Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition.

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the Epimedium Genus, has been proven to inhibit the proliferation and stemness of breast cancer cells. Our previous study demonstrated that IC2, a derivative of ICT, could induce breast cancer cell apoptosis by Stearoyl-CoA desaturase 1 (SCD1) inhibition. The present study further investigated the mechanism of the inhibitory effects of IC2 on breast cancer cells in vitro and in vivo. Our results proved that IC2 could stimulate autophagy in breast cancer cells with the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling and mitogen-activated protein kinase (MAPK) signaling. Combination treatment of the AMPK inhibitor decreased IC2-induced autophagy while it markedly enhanced IC2-induced apoptosis. In common with IC2-induced apoptosis, SCD1 overexpression or the addition of exogenous oleic acid (OA) could also alleviate IC2-induced autophagy. In vivo assays additionally demonstrated that IC2 treatment markedly inhibited tumor growth in a mouse breast cancer xenograft model. Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer.

Identification of icaritin derivative IC2 as an SCD-1 inhibitor with anti-breast cancer properties through induction of cell apoptosis.

BACKGROUND: Breast cancer is the most common malignancy affecting women, yet effective targets and related candidate compounds for breast cancer treatment are still lacking. The lipogenic enzyme, stearoyl-CoA desaturase-1 (SCD1), has been considered a potential target for breast cancer treatment. Icaritin (ICT), a prenylflavonoid derivative from the Traditional Chinese Medicine Epimedii Herba, has been reported to exert anticancer effects in various types of cancer. The purpose of the present study was to explore the effect of the new ICT derivative, IC2, targeting SCD1 on breast cancer cells and to explore the specific mechanism. METHODS: Immunohistochemistry and semiquantitative evaluation were performed to detect the expression level of SCD1 in normal and tumor samples. Computer-aided drug design (CADD) technology was used to target SCD1 by molecular docking simulation, and several new ICT derivatives were prepared by conventional chemical synthesis. Cell viability was evaluated by an MTT assay and dead cell staining. SCD1 expression in cancer cells was determined by Western blot and qRT-PCR analyses. The enzymatic activity of SCD1 was evaluated by detecting the conversion rate of [d31] palmitic acid (PA) using Gas chromatography-mass spectrometry (GC-MS). DAPI staining, flow cytometry and Western blot were used to detect cell apoptosis. Mitochondrial membrane potential and reactive oxygen species (ROS) assays were used to determine cell mitochondrial function. Lentiviral transduction was utilized to generate SCD1-overexpressing cell lines. RESULTS: We found that SCD1 was overexpressed and correlated with poor prognosis in breast cancer patients. Among a series of ICT derivatives, in vitro data showed that IC2 potentially inhibited the viability of breast cancer cells, and the mechanistic study revealed that IC2 treatment resulted in ROS activation and cellular apoptosis. We demonstrated that IC2 inhibited SCD1 activity and expression in breast cancer cells in a dose-dependent manner. Moreover, SCD1 overexpression alleviated IC2-induced cytotoxicity and apoptosis in breast cancer cells. CONCLUSIONS: The new ICT derivative, IC2, was developed to induce breast cancer cell apoptosis by inhibiting SCD1, which provides a basis for the development of IC2 as a potential clinical compound for breast cancer treatment.

Solasodine Induces Apoptosis, Affects Autophagy, and Attenuates Metastasis in Ovarian Cancer Cells.

Solasodine, a steroidal alkaloid isolated from solanaceous species, exhibits anticancer activities on several cell lines. This study aimed to explore the antitumor potential of solasodine on ovarian cancer cells. The MTT assay, lactate dehydrogenase release assay, Hoechst 33342 staining, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine staining assay, and Annexin V/PI assay were conducted to investigate the antiproliferation and apoptosis-inducing effects of solasodine. Monodansylcadaverine staining was performed to label the acidic puncta on ovarian cancer HEY cells. A wound healing assay and Transwell assay were carried out to determine whether solasodine elicits an antimetastatic effect on HEY cells. A gelatin zymography assay was applied to detect the enzymatic activities of matrix metalloproteinases. Western blot was employed to examine relevant protein expression. Results revealed that solasodine inhibited cell viabilities in a time- and dose-dependent manner, triggered apoptotic body formation, reduced cell mitochondrial membrane potential, and interfered with autolysosome degradation in ovarian cancer cells. Solasodine also suppressed the migration and invasion of HEY cells by downregulating matrix metalloproteinase expression and activities. This study could be used as a basis for further studies on the molecular mechanisms of the antiproliferation, apoptosis-inducing, autophagy-modifying, and antimetastatic activities of solasodine.

Comprehensive analysis of stearoyl-coenzyme A desaturase in prostate adenocarcinoma: insights into gene expression, immune microenvironment and tumor progression.

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.

Subvacuum environment-enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation.

Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+ ) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p-PI3K, AKT1, p-AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.

Single-cell transcriptome profiling of sepsis identifies HLA-DRlowS100Ahigh monocytes with immunosuppressive function.

BACKGROUND: Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. METHODS: We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. RESULTS: ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression. CONCLUSIONS: This study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

E2F1 enhances 8-chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells.

The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in response to DNA damage is less clear. 8-Chloro-adenosine (8-Cl-Ado), a nucleoside analog, can inhibit proliferation in a variety of human tumor cells. However, it is still elusive how the agent acts on tumors. Here we show that A549 and H1299 cells formed DNA double-strand breaks after 8-Cl-Ado exposure, accompanied by E2F1 upregulation at protein level. Overexpressed wild-type (E2F1-wt) colocalized with double-strand break marker γ-H2AX and promoted G2/M arrest in 8-Cl-Ado-exposed A549 and H1299, while expressed S31A mutant of E2F1 (E2F1-mu) significantly reduced ability to accumulate at sites of DNA damage and G2/M arrest, suggesting that E2F1 is required for activating G2/M checkpoint pathway upon DNA damage. Transfection of either E2F1-wt or E2F1-mu plasmid promoted apoptosis in 8-Cl-Ado-exposed cells, indicating that 8-Cl-Ado may induce apoptosis in E2F1-dependent and E2F1-independent ways. These findings demonstrate that E2F1 plays a crucial role in 8-Cl-Ado-induced G2/M arrest but is dispensable for 8-Cl-Ado-induced apoptosis. These data also suggest that the mechanism of 8-Cl-Ado action is complicated.

Furanodiene induces endoplasmic reticulum stress and presents antiproliferative activities in lung cancer cells.

Furanodiene (FUR) is a natural terpenoid isolated from Curcumae Rhizoma, a well-known Chinese medicinal herb that presents antiproliferation activities in several cancer cell lines. In this study, we demonstrated that FUR concentration dependently inhibits the cell proliferation of A549, NIH-H1299, and 95-D lung cancer cells. ß-elemene, another terpenoid isolated from Curcumae Rhizoma, exhibited weaker antiproliferative effects in A549 and NIH-H1299 cells and activities similar to FUR in 95-D cells. FUR significantly inhibited colony formation in A549 and 95-D cells and upregulated both the mRNA and protein expression levels of binding immunoglobulin protein (BIP) and C/EBP homologous protein (CHOP), indicating that endoplasmic reticulum (ER) stress is induced. FUR treatment led to the accumulation of CHOP in the nucleus, which further confirms induction of ER stress. Furthermore, combined treatment of FUR with paclitaxel showed significant synergetic activities in NIH-H1299 and 95-D cells, suggesting its potential roles in combination therapy. These findings provide a basis for the further study of the anticancer effects in vivo and the internal mechanisms of FUR.

Anatomic study of fabella and its surrounding structures in a Chinese population.

PURPOSE: To explore the anatomic features of the fabella and its relationship with the common peroneal nerve and the fabellofibular ligament, so as to provide anatomical evidence for clinical diagnosis and treatment of fabella diseases in a Chinese population. METHODS: Sixty-one formalin-fixed knee specimens were obtained for anatomic dissection. Structural features of the fabella were investigated by radiological and histological tests. RESULTS: There were 53 cases (86.89%) with fabellae in the lateral head of the gastrocnemius muscle, including 34 bony ones (55.74%), whereas only 6 cases had fabellae in the medial head (9.84%). The fabellae were accompanied by common peroneal nerves on their surfaces in 11 cases (20.8%), and the presence of the fabella was not generally predictive of a fabellofibular ligament. As much as 57.9% of the cartilage fabellae were not visualized on radiograph. The structure of the ossified fabella is similar to a typical long bone. CONCLUSIONS: Fabellae were mainly present in the lateral head of the gastrocnemius muscle in a large proportion of the Chinese population. More than half of the cartilage fabellae were not visualized on radiograph. Its clinical significance could not be ignored by physicians and anatomists.

[Effect of hepatocyte growth factor and transforming growth factor-ß(1) on atrial fibroblasts fibrosis].

OBJECTIVE: To investigate the effect of hepatocyte growth factor (HGF) and transforming growth factor-ß(1) (TGFß(1)) on the expression of α-smooth muscle actin (α-SMA) and collagen I in human atrial fibroblast in vitro, and to explore the possible molecular mechanism of atrial fibrosis in patients with atrial fibrillation (AF). METHODS: Human atrial fibroblast, isolated from aseptic right atrial appendage tissues of 10 sinus rhythm (SR) and 10 chronic atrial fibrillation (CAF) patients, were cultured with HGF and TGFß(1). mRNA expressions of collagen I and α-SMA were detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), the protein expression of α-SMA was determined by immunofluorescence and Western blot. RESULTS: (1) Compared with SR group, left atrium was significantly dilated in CAF group (t = 2.692, P < 0.05), the mRNA expression of collagen I and α-SMA of atrial fibroblasts were significantly upregulated (all P < 0.01), mRNA expression of collagen I was positively correlated with left atrial dimension (LAD) (r = 0.836, P = 0.014), AF duration (r = 0.739, P = 0.045) and α-SMA mRNA level (r = 0.886, P = 0.012). (2) Compared with SR group, the expression of α-SMA protein in CAF atrial fibroblasts were significantly increased (P < 0.01). (3) TGFß(1) further stimulated while HGF significantly attenuated the expression of collagen I and α-SMA in CAF atrial fibroblasts (all P < 0.01). CONCLUSIONS: Increasing expression of collagen I and α-SMA in human atrial fibroblasts might promote atria remodeling leading to the development and sustaining of AF. HGF is involved in the negative regulation on the expression of α-SMA and collagen I.

Combination of transcriptional biomarkers and clinical parameters for early prediction of sepsis indued acute respiratory distress syndrome.

Objective: As a common yet intractable complication of severe sepsis, acute respiratory distress syndrome (ARDS) is closely associated with poor clinical outcomes and elevated medical expenses. The aim of the current study is to generate a model combining transcriptional biomarkers and clinical parameters to alarm the development of ARDS in septic patients. Methods: Gene expression profile (GSE66890) was downloaded from the Gene Expression Omnibus database and clinical data were extracted. Differentially expressed genes (DEGs) from whole blood leukocytes were identified between patients with sepsis alone and septic patients who develop ARDS. ARDS prediction model was constructed using backward stepwise regression and Akaike Information Criterion (AIC). Meanwhile, a nomogram based on this model was established, with subsequent internal validation. Results: A total of 57 severe septic patients were enrolled in this study, and 28 (49.1%) developed ARDS. Based on the differential expression analysis, six DEGs (BPI, OLFM4, LCN2, CD24, MMP8 and MME) were screened. According to the outcome prediction model, six valuable risk factors (direct lung injury, shock, tumor, BPI, MME and MMP8) were incorporated into a nomogram, which was used to predict the onset of ARDS in septic patients. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. The area under the receiver operating characteristic (AUROC) for the prediction of ARDS occurrence in septic patients by the nomogram was 0.86 (95% CI = 0.767-0.952). A sensitivity analysis showed that the AUROC for the prediction of ARDS development in septic patients without direct lung injury was 0.967 (95% CI = 0.896-1.0). Conclusions: The nomogram based on transcriptional biomarkers and clinical parameters showed a good performance for the prediction of ARDS occurrence in septic patients.

Association of Preadmission Statin Use and Mortality in Critically Ill Patients: A Meta-Analysis of Cohort Studies.

Background: A large number of studies have been conducted to determine whether there is an association between preadmission statin use and improvement in outcomes following critical illness, but the conclusions are quite inconsistent. Therefore, this meta-analysis aims to include the present relevant PSM researches to examine the association of preadmission use of statins with the mortality of critically ill patients. Methods: The PubMed, Web of Science, Embase electronic databases, and printed resources were searched for English articles published before March 6, 2020 on the association between preadmission statin use and mortality in critically ill patients. The included articles were analyzed in RevMan 5.3. The Newcastle-Ottawa Scale (NOS) was used to conduct quality evaluation, and random/fixed effects modeling was used to calculate the pooled ORs and 95% CIs. We also conducted subgroup analysis by outcome indicators (30-, 90-day, hospital mortality). Results: All six PSM observational studies were assessed as having a low risk of bias according to the NOS. For primary outcome-overall mortality, the pooled OR (preadmission statins use vs. no use) across the six included studies was 0.86 (95% CI, 0.76-0.97; P = 0.02). For secondary outcome-use of mechanical ventilation, the pooled OR was 0.94 (95% CI, 0.91-0.97; P = 0.0005). The corresponding pooled ORs were 0.67 (95% CI, 0.43-1.05; P = 0.08), 0.91 (95% CI, 0.83-1.01; P = 0.07), and 0.86 (95% CI, 0.83-0.89; P < 0.00001) for 30-, 90-day, and hospital mortality, respectively. Conclusions: Preadmission statin use is associated with beneficial outcomes in critical ill patients, indicating a lower short-term mortality, less use of mechanical ventilation, and an improvement in hospital survival. Further high-quality original studies or more scientific methods are needed to draw a definitive conclusion.

Calcium signal-initiated early activation of NF-kappaB in neurons is a neuroprotective event in response to kainic acid-induced excitotoxicity.

We demonstrate that activation of nuclear factor kappaB (NF-kappaB) in neurons is neuroprotective in response to kainic acid (KA)-induced excitotoxicity. Combination of Western blotting, immunocytochemistry, and electrophoresis mobility shift assay showed that KA exposure induced a fast but transient nuclear translocation of the NF-kappaB p65 subunit and increased DNA-binding activity of NF-kappaB in primary cultured cortical neurons. The transient NF-kappaB activity was associated with upregulation of antiapoptotic Bcl-xL and XIAP gene products revealed by real-time PCR. Knockdown of p65 decreased neuronal viability and antiapoptotic gene expression. In addition, we showed that KA-stimulated DNA-binding activity of NF-kappaB was associated with reactive oxygen species and calcium signals, using AMPA/KA receptor antagonist, calcium chelator, and antioxidant. These results suggest that the fast and transient activation of NF-kappaB initiated by calcium signals is one of the important proximal events in response to KA-induced excitotoxicity, which has neuroprotective effect against KA-induced apoptosis.

[The effect and influencing factors of schistosomiasis control by forbidding livestock denaturing on marshland with Oncomelania snails].

OBJECTIVE: To evaluate the effect of schistosomiasis control by forbidding livestock denaturing on marshland with Oncomelania snails and to analyse its influencing factors. METHODS: The village of Aiguo, Xinhe, Huangjia, Fanrong, Fengfu and Caomen and its respective nearby marshland, i.e., Aiguoniu, Liulingwei, Huangjianiu, Da, Goulian, and Litouzui, in Jinxian county, Jiangxi province were selected as the pilot areas for implementing the measures of forbidding livestock denaturing on the marshlands with Oncomelania snails during the period of the year 2005 to 2007. A total of 300 residents in each village were randomly chosen for stool examination with the Kato-Katz technique every year. The snail survey was carried out in spring and autumn every year on the marshlands close to the villages with systemic sampling method. The marshlands with a height 16.5 m above the sea level in Futian was selected for snail survey and planting with sesame. The residents aged 20 - 50 years old in Fengfu and Aiguo villages were studied by using questionnaire on the compliance of forbidding livestock pasturing on marshlands with Oncomelania snails. RESULTS: Before implementation of the measures, human infection rate with Schistosoma japonicum was 11.35% (90/793) in Aiguo, 4.00% (12/300) in Xinhe, 4.00% (6/150) in Huangjia, 8.00% (12/150) in Fanrong, 3.17% (4/126) in Fengfu and 6.64% (14/211) in Caomen. After implementation in 2008, human schistsome infection rate in the aforementioned 6 villages was declined to 0.18% (1/551), 0.00% (0/348), 0.00% (0/316), 2.27% (7/308), 1.17% (5/428) and 1.16% (5/430), respectively. Only in Fengfu village the decline of the human prevalence was not significant (χ(2) = 2.4, P = 0.12), while in the other 5 villages, human prevalence rate had been declined significantly (χ(2) = 126.77, P < 0.01; χ(2) = 16.31, P < 0.01; χ(2) = 18.79, P < 0.01; χ(2) = 10.39, P < 0.01; χ(2) = 14.17, P < 0.01, respectively). Infected snails were not found in 5 out of the 6 marshlands close to the villages. Three infected snails were founded in Da marshland because of poor environmental isolation. Before planting, the living snail density was 0.063/0.11 m(2) (34/540), and after planting, the living snail density was 0.0074/0.11 m(2) (4/538), a 88.25% reduction (Z = 12.47, P < 0.01) was recorded through economy crop planting at Futiandaan marshland in 2008. A total of 986 pieces of questionnaire were provided, and 968 valid ones were collected. The results of questionnaire indicate that compliance of forbidding livestock denaturing on marshland with Oncomelania snails in Aiguo and Fengfu villages was 84.38% (216/256) and 75.42% (537/712), respectively. Using logistic regression model, knowledge level on harmfulness of livestock denaturing on marshland with Oncomelania snails, willingness of culture with machine to substitute traditional cattle culture, and willingness of investment to marshland culture development are 3 varieties that affect residents' implementation of forbidding livestock denaturing on marshland with Oncomelania snails. CONCLUSION: The infected snail density and human schistosome infection rate were reduced on the marshlands of well environmental isolation after 2 - 3 years implementation of forbidding livestock denaturing on marshlands with Oncomelania snails. The key influencing factors of forbidding livestock denaturing on marshland with Oncomelania snails are knowledge level on harmfulness of livestock denaturing on the snail infested marshlands, the willingness of machine culture to substitute cattle culture, and the willingness of investment to marshland culture development.

Publication Trends of Research on Sepsis and Host Immune Response during 1999-2019: A 20-year Bibliometric Analysis.

Introduction: Sepsis is an intractable disorder, which is associated with high risk of organ dysfunction and even death, while its pathogenesis remains largely unclear. Our study aims to study the research trend on sepsis and host immune response, and compare the contribution of publications from different countries, institutions, journals and authors. Materials and Methods: We extracted all relevant publications with regard to sepsis and immune response during 1999-2019 from Web of Science. GraphPad Prism 6, and VOSviewer software were used to collect and analyze the publication trend in related field. Results: We identified a total of 1225 publications with citation frequency of 40511 times up to March 30, 2019. The United States accounted for the largest number of publications (36.3%), 51.9% of total citations as well as the highest H-index (72). The sum of publications from China ranked the second, while the overall citations (1935) and H-index (22) ranked the eighth and the seventh, respectively. Journal of Shock had published most papers related to the topic on sepsis and immune response. Ayala A SA, has published the most papers in this field (31), while Hotchkiss RS presented with the most citation frequency (3532). The keyword "regulatory T cell" appeared most recently with an average appearing years of 2014.0. The "immunosuppression related research" seemed to be the hotspot in relevant scope. Conclusions: The United States made the most outstanding contribution within this important field. There is a mismatch between the quantity and quality of publications from China. Latest progress can be tracked in journal of Shock. Immunosuppression related researches may be hotspots in the near future.

New mutation in EPCAM for congenital tufting enteropathy: A case report.

BACKGROUND: Congenital tufting enteropathy (CTE) is a rare cause of diarrhea in children. However, it can result in early-onset of chronic diarrhea and failure to thrive. Children with this disease have to depend on total parenteral nutrition (TPN), and eventually small intestine transplantation. The epithelial cell adhesion molecule (EPCAM) gene was identified to be associated with CTE. Here, we present a case of an infant with CTE due to a mutation not reported in the literature before. CASE SUMMARY: A 1-year and 7-mo infant boy exhibited intractable watery diarrhea and mushy stool within 1 wk after birth, for which he had required medical treatment and hospitalization several times. His sister presented similar symptoms and died at the age of two. On admission, his body weight was 5700 g (-4.8SDS) and measured 66 cm (-5.4SDS) in height. Meanwhile, he cannot speak or climb. He exhibited mild anemia, hypocalcemia, hypomagnesemia, and an infection in the upper respiratory tract. Microvilli sparse and vacuolar degeneration of epithelial cells were reported by small intestine biopsy. Whole-exome sequencing showed a novel homozygous splice mutation (c.657+1[IVS6] G>A) in the EPCAM gene. He was treated with TPN and recombinant human growth hormone. After 2 mo, his body weight was up to 8500 g and he has been waiting for small bowel transplantation. CONCLUSION: CTE is rare but fatal. Patients with CTE require rapid diagnosis and therapy to improve their survival.

Is intensive glucose control bad for critically ill patients? A systematic review and meta-analysis.

Background: The monitoring and management of blood glucose concentration are standard practices in critical settings as hyperglycaemia has been shown close association with poorer outcomes. Several meta-analyses have revealed that intensive glucose control has no benefit in decreasing short-term mortality among critically ill patients, while the studies these meta-analyses have incorporated have been largely divergent. We aim to perform a more comprehensive meta-analysis addressing this problem to provide stronger evidence. Methods: We conducted comprehensive searches for relevant randomized controlled studies in online databases, including the Cochrane Library, EMBASE, and PubMed databases, up to September 1, 2018. The clinical data, which included all-cause mortality, severe hypoglycemia, need for RRT, infection resulting in sepsis, ICU mortality, 90-day mortality, 180-day mortality, and hospital and ICU lengths of stay, were screened and analyzed after data extraction. We applied odds ratios (ORs) to analyze dichotomous outcomes and mean differences for continuous outcomes with a random effects model. Results: A total of 57 RCTs involving a total of 21840 patients were finally included. Patients admitted to the ICU who underwent intensive glucose control showed significantly reduced all-cause mortality (OR: 0.89; 95% CI: 0.80-1.00; P=0.04; I2=32%), reduced infection rate (OR: 0.65, 95% CI: 0.51-0.82, P=0.0002; I2=47%), a lower occurrence of acquired sepsis (OR: 0.80, 95% CI: 0.65-0.99, P=0.04; I2=0%) and shortened length of ICU stay (MD: -0.70, 95% CI: -1.21--0.19, P=0.007, I2=70%) when compared to the same parameters as those treated with the usual care strategy. However, patients in the intensive glucose control group presented with a significantly higher risk of severe hypoglycemia (OR: 5.63, 95% CI: 4.02-7.87, P<0.00001; I2=67%). Conclusions: Critically ill patients undergoing intensive glucose control showed significantly reduced all-cause mortality, length of ICU stay and incidence of acquired infection and sepsis compared to the same parameters in patients treated with the usual care strategy, while the intensive glucose control strategy was associated with higher occurrence of severe hypoglycemic events.

Diagnostic blood loss from phlebotomy and hospital acquired anemia in patients with severe burns.

PURPOSE: The study was performed to estimate the diagnostic blood loss (DBL) volume during hospitalization and investigate its relationship with the development of moderate to severe hospital acquired anemia (HAA) and increased number of red blood cell (RBC) transfusion following extensive burns. MATERIALS AND METHODS: This was a retrospective study of adult burned patients with total body surface area (TBSA) burn larger than 40%, who were admitted to burn center of Changhai hospital between January 2005 and December 2017. RESULTS: We included a final number of 157 patients in the present study. Moderate to severe HAA within the fourth week postburn was developed in 46 of 121 patients who stayed over 28-day hospitalization. Patients with moderate to severe HAA had both significantly higher total DBL volume [245 (IQR: 183.75, 325.25) mL vs 168 (119, 163) mL ; P = 0.001] and DBL volume per day [10.22 (IQR: 8.57, 12.38) mL vs 6.63 (5.22, 10.42) mL/day; P = 0.005]. Logistic regression analysis revealed that both DBL volume per day and TBSA burn were independent risk factors for the development of moderate to severe HAA. CONCLUSIONS: Severely burned patients appear to be prone to develop HAA during hospitalization. The DBL volume contribute to the occurrence of moderate to severe HAA, which might be a modifiable target for preventing HAA.

Clinical Efficiency of Vasopressin or Its Analogs in Comparison With Catecholamines Alone on Patients With Septic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND: Vasopressin is an efficient remedy for septic shock patients as its great capacity in promoting hemodynamic stabilization. The aim of current systematic review and meta-analysis is to compare the clinical efficiency of vasopressin or its analogs with sole catecholamines on patients with septic shock. METHODS: A systematic search of Cochrane Library, EMBASE, and PubMed online databases was performed up to 30 Oct 2019 to identify randomized controlled trials comparing use of vasopressin or its analogs (e.g., terlipressin, selepressin) with administration of catecholamines alone. RESULTS: We included 23 RCTs with 4,225 patients in the current study. Compared with solely use of catecholamines, administration of vasopressin or its analogs was not associated with reduced 28-day or 30-day mortality among patients with septic shock [RR=0.94 (95% CI, 0.87-1.01), P=0.08, I2 = 0%]. The result of primary endpoint remained unchanged after conducting sensitivity analysis. Despite a significantly higher risk of digital ischemia in patients receiving vasopressin or its analogs [RR=2.65 (95% CI, 1.26-5.56), P < 0.01, I2 = 48%], there was no statistical significance in the pooled estimate for other secondary outcomes, including total adverse events, arrhythmia, acute myocardial infarction (AMI) and cardiac arrest, acute mesenteric ischemia, ICU/hospital length of stay, and mechanical ventilation (MV) duration. CONCLUSIONS: The administration of vasopressin or its analogs was not associated with reduced 28-day or 30-day mortality among patients with septic shock, while an increased incidence of digital ischemia should be noted in patients receiving agonists for vasopressin receptors.

Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury.

Acute lung injury (ALI) and respiratory distress syndrome are common, potentially lethal injuries that predominantly occur following chest trauma. Circular RNAs (circRNAs) are stable conserved non-coding RNAs that are widely expressed in different organs. To the best of our knowledge, no previous studies have shown whether circRNAs are involved in traumatic lung injury (TLI). The aim of the present study was to identify highly expressed circRNAs in plasma samples from patients with TLI and explore their potential functions in the pathogenesis of TLI. A high-throughput circRNA microarray was used to investigate the expression profile of circRNAs in plasma samples from five patients with TLI and paired control samples. Subsequently, a total of five abnormally expressed circRNAs were investigated using reverse transcription-quantitative PCR (RT-qPCR). A bioinformatics analysis was performed to predict a competitive endogenous RNA (ceRNA) network. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the main biological processes and pathways. Finally, additional samples were tested to identify the expression profiles of the selected circRNAs. Among the 310 circRNAs that were highly expressed in the microarray analysis, 60 were upregulated and 250 were downregulated in patients with TLI. RT-qPCR results indicated that two downregulated circRNAs (circ_102927 and circ_100562) and one upregulated circRNA (circ_101523) matched the microarray results. The bioinformatics analysis constructed a targeting network based on the three validated circRNAs. GO and KEGG analyses identified the top ten enriched annotations. The expression of homo sapiens circular RNA 102927 (hsa_circRNA_102927) in the plasma of patients with TLI was 0.34-fold compared with the control group in expanded size validation. The results of the present study identified the differentially expressed circRNAs in the plasma of patients with TLI and provided evidence that highly expressed circRNAs involved in the ceRNA network may serve a role in the pathophysiology of TLI.