of lung function. This paper provides clinical evidence for the application of modified Sanxiaoyin in the treatment of mild or moderate COVID-19.

Clinical observation on filiform-fire needling of "Biaoben acupoint combination" for 33 cases of sequelae of coronavirus disease 2019 during recovery period / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period.@*METHODS@#A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated.@*RESULTS@#After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%.@*CONCLUSION@#The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

Multi-index components of Scutellariae Barbatae Herba according to UHPLC-QTRAP-MS coupled with chemometrics / 中国中药杂志

The present study developed an ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap composite mass spectrometry(UHPLC-QTRAP-MS) to simultaneously determine the content of potential active components in Scutellariae Barbatae Herba and also to provide a reference approach for screening out the differential quality control components among different batches of Scutellariae Barbatae Herba. Chromatographic separations were conducted on a Thermo Acclaim~(TM) RSLC 120 C_(18) column(3.0 mm×100 mm, 2.2 μm) in a gradient program. The mobile phase consisted of 0.1% aqueous formic acid and acetonitrile, and the column temperature was maintained at 40 ℃. The flow rate was 0.4 mL·min~(-1) and the injection volume was 2 μL. The targeted compounds were monitored in the multiple reaction monitoring(MRM) mode. The acquired data were processed by hierarchical cluster analysis(HCA) and partial least square discriminant analysis(PLS-DA). Sixteen compounds all showed good linear relationship within the corresponding linear ranges and the R~2 values were all higher than 0.993 2. The RSDs of precision, repeatability, and stability were less than or equal to 3.7%. Mean recovery rates were in the range of 95.67% and 104.8% with RSDs≤3.2%. According to HCA and PLS-DA, all samples were clustered into four categories. Scutellarin, acteoside, scutellarein, and scutebarbatine X(VIP>1) were considered as differential chemical markers in the four categories. In conclusion, the developed method can be used for the simulta-neous determination of the multiple components and quality control of Scutellariae Barbatae Herba.

Investigation on the mechanism of acupuncture in treatment of diabetes mellitus type 2 based on the network of islet macrophages-pancreatic adipose cells-islet β cells / 中国针灸

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.

Thumb-tack needles based on "Biaoben acupoint compatibility" for sequela of COVID-19 during recovery period / 中国针灸

OBJECTIVE@#To observe the effect of thumb-tack needles based on "Biaoben acupoint compatibility" on sequela symptoms, mental state and pulmonary ventilation function in patients with coronavirus disease 2019 (COVID-19) during recovery period.@*METHODS@#Fifty cases of COVID-19 during recovery period were randomly divided into an observation group and a control group, 25 cases in each group. The patients in the observation group were treated with thumb-tack needles at Guanyuan (CV 4), Zusanli (ST 36) and Taiyuan (LU 9). The patients in the control group were treated with sham thumb-tack needles at identical acupoints as the observation group. The treatment in the two groups was given once a day, 7-day treatment was taken as a course of treatment, and totally two courses of treatment were given. The TCM symptom score, Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, pulmonary function (forced vital capacity [FVC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF]), the severity of pulmonary ventilation dysfunction and pulmonary imaging changes in the two groups were compared before and after treatment.@*RESULTS@#Compared before treatment, the total scores and each item scores of TCM symptom scale, HAMA scores and HAMD scores in the two groups were reduced after treatment (P<0.05). Except for the symptom scores of dry throat and dry stool, the total score and each item score of TCM symptom scale, HAMA score and HAMD score in the observation group were lower than those in the control group (P<0.05). Compared before treatment, FVC, FEV1 and PEF in the two groups were increased after treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The severity of pulmonary ventilation dysfunction in the two groups was reduced after treatment (P<0.05), and the severity in the observation group was better than that in the control group (P<0.05). After treatment, the lung shadow area in the two groups was decreased (P<0.05), and that in the observation group was smaller than the control group (P<0.05). The improvement of imaging change in the observation group was better than that in the control group (P<0.05).@*CONCLUSION@#The thumb-tack needles based on "Biaoben acupoint compatibility" could significantly reduce the sequela symptoms, anxiety and depression in patients with COVID-19 during recovery stage, and improve the pulmonary ventilation function.

Research and development of intelligent medical equipment and internationalization of acupuncture and moxibustion: thoughts from researchers of acupuncture robot / 中国针灸

Under the background of artificial intelligence, the internationalization of acupuncture and moxibustion has braced an important opportunity. Intelligent medical equipment for acupuncture and moxibustion has entered from the laboratory into the clinic. However, the current research focuses on optimizing acupuncture treatment technology rather than innovating acupuncture theory. Internationally, the westernization of traditional acupuncture and the dilution of its characteristics are worrying. It is urgent to promote the China-led international standards of acupuncture and moxibustion and the patent protection of traditional acupuncture and moxibustion. Intelligent medical equipment will play the role of media, and promote the internationalization of traditional acupuncture and moxibustion with standardized and highly-integrated intelligent medical equipment for acupuncture and moxibustion, and integrate modern scientific and technological achievements. It is a feasible way for the internationalization of acupuncture and moxibustion.

Research progress of Yuebi Decoction / 国际中医中药杂志

Yuebi Decoction is a classic prescription derived from Synopsis of the Golden Chamber. It has significant clinical efficacy and wide application. Scholars of different dynasties have different opinions on its prescription name and put forward different understandings on the dosage of Ephedrae Herba and Gypsum Fibrosum in the prescription. There is a dispute between relieving exterior prescription and draining dampness prescription in the main syndrome. In this article, it is found that there is no contradiction between relieving exterior and draining dampnes, but they promote each other and play the role of "lifting the pot to uncover the cover". In terms of clinical application, this article introduces the cases of this prescription and its addition and subtraction used in the treatment of diseases of respiratory system, urinary system and other systems in recent years. It is found that clinical use of this prescription is mainly for "sweating and promoting diuresis", which reflects the thought of "treating different diseases with the same treatment" in Traditional Chinese Medicine.

Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network / 中国针灸

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.

Ferroptosis in laryngeal squamous cell carcinoma and its regulation by M2 macrophage-derived exosomes / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.

Clinical efficacy observation of 'Tong Du Yun Pi' manipulation for infantile diarrhea in autumn / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of 'Tong Du Yun Pi' (Governor Vessel-unblocking and spleen-promoting) manipulation in treating infantile diarrhea in autumn. Methods: Eighty-four kids were divided into a control group and an observation group using the random number table method, with 42 cases in each group. The control group was intervened by oral administration of montmorillonite powder, and the observation group was given additional 'Tong Du Yun Pi' pediatric massage (tuina) treatment. After treatment, the traditional Chinese medicine (TCM) symptoms scores, symptom improvement time, clinical efficacy and immune function indicators were compared between the two groups. Results: After treatment, the total effective rate was 95.2％ in the observation group versus 76.2％ in the control group, and the between-group difference was statistically significant (P<0.05); each item score in TCM symptoms was notably lower in the observation group than in the control group (all P<0.05); among the effective cases, the times to restore normal defecation, relieve abdominal bloating, arrest vomiting, and bring down the fever were markedly shorter in the observation group than in the control group, and the between-group differences were statistically significant (all P<0.05); the levels of immunoglobulin (Ig) G, IgM, CD4+ and CD4+/CD8+ were significantly higher and CD8+ was significantly lower in the observation group than in the control group (all P<0.05). Conclusion: In the treatment of infantile diarrhea in autumn, based on oral administration of montmorillonite powder, 'Tong Du Yun Pi' manipulation can notably improve diarrheal symptoms, shorten disease duration, and strengthen the immunity of kids, producing more significant efficacy than oral administration of montmorillonite powder.

Quantitative evaluation of extracellular volume in patients with heart failure using dual-layer spectral detector CT: a feasibility study / 中华放射学杂志

Objective:To explore the feasibility in evaluating segmental extracellular volume (ECV) using dual-layer spectral detector CT in patients with heart failure with various percentages of delayed hyper-enhanced volume, using MRI as a reference.Methods:Twenty-seven patients with heart failure in Peking Union Medical College Hospital were prospectively enrolled in this study from July 2019 to January 2021. All the patients underwent both CT late iodine enhancement and MR late gadolinium enhancement imaging within a week. According to percentages of hyper-enhanced volume on cardiac MR image, myocardial segments were classified into 3 groups: 0-4% (group A), 5%-49% (group B) and 50%-100% (group C). ECV images were independently observed by 2 experienced radiologists. The correlation and agreement between CT-ECV and MRI-ECV for the whole myocardial assessment and for the segmental assessment were evaluated using Spearman correlation and Bland-Altman analysis. Inter-observer agreement was assessed using the ICC.Results:Of the 27 patients, 432 segments were analyzed, with 199 segments in group A, 151 segments in group B and 82 segments in group C. In the whole myocardial analysis, the CT-ECV and MRI-ECV were 32.25% (28.04%, 34.28%) and 32.27% (28.35%, 34.77%), respectively. A good correlation was found between CT-ECV and MRI-ECV ( r=0.969, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias (0.4%), with 95% limits of agreement of -6.9% to 7.8%. as for the segmental myocardial assessment, the CT-ECV was 28.23% (26.18%, 29.92%) for group A, 33.29% (30.16%, 35.96%) for group B and 40.22% (34.06%, 46.70%) for group C. There was statistically significant difference in ECV among three groups (all P<0.001). Good correlations between CT-ECV and MRI-ECV were found in group A ( r=0.614, P<0.001), group B ( r=0.852, P<0.001) and group C ( r=0.953, P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias 2.0% (95% limits of agreement:-17.6%-21.6%) in group A, a small bias -0.4% (95% limits of agreement: -13.8%-12.9%) in group B and a small bias -1.8% (95% limits of agreement: -17.4%-13.9%) in group C. The ICC values between 2 observers were 0.877 and 0.945 on CT-ECV and MRI-ECV, respectively. Conclusions:The larger percentage of hyper-enhanced volume on cardiac MR image, the stronger correlation are between the CT-ECV and MRI-ECV. CT-ECV may be taken as an alternative tool for quantitative evaluation of myocardial tissue in patients with heart failure.

Sepsis induces variation of intestinal barrier function in different phase through nuclear factor kappa B signaling

The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion  process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Sepsis induces variation of intestinal barrier function in different phase through nuclear factor kappa B signaling

The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion  process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.