Identification and experimental verification of an anoikis and immune related signature in prognosis for lung adenocarcinoma.

Background: Both metastasis and immune resistance are huge obstacle in lung adenocarcinoma (LUAD) treatment. Multiple studies have shown that the ability of tumor cells to resist anoikis is closely related to the metastasis of tumor cells. Methods: In this study, the risk prognosis signature related to anoikis and immune related genes (AIRGs) was constructed by cluster analysis and the least absolute shrinkage and selection operator (LASSO) regression by using The Cancer Genome Atlas (TCGA) Program and the Gene Expression Omnibus (GEO) database. Kaplan-Meier (K-M) curve described the prognosis in the different groups. Receiver operating characteristic (ROC) was applied to evaluate the sensitivity of this signature. Principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), independent prognostic analysis, and nomogram were utilized to assess the validity of the signature. In addition, we used multiple bioinformatic tools to analyze the function between different groups. Finally, mRNA levels were analyzed by quantitative real-time PCR (qRT-PCR). Results: The K-M curve showed a worse prognosis for the high-risk group compared to that for the low-risk group. ROC, PCA, t-SNE, independent prognostic analysis and nomogram showed well predictive capabilities. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that differential genes were mainly enriched in immunity, metabolism, and cell cycle. In addition, multiple immune cells and targeted drugs differed in the two risk groups. Finally, we found that the mRNA levels of AIRGs were remarkably different in normal versus cancer cells. Conclusions: In short, we established a new model about anoikis and immune, which can well predict prognosis and immune response.

Short-term outcomes of neoadjuvant sintilimab with chemotherapy in stage III non-small cell lung cancer: a case series.

Background: Neoadjuvant chemoimmunotherapy seems to be a promising treatment option for stage III non-small cell lung cancer (NSCLC). Sintilimab, as a programmed death receptor-1 inhibitor, has exhibited a fine performance in treating NSCLC. However, the efficiency of sintilimab combined with chemotherapy for stage IIIA/IIIB NSCLC remains inconclusive. The purpose of this study was to share our experience on sintilimab in neoadjuvant chemoimmunotherapy for stage III NSCLC. Methods: This study retrospectively reviewed patients who received surgical resection following 1-3 cycles of neoadjuvant sintilimab (200 mg) with chemotherapy for stage III NSCLC between June 2020 and March 2022 in our center. Patients characteristics, surgical factors, surgery-related complications 30 days postoperatively, and treatment-related adverse events (TRAEs) before surgery were recorded through reviewing medical record data and telephone follow-up. Results: A total of eight patients were enrolled, including six cases of squamous cell carcinoma and two cases of adenocarcinoma. All of the patients received 1-3 cycles of neoadjuvant therapy. There were no treatment-related surgical delays. All patients underwent lobectomy, among which two underwent sleeve lobectomy and one received bronchoplasty. Five patients underwent open thoracotomy. Fibrosis of the primary tumor and lymph nodes was observed in all the cases. There were no surgery-related complications > grade 2 at 30 days postoperatively. According to the radiographic findings, one patient had stable disease and all of the others achieved a partial response. The median of maximum standardized uptake value change from baseline was a 52.75% reduction (range, 37.2-68.8%). Five patients achieved a major pathological response. R0 resection was achieved in all eight cases. One grade 4 event was observed. Neutropenia was the most common TRAE > grade 2 (3/8). There were no cases of treatment discontinuation or dose reduction due to TRAEs. Conclusions: The current study found that neoadjuvant sintilimab plus chemotherapy bring a high rate of major pathological response and acceptable TRAEs. Even though it increased the difficulties of surgery, there is still no evidence suggesting that it will brings additional surgical death. We believe that neoadjuvant sintilimab plus chemotherapy might be feasible for stage III NSCLC.

Identification of Crucial Genes and Key Functions in Type 2 Diabetic Hearts by Bioinformatic Analysis.

Type 2 diabetes (T2D) patients with SARS-CoV-2 infection hospitalized develop an acute cardiovascular syndrome. It is urgent to elucidate underlying mechanisms associated with the acute cardiac injury in T2D hearts. We performed bioinformatic analysis on the expression profiles of public datasets to identify the pathogenic and prognostic genes in T2D hearts. Cardiac RNA-sequencing datasets from db/db or BKS mice (GSE161931) were updated to NCBI-Gene Expression Omnibus (NCBI-GEO), and used for the transcriptomics analyses with public datasets from NCBI-GEO of autopsy heart specimens with COVID-19 (5/6 with T2D, GSE150316), or dead healthy persons (GSE133054). Differentially expressed genes (DEGs) and overlapping homologous DEGs among the three datasets were identified using DESeq2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were conducted for event enrichment through clusterProfile. The protein-protein interaction (PPI) network of DEGs was established and visualized by Cytoscape. The transcriptions and functions of crucial genes were further validated in db/db hearts. In total, 542 up-regulated and 485 down-regulated DEGs in mice, and 811 up-regulated and 1399 down-regulated DEGs in human were identified, respectively. There were 74 overlapping homologous DEGs among all datasets. Mitochondria inner membrane and serine-type endopeptidase activity were further identified as the top-10 GO events for overlapping DEGs. Cardiac CAPNS1 (calpain small subunit 1) was the unique crucial gene shared by both enriched events. Its transcriptional level significantly increased in T2D mice, but surprisingly decreased in T2D patients with SARS-CoV-2 infection. PPI network was constructed with 30 interactions in overlapping DEGs, including CAPNS1. The substrates Junctophilin2 (Jp2), Tnni3, and Mybpc3 in cardiac calpain/CAPNS1 pathway showed less transcriptional change, although Capns1 increased in transcription in db/db mice. Instead, cytoplasmic JP2 significantly reduced and its hydrolyzed product JP2NT exhibited nuclear translocation in myocardium. This study suggests CAPNS1 is a crucial gene in T2D hearts. Its transcriptional upregulation leads to calpain/CAPNS1-associated JP2 hydrolysis and JP2NT nuclear translocation. Therefore, attenuated cardiac CAPNS1 transcription in T2D patients with SARS-CoV-2 infection highlights a novel target in adverse prognostics and comprehensive therapy. CAPNS1 can also be explored for the molecular signaling involving the onset, progression and prognostic in T2D patients with SARS-CoV-2 infection.

Efficacy of Acupuncture Combined with Rehabilitation Training for Intensive Care Unit-Acquired Muscle Weakness: A Protocol for a Randomized, Sham-Procedure-Controlled Clinical Trial.

To evaluate the efficacy of acupuncture combined with rehabilitation training in patients with intensive care unit (ICU)-acquired muscle weakness (ICUAW), a single-blinded, randomized, sham-controlled clinical trial is designed for execution. In total, 56 participants with ICUAW will be randomly assigned to the treatment and control groups with 28 participants in each group. The participants will be treated with acupunctures or sham procedures at LI15, LI11, ST36, GB34, and ST31, 5 times per week for a total of 20 sessions in 4 weeks while they will receive rehabilitation training. Patients will be followed up every month for 3 months after treatment. The primary outcomes include changes in quadriceps femoris muscle area, thickness, vastus intermediate muscle thickness, subcutaneous tissue thickness, and ultrasonic intensities of the rectus femoris. The secondary outcomes consist of the modified Barthel index score and the Medical Research Council total score. Participants' mechanical ventilation, the rate of detachment at the second week, the 28-day survival rate, and the occurrence of adverse reactions will be measured, and any side effects will be reported and recorded. Patient outcomes between the treatment and control groups will be compared and statistically tested. We anticipate that the therapeutic regimen of acupuncture combined with rehabilitation training would be more effective than the rehabilitation training alone for the treatment of the ICUAW. The findings of this study could help develop a better strategy for the treatment of the ICUAW disease and explore a clinical application of an acupuncture technique. Trial registration: Chinese Clinical Trial Register ChiCTR2000038779. Registered 30 September, 2020, https://www.chictr.org.cn/showproj.aspx?proj=62284.

MicroRNA 181a-2-3p Alleviates the Apoptosis of Renal Tubular Epithelial Cells via Targeting GJB2 in Sepsis-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is the most common complication of sepsis. MicroRNAs (miRNAs) play important roles in the sepsis-induced AKI. This paper aimed to explore the role of miRNA 181a-2-3p (miR-181a-2-3p) in the sepsis-induced AKI and the underlying mechanism. Our results revealed that miR-181a-2-3p showed low expression levels in patients with sepsis and mouse models undergoing cecal ligation and puncture (CLP). The addition of miR-181a-2-3p antagonists aggravated the sepsis-induced kidney injuries and inflammatory response in CLP mouse models, as suggested by hematoxylin and eosin (H&E) staining and quantitative real-time PCR (qRT-PCR). In addition, miR-181a-2-3p mimic alleviated the lipopolysaccharide (LPS)-induced inflammatory response, along with apoptosis of TCMK-1. Moreover, results from the GSE46955 data set indicated that GJB2 was highly expressed in septic patients but lowly expressed after recovery. Further, the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out, which confirmed that GJB2 was a target of miR-181a-2-3p, and overexpression of GJB2 reversed the anti-inflammatory and antiapoptotic effects of miR-181a-2-3p mimic on the LPS-induced sepsis cell models. In conclusion, miR-181a-2-3p alleviates the inflammatory response and cell apoptosis of septic patients and animal models by upregulating GJB2 expression, which may provide a new therapeutic strategy for sepsis.

Primary yolk sac tumor of pterygopalatine fossa with loss of vision: A case report.

INTRODUCTION: Primary yolk sac tumor (YST) is an infrequently-diagnosed malignant extragonadal germ cell tumors. It is likely to recur locally and may present with widespread metastases once diagnosed. Primary YST of the head is uncommon but can cause severe complications, such as loss of vision once the tumor mass invades the optic nerve. PATIENT CONCERNS: A 20-month-old boy presented to the general clinic of the local children's hospital with a complaint of swelling of left face for 1 year and proptosis of the left eye for over 2 weeks as stated by his parents. Initially, he did have some vision, as he could walk by himself, but a special ophthalmologic examination was not performed. DIAGNOSES: Cranial computed tomography and magnetic resonance imaging revealed a large tumor accompanied by peripheral bone destruction in the left pterygopalatine fossa that extended to sphenoid, ethmoid, left maxillary sinuses, left nasoethmoid, and left orbit. The optic nerve was invaded on both sides. Chest and abdominal imaging were normal. A primary diagnosis of Langerhans cell hyperplasia was made. However, blood tests on the second day of hospitalization revealed significantly elevated serum alpha-fetoprotein levels. On the third day, the boy lost his eyesight, with loss of pupillary and no light sensation during flashlight stimulation on both sides. INTERVENTIONS: Nasal endoscopy was performed on the fourth day, the vast majority of soft tissue mass was resected for biopsy. Histopathological examination revealed features of endodermal sinus tumor. A final diagnosis of primary YST of pterygopalatine fossa was made. Because the mass could not be resected completely, he received combined chemotherapy with bleomycin, etoposide, and carboplatin for 6 cycles over six months. OUTCOMES: The patient recovered with significant tumor shrinkage and without secondary metastasis after 18 months but left permanently blind. CONCLUSION: The worst complication of loss of vision after Primary YST of pterygopalatine fossa alerts us that close physical examination during the initial investigation should be performed, which is especially important in young children who cannot express complaints well. Early detection and treatment with surgical resection and chemotherapy may contribute to satisfactory outcomes and avoidance of visual impairment.

Insights into chemosensory genes of Pagiophloeus tsushimanus adults using transcriptome and qRT-PCR analysis.

Pagiophloeus tsushimanus is a new, destructive, and monophagous weevil pest that thrives on Cinnamomum camphora, found in Shanghai. The functions of chemosensory genes involved in the host location and intraspecific communication of P. tsushimanus remain unknown. The male-female transcriptomes of P. tsushimanus adults were assembled using Illumina sequencing, and we focused on all chemosensory genes in transcriptomes. In general, 58,088 unigenes with a mean length of 1018.19 bp were obtained. In total, 39 odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 22 olfactory receptors (ORs), 16 gustatory receptors (GRs), eight ionotropic receptors (IRs), and five sensory neuron membrane proteins (SNMPs) were identified. PtsuOBPs comprised four subfamilies (20 Minus-C, one Plus-C, two Dimer, and 15 Classic). Both PtsuOBPs and PtsuCSPs contained a highly conserved sequence motif of cysteine residues. PtsuORs including one olfactory receptor co-receptors (Ptsu/Orco) comprised seven predicted transmembrane domains. Phylogenetic analysis revealed that PtsuOBPs, PtsuCSPs, and PtsuORs in P. tsushimanus exhibited low homology compared to other insect species. The results of tissue- and sex-specific expression patterns indicated that PtsuOBPs and PtsuORs were highly abundant in the antennae; whereas, PtsuCSPs were not only highly abundant in antennae, but also abdominal apexes, wings, and legs. In conclusion, these results enrich the gene database of P. tsushimanus, which may serve as a basis for identifying novel targets to disrupt olfactory key genes and may provide a reverse validation method to identify attractants for formulating potential eco-friendly control strategies for this pest.

Three-Field Lymphadenectomy in Minimally Invasive Esophagectomy for Squamous Cell Carcinoma.

BACKGROUND: Minimally invasive esophagectomy (MIE) has been used widely for the treatment of esophageal cancer. However, there is still a lack of consensus on the extent of lymphadenectomy in MIE. The objective of this study was to investigate the safety and efficacy of three-field lymphadenectomy (3-FL) in MIE, compared with the standard two-field lymphadenectomy (2-FL). METHODS: A single-center randomized controlled trial was conducted, enrolling patients with resectable thoracic esophageal cancer (cT1-3,N0-3,M0) between June 2016 and May 2019. Eligible patients were randomized into two groups to receive either 3-FL or 2-FL during MIE procedures. Perioperative outcomes of the two groups were compared. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-16007957). RESULTS: Seventy-six eligible patients were randomly assigned to the 3-FL group (n = 38) and the 2-FL group (n = 38). Compared with patients in the 2-FL group, patients in the 3-FL group had more lymph nodes harvested (54.7 ± 16.5vs 30.9 ± 9.6, P < .001) and more metastatic lymph nodes identified (3.5 ± 4.5 vs 1.7 ± 2.0, P = .027). Patients in the 3-FL group were diagnosed with a more advanced final pathologic TNM stage than patients in the 2-FL group. There was no significant difference between the two groups in blood loss, major postoperative complications, or duration of hospital stay, except that the operation time was longer in the 3-FL group than in the 2-FL group (270.5 ± 45.4 minutes vs 236.7 ± 47.0 minutes, P = .002). CONCLUSIONS: Three-field lymphadenectomy allowed harvesting of more lymph nodes and more accurate staging without increased surgical risks compared with 2-FL MIE for esophageal cancer.

Gastric perforation following improper cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

Gastric perforation is a rare complication of cardiopulmonary resuscitation (CPR), mostly resulting from incorrect airway management. If left unrecognized, it is associated with high mortality and morbidity. We present a case of gastric perforation after improper CPR. A 56-year-old drunken male was sent to the emergency department due to coma after fall onto the ground. He was thought to have cardiac arrest at scene and was saved with CPR maneuver by his friends who has never been trained before. He was taken to the hospital by emergency medical service personnel and presented with abdominal distention and extensive pneumoperitoneum. Emergency laparotomy was performed which revealed gastric perforation at the lesser curvature of the stomach. The laceration was repaired without any difficulty and the patient was discharged home without any neurological deficit. The aim of this report is to remind the public and emergency physicians that gastric perforation should be suspected in patients with distended abdomen and pneumoperitoneum after CPR. Because the most common risk factor for CPR-related gastric perforation is the bystander-provided resuscitation, it is encouraged for the public to take formal CPR training.

Efficacy of acupuncture at three nasal acupoints plus acupoint application for perennial allergic rhinitis: A multicenter, randomized controlled trial protocol.

BACKGROUND: Many studies have shown the potential therapeutic effect of acupuncture on allergic rhinitis. Most of these studies were limited by low-quality evidence. Preliminary experiments showed that the use of acupuncture at three nasal acupoints plus acupoint application (AAP) achieves a more persistent effect in the treatment of perennial allergic rhinitis than acupuncture alone. In this study, a multicenter, single-blind, randomized controlled trial will be performed, in which acupuncture at nonmeridian acupoints and sham AAP will be used as the control group to evaluate the effect of AAP through long-term observation. METHODS: The trial is designed on the basis of the Consolidated Standards of Reporting Trials 2010 guidelines and Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 120 participants with perennial allergic rhinitis will be randomly assigned to a treatment or control group. A specially appointed investigator will be in charge of randomization. The participants in the treatment group will be treated with acupuncture at EX-HN3, LI20, and EX-HN8 thrice per week for a total of 12 sessions. In addition, they will undergo AAP at DU14, BL13, EX-BI, and RN22. The participants in the control group will be treated with sham AAP. The primary outcome will be the change in the Total Nasal Symptom Score from baseline to the completion of 4-week treatment. Secondary outcomes include changes in visual analog scale and total non-nasal symptom scores from baseline to the second and fourth weeks of treatment, as well as 1, 3, and 6 months after the completion of treatment. Peripheral blood IL-4, IL-5, IL-6, IL-8, and IL-10 levels will be measured, and any side effects related to treatment will be observed and recorded. DISCUSSION: It is expected that this randomized clinical trial will provide evidence to determine the effects of AAP compared with acupuncture at nonmeridian acupoints and sham AAP, particularly the long-term effect. These findings will help improve the clinical application of this technique. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry AMCTR-ICR-18000179. Registered on 12 April 2018.

[Exosomes and their roles in diabetes mellitus and its complications: from pathogenic, diagnostic and therapeutical perspectives].

Exosome is a kind of nanoscale-size extracellular vesicles secreted by the means of cell active stimulation with outer membrane structure of vacuoles corpuscle. It can carry and transfer a lot of biological molecules, such as DNA fragments, circular RNA (circRNA), messenger RNA (mRNA), microRNA (miRNA), functional proteins, transcription factors, etc., so as to achieve the goal of information transmission between cells. The relationship between exosomes and diabetes has received extensive attention in recent years. The exosomes play an important role in insulin sensitivity, glucose homeostasis and vascular endothelial function. This paper reviews the role of exosomes in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes as a target for diabetes treatment and its role in the diagnosis and treatment of diabetes.

Determination of Electroacupuncture Effects on circRNAs in Plasma Exosomes in Diabetic Mice: An RNA-Sequencing Approach.

circRNAs are involved in diabetes mellitus pathogenesis. Electroacupuncture (EA) is an effective therapeutic strategy for diabetes mellitus. However, whether the mechanism of action of EA on diabetes mellitus is related to altered circRNAs is unclear. The aim of this study was to reveal the effect of EA on circRNA expression in plasma exosomes and the underlying signaling pathway in mice with type 2 diabetes mellitus (T2DM). In total, 10 mice were randomly categorized into a normal group and 20 mice were used for the T2DM model preparation and randomly divided into the model and model + EA groups. Mice in the model + EA group were administered EA treatment. Changes in the fasting blood glucose (FBG) level and islet structure were evaluated. Plasma exosomes were subjected to RNA sequencing, and then bioinformatics analysis and real-time quantitative PCR (qPCR) verification were performed. EA treatment reduced the FBG level, preserved the islet structure, and reduced the islet ß cell apoptotic rate in T2DM mice. After EA treatment, 165 differentially expressed circRNAs were found. GO and KEGG analyses revealed that thyroid hormone signaling was actively regulated by EA. circRNA/miRNA interaction analysis revealed mmu-mir-7092-3p to be closely associated with circINPP4B, suggesting that the phosphatidylinositol signaling pathway may be affected by EA. qPCR confirmed that 12 circRNAs had significant differences. These findings suggested that EA intervention can significantly protect islet function and improve the FBG level in T2DM, possibly via regulation of thyroid hormone and phosphatidylinositol signaling.

Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1-dependent mitochondrial oxidative damage.

BACKGROUND AND PURPOSE: Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1. EXPERIMENTAL APPROACH: I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA). KEY RESULTS: In vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS: Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

[A case-control study on the treatment of carpal tunnel syndrome with needle Dao].

OBJECTIVE: To study clinical effects of needle Dao for the treatment of carpal tunnel syndrome. METHODS: From July 2014 to December 2016, 60 patients with carpal tunnel syndrome were divided into two groups: needle Dao treatment group(treatment group), and brace and medicine treatment group(control group), 30 cases in each group. There were 8 males and 22 females in the treatment group, with an average age of (49.38±7.43) years old. There were 7 males and 23 females in the control group, with an average age of (50.23±8.71) years old. There were no statistically significant differences between two groups before treatment in age, sex, course of disease, sensory nerve conduction velocity (SCV), sensory nerve action potential (SNAP), and distal motor latency(DML). The patients in the treatment group were treated with needle Dao for 1 to 2 times, while the patients in the control group were given celecoxib, vitamin B1 and vitamin B12, with the brace fixed. After treatment, the changes of SCV, SNAP and DML in two groups were observed. RESULTS: After treatment, the SCV were (48.63±7.33) m/s and (41.24±6.15) m/s in treatment group and control group separately, the SNAP were (9.89±3.71) m/s and (8.22±2.19) m/s, and the DML were(5.11±2.28) m/s and (6.13±2.23) m/s. The SCV, SNAP and DML after treatment were better than those before treatment(P<0.05). And the results of SCV, SNAP and DML of patients in the treatment group were better than those of patients in the control group(P<0.001). CONCLUSIONS: Needle Dao can effectively improve the overall treatment efficiency of patients with carpal tunnel syndrome and reduce the symptoms of patients, which is feasible and suitable to use in clinical.

Atrial Natriuretic Peptide: A Potential Early Therapy for the Prevention of Multiple Organ Dysfunction Syndrome Following Severe Trauma.

Trauma remains a tremendous medical burden partly because of increased expenditure for the management of multiple organ dysfunction syndrome (MODS) developed during hospital stay. The intestinal barrier injury continues to be a second insult resulting in MODS which currently lacks efficient strategies for prevention. Recent studies have uncovered multi-organ protective benefits of atrial natriuretic peptide (ANP) in cardiovascular disease. However, the role of ANP in the prevention of MODS following severe trauma has not been understood. In our laboratory study, 1-h infusion of exogenous ANP during hemorrhagic shock following severe trauma induced high-level expression of endogenous serum ANP after 24 h, this effect was related to the improved level of functional biomarkers in multiple organs. Such phenomenon has not been found in other laboratories. A thorough literature review consequently was performed to uncover the potential mechanisms, to appraise therapy safety, and to propose uncertainties. In severe trauma, short-term exogenous ANP therapy during hemorrhagic shock may promote sustained endogenous expression of ANP from intestinal epithelium through activating a positive feedback loop mechanism involving phospholipase C-γ1 and reactive oxygen species crosstalk. This feedback loop may prevent MODS through multiple signaling pathways. Administration of ANP during hemorrhagic shock is thought to be safe. Further studies are required to confirm our proposed mechanisms and to investigate the dose, duration, and timing of ANP therapy in severe trauma.

Malaria focus investigation and disposal in Tengchong City between 2015 and 2016 / 中国血吸虫病防治杂志

Objective To analyze the results of malaria focus investigation and disposal in Tengchong City,Yunnan Prov-ince between 2015 and 2016,so as to provide evidences for interrupting potential malaria transmission. Methods The malaria foci were investigated and disposed according to the malaria cases reported from"China Information System for Disease Control and Prevention"in Tengchong City between 2015 and 2016. The mosquitoes were captured by mosquito-lured lamp overnight to investigate the malaria vector in local. The peripheral blood samples were collected from the local residents with a febrile history in the foci within two weeks and the accompanists of the cases,and then the rapid malaria diagnosis tests were used to screen the malaria carriers. Results Totally 145 imported malaria cases were reported in Tengchong City between 2015 and 2016,and the focus investigation and disposal rate within 7 d was 100%(145/145). A total of 16186 mosquitoes of 12 species of Anopheles were captured,among which An. sinensis was the predominant,accounting for 64.31%(10410/16186),followed by An. kun-mingensis and An. minimus,with the constituent ratios of 14.15%(2291/16186)and 11.66%(1887/16186),respectively. One person(1.96%,1/51)in the 51 accompanists of the cases was positive in the malaria rapid diagnosis test. Conclusions The malaria transmission vectors such as An. sinensis,An. kunmingensis,An. minimus etc. are still distributed in Tengchong City,and An. sinensis is the predominant species. Therefore,the relevant authorities should continue to strengthen the focus in-vestigation and disposal to interrupt the potential introduced malaria transmission by imported cases in the future.

Early goal-directed resuscitation for patients with severe sepsis and septic shock: a meta-analysis and trial sequential analysis.

BACKGROUND: The aim of this study was to explore whether early goal-directed therapy (EGDT) was associated with a lower mortality rate in comparison to usual care in patients with severe sepsis and septic shock. METHODS: PubMed, EMBASE, Cochrane library and a Chinese database (SinoMed) were searched systematically to identify randomized controlled trials (RCTs) comparing standard EGDT with usual care in resuscitation of patients with severe sepsis and septic shock and the search time could date back to the publication of the study by Rivers in 2001. The study selection, data extraction and methodological evaluation were performed by two investigators independently. The primary outcome was all-cause mortality. The present meta-analysis had been registered in PROSPERO (CRD42015017667). RESULTS: Our meta-analysis identified 6 studies and enrolling 4336 patients. There was no significant difference in mortality between the two groups, and the pooled odds ratio (OR) was 0.83 (95 % confident interval, CI, 0.64-1.08) with significant heterogeneity (p = 0.02, I(2) = 64%). However, the pooled OR of 3 multicenter RCTs was 1.03 (95% CI, 0.89-1.21) with no heterogeneity (p = 0.78, I(2) = 0%). The effects of EGDT on length of stay in the emergency department and intensive care unit were uncertain, and there was no effect of EGDT on hospital length of stay. There were no differences of mechanical ventilation rate and renal replacement therapy rate between the two groups, and patients in the EGDT group were more admitted in ICU than patients in the control group. During the early 6-h intervention period, patients in the EGDT group received more intravenous fluids, had a higher vasopressor usage rate, higher dobutamine usage rate and higher blood transfusion rate, than patients in the control group. Finally, there was no difference in the incidence of adverse events between the two groups, and the pooled OR was 1.06 (95%CI 0.80-1.39) with moderate heterogeneity (I(2) = 62%, p = 0.07). DISCUSSION: Our meta-analysis showed that the application of EGDT was not associated with lower mortality rate currently. However it does not mean that it is useless of EGDT in patients with sever sepsis and septic shock. On the contrary, there was no difference in mortality rate between the two groups may be due to the improvement of therapeutic strategies in these patients. And the results may be related to the different compliance rate of EGDT resuscitation bundle. CONCLUSIONS: The current evidence does not support the significant advantage of Early goal-directed therapy (EGDT) in the resuscitation of patients with severe sepsis and septic shock.

Ideal target arterial pressure after control of bleeding in a rabbit model of severe traumatic hemorrhagic shock: results from volume loading-based fluid resuscitation.

BACKGROUND: Previously reported ideal target mean arterial pressure (MAP) after control of bleeding in traumatic hemorrhagic shock (THS) requires further verification in more clinically related models. The authors explored this issue via gradient volume loading without vasopressor therapy. As certain volume loading can induce secretion of atrial natriuretic peptide (ANP), which has been shown to be protective, the authors also observed its potential role. MATERIALS AND METHODS: Fifty male New Zealand rabbits were submitted to 1.5 h of uncontrolled THS (with another eight rabbits assigned to the sham group). After bleeding control, treated rabbits were randomly (n = 10, respectively) resuscitated with blood and Ringer lactate (1:2) to achieve target MAP of 50, 60, 70, 80, and 90 mm Hg within 1 h. During the following 2 h, they were resuscitated toward baseline MAP. Rabbits were observed until 7 h. RESULTS: After resuscitation, infused fluid was lower and oxidative stress injury was milder in the 70 mm Hg group. Fluid volume loaded during the initial hour after hemostasis was negatively correlated with pH, oxygen saturation, and base excess at the end of resuscitation. It also correlated positively with proinflammatory responses in bronchoalveolar lavage fluid at 7 h and 7-h mortality. Moreover, after volume loading, the 80 mm Hg group showed significantly increased serum ANP level, which correlated with the expression of Akt protein in the jejunum at 7 h. CONCLUSIONS: In rabbits the ideal target MAP during the initial resuscitation of severe THS after hemostasis was 70 mm Hg. ANP may have a critical role in gut protection.

Full-length cDNA cloning, molecular characterization and differential expression analysis of peroxiredoxin 6 from Ovis aries.

Peroxiredoxin 6 (Prdx6), an important antioxidant enzyme that can eliminate reactive oxygen species (ROS) to maintain homeostasis, is a bifunctional protein that possesses the activities of both glutathione peroxidase and phospholipase A2. In this study, a novel full-length Prdx6 cDNA (OaPrdx6) was cloned from Sheep (Ovis aries) using rapid amplification of cDNA ends (RACE). The full-length cDNA of OaPrdx6 was 1753bp containing a 5'-untranslated region (UTR) of 93bp, a 3'-UTR of 985bp with a poly(A) tail, and an open reading frame (ORF) of 675bp encoding a protein of 224 amino acid residues with a predicted molecular weight of 25.07kDa. The recombinant protein OaPrdx6 was expressed and purified, and its DNA protection activity was identified. In order to analyze the Prdx6 protein expression in tissues from O. aries, monoclonal antibodies against OaPrdx6 were prepared. Western blotting results indicated that OaPrdx6 protein could be detected in heart, liver, spleen, lung, kidney, stomach, intestine, muscle, lymph node and white blood cells, and the highest expression was found in lung while the lowest expression in muscle. Compared to the normal sheep group, the mRNA transcription level of Prdx6 in buffy coat was up-regulated in the group infected with a virulent field strain of Brucella melitensis, and down-regulated in the group inoculated with a vaccine strain S2 of brucellosis. The results indicated that Prdx6 was likely to be involved in the host immune responses against Brucella infection, and probably regarded as a molecular biomarker for distinguishing between animals infected with virulent Brucella infection and those inoculated with vaccine against brucellosis.