Recent progress on cGAS-STING pathway in tumor radiotherapy / 中华放射肿瘤学杂志

Radiotherapy is widely used in the treatment of primary and metastatic malignant tumors. It is traditionally believed that the killing effect of radiotherapy on tumor is based on the direct or indirect damage of ionizing radiation to DNA. In recent years, the anti-tumor role and mechanism of anti-tumor immune response induced by ionizing radiation have captivated widespread attention and achieved significant progress. Among them, Cyclic GMP-AMP synthase (cGAS)-stimulator of interference genes (STING) pathway is considered to be one of the key regulatory hubs. cGAS is a cytoplasmic DNA receptor that can bind to tumor-derived double-stranded DNA and activate the downstream STING, thereby activating anti-tumor immune response of the host. In view of the latest progress in this field, the important role and potential mechanism of cGAS-STING pathway in radiotherapy immune effect were mainly summarized, and the application prospect of targeting cGAS-STING pathway in radiotherapy sensitization was explored.

Treatment and factors associated with prognosis of hyperkalemia in the emergency department / 中华危重病急救医学

Objective:To survey treatment and prognosis of hyperkalemia patients in the emergency department and to analyze factors associated with all-cause in-hospital mortality.Methods:We implemented electronic hospital information system, extracted demographic characteristics, underlying diseases, laboratory findings, potassium lowering therapy and prognosis of hyperkalemia patients [age ≥ 18 years, serum potassium (K +) concentration ≥ 5.5 mmol/L] in the emergency department of Peking Union hospital in Beijing between June 1st 2019 to May 31st 2020. The enrolled subjects were divided into the non-survival group and the survival group according to their prognosis. Univariate analysis and Cox regression model were adopted to analyze factors affecting all-cause in-hospital mortality of hyperkalemia patients. Results:A total of 579 patients [median age 64 (22) years; 310 men (53.5%) and 269 women (46.5%)] with hyperkalemia were enrolled, among which, 317 (54.7%), 143 (24.7%) and 119 (20.6%) were mild, moderate, and severe hyperkalemia, respectively. 499 (86.20%) patients received potassium-lowering therapy, forty-four treatment regimens were administered. Insulin and glucose (I+G, 61.3%), diuretics (Diu, 57.2%), sodium bicarbonate (SB, 41.9%) and calcium gluconate/chloride (CA, 44.4%) were commonly used for the treatment of hyperkalemiain the emergency department. The combination of insulin and glucose, calcium gluconate/chloride, diuretics and sodium bicarbonate (I+G+CA+Diu+SB) was the most favored combined treatment regimen of hyperkalemia in the emergency department. The higher serum potassium concentration, the higher proportion of administrating combined treatment regimen and/or hemodialysis (HD) (the proportion of administrating combined treatment regimen in mild, moderate, and severe hyperkalemia patients were 58.4%, 82.5% and 94.8%; the proportion of administrating HD in mild, moderate, and severe hyperkalemia patients were 9.7%, 13.3% and 16.0%, respectively). The proportion of achievement of normokalaemia elevated as the kinds of potassium lowering treatment included in the combined treatment regimen increased. The proportion of achievement of normokalaemia was 100% in the combined treatment regimen including 6 kinds of potassium lowering therapy. Among various potassium lowering treatments, HD contributed to the highest rate of achievement of normokalaemia (93.8%). 111 of 579 (19.20%) hyperkalemia patients died in hospital. Cox regression model revealed that complicated with cardiac dysfunction predicted higher mortality [hazard ratio ( HR) = 1.757, 95% confidence interval (95% CI) was 1.155-2.672, P = 0.009]. Achievement of normokalaemia and administration of diuretics attributed to lower mortality ( HR = 0.248, 95% CI was 0.155-0.398, P = 0.000; HR = 0.335, 95% CI was 0.211-0.531, P = 0.000, respectively). Conclusions:Treatment of hyperkalemia in the emergency department were various. Complicated with cardiac dysfunction were associated with higher mortality. Achieving normokalaemia was associated with decreased mortality.

Status survey and countermeasures for trainees in standardized residency training of ultrasound professional base under the novel coronavirus pneumonia epidemic / 中华医学教育探索杂志

Objective:To investigate the behavior and emotion of trainees (residents) in the standardized residency training under the novel coronavirus pneumonia (NCP) epidemic, and adjust the training plan and mode of standardized residency training during the NCP epidemic according to the survey results.Methods:A real-name closed questionnaire survey was conducted among 40 residents (27 ultrasound majors and 13 other majors) in ultrasound department using the "Questionnaire Star" WeChat applet, including basic personal information, questions related to NCP, behavioral change survey, behavioral attitude survey and emotional status survey. All the collected data were further statistically analyzed by Chi-square test and rank sum test using SPSS 19.0Results:There were forty valid questionnaires and the participation rate was 100.0%. The accuracy of 24 NCP-related questions was not significantly different between residents majoring in ultrasound and other specialties [92.0%(596/648) vs. 93.6%(292/312), P>0.05]. All the residents had a good understanding of NCP. The main behaviors of going out were significantly reduced, while various behaviors of being at home were significantly increased. Their interest in learning declined. When the epidemic happened (or possibly) in the community or village they lived in, their negative emotions, such as nervousness, fear pessimism and depression, were obviously expressed. Network teaching and evaluation through WeChat public number were adopted and we guided residents to adjust their home behaviors and emotions according to the survey results. Conclusion:Under the NCP epidemic, the behaviors and emotions of residents had been extensively changed. The training center should adjust the teaching plan and mode of training in time, and provide more counselling service in psychology and learning for residents during the epidemic.

Research progress of targeted degradation of Mycobacterium tuberculosis proteins / 药学学报

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), is still one of the significant threats to human life. In recent years, the continuous exploration of small molecule inhibitors represented by bedaquinoline has brought new vitality into the field of tuberculosis. However, small molecule inhibitors will inevitably occur acquired drug resistance during clinical medication. As a new pharmacological mechanism, targeted protein degradation (TPD) achieves efficacy by destroying rather than inhibiting protein targets. It might be an excellent strategy to develop anti-tuberculosis drugs based on the TPD concept to solve drug resistance. This article reviews the protein degradation pathways of Mtb, such as the Pup proteasome system and the ClpP-ClpC1 complex enzyme system. The future development of these strategies into TPD drugs was prospected and summarized.

A new perspective in the treatment of liver fibrosis: Targeting macrophage metabolism / 临床肝胆病杂志

Liver fibrosis is a pathological process of fibrous scar formation caused by excessive accumulation of extracellular matrix due to various etiologies. At present, etiological treatment, such as effective antiviral therapy, is still the main treatment strategy for liver fibrosis. As the core participant of liver fibrosis, liver macrophages affect the progression and regression of liver fibrosis and are thus considered an important target for the treatment of liver fibrosis. With the recent advances in the field of immune metabolism, metabolic reprogramming has become a key factor for determining the outcome of macrophages and promoting the development of diseases. This article reviews the role and metabolic changes of macrophages during liver fibrosis and discusses the anti-fibrotic potential of targeting macrophage metabolism, so as to provide new ideas for the development, progression, and treatment of liver fibrosis.

Research progress on anhepatic phase in rat liver transplantation / 器官移植

With persistent advancement of surgical instruments, methods and techniques, clinical efficacy of liver transplantation has been steadily enhanced. However, the length of anhepatic phase is still an important factor affecting the efficacy of liver transplantation. Rat is one of the major animal models for liver transplantation-related basic research. In this article, multiple approaches for prolonging the anhepatic phase and shortening the operation time during anhepatic phase in rat liver transplantation were reviewed, which consisted of sevoflurane inhalation anesthesia, intravenous infusion via jugular vein indwelling needle, clamping of the abdominal aorta before anhepatic phase, injection of normal saline into portal vein before anhepatic phase, subcutaneous transposition of the spleen, electrocoagulation of hepatic esophageal artery, magnetic ring anastomosis of the superior and inferior hepatic vena cava, cannula anastomosis of the superior and inferior hepatic vena cava, stent anastomosis of the superior and inferior hepatic vena cava, rapid connection device and cannula of portal vein, and ring-shaped cannula of hepatic tissue-preserving inferior hepatic vena cava, aiming to add evidence for prolonging the duration of anhepatic phase, improving the operation efficiency during anhepatic phase and elevating the success rate of rat liver transplantation.

Effect of lung protective ventilation on lung ventilation function, serum serum Clara cell protein 16 level and prognosis in patients undergoing gynecological laparoscopic surgery / 中国医师进修杂志

Objective:To analyze the effect of lung protective ventilation on lung ventilation function and serum Clara cell protein 16 (CC16) level in patients undergoing gynecological laparoscopic surgery.Methods:The clinical data of 80 gynecological patients who underwent laparoscopic surgery in Yancheng City Jianhu County People′s Hospital from October 2018 to December 2020 were randomly divided into group A and group B by random number table, each group with 40 cases. The patients in group A were treated with intermittent positive-pressure ventilation, and the patients in group B were ventilated with whole course ventilation mode. The pulmonary ventilation function, CC16 level and postoperative pulmonary complications were observed before anesthesia, 10 min of pneumoperitoneum, 30 min of pneumoperitoneum, 5 min of pneumoperitoneum stop and 2 h after operation. The patients were divided into groups according to whether with pulmonary complications, and their pulmonary ventilation function and serum CC16 level were compared. The predictive value of the above indexes for pulmonary complications was analyzed by receiver operating characteristic (ROC) curve.Results:Repeated measurement analysis of variance showed that alveolar arterial oxygen differential pressure (PA-aDO 2) were significant differences in time point factors, time point interaction factors and group factors ( P<0.05); CC16 index were significant differences in time point factor and group factor ( P<0.05). According to the observation from postoperative to discharge, 4 patients (10.0%) in group A had pulmonary complications, 15 cases (37.5%) had pulmonary complications in group B, the levels of PA-aDO 2 and CC16 in patients with complications were significantly higher than those in patients without complications: group A:(332.9 ± 2.0) mmHg (1 mmHg = 0.133 kPa) vs. (290.4 ± 13.2) mmHg, (53.5 ± 1.5) μg/L vs. (39.5 ± 6.5) μg/L; group B: (339.1 ± 8.8) mmHg vs. (305.7 ± 17.9) mmHg, (41.5 ± 4.2) μg/L vs. (39.7 ± 5.8) μg/L, there were statistical differences ( P<0.05). ROC curve analysis showed that the area under the curve(AUC) of PA-aDO 2 and CC16 in predicting pulmonary complications in group A were 0.882 and 0.833, in group B was 0.885 and 0.731. Conclusions:Lung protective ventilation has little effect on lung ventilation function and serum CC16 in patients with gynecological laparoscopic surgery, and the probability of pulmonary complications is lower. The pulmonary ventilation function and CC16 have certain value in predicting postoperative pulmonary complications.

Discussion on hot issues in liver transplantation for hepatocellular carcinoma / 中华消化外科杂志

Liver diseases are common in China and the incidence and mortality of primary liver cancer are among the top in the world. As one of the therapeutic methods for hepatocellular carcinoma (HCC), liver transplantation has become an important technique in hepatic surgery. Most of patients with HCC have progressed to stage B or C of Barcelona Clinic Liver Cancer staging when diagnosed. How to reduce the dropout rate of HCC patients due to the progression of tumor when waiting for liver transplantation, develop individualized immunosuppressant plans for HCC patients after liver transplantation, and accurately manage patients with HCC recurrence after liver transplan-tation are the current hotspots of research. The authors review the relevant literature, summarize the treatment experience, and discuss the hot issues in liver transplantation for HCC, in order to provide reference for related treatment.

High-flow nasal cannula oxygen therapy versus non-invasive ventilation for chronic obstructive pulmonary diseases with acute-moderate hypercapnic respiratory failure: a randomized controlled trial of non-inferiority / 中华急诊医学杂志

Objective:To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with moderate typeⅡ respiratory failure, to clarify the feasibility of HFNC in the treatment of AECOPD, and to explore the influencing factors of HFNC failure.Methods:This study was a randomized controlled trial of non-inferiority. Patients with AECOPD with moderate type Ⅱ respiratory failure [arterial blood gas pH 7.25-7.35, partial pressure of arterial blood carbon dioxide (PaCO 2)> 50 mmHg] admitted to the Intensive Care Unit (ICU) from January 2018 to December 2021 were randomly assigned to the HFNC group and NIV group to receive respiratory support. The primary endpoint was the treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 h, 12 h, and 48 h, total duration of respiratory support, 28-day mortality, comfort score, ICU length of stay, and total length of stay. Multivariate logistic regression analysis was used to evaluate the failure factors of HFNC treatment. Results:Totally 228 patients were randomly divided into two groups, 108 patients in the HFNC group and 110 patients in the NIV group. The treatment failure rate was 29.6% in the HFNC group and 25.5% in the NIV group. The risk difference of failure rate between the two groups was 4.18% (95% CI: -8.27%~16.48%, P=0.490), which was lower than the non-inferiority value of 9%. The most common causes of failure in the HFNC group were carbon dioxide retention and aggravation of respiratory distress, and the most common causes of failure in the NIV group were treatment intolerance and aggravation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (-29.02%, 95% CI -49.52%~-7.49%; P=0.004). After 1 h of treatment, the pH in both groups increased significantly, PaCO 2 decreased significantly and the oxygenation index increased significantly compared with baseline (all P < 0.05). PaCO 2 in both groups decreased gradually at 1 h, 12 h and 48 h after treatment, and the pH gradually increased. The average number of daily airway care interventions and the incidence of nasal and facial lesions in the HFNC group were significantly lower than those in the NIV group ( P < 0.05), while the comfort score in the HFNC group was significantly higher than that in the NIV group ( P=0.021). There was no significant difference between the two groups in the total duration of respiratory support, dyspnea score, ICU length of stay, total length of stay and 28-day mortality (all P > 0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health evaluation Ⅱ score (≥15), family NIV, history of cerebrovascular accident, PaCO 2 (≥60 mmHg) and respiratory rate (≥32 times/min) at 1 h were independent predictors of HFNC failure. Conclusions:HFNC is not inferior to NIV in the treatment of AECOPD complicated with moderate type Ⅱ respiratory failure. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

The Action Effect of Two Kinds of Lumbar Massage Obliquity Manipulation with Different Lumbar Degeneration Degrees: A Comparative Study / 医用生物力学

Objective To compare the action effect of traditional and modified lumbar massage obliquity manipulation with different degrees of lumbar degeneration. Methods The biomechanical model of quality-spring-damping system lumbar spine was established and massage forces from professional massage doctors were collected. The force was used as input of the model, and lumbar degeneration was simulated by increasing elastic coefficient of the spring and damping coefficient of the damping in the model. By using MATLAB/ Simulink simulation technology, the effects of massage obliquity manipulation ( the maximum relative displacement and maximum acceleration) with different degrees of lumbar degeneration were obtained for comparative analysis.Results When the lumbar spine was degenerative, the maximum relative displacement and maximum acceleration of each segment were obtained under two manipulations. With the increase of lumbar degenerationdegree, the maximum relative displacement and maximum acceleration of each segment under two manipulations showed a downward trend, and the attenuation rate of the maximum relative displacement and maximum acceleration of each segment under two manipulations was obtained. Conclusions When degenerative changes in the spine do not occur, the effectiveness of traditional lumbar massage obliquity manipulation is slightly better than that of modified lumbar massage obliquity manipulation, but the safety of modified lumbar massage obliquity manipulation is obviously better than that of the traditional lumbar massage obliquity manipulation, so the modified lumbar massage obliquity manipulation should be used. With the aggravation of lumbar degeneration, the action effects of two manipulations are attenuated in a power function. The attenuation rate of effectiveness of modified lumbar massage obliquity manipulation is significantly faster than that of traditional lumbar massage obliquity manipulation, indicating that the modified lumbar massage obliquity manipulation should not be used in the caseof lumbar degeneration.

Multi-tissue segmentation model of whole slide image of pancreatic cancer based on multi task and attention mechanism / 生物医学工程学杂志

Accurate segmentation of whole slide images is of great significance for the diagnosis of pancreatic cancer. However, developing an automatic model is challenging due to the complex content, limited samples, and high sample heterogeneity of pathological images. This paper presented a multi-tissue segmentation model for whole slide images of pancreatic cancer. We introduced an attention mechanism in building blocks, and designed a multi-task learning framework as well as proper auxiliary tasks to enhance model performance. The model was trained and tested with the pancreatic cancer pathological image dataset from Shanghai Changhai Hospital. And the data of TCGA, as an external independent validation cohort, was used for external validation. The F1 scores of the model exceeded 0.97 and 0.92 in the internal dataset and external dataset, respectively. Moreover, the generalization performance was also better than the baseline method significantly. These results demonstrate that the proposed model can accurately segment eight kinds of tissue regions in whole slide images of pancreatic cancer, which can provide reliable basis for clinical diagnosis.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Epidemiological characteristics of influenza among the elderlyin Heilongjiang Province / 预防医学

Objective @#To investigate the epidemiological characteristics of influenza among the elderly in Heilongjiang Province from 2017 to 2021 (April 2017 to March 2022), so as to provide insights into influenza control among the elderly.@*Methods @#The data pertaining to surveillance of patients with influenza-like illness (ILI) at ages of 60 years and older in Heilongjiang Province from 2017 to 2021 were retrieved from Chinese Influenza Surveillance Information Management, and the temporal distribution of ILI cases and the results of influenza virus tests were descriptively analyzed. @*Results @#Totally 26 908 ILI cases at ages of 60 years and older were reported in Heilongjiang Province from 2017 to 2021, with an ILI prevalence rate of 0.17%. The prevalence of ILI appeared a tendency towards a rise in Heilongjiang Province from 2017 to 2021 (χ2trend=268.554, P<0.001), and the epidemic peaked in the 3rd to 7th weeks of 2019 and 2020. The overall positive rate of influenza virus was 6.80%, and the positive rate of influenza virus showed a tendency towards a decline from 2017 to 2021 (χ2trend=425.268, P<0.001). Influenza A (H1N1) pdm09 (46.82%) and A (H3N2) (22.79%), as well as influenza B virus lineages B/Victoria (12.11%) and B/Yamagata (18.28%) were predominant types, which changes among the study period. The detection of influenza virus-positive samples peaked from December to March of the next year, and a high positive rate of influenza virus was detected in Hegang (12.35%), Heihe (11.47%) and Daqing cities (11.07%). There was no significant correlation between the prevalence of ILI and the positive rate of influenza virus in Heilongjiang Province from 2017 to 2021 (rs=-0.800, P=0.104).@*Conclusions@# The prevalence of ILI appeared a tendency towards a rise among the elderly at ages of 60 years and older in Heilongjiang Province from 2017 to 2021, and the epidemic peaked in winter and spring. Influenza A (H1N1) pdm09, A (H3N2), B/Victoria, B/Yamagata were alternately prevalent and there was no obvious correlation between ILI prevalence and the positive rate of influenza virus.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Effect of fraction of inspired oxygen baseline level on the mask ventilation time before intubation in emergency patients by monitoring of expiratory oxygen concentration / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of different fraction of inspired oxygen (FiO2) baseline levels before endotracheal intubation on the time of expiratory oxygen concentration (EtO2) reaching the standard in emergency patients with the EtO2 as the monitoring index.@*METHODS@#A retrospective observational study was conducted. The clinical data of patients receiving endotracheal intubation in the emergency department of Peking Union Medical College Hospital from January 1 to November 1 in 2021 were enrolled. In order to avoid interference with the final result due to inadequate ventilation caused by non-standard operation or air leakage, the process of the continuous mechanical ventilation after FiO2 was adjusted to pure oxygen in patients who had been intubated was selected to simulate the process of mask ventilation under pure oxygen before intubation. Combined with the electronic medical record and the ventilator record, the changes of the time required to reach 0.90 of EtO2 (that was, the time required to reach the standard of EtO2) and the respiratory cycle required to reach the standard after adjusting FiO2 to pure oxygen under different baseline levels of FiO2 were analyzed.@*RESULTS@#113 EtO2 assay records were collected from 42 patients. Among them, 2 patients had only one EtO2 record due to the FiO2 baseline level of 0.80, while the rest had two or more records of EtO2 reaching time and respiratory cycle corresponding to different FiO2 baseline level. Among the 42 patients, most of them were male (59.5%), elderly [median age was 62 (40, 70) years old] patients with respiratory diseases (40.5%). There were significant differences in lung function among different patients, but the majority of patients with normal function [oxygenation index (PaO2/FiO2) > 300 mmHg (1 mmHg ≈ 0.133 kPa), 38.0%]. In the setting of ventilator parameters, combined with the slightly lower arterial partial pressure of carbon dioxide of patients [33 (28, 37) mmHg], mild hyperventilation phenomenon was considered to be widespread. With the increased in FiO2 baseline level, the time of EtO2 reaching standard and the number of respiratory cycles showed a gradually decreasing trend. When the FiO2 baseline level was 0.35, the time of EtO2 reaching the standard was the longest [79 (52, 87) s], and the corresponding median respiratory cycle was 22 (16, 26) cycles. When the FiO2 baseline level was increased from 0.35 to 0.80, the median time of EtO2 reaching the standard was shortened from 79 (52, 78) s to 30 (21, 44) s, and the median respiratory cycle was also reduced from 22 (16, 26) cycles to 10 (8, 13) cycles, with statistically significant differences (both P < 0.05).@*CONCLUSIONS@#The higher the FiO2 baseline level of the mask ventilation in front of the endotracheal intubation in emergency patients, the shorter the time for EtO2 reaching the standard, and the shorter the mask ventilation time.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Noise Exposure and Stress Hormone Levels:A Review / 中国医学科学院学报

Noise is one of the most common environmental hazards to which people are exposed,and the exposure to noise can cause not only hearing but also non-hearing damage.Although noise under safety limits may not affect the auditory system,it can cause changes in stress hormone levels,which is harmful to health.However,the current studies about the impact of noise on health mainly focus on the auditory system,and little is known about the relationship between noise and stress hormone levels.Therefore,this paper reviews the studies involving noise exposure and stress hormone levels,aiming to provide ideas for strengthening the prevention and control of noise hazards.

Research Progress in Diagnostic Reference Levels in Interventional Radiology / 中国医学科学院学报

During interventional procedures,subjects are exposed to direct and scattered X-rays.Establishing diagnostic reference levels is an ideal way to optimize the radiation dose and reduce radiation hazard.In recent years,diagnostic reference levels in interventional radiology have been established in different countries.However,because of the too many indicators for characterizing the radiation dose,the indicators used to establish diagnostic reference levels vary in different countries.The research achievements in this field remain to be reviewed.We carried out a retrospective analysis of the definition,establishment method,application,and main factors influencing the dose difference of the diagnostic reference level,aiming to provide a basis for establishing the diagnostic reference level for interventional procedures in China.

Optimization of quality assessment system of clinical blood transfusion records / 中国输血杂志

【Objective】 To determine the value of quality assessment system in supervising standard clinical blood use and improving the quality of clinical blood transfusion medical records. 【Methods】 The clinical blood transfusion records of Children′s Hospital, Zhejiang University School of Medical every quarter from January 2019 to December 2022 were selected and extracted for evaluation by 5% to 10% for the current season. These blood transfusion medical records were scored and graded A(≥90 points)/B(80-89 points)/C(<80 points)according to the Evaluation Table of Clinical Science Rational Use of Blood in Children′s Hospital of Zhejiang University, and the annual A rate was statistically analyzed. After summarizing the deduction points, a rectification plan was submitted to the medical department and publicized on the hospital network. 【Results】 A total of 1 975 blood transfusion medical records were analyzed from January 2019 to December 2022, including 343 in 2019 (17.37%), 517 in 2020 (26.18%), 556 in 2021 (28.15%) and 559 in 2022 (28.30%), with Grade A rates at 67.06%, 92.07%, 93.17% and 91.06%, respectively. According to Pearson Chi-square test, the Grade A rates of blood transfusion records in 2020, 2021 and 2022 were significantly higher than those in 2019 (P<0.000 1). In the assessment, the main reasons for deduction of points were missed pre-transfusion immunization tests and missed blood transfusion course records. From 2019 to 2022, the missed rates of pre-transfusion immunization tests were 22.68%, 6.47%, 1.26% and 2.49%, and the missed rates of blood transfusion course records were 32.21%, 10.59%, 5.57% and 6.61%, respectively. 【Conclusion】 The regular and reasonable assessment and publicity system of blood transfusion medical records is conducive to improving the quality of blood transfusion medical records, promoting rational blood use and ensuring the safety of blood use for children.