Issue Ebook
cover story
Latest Issue
Volume 10 ， Issue 3 ， 2023
-
Abstract：Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.Keywords：sepsis;Immune function monitoring;Immunomodulatory therapy;immunosuppression100|8|0Updated：2023-07-07
POSITION ARTICLE AND GUIDELINES
-
Abstract：Background:Data on severe and extensive burns in China are limited, as is data on the prevalence of a range of related gastrointestinal (GI) disorders [such as stress ulcers, delayed defecation, opioid-related bowel immotility, and abdominal compartment syndrome (ACS)]. We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality.Methods:This retrospective analysis was conducted on patients with severe [≥ 20% total burn surface area (TBSA)] and extensive (>50% TBSA or >25% full-thickness TBSA) burns admitted to three university teaching institutions in China between January 1, 2011 and December 31, 2020. Both 30- and 90-day mortality were assessed by collating demographic data, burn causes, admission TBSA, % full-thickness TBSA, Baux score, Abbreviated Burn Severity Index (ABSI) score, and Sequential Organ Failure Assessment (SOFA) score, shock at admission and the presence of an inhalation injury. GI dysfunction included abdominal distension, nausea/vomiting, diarrhoea/constipation, GI ulcer/haemorrhage, paralytic ileus, feeding intolerance and ACS. Surgeries, length of intensive care unit (ICU) stay, pain control [in morphine milligram equivalents (MME)] and overall length of hospital stay (LOHS) were recorded.Results:We analyzed 328 patients [75.6% male, mean age: (41.6±13.6) years] with a median TBSA of 62.0% (41.0%–80.0%); 256(78.0%) patients presented with extensive burns. The 90-day mortality was 23.2%(76/328), with 64(84.2%) of these deaths occurring within 30 d and 25(32.9%) occurring within 7 d. GI dysfunction was experienced by 45.4% of patients and had a significant effect on 90-day mortality [odds ratio (OR)=14.070, 95% confidence interval (CI) 5.886–38.290, P<0.001]. Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and % full-thickness TBSA. Overall, 88.2%(67/76) of deceased patients had GI dysfunction [hazard ratio (HR) for death of GI dysfunction=5.951], with a survival advantage for functional disorders (diarrhoea, constipation, or nausea/vomiting) over GI ulcer/haemorrhage (P<0.001).Conclusion:Patients with severe burns have an unfavourable prognosis, as nearly one-fifth died within 90 d. Half of our patients had comorbidities related to GI dysfunction, among which GI ulcers and haemorrhages were independently correlated with 90-day mortality. More attention should be given to severe burn patients with GI dysfunction.Keywords：Severe burn;Gastrointestinal dysfunction;Mortality;sepsis;Gastrointestinal haemorrhage;Continuous analgesia50|4|0Updated：2023-07-21 -
Abstract：Background:Posttraumatic stress disorder (PTSD) has been associated with volumetric and white matter microstructural changes among general and veteran populations. However, regions implicated have greatly varied and often conflict between studies, potentially due to confounding comorbidities within samples. This study compared grey matter volume and white matter microstructure among Australian combat veterans with and without a lifetime diagnosis of PTSD, in a homogenous sample assessed for known confounding comorbidities.Methods:Sixty-eight male trauma-exposed veterans (16 PTSD-diagnosed; mean age 69 years) completed a battery of psychometric assessments and underwent magnetic resonance and diffusion tensor imaging. Analyses included tract-based spatial statistics, voxel-wise analyses, diffusion connectome-based group-wise analysis, and volumetric analysis.Results:Significantly smaller grey matter volumes were observed in the left prefrontal cortex (P=0.026), bilateral middle frontal gyrus (P=0.021), and left anterior insula (P=0.048) in the PTSD group compared to controls. Significant negative correlations were found between PTSD symptom severity and fractional anisotropy values in the left corticospinal tract (R2=0.34, P=0.024) and left inferior cerebellar peduncle (R2=0.62, P=0.016). No connectome-based differences in white matter properties were observed.Conclusions:Findings from this study reinforce reports of white matter alterations, as indicated by reduced fractional anisotropy values, in relation to PTSD symptom severity, as well as patterns of reduced volume in the prefrontal cortex. These results contribute to the developing profile of neuroanatomical differences uniquely attributable to veterans who suffer from chronic PTSD.Keywords：Posttraumatic stress disorder (PTSD);Veterans;Diffusion tensor imaging;Magnetic resonance imaging (MRI);Fractional anisotropy28|1|0Updated：2023-07-21 -
Abstract：Background:Tumor cell heterogeneity mediated drug resistance has been recognized as the stumbling block of cancer treatment. Elucidating the cytotoxicity of anticancer drugs at single-cell level in a high-throughput way is thus of great value for developing precision therapy. However, current techniques suffer from limitations in dynamically characterizing the responses of thousands of single cells or cell clones presented to multiple drug conditions.Methods:We developed a new microfluidics-based "SMART" platform that is Simple to operate, able to generate a Massive single-cell array and Multiplex drug concentrations, capable of keeping cells Alive, Retainable and Trackable in the microchambers. These features are achieved by integrating a Microfluidic chamber Array (4320 units) and a six-Concentration gradient generator (MAC), which enables highly efficient analysis of leukemia drug effects on single cells and cell clones in a high-throughput way.Results:A simple procedure produces 6 on-chip drug gradients to treat more than 3000 single cells or single-cell derived clones and thus allows an efficient and precise analysis of cell heterogeneity. The statistic results reveal that Imatinib (Ima) and Resveratrol (Res) combination treatment on single cells or clones is much more efficient than Ima or Res single drug treatment, indicated by the markedly reduced half maximal inhibitory concentration (IC50). Additionally, single-cell derived clones demonstrate a higher IC50 in each drug treatment compared to single cells. Moreover, primary cells isolated from two leukemia patients are also found with apparent heterogeneity upon drug treatment on MAC.Conclusions:This microfluidics-based "SMART" platform allows high-throughput single-cell capture and culture, dynamic drug-gradient treatment and cell response monitoring, which represents a new approach to efficiently investigate anticancer drug effects and should benefit drug discovery for leukemia and other cancers.Keywords：Microfluidics;Single-cell analysis;leukemia;High-throughput drug screening;Single-cell cloning33|6|0Updated：2023-07-21 -
Abstract：Background:Abnormal myocardial voltage-gated sodium channel 1.5 (Nav1.5) expression and function cause lethal ventricular arrhythmias during myocardial ischemia–reperfusion (I/R). Protein inhibitor of activated STAT Y (PIASy)-mediated caveolin-3 (Cav-3) small ubiquitin-related modifier (SUMO) modification affects Cav-3 binding to the Nav1.5. PIASy activity is increased after myocardial I/R, but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias.Methods:Using recombinant adeno-associated virus subtype 9 (AAV9), rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA (shRNA). After two weeks, rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias. Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements.Results:PIASy was upregulated by I/R (P<0.01), with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density (P<0.01). AAV9-PIASy shRNA intraventricular injection into the rat heart down-regulated PIASy after I/R, at both mRNA and protein levels (P<0.05 vs. Scramble-shRNA+I/R group), decreased SUMO-modified Cav-3 levels, enhanced Cav-3 binding to Nav1.5, and prevented I/R-induced decrease of Nav1.5 and Cav-3 co-localization in the intercalated disc and lateral membrane. PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias, which was reflected by a modest decrease in the duration of ventricular fibrillation (VF; P<0.05 vs. Scramble-shRNA+I/R group) and a significantly reduced arrhythmia score (P<0.01 vs. Scramble-shRNA+I/R group). The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia (VT), sustained VT and VF, especially at the time 5–10 min after ischemia (P<0.05 vs. Scramble-shRNA+IR group). Using in vitro human embryonic kidney 293 T (HEK293T) cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation (H/R), we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R. Mutation of SUMO consensus lysine sites in Cav-3 (K38R or K144R) altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells.Conclusions:I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias. Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes, and subsequent ventricular arrhythmias in rats. PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.Keywords：Ventricular arrhythmia;Nav1.5;Caveolin-3;Protein inhibitor of activated STAT Y;SUMOylation35|1|0Updated：2023-07-21
RESEARCH
-
Abstract：Extracellular RNAs (exRNAs) are novel circulating factors that can be used as biomarkers in various diseases. Their unique and diverse kinds, as well as their role as biomarkers, make them significant biomarkers. There has been immense work carried out since the discovery of exRNAs in circulation and other biological fluids to catalog and determine whether exRNAs may be utilized as indicators for health and illness. In this review, we aim to understand the current state of exRNAs in relation to various diseases and their potential as biomarkers. We will also review current issues and challenges faced in using exRNAs, with clinical and lab trials, that can be used as viable markers for different diseases.Keywords：Extracellular RNAs (exRNAs);Extracellular vehicles (EVs);Cancer;Biomarkers;Exosomes22|1|0Updated：2023-07-21 -
Abstract：Because of its simplicity, reliability, and replicability, the Masquelet induced membrane technique (IMT) has become one of the preferred methods for critical bone defect reconstruction in extremities. Although it is now used worldwide, few studies have been published about IMT in military practice. Bone reconstruction is particularly challenging in this context of care due to extensive soft-tissue injury, early wound infection, and even delayed management in austere conditions. Based on our clinical expertise, recent research, and a literature analysis, this narrative review provides an overview of the IMT application to combat-related bone defects. It presents technical specificities and future developments aiming to optimize IMT outcomes, including for the management of massive multi-tissue defects or bone reconstruction performed in the field with limited resources.Keywords：bone defect;Induced membrane technique;Gunshot wound;Low resources;Masquelet technique;Military;War surgery27|3|0Updated：2023-07-21 -
Abstract：The advent of single-cell RNA sequencing (scRNA-seq) has provided insight into the tumour immune microenvironment (TIME). This review focuses on the application of scRNA-seq in investigation of the TIME. Over time, scRNA-seq methods have evolved, and components of the TIME have been deciphered with high resolution. In this review, we first introduced the principle of scRNA-seq and compared different sequencing approaches. Novel cell types in the TIME, a continuous transitional state, and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer. Thus, we concluded novel cell clusters of cancer-associated fibroblasts (CAFs), T cells, tumour-associated macrophages (TAMs) and dendritic cells (DCs) discovered after the application of scRNA-seq in TIME. We also proposed the development of TAMs and exhausted T cells, as well as the possible targets to interrupt the process. In addition, the therapeutic interventions based on cellular interactions in TIME were also summarized. For decades, quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer. Summarizing the current findings, we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy, which can subsequently be implemented in the clinic. Finally, we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.Keywords：Single-cell RNA sequencing (scRNA-seq);Tumour immune microenvironment (TIME);Trajectory;Cellular interactions;Therapeutic targets22|0|0Updated：2023-07-21
REVIEW
-
Abstract：Traditional treatments for advanced hepatocellular carcinoma (HCC), such as surgical resection, transplantation, radiofrequency ablation, and chemotherapy are unsatisfactory, and therefore the exploration of powerful therapeutic strategies is urgently needed. Immunotherapy has emerged as a promising strategy for advanced HCC treatment due to its minimal side effects and long-lasting therapeutic memory effects. Recent studies have demonstrated that icaritin could serve as an immunomodulator for effective immunotherapy of advanced HCC. Encouragingly, in 2022, icaritin soft capsules were approved by the National Medical Products Administration (NMPA) of China for the immunotherapy of advanced HCC. However, the therapeutic efficacy of icaritin in clinical practice is impaired by its poor bioavailability and unfavorable in vivo delivery efficiency. Recently, functionalized drug delivery systems including stimuli-responsive nanocarriers, cell membrane-coated nanocarriers, and living cell-nanocarrier systems have been designed to overcome the shortcomings of drugs, including the low bioavailability and limited delivery efficiency as well as side effects. Taken together, the development of icaritin-based nanomedicines is expected to further improve the immunotherapy of advanced HCC. Herein, we compared the different preparation methods for icaritin, interpreted the HCC immune microenvironment and the mechanisms underlying icaritin for treatment of advanced HCC, and discussed both the design of icaritin-based nanomedicines with high icaritin loading and the latest progress in icaritin-based nanomedicines for advanced HCC immunotherapy. Finally, the prospects to promote further clinical translation of icaritin-based nanomedicines for the immunotherapy of advanced HCC were proposed.Keywords：Icaritin;Nanomedicine;Advanced hepatocellular carcinoma;Immunotherapy;Clinical translation35|1|0Updated：2023-07-21
PERSPECTIVE
- Keywords：polymerase chain reaction (PCR);Test evaluation;infection;Deployment;Military medicine;Surveillance;screening;Diagnostic accuracy21|0|0Updated：2023-07-21
-
Keywords：Adeno-associated virus;gene therapy;Rheumatoid arthritis;TNF-α-induced protein 3 (A20)32|1|0Updated：2023-07-21
LETTER TO THE EDITOR
- Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19
京公网安备11010802024621 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.
0