Mortality and cardiac arrest rates of emergency surgery in developed and developing countries: a systematic review and meta-analysis.

BACKGROUND: The magnitude of the risk of death and cardiac arrest associated with emergency surgery and anesthesia is not well understood. Our aim was to assess whether the risk of perioperative and anesthesia-related death and cardiac arrest has decreased over the years, and whether the rates of decrease are consistent between developed and developing countries. METHODS: A systematic review was performed using electronic databases to identify studies in which patients underwent emergency surgery with rates of perioperative mortality, 30-day postoperative mortality, or perioperative cardiac arrest. Meta-regression and proportional meta-analysis with 95% confidence intervals (CIs) were performed to evaluate global data on the above three indicators over time and according to country Human Development Index (HDI), and to compare these results according to country HDI status (low vs. high HDI) and time period (pre-2000s vs. post-2000s). RESULTS: 35 studies met the inclusion criteria, representing more than 3.09 million anesthetic administrations to patients undergoing anesthesia for emergency surgery. Meta-regression showed a significant association between the risk of perioperative mortality and time (slope: -0.0421, 95%CI: from - 0.0685 to -0.0157; P = 0.0018). Perioperative mortality decreased over time from 227 per 10,000 (95% CI 134-380) before the 2000s to 46 (16-132) in the 2000-2020 s (p < 0-0001), but not with increasing HDI. 30-day postoperative mortality did not change significantly (346 [95% CI: 303-395] before the 2000s to 292 [95% CI: 201-423] in the 2000s-2020 period, P = 0.36) and did not decrease with increasing HDI status. Perioperative cardiac arrest rates decreased over time, from 113 per 10,000 (95% CI: 31-409) before the 2000s to 31 (14-70) in the 2000-2020 s, and also with increasing HDI (68 [95% CI: 29-160] in the low-HDI group to 21 [95% CI: 6-76] in the high-HDI group, P = 0.012). CONCLUSIONS: Despite increasing baseline patient risk, perioperative mortality has decreased significantly over the past decades, but 30-day postoperative mortality has not. A global priority should be to increase long-term survival in both developed and developing countries and to reduce overall perioperative cardiac arrest through evidence-based best practice in developing countries.

Preparation, Characterization and Molecular Dynamics Simulation of Rutin-Cyclodextrin Inclusion Complexes.

Rutin is a natural flavonoid that carries out a variety of biological activities, but its application in medicine and food is limited by its water solubility. One of the classical methods used to enhance drug solubility is encapsulation with cyclodextrins. In this paper, the encapsulation of different cyclodextrins with rutin was investigated using a combination of experimental and simulation methods. Three inclusions of rutin/beta-cyclodextrin (ß-CD), rutin/2-hydroxypropyl beta-cyclodextrin (HP-ß-CD) and rutin/2,6-dimethyl beta-cyclodextrin (DM-ß-CD) were prepared by the freeze-drying method, and the inclusions were analyzed using Fourier infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and ultraviolet-visible spectroscopy (UV) to characterize and demonstrate the formation of the inclusion complexes. Phase solubility studies showed that rutin formed a 1:1 stoichiometric inclusion complex and significantly increased its solubility. ß-CD, HP-ß-CD, DM-ß-CD, rutin and the three inclusion complexes were modeled by using MS2018 and AutoDock 4.0, and molecular dynamics simulations were performed to calculate the solubility parameters, binding energies, mean square displacement (MSD), hydrogen bonding and radial distribution functions (RDF) after the equilibration of the systems. The results of simulation and experiment showed that rutin/DM-ß-CD had the best encapsulation effect among the three cyclodextrin inclusion complexes.

A Hypoxia-Sensitive Drug Delivery System Constructed by Nitroimidazole and its Application in the Treatment of Hepatocellular Carcinoma.

Hypoxia is an important pathological phenomenon, and it can induce many tumor microenvironment changes, such as accumulations of intracellular lactic acid, decrease of tumor microenvironment pH value, and regulate a series of physiological and pathological processes such as adhesion, metastasis, and immune escape. Hypoxic tumor cells act as a key target for treating tumor. In this research, we designed and prepared PEG-nitroimidazole grafts, PEG-NI, and FA-PEG-NI. We first explored their physical and chemical properties to serve as a drug carrier. Then, the hypoxia-sensitive properties such as particle size changes and drug release were investigated. Finally, the tumor targeting ability was studied in vitro and in vivo, and anti-tumor capacity was determined. Both grafts showed excellent property as a nanodrug carrier and showed favorable drug encapsulation ability of sorafenib with the help of the hydrophobic chain of 6-(BOC-amino) hexyl bromide. The micelles responded to the hypoxic tumor environment with chemical and spatial structure changes leading to sensitive and fast drug release. With the modification of folic acid, FA-PEG-NI gained tumor targeting ability in vivo. FA-PEG-NI graft proved a potential targeting drug delivery system in the treatment of hypoxic hepatocellular carcinoma.

H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through miR-3163/YAP1 axis.

Long noncoding RNAs (lncRNAs) are found to be aberrantly expressed and pose significant impacts in colorectal cancer (CRC), the most prevalent type malignancy in the gastrointestinal tract. This study aimed to find out the regulation of lncRNA EIF3J antisense RNA 1 (EIF3J-AS1) on CRC progression. Expressions of EIF3J-AS1, microRNA-3163 (miR-3163), and Yes-associated protein 1 (YAP1) in tissues and cells were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Association of EIF3J-AS1 with CRC prognosis was analyzed through the online bioinformatics tool GEPIA. The biological function of EIF3J-AS1 in CRC was investigated by Cell Counting Kit-8, colony formation, caspase-3 activity, and TUNEL staining. Competitive endogenous RNA (ceRNA) network of EIF3J-AS1/miR-3163/YAP1 was determined by luciferase reporter and RNA immunoprecipitation assays. Results showed that EIF3J-AS1 was upregulated in CRC tissues and cell lines, indicating poor prognosis of CRC patients. The silence of EIF3J-AS1 led to reduced proliferation and facilitated apoptosis of CRC cells. Mechanistcally, EIF3J-AS1 was upregulated by cAMP-response element-binding protein-binding protein-mediated histone H3 on lysine 27 acetylation (H3K27ac) at the promoter region, and EIF3J-AS1 upregulated YAP1 expression through sponging miR-3163 in CRC cells. In conclusion, we first found that H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through the miR-3163/YAP1 axis, which might potentially provide a novel molecular-targeted strategy for CRC treatment.

[Risk Factors for Acute Renal Failure after Thoracoabdominal Aortic Aneurysm Surgery].

Objective To investigate the risk factors associated with acute renal failure (ARF) after thoracoabdominal aortic aneurysm (TAAA) surgery. Methods A total of 156 patients underwent TAAA repair between January 2009 and December 2017. Renal failure was defined based on the Kidney Disease Improving Global Outcomes criteria. The patients were divided into ARF group and non-ARF group based on the presence/absence of postoperative ARF. The risk factors of ARF were analyzed by univariate analysis and multivariate logistic analysis. Results The subjects included 111 males and 45 females aged (40.4±10.9) years (range:19-65 years). The surgical reasons included aortic dissection (n=130,83.3%),aneurysm (n=22,14.1%),and pseudoaneurysm (n=4,2.6%). The degrees of repair included Crawford extent I in 6 patients (3.8%),extent Ⅱ in 128 patients (82.1%),extent Ⅲ in 20 patients (12.8%),and extent Ⅳ in 2 patients(1.3%). There were 3 patients presented with aortic rupture and 6 patients received emergent operations. Nine patients (5.8%) died within 30 days after surgery,and 8 patients (5.1%) suffered from permanent paraplegia. Thirty-six patients (23.1%) had ARF after surgery,and 18 of them needed dialysis. Multivariate logistic analysis showed that smoking (OR =2.637,95%CI=1.113-6.250,P=0.028),packed red blood cell usage in operation (≥6 U) (OR =5.508,95%CI=2.144-11.930,P=0.000),reoperation for bleeding (OR=3.529,95%CI=1.298-9.590,P=0.013) were independent risk factors for ARF after TAAA repair. Conclusion Smoking,packed red blood cell usage in operation (≥6 U),reoperation for bleeding are the independent risk factors of ARF after TAAA surgery.

[Outcomes after Surgical Repair of Thoracoabdominal Aortic Aneurysm with Distal Aortic Dissection:DeBakey Type â versus Type â ¢].

Objective To evaluate the early and mid-term results after surgical repair of thoracoabdominal aortic aneurysm(TAAA)in patients with DeBakey typeⅠor Ⅲ aortic dissection. Methods The clinical data of 130 patients who underwent TAAA repair for chronic DeBakey typeⅠ(groupⅠ, n=47)or type Ⅲ(group Ⅲ, n=83)aortic dissections in our center between January 2009 and December 2017 were retrospectively analyzed.Early postoperative results,midterm survival,and re-interventions were compared between these two groups. Results The 30-day mortality rate was 6.9%(n=9)in the overall cohort,with no statistic difference between groupⅠand group Ⅲ(10.6% vs. 4.8%;χ2=0.803, P=0.370).The incidence of major adverse events(38.3% vs. 51.8%;χ2=2.199, P=0.138),5-year actuarial survival rate [(81.7±5.9)% vs.(87.2±4.2)%;χ2=0.483, P=0.487],and 5-year actuarial freedom from all reinterventions [(84.5±6.7)% vs.(85.5±4.8)%;χ2=0.010, P=0.920] showed no significant differences between these two groups. Conclusions The early and mid-term outcomes after surgical repair of TAAA are similar for DeBakey typeⅠ and type Ⅲ patients.However,studies with larger sample sizes are still required.

Single Stage Hybrid Repair for DeBakey Type I Aortic Dissection in High Risk Patients.

OBJECTIVES: To evaluate the efficacy of the less invasive hybrid zone 0 (Z0) total aortic arch repair (HAR, ascending repair + complete debranching + thoracic endovascular aortic repair [TEVAR]) without deep hypothermic circulatory arrest in management of DeBakey type I aortic dissection (IAD). The adverse outcome was defined as a single composite endpoint comprising peri-operative mortality, permanent neurological deficit, and renal failure necessitating haemodialysis at discharge. METHODS: A retrospective review of prospectively collected data was conducted of 120 consecutive patients (mean EuroSCORE = 11.6%) with IAD undergoing HAR (urgent/emergency, n = 97, 80.8%) involving reconstruction of the ascending aorta (zone 0) and total arch exclusion with TEVAR during a 7.5 year period. Multivariable analysis of 27 potential pre-operative and intra-operative risk factors was performed to examine the early composite endpoint and short and long-term overall mortality. RESULTS: The total early (30 day or in hospital) mortality was 9.2% (n = 11). The incidence of the composite endpoint was 11.7% (n = 14). On multivariable analysis, malperfusion syndromes were predictors of the composite endpoint (odds ratio [OR], 4.789; 95% CI 1.362-16.896; p = .015), and previous cerebrovascular accident (OR, 13.74; 95% CI 2.330-81.039; p = .004) and myocardial ischaemia time (OR, 1.038; 95% CI 1.015-1.061; p = .001) predicted short and long-term overall mortality. The overall survival was 84.7% during a median follow up of 3.4 years. Freedom from late aortic adverse events was 93.1% at 5 years, including secondary aortic intervention and endoleak. The maximum diameters of the true lumen increased significantly in stented thoracic (14.4 ± 6.5 mm to 29.7 ± 5.3 mm, p < .001), lower thoracic (14.2 ± 6 mm to 21.6 ± 7.2 mm, p < .001) and abdominal (11.7 ± 4.8 mm to 17.4 ± 4.1 mm, p < .001) aorta. Complete thrombosis of the peri-stent false lumen was achieved in 88.2% of CT scans (82/93) performed a mean of 12 ± 17 months (median 5 months; 25-75% quartile, 2-12 months) post-operatively. CONCLUSIONS: IAD was treated safely and durably by Z0 HAR, and peri-operative mortality and morbidity were not substantially higher despite the older age and high risk of patients.

Effect of the Serum Inhibited Gene (Si1) on Autophagy and Apoptosis in MCF-7 Breast Cancer Cells.

BACKGROUND/AIMS: The serum inhibited gene (Si1) was named according to its inhibited expression in response to serum exposure. Si1 has an important relationship with tumors. Autophagy and apoptosis are two types of cell death. However, there are few studies regarding the association between Si1 and autophagy, or apoptosis in tumors. In this, we investigated the effect of Si1 on the proliferation and cell cycle progression of MCF-7 cells and its influence on autophagy and apoptosis in MCF-7 cells. METHODS: To investigate these functions of Si1 in tumor cells, we firstly constructed a pEGFP-Si1 overexpression vector and a pSilencer-Si1 interference vector, and we subsequently tested the proliferation and cell cycle progression of MCF-7 cells using the MTT assay and flow cytometry, and we then detected autophagy by western blotting and MDC (Monodansylcadaverine) staining as well as apoptosis by western blotting and Hoechst 33258 staining. RESULTS: We found that the Si1 gene can significantly inhibit the viability of MCF-7 cells and arrest the cell cycle at the G2/M phase. Si1 can induce autophagy through upregulation of LC3-II and Beclin1, it can induce apoptosis through cleavage of PARP in MCF-7 cells. CONCLUSION: Altogether, our study indicated that Si1 can inhibit cell proliferation of MCF-7, and also induces autophagy and apoptosis. This study firstly investigated the effect of Si1 on autophagy and apoptosis in MCF-7 cells. Moreover, it also improves the current understanding of the mechanisms related to the effect of Si1 on tumor cells and also provides a foundation for gene-targeted therapy.

Study on the dust migration law and a spray dust suppression scheme in transportation roadway.

To solve the problem of excessive dust concentration in the belt transportation roadway of the mine. Numerical simulations were used to study the dust migration in the belt transportation roadway under 1.5 m/s ventilation conditions. The simulation results show the process of dust ejection from the inflow chute to contamination of the whole belt transportation roadway, and the spatial distribution of dust velocity. A comprehensive dust reduction scheme of "central suppression and bilateral splitting" was designed according to the dust distribution, with simultaneous control of the infeed chute and the roadway. In practical application, pneumatic spraying greatly reduces the amount of dust in the guide chute. The misting screen has a significant effect on dust collection and segregation. The solution effectively controls the dust in the space of 20 m on both sides of the transfer point, and the dust removal efficiency reaches more than 90%.

Numerical simulation of the fine kinetics of dust reduction using high-speed aerosols.

A numerical model of single-particle fog-dust collision coupling in a high-speed airflow based on three-phase flow theory. The effect of the fog-to-dust particle size ratio, relative velocity between the fog and dust particles, collision angle and contact angle at the wetting humidity function of dust particles is investigated. Different particle size ratios are determined for achieving the optimal wetting humidity for the interaction of high-velocity aerosols with dust particles of different sizes, for differ, that is, kPM2.5 = 2:1, kPM10 = 3.5:1 and kPM20 = 1.5:1. The optimal humidity increases with the relative velocity U between the fog and dust particles in the high-speed airflow. The larger the collision angle is, the lower the wetting rate is.The smaller the contact angle between the solid and liquid is, the better droplet wetting on dust is. The fine kinetic mechanism of single-particle fog-dust collision-coupling in a high-speed airflow is elucidated in this study.

Production, purification and characterization of mouse monoclonal antibodies against human mitochondrial transcription termination factor 2 (MTERF2).

Human mitochondrial transcription termination factor 2 (MTERF2) is a member of the mitochondrial transcription termination factors (MTERFs) family and a cell growth inhibitor. To create a specific mouse monoclonal antibody against human MTERF2, the full-length His-tag MTERF2 protein (1-385 aa) was expressed in Escherichia coli, and purified recombinant protein was injected into three BALB/c mice to perform an immunization procedure. Eight stable positive monoclonal cell lines were screened and established. ELISA results demonstrated that all antibody light chains were kappa, while the heavy chains displayed three subtypes IgG1, IgG2a, and IgG2b respectively. The sensitivity and specificity of the monoclonal antibodies against human MTERF2 were determined using immunoblotting, immunoprecipitation and immunofluorescence analyses. Furthermore, serum regulation of human MTERF2 protein expression levels in human glioma U251 cells was examined with these monoclonal antibodies and the results demonstrated that the expression level of MTERF2 protein was dramatically inhibited by the addition of serum to serum-starved cells. Taken together, our results demonstrate the functionality of these mouse anti-human MTERF2 monoclonal antibodies, which may provide a useful tool to elucidate the role of MTERF2 in human mitochondrial transcription as well as other potential activities. To our knowledge, this is the first report on the preparation and characterization of mouse monoclonal antibodies against human MTERF2.

Regulation of the cell cycle via mitochondrial gene expression and energy metabolism in HeLa cells.

Human cervical cancer HeLa cells have functional mitochondria. Recent studies have suggested that mitochondrial metabolism plays an essential role in tumor cell proliferation. Nevertheless, how cells coordinate mitochondrial dynamics and cell cycle progression remains to be clarified. To investigate the relationship between mitochondrial function and cell cycle regulation, the mitochondrial gene expression profile and cellular ATP levels were determined by cell cycle progress analysis in the present study. HeLa cells were synchronized in the G0/G1 phase by serum starvation, and re-entered cell cycle by restoring serum culture, time course experiment was performed to analyze the expression of mitochondrial transcription regulators and mitochondrial genes, mitochondrial membrane potential (MMP), cellular ATP levels, and cell cycle progression. The results showed that when arrested G0/G1 cells were stimulated in serum-containing medium, the amount of DNA and the expression levels of both mRNA and proteins in mitochondria started to increase at 2 h time point, whereas the MMP and ATP level elevated at 4 h. Furthermore, the cyclin D1 expression began to increase at 4 h after serum triggered cell cycle. ATP synthesis inhibitor-oligomycin-treatment suppressed the cyclin D1 and cyclin B1 expression levels and blocked cell cycle progression. Taken together, our results suggested that increased mitochondrial gene expression levels, oxidative phosphorylation activation, and cellular ATP content increase are important events for triggering cell cycle. Finally, we demonstrated that mitochondrial gene expression levels and cellular ATP content are tightly regulated and might play a central role in regulating cell proliferation.

Oxytocin in Women's Health and Disease.

Oxytocin (OT) is a nonapeptide mainly produced in the supraoptic and paraventricular nuclei. OT in the brain and blood has extensive functions in both mental and physical activities. These functions are mediated by OT receptors (OTRs) that are distributed in a broad spectrum of tissues with dramatic sexual dimorphism. In both sexes, OT generally facilitates social cognition and behaviors, facilitates parental behavior and sexual activity and inhibits feeding and pain perception. However, there are significant differences in OT levels and distribution of OTRs in men from women. Thus, many OT functions in men are different from women, particularly in the reproduction. In men, the reproductive functions are relatively simple. In women, the reproductive functions involve menstrual cycle, pregnancy, parturition, lactation, and menopause. These functions make OT regulation of women's health and disease a unique topic of physiological and pathological studies. In menstruation, pre-ovulatory increase in OT secretion in the hypothalamus and the ovary can promote the secretion of gonadotropin-releasing hormone and facilitate ovulation. During pregnancy, increased OT synthesis and preterm release endow OT system the ability to promote maternal behavior and lactation. In parturition, cervix expansion-elicited pulse OT secretion and uterine OT release accelerate the expelling of fetus and reduce postpartum hemorrhage. During lactation, intermittent pulsatile OT secretion is necessary for the milk-ejection reflex and maternal behavior. Disorders in OT secretion can account for maternal depression and hypogalactia. In menopause, the reduction of OT secretion accounts for many menopausal symptoms and diseases. These issues are reviewed in this work.

Study on coal dust diffusion law and new pneumatic spiral spray dedusting technology at transfer point of mine cross roadway.

In order to solve the problem of coal dust pollution at the transfer point, a three-dimensional numerical model of wind flow-coal dust at the loading point of underground rubber run was established by computational fluid dynamics (CFD) discrete particle model and finite element method and k-ε turbulence model, and the coal dust diffusion pollution phenomenon caused by the coal flow transfer under the intersection of wind flow in the cross tunnel was studied. Based on the simulation results of wind flow velocity contour, pressure contour and isochronous flow vector distribution, the influence mechanism of wind flow and coal dust characteristics on the distribution of wind flow and coal dust diffusion in the roadway is analysed, and a dust control and reduction system and treatment scheme with new pneumatic screw spray technology as the core is proposed to suppress coal dust pollution at the reloading point. The results of the study show that the wind flow distribution is mainly influenced by the intersection of tape traction and cross-roadway wind flow, showing a complex multi-layer distribution along the roadway and in the normal direction; the diffusion of coal dust of different particle sizes is influenced by the roadway wind flow, and coal dust with particle sizes in the range of 10µm~20µm is more easily diffused, and the dust with particle sizes in the range of 20µm~45µm is mainly collected and suspended near the vortex wind flow at the cross-roadway. The coal dust in the range of 20 µm~45 µm is more likely to gather in the vortex; the treatment system effectively controls the coal dust inside the dust cover, and the spiral-shaped transported droplet particle group formed by the pneumatic spiral spray combines with it efficiently, which verifies the dust control and reduction effect of the pneumatic spiral spray system at the transfer point, and the dust removal efficiency reaches 89.35%~93.06%, which provides relevant theoretical support for the treatment of dust pollution at the coal transfer point in underground coal mines It provides the theoretical support and means to control dust pollution at underground coal transfer points.

Structural Model Construction and Optimal Characterization of High-Volatile Bituminous Coal Molecules.

The structural characteristics of coal at the molecular level are important for its efficient use. Bituminous coal from the Baozigou Coal Mine is investigated, using elemental analysis, 13C nuclear magnetic resonance, X-ray photoelectron spectroscopy, and Fourier transform infrared. The molecular structure was determined. The aromatic compounds of bituminous coal molecules are primarily two- and three-ring structures, and the aliphatic structures are primarily in the form of methyl, ethyl side chains, and naphthenic hydrocarbons. The ratio of aromatic bridge carbon to peripheral carbon in the molecular structure is 0.279. Oxygen atoms in the form of carbonyl, phenolic hydroxyl and C-O, and nitrogen atoms in pyrroles. Thus, the average structure model of bituminous coal macromolecules was constructed; the molecular formula was C169H128O10N2S, and the molecular weight was 2378. The aromatic structural units in the macromolecular structure of coal include four naphthalenes, three anthracenes, two tetracenes, and heteroatoms in the form of three carbonyl groups, one phenolic hydroxyl group, one pyrrole, and one pyridine. The structure optimization and annealing kinetic simulation of a single macromolecular structure model were performed. Chemical bonds such as bridge bonds and aliphatic bonds were found to be twisted, and π-π interactions between the aromatic sheets in the molecule produced adjacent aromatic sheets. This arrangement tends to be approximately parallel, and the total energy decreases from 6713.401 to 2667.595 kJ/mol, among which the bond stretching energy and van der Waals energy dominate. We used 20 bituminous coal macromolecular models to construct aggregated structural models. After optimization by molecular dynamics simulation, the macromolecules were constrained by the surrounding molecules, and the sheet-like aromatic carbon structures that were originally approximately parallel were distorted. The macromolecular structure model of bituminous coal constructed in this study provides a theoretical model basis for the optimal surfactant.

Study on dust migration law and spray dedusting technology in parallel double belt transportation.

To effectively solve the problem of dust pollution caused by the parallel double-belt transportation of coal in a coal preparation plant, taking the Huangyuchuan coal preparation plant as an example, a numerical model of the air flow-dust distribution was established by means of simulation. The flow lines between the strips of tape and the tail of the tape machine will gather, and there will be backflow on the right side of the 3001 tape and left side of the 3002 tape. Under the action of wind current, most of the dust particles larger than 10 µm are distributed in the range of 0-5 m on both sides of the tape; dust particles smaller than 10 µm spread to the entire preparation workshop. Combined with field test verification, dust pollution is mainly concentrated at the guide trough, the feed inlet, the rear of the machine, and the joint of the belt corridor. Based on this, a targeted spray dust reduction treatment plan is proposed. By measuring the dust concentration before and after the treatment of dust-polluted areas, it is proven that the dust reduction efficiency of this plan can reach more than 90%.

The role of NGF and IL-2 serum level in assisting the diagnosis in first episode schizophrenia.

Development of reliable diagnostic bio-markers for schizophrenia remains a diagnostic challenge. Serum NGF and IL-2 were analyzed to examine the diagnostic efficiency and predictive capability of these two biomarkers in relation to schizophrenia diagnosis. Thirty neuroleptic naïve subjects with first-episode schizophrenia, thirty patients with major depressive disorder (MDD) and twenty-eight healthy control subjects participated in the study. One-way ANOVA demonstrated significantly lower serum IL-2 and NGF among schizophrenic patients and patients with MDD compared with healthy controls. Receiver operating characteristic (ROC) curve analysis was used to ascertain diagnostic efficiency of serum IL-2 and NGF levels. Area under the ROC curve (AUC) revealed a high level of differentiation between schizophrenic patients and healthy controls for both IL-2 and NGF serum concentrations. Diagnostic efficiency of combined NGF and IL-2 serum levels was also high in schizophrenic patients compared with healthy controls. Serum NGF and IL-2 are promising as potential screening or diagnostic biomarkers for schizophrenia and may be a useful adjunct for clinical assessment.

Mitochondrial transcription termination factor 2 binds to entire mitochondrial DNA and negatively regulates mitochondrial gene expression.

Mitochondrial transcription termination factor 2 (mTERF2) is a mitochondrial matrix protein that binds to the mitochondrial DNA. Previous studies have shown that overexpression of mTERF2 can inhibit cell proliferation, but the mechanism has not been well defined so far. This study aimed to present the binding pattern of mTERF2 to the mitochondrial DNA (mtDNA) in vivo, and investigated the biological function of mTERF2 on the replication of mtDNA, mRNA transcription, and protein translation. The mTERF2 binding to entire mtDNA was identified via the chromatin immunoprecipitation analysis. The mtDNA replication efficiency and expression levels of mitochondria genes were significantly inhibited when the mTERF2 was overexpressed in HeLa cells. The inhibition level of mtDNA content was the same with the decreased levels of mRNA and mitochondrial protein expression. Overall, the mTERF2 might be a cell growth inhibitor based on its negative effect on mtDNA replication, which eventually down-regulated all of the oxidative phosphorylation components in the mitochondria that were essential for the cell's energy metabolism.

Strategic enhancement of immune checkpoint inhibition in refractory Colorectal Cancer: Trends and future prospective.

Colorectal cancer (CRC), known as a frequently fatal disease, ranking as the third most common malignancy, is the second leading cause of cancer related mortality worldwide. Metastases are common in CRC patients which account for approximately 25% of the patients at diagnosis, 50% of patients during treatment which is associated closely with CRC mortality. Conventional therapies such as surgery, chemotherapy, and radiotherapy are standards of care for the treatment of CRC patients. However, primary tumor recurrence and secondary disease in patients receiving standard of care treatment modalities occur in 50% of patients so that new treatment modalities are needed. Immune checkpoint inhibition (ICI) has transformed the management of patients suffered from metastatic CRC (mCRC) with mismatch repair deficiency (dMMR) and microsatellite instability (MSI) -high (MSI-H) while manifests ineffectiveness in preserved mismatch repair (pMMR) or microsatellite stable (MSS) "cold" tumors which makes up the majority (95%) of mCRC. In this review, we mainly lay emphasis on the development of combinations in therapy strategies with ICIs with other immune based treatment approaches to increase the intra-tumoral immune response and render tumors 'immune-reactive', thereby increasing the efficacy of tumor immunotherapy.

Reconstruction and seepage simulation of a coal pore-fracture network based on CT technology.

The distribution of multiscale pores and fractures in coal and rock is an important basis for reflecting the capacity of fluid flow in coal seam seepage passages. Accurate extraction and qualitative and quantitative analysis of pore-fracture structures are helpful in revealing the flow characteristics of fluid in seepage channels. The relationship between pore and fracture connectivity can provide a scientific reference for optimizing coal seam water injection parameters. Therefore, to analyse the change in permeability caused by the variability in the coal pore-fracture network structure, a CT scanning technique was used to scan coal samples from the Leijia District, Fuxin. A total of 720 sets of original images were collected, a median filter was used to filter out the noise in the obtained images, and to form the basis of a model, the reconstruction and analysis of the three-dimensional pore-fracture morphology of coal samples were carried out. A pore-fracture network model of the coal body was extracted at different scales. Using the maximum sphere algorithm combined with the coordination number, the effect of different quantitative relationships between pore size and pore throat channel permeability was studied. Avizo software was used to simulate the flow path of fluid in the seepage channels. The change trend of the fluid velocity between different seepage channels was discussed. The results of the pore-fracture network models at different scales show that the pore-fracture structure is nonuniform and vertically connected, and the pores are connected at connecting points. The pore size distribution ranges from 104 µm to 9425 µm. The pore throat channel length distribution ranges from 4206 µm to 48073 µm. The size of the coordination number determines the connectivity and thus the porosity of the coal seam. The more connected pore channels there are, the larger the pore diameters and the stronger the percolation ability. During flow in the seepage channels of the coal, the velocity range is divided into a low-speed region, medium-speed region and high-speed region. The fluid seepage in the coal seam is driven by the following factors: pore connectivity > pore and pore throat dimensions > pore and pore throat structure distribution. Ultimately, the pore radius and pore connectivity directly affect the permeability of the coal seam.