Quantitative prediction of postpartum hemorrhage in cesarean section on machine learning.

BACKGROUND: Cesarean section-induced postpartum hemorrhage (PPH) potentially causes anemia and hypovolemic shock in pregnant women. Hence, it is helpful for obstetricians and anesthesiologists to prepare pre-emptive prevention when predicting PPH occurrence in advance. However, current works on PPH prediction focus on whether PPH occurs rather than assessing PPH amount. To this end, this work studies quantitative PPH prediction with machine learning (ML). METHODS: The study cohort in this paper was selected from individuals with PPH who were hospitalized at Shijiazhuang Obstetrics and Gynecology Hospital from 2020 to 2022. In this study cohort, we built a dataset with 6,144 subjects covering clinical parameters, anesthesia operation records, laboratory examination results, and other information in the electronic medical record system. Based on our built dataset, we exploit six different ML models, including logistic regression, linear regression, gradient boosting, XGBoost, multilayer perceptron, and random forest, to automatically predict the amount of bleeding during cesarean section. Eighty percent of the dataset was used as model training, and 20 % was used for verification. Those ML models are constantly verified and improved by root mean squared error(RMSE) and mean absolute error(MAE). Moreover, we also leverage the importance of permutation and partial dependence plot (PDP) to discuss their feasibility. RESULT: The experiment results show that random forest obtains the highest accuracy for PPH amount prediction compared to other ML methods. Random forest reaches the mean absolute error of 21.7, less than 5.4 % prediction error. It also gains the root mean squared error of 33.75, less than 9.3 % prediction error. On the other hand, the experimental results also disclose indicators that contributed most to PPH prediction, including Ca, hemoglobin, white blood cells, platelets, Na, and K. CONCLUSION: It effectively predicts the amount of PPH during a cesarean section by ML methods, especially random forest. With the above insight, ML predicting PPH amounts provides early warning for clinicians, thus reducing complications and improving cesarean sections' safety. Furthermore, the importance of ML and permutation, complemented by incorporating PDP, promises to provide clinicians with a transparent indication of individual risk prediction.

TRPC6 promotes daunorubicin-induced mitochondrial fission and cell death in rat cardiomyocytes with the involvement of ERK1/2-DRP1 activation.

Daunorubicin (DNR-) induced cardiotoxicity seriously restricts its clinical application. Transient receptor potential cation channel subfamily C member 6 (TRPC6) is involved in multiple cardiovascular physiological and pathophysiological processes. However, the role of TRPC6 anthracycline-induced cardiotoxicity (AIC) remains unclear. Mitochondrial fragmentation greatly promotes AIC. TRPC6-mediated ERK1/2 activation has been shown to favor mitochondrial fission in dentate granule cells. The aim of the present study was to elucidate the effects of TRPC6 on daunorubicin- induced cardiotoxicity and identify the mechanisms associated with mitochondrial dynamics. The sparkling results showed that TRPC6 was upregulated in models in vitro and in vivo. TRPC6 knockdown protected cardiomyocytes from DNR-induced cell apoptosis and death. DNR largely facilitated mitochondrial fission, boosted mitochondrial membrane potential collapse and damaged debilitated mitochondrial respiratory function in H9c2 cells，these effects were accompanied by TRPC6 upregulation. siTRPC6 effectively inhibited these mitochondrial adverse aspects showing a positive unexposed effect on mitochondrial morphology and function. Concomitantly, ERK1/2-DRP1 which is related to mitochondrial fission was significantly activated with amplified phosphorylated forms in DNR-treated H9c2 cells. siTRPC6 effectively suppressed ERK1/2-DPR1 over activation, hinting at a potential correlation between TRPC6 and ERK1/2-DRP1 by which mitochondrial dynamics are possibly modulated in AIC. TRPC6 knockdown also raised the Bcl-2/Bax ratio, which may help to block mitochondrial fragmentation-related functional impairment and apoptotic signaling. These findings suggested an essential role of TRPC6 in AIC by intensifying mitochondrial fission and cell death via ERK1/2-DPR1, which could be a potential therapeutic target for AIC.

Three-compartment septic tanks as sustainable on-site treatment facilities? Watch out for the potential dissemination of human-associated pathogens and antibiotic resistance.

Improved sanitation is critical important to reduce the spread of human deposited pathogens and antibiotic resistance genes (ARGs). In the China's rural "Toilet Revolution", three-compartment septic tanks (SPTs) are widely used as household domestic sewage treatment facilities. The effluents of SPTs are encouraged to be used as fertilizer in agriculture. However, whether SPT could eliminate fecal pathogens and ARGs is still unrevealed which is crucial in risk assessment of SPT effluent utilization. Herein, we employed metagenomic sequencing to investigate the pathogens and ARGs in rural household SPTs from Tianjin, China. We found that rural household SPT effluents conserved pathogens comparable to that of the influents. A total of 441 ARGs conferring resistance to 26 antibiotic classes were observed in rural household SPTs, with the relative abundance ranging from 709 to 1800 ppm. Results of metagenomic assembly indicated that some ARG-MGE-carrying contigs were carried by pathogens, which may pose risk to human and animal health after being introduced to the environment. This study raises the question of SPTs as sustainable on-site treatment facilities for rural domestic sewage and underscores the need for more attention to the propagation and dissemination of antibiotic-resistant pathogens from SPT to the environments, animals, and humans.

Burkholderia pseudomallei was Identified in a Melioidosis Aneurysm using Polymerase Chain Reaction Targeting 23S rRNA.

Melioidosis abdominal aortic aneurysm and splenic abscesses lead to poor prognosis and high mortality rate as high as 50% due to delayed/missed diagnosis. We describe an attempt to identify Burkholderia pseudomallei immediately, which was confirmed by polymerase chain reaction (PCR) and gene sequence analysis of 23S rRNA gene. PCR is not only an unambiguous identification of B. pseudomallei but also a rapid detection because B. pseudomallei may not be readily isolated. For patients of melioidosis abdominal aortic aneurysm with spleen abscess, prolonged antibiotic therapy, splenectomy and artificial vessel replacement provided an excellent result in our study. The progression, roentgenographic findings and histopathology character of melioidosis are similar to those of tuberculosis disease. PCR is useful to differentiate B. pseudomallei from Mycobacterium tuberculosis.

Lamprey: an important animal model of evolution and disease research.

Lamprey is one representative of the extant jawless vertebrates, known as "living fossils", with a history of more than 500 million years. The ancient lamprey has attracted the attention of many scholars due to its unique functional characteristics and evolutionary status. In terms of immune system, the lamprey has adaptive immune system and immune molecules different from those of jawed vertebrates. Based on the evolutionary status, lamprey is an important developmental and evolutionary animal model for analyses of evolutionary conservation and derivative characteristics of vertebrates. Lamprey pallium provides an evolutionary blueprint for mammalian cerebral cortex. In disease research, lamprey has provided various results as a pathological model of spinal cord injury and biliary atresia. In this review, the life cycle, immune molecules, developmental evolution and physiological structure of lamprey are presented in details in reference with relevant reports from China and abroad. We believe that in-depth studies of lamprey could promote an effective outcome(s) in the research on genetics of animal development and biomedicine.

Identification of surrogate prognostic biomarkers for allergic asthma in nasal epithelial brushing samples by WGCNA.

BACKGROUND: Allergic asthma is a lower respiratory tract disease of Th2 inflammation with multiple molecular mechanisms. The upper and lower airways can be unified by the concept of a united airway and, as such, gene expression studies of upper epithelial cells may provide effective surrogate biomarkers for the prognostic study of allergic asthma. OBJECTIVE: To identify surrogate biomarkers in upper airway epithelial cells for the prognostic study of allergic asthma. METHODS: Nasal epithelial cell gene expression in 40 asthmatic and 17 healthy control subjects were analyzed by weighted gene coexpression network analysis (WGCNA) to identify gene network modules and profiles in allergic asthma. Functional enrichment analysis was performed on the coexpression genes in certain highlighted modules. RESULTS: A total of 13 coexpression modules were constructed by WGCNA from 2804 genes in nasal epithelial brushing samples of the 40 asthmatic and 17 healthy subjects. The number of genes in these modules ranged from 1086 (Turquoise module) to 45 (Salmon). Eight coexpression modules were found to be significantly correlated (P < 0.05) with two clinic traits, namely disease status, and severity. Four modules were positively correlated ( P < 0.05) with the traits and these, therefore, contained genes that are mostly overexpressed in asthma. Contrastingly, the four other modules were found to be negatively correlated with the clinic traits. Functional enrichment analysis of the positively correlated modules showed that one (Magenta) was mainly enriched in mast cell activation and degranulation; another (Pink) was largely involved in immune cell response; the third (Yellow) was predominantly enriched in transmembrane signal pathways; and the last (Blue) was mainly enriched in substructure components of the cells. The hub genes in the modules were KIT, KITLG, GATA2, CD44, PTPRC, and CFTR, and these were confirmed as having significantly higher expression in the nasal epithelial cells. Combining the six hub genes enabled a relatively high capacity for discrimination between asthmatics and healthy subjects with an area under the receiver operating characteristic (ROC) curve of 0.924. CONCLUSIONS: Our findings provide a framework of coexpression gene modules from nasal epithelial brushing samples that could be used for the prognostic study of allergic asthma.

RNF135 is a positive regulator of IFN expression and involved in RIG-I signaling pathway by targeting RIG-I.

RIG-I-like receptors (RLRs) play a key role in antiviral and inflammatory responses. Increasing evidence indicates that ubiquitination is crucial for regulation of RIG-I signaling pathway. Several ubiquitin ligases were reported to be involved in RIG-I-mediated signal transduction. In the present study, we demonstrated zebrafish RING finger protein 135 (zbRNF135) was a critical player in the regulation of RIG-I signaling pathway. zbRNF135 mRNA was widely expressed in different tissues of zebrafish. The expression of zbRNF135 was up-regulated post poly(I:C) treatment in vivo and in vitro. Furthermore, the expression profiles of RIG-I signaling pathway related genes (LGP2, MDA5, RIG-I, MAVS, TRAF3, IRF3 and IRF7), together with its downstream molecules (IFN1, ISG15, Mx and PKR), were up-regulated by overexpression of zbRNF135 in ZF4 cells. Luciferase and ubiquitination assays revealed that overexpression of zbRNF135 facilitated zebrafish RIG-I (zbRIG-I)-mediated IFN1 promoter activation by mediating K63-linked ubiquitination of zbRIG-I. The co-immunoprecipitation assay showed that zbRNF135 specifically interacted with zbRIG-I. Our study indicated that zbRNF135 participated in innate immune response through modulating RIG-I signaling pathway.

A large lung gene expression study identifying IL1B as a novel player in airway inflammation in COPD airway epithelial cells.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease characterized by a mixture of small airway disease and lung tissue parenchymal destruction. Abnormal inflammatory responses to cigarette smoking and other noxious particles are generally thought to be responsible for causing of COPD. Since airway inflammation is a key factor in COPD progress, it is crucial to unravel its underlying molecular mechanisms. Unbiased analysis of genome-wide gene expression profiles in lung small airway epithelial cells provides a powerful tool to investigate this. METHODS: Gene expression data of GSE611906, GSE20257, GSE8545 were downloaded from GEO database. All 288 lung small airway samples in these cohorts, including donors with (n = 61) and without (n = 227) COPD, were chosen for differential gene expression analysis. The gene ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses, gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed. Subsequently, the analyses of IL1B expression level, the Pearson correlation between IL1B and several COPD biomarkers were performed using other cohorts to validate our main findings. RESULTS: With a change ≥ twofold and P value < 0.05 cutoff, we found 38 genes were up-regulated and 114 genes were down-regulated in patients with COPD compared with health controls, while using cutoff fold change 1.5 and P value < 0.05, there were 318 genes up-regulated and 333 genes down-regulated. Among the most up-regulated genes were IL1B, CCL2, CCL23, and CXCL14, all implicated in inflammation triggering. GO, KEGG and WGCNA analysis all disclosed IL1B was highly correlated to COPD disease trait. The expression profile of IL1B was further validated using independent cohorts from COPD airway epithelium, lung tissue, sputum, and blood. We demonstrated higher IL1B gene expression in COPD small airway epithelial cells, but not in COPD lung tissue, sputum, and blood. Strong co-expression of IL1B with COPD biomarkers, such as DUOX2, MMP12, CCL2, and CXCL14, were validated in silico analysis. Finally, PPI network analysis using enriched data showed IL1B, CCL2, CCL7 and BMP7 were in the same hub node with high degrees. CONCLUSIONS: We identified IL1B was significantly up-regulated in COPD small airway epithelial cells and propose IL1B as a novel player in airway inflammation in COPD.

Reconstruction of Tragus and External Auditory Meatus using Remnant Auricle during Microtia Reconstruction.

This article investigates an effective method with which to reconstruct the tragus and external auditory meatus for microtia reconstruction. The external ear was reconstructed using a delayed postauricular skin flap in patients with congenital microtia. After the first stage of delaying the postauricular skin flap and the second stage of otoplasty with ear framework fabricated from autogenous rib cartilage draping with the delayed skin flap, the third stage involved tragus and external auditory meatus canaloplasty. After designing the remnant auricle flap, the lower part was trimmed and the tragus was reconstructed. The upper part was trimmed into a thin skin flap, which was rotated and used to cover the hollowed wound posterosuperior to the tragus so as to mimic the external auditory meatus. If remnant wounds were present, skin grafting was conducted. In total, 121 patients with congenital microtia were treated from March 2010 to March 2016. The reconstructed tragus and external auditory meatus were well formed, and all wounds healed well. No severe complications such as flap necrosis occurred. Six months postoperatively, the morphology of the reconstructed tragus and external auditory meatus was good. Overall, the patients and their families were satisfied. The use of remnant auricle to reconstruct the tragus and external auditory meatus is an effective auricular reconstruction technique.

Nonlinear third harmonic generation at crystalline sapphires.

Third harmonic generation (THG) is a nonlinear optical phenomenon which can be applied in diverse research areas including interfacial studies, sub-wavelength light manipulation, and high sensitivity bio-molecular detection. Most precedent studies on THG have focused on dielectric and metallic materials, including silicon, gold, and germanium, due to their high nonlinear susceptibility. Sapphire, a widely-used optical substrate, has not been studied in depth for its third harmonic characteristics, despite its excellent optical transmission in the UV-visible range, high thermal conductance, and superior physical and chemical stability. In this research, we comprehensively studied THG at thin air-dielectric interfaces of sapphire wafers by controlling the wafer cutting planes, focusing depth, incidence angle, laser intensity, and input polarization of the input laser beam. These findings can lead to broader use of third harmonics for high-precision sapphire characterization, such as surface quality inspection, crystallinity determination, interfacial studies, delamination check, and real-time monitoring of crack propagation.

[Inlaid labial versus bladder mucosal graft repair for complex urethral skin fistula].

OBJECTIVE: To compare the effect of inlaid labial mucosal graft repair (LMGR) with that of bladder mucosal graft repair (BMGR) in the treatment of complex urethral skin fistula after hypospadias repair. METHODS: This study included 55 cases of complex urethral skin fistula following hypospadias repair. We randomly assigned them to receive inlaid LMGR (n=36) or BMGR (n=19). After surgery, we compared the incidence of complications and recurrence rate of urinary fistula between the two groups of patients. RESULTS: The success rates of operation were 91.7% and 84.2% in the LMGR and BMGR groups, respectively, and the penile appearance was desirable in both groups. Postoperative complications included 2 cases of urinary fistula and 1 case of urethral stricture in each group. There were no statistically significant differences between the two groups in the success rate of operation (P>0.05) or the incidence rate of postoperative complications (P>0.05). CONCLUSIONS: Both inlaid LMGR and BMGR yield satisfactory results in the treatment of complex urethral skin fistula. However, LMGR involves less injury in mucosa collection and is easier to perform and therefore deserves more clinical attention.

Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer.

The epigenetic regulation of N6-methyladenosine (m6A) has attracted considerable interest in tumor research, but the potential roles of m6A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m6A regulators (including novel anti-readers) was employed to identify m6A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m6A regulator-related patterns were identified through the unsupervised clustering of 56 m6A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m6A-related scoring system was developed to quantify the m6A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m6A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m6A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.

Application of a traction metal clip with a fishhook-like device in wound sutures after endoscopic resection.

BACKGROUND/AIMS: Endoscopic wound suturing is an important factor that affects the ability to remove large and full-thickness lesions during endoscopic resection. We aimed to evaluate the effect of a traction metal clip with a fishhook-like device on wound sutures after endoscopic resection. METHODS: From July 2020 to April 2021, patients who met the enrollment criteria were treated with a fishhook-like device during the operation to suture the postoperative wound (group A). Patients with similar conditions and similar size wounds who were treated with a "purse-string suture" to suture the wounds were retrospectively analyzed as the control group (group B). Difference in the suture rate, adverse events, time required for suturing, and number of metal clips were compared between the two groups. RESULTS: The time required for suturing was 7.72±0.51 minutes in group A and 11.50±0.91 minutes in group B. This difference was statistically significant (F=13.071, p=0.001). The number of metal clamps used in group A averaged 8.1 pieces/case, and the number of metal clamps used in group B averaged 7.3 pieces/case. This difference was not statistically significant (F=0.971, p>0.05). CONCLUSION: The traction metal clip with the fishhook-like device is ingeniously designed and easy to operate. It has a good suture effect on the wound after endoscopic submucosal dissection and effectively prevents postoperative adverse events.

Transcatheter closure of patent foramen ovale in Chinese patients with paradoxical embolism. -Immediate results and long-term follow-up-.

BACKGROUND: The aim of the present study was to assess immediate and long-term clinical outcome of Chinese patent foramen ovale (PFO) patients with paradoxical embolism who underwent transcatheter PFO closure. METHODS AND RESULTS: One hundred and ninety-two patients underwent transcatheter PFO closure for secondary prevention of thromboembolic events (TE). During the procedure, 7 patients had frequent atrial premature beats or transient atrial tachycardia in implantation and 1 patient had a transitory ST-elevation in leads II, III and aV(F). These complications converted spontaneously after a few minutes. No cases of procedure-related death or TE were observed during hospitalization. Minor adverse events, including chest discomfort (11%), palpitations (25%) and dyspnea (1%) were reported within 1 month of the procedure. These symptoms had disappeared in most patients by 6-month follow-up. One patient had a new occurrence of migraine at 27 months after the implantation. Within a median follow-up of 49 ± 8 months, no residual shunt of the atrial level was identified and correct positioning of the device was confirmed on transthoracic echocardiography in all patients. No death related to any cause or recurrent TE were recorded. CONCLUSIONS: Transcatheter PFO closure is a minimally invasive procedure with a high success rate, low complication rate and an excellent long-term outcome, and appears to be a wise approach for secondary prevention of recurrent embolic events in symptomatic patients.

[Immediately effects of inhaled aerosolised iloprost in adult patients with severe pulmonary hypertension secondary to congenital heart diseases].

OBJECTIVE: To investigate the immediately effects of inhaled aerosolized iloprost in adult patients with severe pulmonary arterial hypertension (PAH) secondary to congenital heart diseases (CHD). METHODS: Adult patients with severe PAH secondary to CHD (n = 165) were included in this study. Right heart catheterization was performed, Pulmonary and systemic blood flow, the oxygen consumption VO(2) (ml/min) were calculated using Fick's principle. Pulmonary vascular resistances (PVR) were calculated with standard formulas and indexed to body surface area. Hemodynamic parameters were measured before and after iloprost inhalation (20 µg). RESULTS: Post iloprost inhalation, heart rate, mean aortic pressure, pulmonary systolic pressure to aortic systolic pressure ratio all remained un changed (P > 0.05), while pulmonary artery pressure (PAP) were significantly reduced and Qp significantly increased from (7.2 ± 4.8) L/min to (9.9 ± 7.2) L/min (P < 0.01), PVR was also significantly reduced from (13.4 ± 8.7) Wood units to (9.5 ± 6.6) Wood units (P < 0.01), and left-to-right shunt volume increased from (3.2 ± 4.4) L/min to (5.5 ± 7.0) L/min (P < 0.01) and right-to-left shunt volume decreased from (1.0 ± 1.0) L/min to (0.7 ± 0.7) L/min (P < 0.01). Subgroup analysis showed that adult patients with patent ductus arteriosus and/or ventricular septal defects are more likely to develop severe pulmonary arterial hypertension or Eisenmenger syndrome than patients with atrial septal defects. CONCLUSIONS: Inhaled Aerosolised iloprost use is effective and safe for adult patients with severe pulmonary arterial hypertension secondary to congenital heart diseases.

Genetic Variants, Circulating Level of MCP1 with Risk of Chronic Obstructive Pulmonary Disease: A Case-Control Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) ranks one of the major causes of mortality worldwide. Inflammation is greatly involved in the pathogenesis of COPD. Monocyte chemoattractant protein-1 (MCP1) has been implicated to play an important role in the inflammatory response of various pathological processes. METHODS: In this study, we conducted a hospital-based case-control study in a Chinese population, aiming to evaluate the potential associations of genetic polymorphisms of the MCP1 gene (rs1024611, rs2857656, and rs4586) and circulating level of MCP1 with COPD risk. RESULTS: We found that rs1024611 (OR=1.37; 95% CI=1.11-1.69; P-value=0.004) and rs4586 (OR=1.33; 95% CI=1.09-1.63; P-value=0.006) were significantly associated with increased COPD risk. In the dominant model, both rs1024611 (OR=1.46; 95% CI=1.11-1.92; P-value=0.006) and rs4586 (OR=1.56; 95% CI=1.18-2.07; P-value=0.002) were significantly associated with increased COPD risk. Genotypes of rs1024611 and rs4586 with minor alleles had a significantly higher circulating level of MCP1 (P<0.001). Meanwhile, a circulating level of MCP1 was significantly associated with increased COPD risk (OR for per quartile increment=1.35, 95% CI=1.21-1.52, P<0.001). CONCLUSION: Our study indicated that genetic polymorphisms of the MCP1 gene and circulating level of MCP1 contributed to the COPD risk in the Chinese population. MCP1 contributed importantly to the pathophysiological process and occurrence of COPD.

Enhanced third harmonic generation in ultrathin free-standing ß-Ga2O3 nanomembranes: study on surface and bulk contribution.

Third harmonic generation (THG) has proven its value in surface and interface characterization, high-contrast bio-imaging, and sub-wavelength light manipulation. Although THG is observed widely in general solid and liquid substances, when laser pulses are focused at nanometer-level ultra-thin films, the bulk THG has been reported to play the dominant role. However, there are still third harmonics (TH) generated at the surface of the thin-films, not inside the bulk solid - so-called surface TH, whose relative contribution has not been quantitatively revealed to date. In this study, we quantitatively characterized the surface and bulk contributions of THG at ultra-thin ß-Ga2O3 nanomembranes with control of both the laser and thin-nanomembranes parameters, including the laser peak power, polarization state, number of layers, and nanomembranes thicknesses. Their contributions were studied in detail by analyzing the TH from freestanding ß-Ga2O3 nanomembranes compared with TH from ß-Ga2O3 nanomembranes on glass substrates. The contribution of the TH field from the ß-Ga2O3-air interface was found to be 5.12 times more efficient than that from the ß-Ga2O3-glass interface, and also 1.09 times stronger than the TH excited at bulk 1-µm-thick ß-Ga2O3. Besides, TH from the ß-Ga2O3-air interface was found to be 20% more sensitive to the crystalline structure than that from the ß-Ga2O3-glass interface. This research work deepens our understanding of surface and bulk THG from crystalline materials and provides new possibilities towards designing highly efficient nonlinear optical materials for bio-imaging, energy-harvesting, and ultrafast laser development.

The Role of HER2 in Self-Renewal, Invasion, and Tumorigenicity of Gastric Cancer Stem Cells.

BACKGROUND: Deregulation of HER2 expression could affect the biological characteristics of gastric cancer cells and treatment option for gastric cancer patients. This research aims to investigate the impact of HER2 on biological characteristics of gastric cancer stem cells (GCSCs) and prognosis of gastric cancer patients. METHODS: HER2 knockdown in GCSCs were constructed by lentivirus transfection. Alterations of proliferation, self-renewal, invasion, migration, colony formation, and tumorigenicity of GCSCs were examined. The changes of gene expressions after HER2 interference in GCSCs were detected by gene microarray. The impact of concentration of serum HER2 and expression of HER2 in tumor tissues on survival of 213 gastric cancer patients was also analyzed. RESULTS: Down-regulation of HER2 decreased the self-renewal, colony formation, migration, invasion, proliferation, and chemotherapy resistance of GCSCs. However, the tumorigenicity of GCSCs in vivo was increased after down-regulation of HER2. The results of gene microarray showed that HER2 gene might regulate the signal transduction of mTOR, Jak-STAT, and other signal pathways and affect the biological characteristics of GCSCs. Furthermore, survival analyses indicated that patients with high concentration of HER2 in serum had a favorable overall survival. However, there was no significant correlation between expression of HER2 in tumor tissue and overall survival. CONCLUSION: Interference of HER2 in GCSCs decreased the capacity of self-renewal, proliferation, colony formation, chemotherapy resistance, invasion, and migration but might increase the tumorigenicity in vivo. Patients with high concentration of HER2 in serum seemed to have a favorable prognosis.

Expression profiles of genes associated with inflammatory responses and oxidative stress in lung after heat stroke.

BACKGROUND: Heat stroke (HS) is a physically dysfunctional illness caused by hyperthermia. Lung, as the important place for gas-exchange and heat-dissipation organ, is often first to be injured. Lung injury caused by HS impairs the ventilation function of lung, which will subsequently cause damage to other tissues and organs. Nevertheless, the specific mechanism of lung injury in heat stroke is still unknown. METHODS: Rat lung tissues from controls or HS models were harvested. The gene expression profile was identified by high-throughput sequencing. DEGs were calculated using R and validated by qRT-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and cell-enrichment were performed using differential expression genes (DEGs). Finally, lung histopathology was accessed by H&E staining. RESULTS: About 471 genes were identified to be DEGs, of which 257 genes were up-regulated, and 214 genes were down-regulated. The most up-regulated and down-regulated DEGs were validated by qRT-PCR, which confirmed the tendency of expression. GO, KEGG, and protein-protein interaction (PPI)-network analyses disclosed DEGs were significantly enriched in leukocyte migration, response to lipopolysaccharide, NIK/NF-kappaB signaling, response to reactive oxygen species, response to heat, and the hub genes were Tnf, Il1b, Cxcl2, Ccl2, Mmp9, Timp1, Hmox1, Serpine1, Mmp8 and Csf1, most of which were closely related to inflammagenesis and oxidative stress. Finally, cell-enrichment analysis and histopathologic analysis showed Monocytes, Megakaryotyes, and Macrophages were enriched in response to heat stress. CONCLUSIONS: The present study identified key genes, signal pathways and infiltrated-cell types in lung after heat stress, which will deepen our understanding of transcriptional response to heat stress, and might provide new ideas for the treatment of HS.

Sodium tanshinone IIA sulfonate protects against acute exacerbation of cigarette smoke-induced chronic obstructive pulmonary disease in mice.

Exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by acute airway inflammation and mucus hypersecretion, which is by far the most costly aspect of its management. Thus, it is essential to develop therapeutics with low side effects for CODP exacerbation. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component of Chinese herbal medicine Danshen. Although it possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, it remains unknown whether STS protects against COPD exacerbation. In this study, we challenged cigarette smoke (CS)-exposed mice with lipopolysaccharide (LPS), and then treated these mice with STS. We found that STS significantly ameliorated pulmonary inflammatory responses, mucus hypersecretion and lung function decline in CS-exposed mice challenged with LPS. STS treatment also significantly attenuated increased IL-6 and IL-8 releases from cigarette smoke extract (CSE)-treated human bronchial epithelial cells (16HBE) challenged with LPS. Mechanistically, STS reduced activation of ERK1/2 and NF-κB in lungs of CS-exposed mice and CSE-treated 16HBE cells challenged with LPS. Taken together, STS protects against acute exacerbation of CS-induced lung injury, which provides a promising and potential therapeutic avenue to halt acute exacerbation of COPD.