Perphenazine modified pillar[5]arene based nano-assemblies for synergistic photothermal and photodynamic cancer therapy.

Nano-assemblies based on perphenazine modified pillar[5]arene were constructed successfully for synergistic photothermal and photodynamic (I&II) cancer therapy.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway.

CONTEXT: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases. OBJECTIVE: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP. MATERIALS AND METHODS: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3ß/mTOR signalling pathway. RESULTS: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway. DISCUSSION AND CONCLUSION: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.

Long non-coding RNA GAS6-AS1 enhances breast cancer cell aggressiveness by functioning as a competing endogenous RNA of microRNA-215-5p to enhance SOX9 expression.

Long non-coding (lnc) RNAs play crucial functions in human cancer. However, until recently, the involvement of the lncRNA GAS6-AS1 in breast cancer (BCa) malignancy has not been studied exhaustively. The roles and underlying mode of action of GAS6-AS1 action in BCa progression were examined through functional experiments. A decline in GAS6-AS1 level led to a significant decrease in BCa cell proliferation, and the ability for colony formation. Here, GAS6-AS1 competed as endogenous RNA by sequestering microRNA-215-5p (miR-215-5p) causing an enhanced expression of SRY-box transcription factor 9 (SOX9). The effects of silencing GAS6-AS1 on BCa malignant phenotypes could be ameliorated by inhibiting miR-215-5p or restoring SOX9. Thus, GAS6-AS1 acted as a lncRNA that drives tumor in BCa, and enabled progression of BCa through miR-215-5p /SOX9 axis regulation. These outcomes show that the GAS6-AS1/miR-215-5p/SOX9 axis is a potentially effective target for cancer treatment and management.

LncRNA PTPRG-AS1 facilitates glycolysis and stemness properties of esophageal squamous cell carcinoma cells through miR-599/PDK1 axis.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is the most significant subtype of esophageal cancer featured with high occurrence. Long noncoding RNAs (lncRNAs) have been proved to modulate the biological properties of cancer cells, including cell proliferation, invasion, migration, and apoptosis. LncRNA protein tyrosine phosphatase receptor type G-antisense RNA 1 (PTPRG-AS1) has been reported to play as an oncogene in diverse cancers. However, the detailed function PTPRG-AS1 may exert in ESCC is unclear. METHODS: PTPRG-AS1 expression in ESCC cells was investigated via quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The effects of PTPRG-AS1 on ESCC cell proliferation, migration, glycolysis, and stemness were verified through functional assays. Mechanism assays including RIP assay, RNA pull down assay, and luciferase reporter assays were performed to verify the molecular mechanism of PTPRG-AS1. RESULTS: PTPRG-AS1 silencing hindered the proliferation, migration, glycolysis and stemness of ESCC cells. PTPRG-AS1 regulated pyruvate dehydrogenase kinase 1 (PDK1) expression via sponging miR-599. The PTPRG-AS1/miR-599/PDK1 axis was further verified to aggravate the progression of ESCC cells. CONCLUSION: PTPRG-AS1 sponged miR-599 to up-regulate PDK1 expression, thereby promoting the proliferation and migration as well as glycolysis and stemness properties of ESCC cells.

Intraoperative Neuromonitoring Auxiliary Significance of DNEP for MEP-positive Event During Severe Spinal Deformity Surgery.

STUDY DESIGN: This was a retrospective analysis. OBJECTIVE: The objective of this study was to assess the intraoperative neuromonitoring auxiliary significance of descending neurogenic-evoked potential (DNEP) for motor-evoked potential (MEP) during severe spinal deformity surgery when MEP-positive event occurs. SUMMARY OF BACKGROUND DATA: MEP detection is the most widely applied neurological monitoring technique in spinal deformity surgery. MEP is quite vulnerable to anesthesia, blood pressure, and other intraoperative factors, leading to a high false-positive rate of MEP (3.2%-45.0%), which has greatly interfered with the surgical process. At present, the widely used "presence-or-absence" alarm criteria of MEP is not enough to solve the problem of false positive of MEP. METHODS: A total of 205 cases undergoing severe spinal deformity correction were retrospectively studied. Overall, 74 MEP-positive cases were classified as 2 subgroups: DNEP (+) and DNEP (-) groups. The MEP recovery, wake-up test, and Frankle grade were used to assess the neurological functions. The perioperative and long-term neurological outcomes were assessed. RESULTS: There were significant differences in preoperative scoliosis angle and kyphosis angle between DNEP (-) and DNEP (+) groups. Patients in DNEP (-) group showed more MEP improvement (81.5%), compared with the DNEP (+) group (53.2%). The Wake-up test showed 59.3% motor function deficit cases in DNEP (-) group, which was lower than the 87.2% in DNEP (+) group. More patients in DNEP (-) group had normal nerve function (Frankel level E) than those in DNEP (+) group immediately after surgery, as well as at follow-up. CONCLUSIONS: MEP-positive cases with intraoperative DNEP (-) showed superior prognosis after severe spinal deformity surgery. Intraoperative DNEP could be regarded as an important quantitative tool to assist MEP to monitor neurological injury and can serve as a temporary substitution monitoring technique after MEP is lost.

Characteristics of lymph node (No.5 and No.6) metastasis and significance of lymph node dissection in Siewert type II esophagogastric junction adenocarcinoma (AEG): No.5 and No.6 lymph node metastases of AEG and clearance.

BACKGROUND: To analyze the characteristics, related risk factors, and prognosis of lymph node metastasis (Number [No.] 5 and No.6) in the group of adenocarcinoma of esophagogastric junction (AEG). METHODS: The patients with Siewert II AEG who underwent total gastrectomy and D2 lymph node dissection from September 2015 to December 2018 in Lanzhou University Second Hospital were enrolled in this study. The pathological features of the postoperative specimens were analyzed (sex, age, maximum diameter, location, depth of invasion, degree of differentiation, neurological and vascular invasion, etc), and the lymph node metastasis rate of No.5, No.6 groups were calculated. The analysis was performed by IBM SPSS statistical software. The risk factors associated with lymph node metastasis in No.5 and No.6 groups were analyzed. Survival analysis was performed by Kaplan-M method, and survival rate was estimated, Log-rank test was used for comparison, and the difference was statistically significant at P < .05. RESULTS: There were 142 cases of Siewert type II AEG with the positive rate of No.5 lymph nodes being 10.81% (8/74), and the positive rate of No.6 lymph nodes was 8.33% (11/132). No.5 and No.6 lymph nodes metastasis were not associated with gender, age, tumor maximum diameter, location (cardiac left/cardiac right) (P > .05), and were associated with invasion depth, differentiation degree, nerve and vascular invasion (P < .05). In the No.5 lymph node-positive group, the 3-year Overall Survival (OS) was 25.0%, and the No.5 lymph node-negative group had a 5-year OS of 57.8%, which was statistically different (P < .05). The 3-year OS was 18.2% in No.6 node-positive group and 53.8% in No.6 node-negative group, and the difference was statistically significant (P < .05). CONCLUSION: For Siewert type II AEG, the lymph node metastasis rate was higher in No.5 and No.6 groups when the tumor invaded all layers of gastric wall and was poorly differentiated complicated with vascular nerve invasion, and the lymph node metastasis rate was lower at 3 years, which may be more appropriate for total gastrectomy +D2 lymph node dissection.

Spatial Isolation-Inspired Ultrafine CoSe2 for High-Energy Aluminum Batteries with Improved Rate Cyclability.

Transition-metal selenides are attractive cathode materials for rechargeable aluminum batteries (RABs) because of their high specific capacity, superior electrical properties, and low cost. To overcome the associated challenges of low structural stability and poor reaction kinetics, a spatial isolation strategy was applied to develop RAB cathodes comprising ultrafine CoSe2 particles embedded in nitrogen-doped porous carbon nanosheet (NPCS)/MXene hybrid materials; the two-dimensional NPCS structures were derived from the self-assembly of metal frameworks on MXene surfaces. This synthetic strategy enabled control over the particle size of the active materials, even at high pyrolysis temperature, thereby allowing investigations into the effect of size on the electrochemical behavior. Spectroscopic analysis revealed that the CoSe2-NPCS electrode exhibited a high discharge capacity (436 mAh g-1 at 1 A g-1), excellent rate capability (122 mA h g-1 at 5 A g-1), and long-term cycling stability (212 mAh g-1 after 500 cycles at 1 A g-1). Theoretical calculations regarding the Co adsorption affinities at various N-doping sites elucidated the synergistic effects of N-C/MXene hybrids for boosting the reaction kinetics and Co adsorption behavior in this system. This work offers an effective material engineering approach for designing electrodes with high rate stability for high-energy RABs.

GFI1 promotes the proliferation and migration of esophageal squamous cell carcinoma cells through the inhibition of SOCS1 expression.

Growth factor­independent 1 (GFI1) has been reported to serve a vital role in hematopoietic development. However, the function and molecular mechanism of GFI1 in esophageal squamous cell carcinoma (ESCC) remains unknown. In the present study, the biological functions and the molecular mechanism of the effects of GFI1 in ESCC were analyzed. The results demonstrated that GFI1 expression levels were significantly upregulated in ESCC compared with those in normal esophageal tissues. Knockdown of GFI1 using small interfering RNA suppressed ESCC cell proliferation and migration. Furthermore, GFI1 enhanced STAT3 and NF­κB signaling by inhibiting the expression of suppressor of cytokine signaling 1 (SOCS1) in ESCC cells. Taken together, the results of the present study demonstrated that GFI1 promoted the proliferation and migration of ESCC cells via inhibition of SOCS1 expression. These results suggested that GFI1 may be a valuable target for ESCC therapy.

Stress increases MHC-I expression in dopaminergic neurons and induces autoimmune activation in Parkinson's disease.

The expression of major histocompatibility complex class I (MHC-I), a key antigen-presenting protein, can be induced in dopaminergic neurons in the substantia nigra, thus indicating its possible involvement in the occurrence and development of Parkinson's disease. However, it remains unclear whether oxidative stress induces Parkinson's disease through the MHC-I pathway. In the present study, polymerase chain reaction and western blot assays were used to determine the expression of MHC-I in 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. The findings revealed that MHC-I was expressed in both models. To detect whether the expression of MHC-I was able to trigger the infiltration of cytotoxic T cells, immunofluorescence staining was used to detect cytotoxic cluster of differentiation 8 (CD8)+ T cell infiltration in the substantia nigra of MPTP-treated mice. The results indicated that the presentation of MHC-I in dopaminergic neurons was indeed accompanied by an increase in the number of CD8+ T cells. Moreover, in MPTP-induced Parkinson's disease model mice, the genetic knockdown of endogenous MHC-I, which was caused by injecting specific adenovirus into the substantia nigra, led to a significant reduction in CD8+ T cell infiltration and alleviated dopaminergic neuronal death. To further investigate the molecular mechanisms of oxidative stress-induced MHC-I presentation, the expression of PTEN-induced kinase 1 (PINK1) was silenced in MPP+-treated SH-SY5Y cells using specific small interfering RNA (siRNA), and there was more presentation of MHC-I in these cells compared with control siRNA-treated cells. Taken together, MPP+-/MPTP-induced oxidative stress can trigger MHC-I presentation and autoimmune activation, thus rendering dopaminergic neurons susceptible to immune cells and degeneration. This may be one of the mechanisms of oxidative stress-induced Parkinson's disease, and implies the potential neuroprotective role of PINK1 in oxidative stress-induced MHC-I presentation. All animal experiments were approved by the Southern Medical University Ethics Committee (No. 81802040, approved on February 25, 2018).

The radiographic, pulmonary, and clinical outcomes of patients with severe rigid spinal deformities treated via halo-pelvic traction.

BACKGROUND: The severe rigid deformity patients with pulmonary dysfunction could not tolerate complicated corrective surgery. Preoperative traction are used to reduce the curve magnitude and improve the pulmonary function before surgery, including halo-gravity traction (HGT) and halo-pelvic traction (HPT). The present study aimed to retrospectively compare the radiographic, pulmonary and clinical outcomes of preoperative HGT and HPT in severe rigid spinal deformity with respiratory dysfunction. METHODS: 81 cases of severe rigid kyphoscoliosis treated with preoperative traction prior to corrective surgery for spinal deformity between 2016 and 2019 were retrospectively reviewed. Two patient groups were compared, HPT group (N = 30) and HGT group (N = 51). Patient demographics, coronal and sagittal Cobb angles and correction rates, pulmonary function, traction time, osteotomy grade, and postoperative neurological complications were recorded for all cases. RESULTS: The coronal Cobb angle was corrected from 140.67 ± 2.63 to a mean of 120.17 ± 2.93° in the HGT group, and from 132.32 ± 4.96 to 87.59 ± 3.01° in the HPT group (mean corrections 15.33 ± 1.53 vs. 34.86 ± 3.11 %) (P = 0.001). The mean major sagittal curve decreased from 134.28 ± 3.77 to 113.03 ± 4.57° in the HGT group and from 129.60 ± 8.45 to 65.61 ± 7.86° in the HPT group (P < 0.001); the mean percentage corrections were 16.50 ± 2.13 and 44.09 ± 9.78 % (P < 0.001). A significant difference in the pulmonary function test results was apparent between the two groups; the mean improvements in the FVC% of the HGT and HPT groups were 6.76 ± 1.85 and 15.6 ± 3.47 % (P = 0.024). The HPT group tended to exhibit more FEV% improvement than the HGT group, but the difference was not significant (5.15 ± 2.27 vs. 11.76 ± 2.22 %, P = 0.91). CONCLUSIONS: Patients with severe rigid kyphoscoliosis who underwent preoperative HPT exhibited better radiographic correction of the deformity, and pulmonary function, and required fewer osteotomies compared to the HGT group. Thus, HPT may be useful for severe rigid spinal deformity patients with pulmonary dysfunction.

A Retrospective Study of Surgical Correction for Spinal Deformity with and without Osteotomy to Compare Outcome Using Intraoperative Neurophysiological Monitoring with Evoked Potentials.

BACKGROUND This study aimed to evaluate the effects of different combined evoked potentials monitoring modes for non-osteotomy and osteotomy surgery of spinal deformity, and to select individualized modes for various surgeries. MATERIAL AND METHODS We retrospectively reviewed a total of 188 consecutive cases undergoing spinal deformity correction. All patients were classified into 2 cohorts: non-osteotomy (Group A) and osteotomy (Group B). According to intraoperative evoked potential monitoring mode, Group A was divided into 2 sub-groups: A1 [spinal somatosensory evoked potential (SSEP)/motor evoked potential (MEP), n=67)] and A2 [SSEP/MEP/descending neurogenic evoked potential (DNEP), n=52]. Group B was classified as B1 (SSEP/MEP, n=27) and B2 (SSEP/MEP/DNEP, n=42). The demographics, surgical parameters, and evoked potential events of different combined monitoring modes were analyzed within each group. RESULTS The baselines of SSEP/MEP/DNEP in all cases were elicited successfully. Three cases with evoked potential (EP) events (2 with MEP changes and 1 with SSEP/MEP change) were noted in Group A1 and 1 with SSEP change in Group A2, with no neurological complications. Thirteen cases in Group B1 were positive for MEP intraoperatively, including 16 EP events (13 with MEP change and 3 with both SSEP+MEP changes), with no neural complications. In Group B2, 15 cases had 21 EP events, including 12 with MEP change and 2 with SSEP+MEP changes, with no complications. Postoperative neurological complications were observed in 5 of the 7 cases with SS4EP/DNEP changes. CONCLUSIONS Intraoperative simultaneous SSEP/MEP can effectively reflect neurological function in non-osteotomy spinal surgery patients. Simultaneous SSEP/MEP/DNEP can effectively avoid the unnecessary interference by false-positive results of MEP during osteotomy.

Multimodality Intraoperative Neuromonitoring in Severe Thoracic Deformity Posterior Vertebral Column Resection Correction.

BACKGROUND: Multimodal intraoperative neuromonitoring (IONM) has been proposed as an effective way to reduce permanent neurologic injury during spinal deformity surgery. However, few studies have reported evoked potential changes at different surgical stages of thoracic posterior vertebral column resection (PVCR). METHODS: A total of 82 cases with severe thoracic deformity (Yang's A type) treated by PVCR in a single institution between January 2010 and March 2015 were reviewed. Multimodal IONM including somatosensory evoked potential, motor evoked potential, and descending neurogenic evoked potential was performed for real-time assessment of spinal cord function during surgery. The risk factors of neuromonitoring events at different surgical stages were documented and analyzed. RESULTS: Multimodal IONM was successfully performed in all 82 cases. Thirty-nine neuromonitoring events presented in 27 (32.9%) cases. Neurologic monitoring events were more likely to occur in patients with larger scoliosis and kyphosis, longer osteotomy closure distance, more Halo gravity traction, more screw insertion, and higher PVCR segments. The reasons for monitoring changes included 6 events during screw insertion, 20 during osteotomy, 9 during osteotomy gap closure, and 4 during deformity correction. New postoperative neurologic deficits were observed in 11 (13.4%) cases including 1 incomplete paraplegia, 8 transient cord deficits, and 2 nerve root injuries. CONCLUSIONS: Multimodal IONM can effectively identify neurologic deficits throughout surgery. Osteotomy and osteotomy gap closure are the surgical stages with the highest neurologic risks during PVCR procedures. It is imperative to improve dexterity since the majority of neuromonitoring events are caused by surgical techniques.

Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Antidiabetic medications (ADMs) can alter the risk of different types of cancer, but the relationship between lung cancer incidence and metformin remains controversial. Our aim was to quantitatively estimate the relationship between incidences of lung cancer and metformin in patients with diabetes in this meta-analysis. METHODS: We performed a search in PubMed, Embase, ISI Web of Science, and Cochrane Library until September 20, 2017. The odds ratio (OR), relative risk (RR) or hazard ratio (HR), and 95% confidence interval (95% CI) were estimated using the random-effect model. The Newcastle-Ottawa Scale (NOS) was used to assess the study quality. RESULTS: A total of 13 studies (10 cohort studies and 3 case-control studies) were included in the meta-analysis. Compared to nonmetformin users, metformin probably decreased lung cancer incidence in diabetic patients (RR = 0.89; 95% CI, 0.83-0.96; P = 0.002) with significant heterogeneity (Q = 35.47, I 2 = 66%, P = 0.0004). Subgroup analysis showed that cohort studies (RR = 0.91; 95% CI, 0.85-0.98; P = 0.008), location in Europe (RR = 0.90; 95% CI, 0.86-0.94; P < 0.0001), the control drug of the sulfonylurea group (RR = 0.91; 95% CI, 0.86-0.96; P = 0.001), and adjusting for smoking (RR = 0.86; 95% CI, 0.75-1.00; P = 0.05) may be related to lower lung cancer risk. No significant publication bias was detected using a funnel plot. CONCLUSION: Metformin use was related to a lower lung cancer risk in diabetic patients compared to nonusers, but this result was retrieved from observational studies and our findings need more well-designed RCTs to confirm the association.

Predictive Value of Spinal Cord Function Classification and Sagittal Deformity Angular Ratio for Neurologic Risk Stratification in Patients with Severe and Stiff Kyphoscoliosis.

BACKGROUND: Three-column osteotomies were developed to treat severe spinal deformities but result in high neurologic complications and require further risk stratification. The present study investigated whether the combination of spinal cord function classification (SCFC) and deformity angular ratio (DAR) could further stratify the neurologic risks in the surgical correction of severe and stiff kyphoscoliosis. METHODS: The patients with kyphoscoliosis who had undergone posterior 3-column osteotomies at the spinal cord level were reviewed. Using our SCFC system, the preoperative neurologic function (type A, B, or C) was classified. The sagittal DAR (S-DAR), coronal, and total DARs were calculated. Intraoperative monitoring events and new neurologic deficits (NNDs) postoperatively were documented and analyzed using the SCFC and DAR or both combined. RESULTS: The NND rates increased significantly from type A to C (P = 0.000) and increased exponentially with an increase in S-DAR in types B and C but not type A. They also increased exponentially with aggravation of the SCFC in the medium and high but not low S-DAR group. All NNDs had recovered at 3 months for type A and most had recovered at 6 months for type B or C. CONCLUSIONS: The NNDs in type A SCFC usually experienced better recovery even with high S-DARs. Type B SCFC with an S-DAR >20° and type C SCFC with any S-DAR resulted in significantly greater intra- and postoperative neurologic risks. The combination of SCFC and S-DAR can further stratify the intra- and postoperative neurologic risks with these procedures.

Serum level of co-expressed hub miRNAs as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma.

Background: Sensitive and specific non-invasive biomarkers are urgently needed in order to improve the survival of patients with pancreatic ductal adenocarcinoma (PDAC), which is the fourth leading cause of cancer-related death. We aim to identify serum hub miRNAs as potential diagnostic and prognostic biomarkers for PDAC. Methods: A total of 2578 serum miRNA expression data from 88 PDAC patients and 19 healthy subjects were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was constructed and significant modules were extracted from the network by WGCNA R package. Network modules and hub miRNAs closely related to PDAC were identified. The prognostic value of hub miRNAs was assessed by Kaplan-Meier overall survival analysis. Results: Two modules strongly associated with PDAC were identified by WGCNA, which were labeled as turquoise and brown respectively. Within each module, twenty hub miRNAs were found. At the functional level, turquoise module was mainly associated with tumorigenesis pathways such as P53 and WNT signaling pathway, while the brown module was mostly related to the pathways of cancer such as RNA transport and MAPK signaling pathway. Utilizing overall survival analyses, five "real" miRNAs were able to stratify PDAC patients into low-risk and high-risk groups. Conclusions: The association of specific Hub miRNAs with the development of pancreatic cancer was established by WGCNA analysis. Five miRNAs (mir-16-2-3p, mir-890, mir-3201, mir-602, and mir-877) were identified as potential diagnostic and prognostic biomarkers for PDAC.

Major complications of minimally invasive Ivor Lewis oesophagectomy using the purse string-stapled anastomotic technique in 215 patients with oesophageal carcinoma.

OBJECTIVES: The purse string-stapled anastomotic technique is a method for minimally invasive oesophagectomy with intrathoracic anastomosis, in which a purse string is hand sewn without the necessity of specialized devices, such as OrVil and Endo-Stitch. Since this technique was first reported by our surgical team in 2012, several measures in the operation have been refined. Furthermore, there are very few literature reports on the major complications of minimally invasive oesophagectomy with this technique. This article studies the major complications of minimally invasive Ivor Lewis oesophagectomy with this technique and explores methods for prevention and treatment. METHODS: Clinical data of 215 patients with oesophageal cancer who underwent thoracoscopic laparoscopic oesophagectomy with intrathoracic anastomosis from October 2011 to December 2015 were analysed. No patients received preoperative radiotherapy and chemotherapy. During the operation, the purse string was simply hand sewn before it was tightened and tied, and anastomosis was performed using a circular stapler. RESULTS: Six (2.79%) patients developed anastomotic leakage, and all of them were treated conservatively. Three (1.40%) patients experienced postoperative haemorrhage; of them, 2 were cured with conservative treatment. The remaining patient was cured by endoscopic management using titanium clips. Thirty-nine (18.14%) patients experienced postoperative pulmonary complications. One (1.47%) patient died due to pulmonary infection with respiratory failure although he had received mechanical ventilator support after tracheotomy. Five (2.33%) patients developed chyle leakage and 5 (2.33%) patients developed recurrent laryngeal nerve injuries. CONCLUSIONS: The incidence of major complications is acceptable for thoracoscopic laparoscopic oesophagectomy with intrathoracic anastomosis using this purse string-stapled anastomotic technique, which is feasible and safe to perform. Some measures designed in the operation will be conducive to reduce the incidence of major complications.

A proposed classification system for guiding surgical strategy in cases of severe spinal deformity based on spinal cord function.

PURPOSE: Spinal cord function classification systems are not useful for guiding surgery in patients with severe spinal deformities. The aim of this study is to propose a classification system for determining a surgical strategy that minimizes the risk of neurological dysfunction in patients with severe spinal deformities. METHODS: The records of 89 patients with severe spinal deformities treated with vertebral column reconstruction from 2008 to 2013 were retrospectively analyzed. Based on neurophysiological monitoring, magnetic resonance imaging, and neurological symptoms patients were categorized into three groups: group A, normal spinal cord, normal evoked potentials and no neurological symptoms; group B, spinal cord abnormalities and/or abnormal evoked potentials but no neurological symptoms; group C, neurological symptoms with or without spinal cord abnormalities/abnormal evoked potentials. Outcomes and complications were compared between the groups. RESULTS: A total of 89 patients (51 male, 38 female) were included with 47 (52.8 %), 16 (18.0 %), and 26 (29.2 %) patients in groups A, B and C, respectively, and a mean follow-up 34.5 months. There were no differences in age, gender, average preoperative scoliosis, and kyphosis among three groups, but there were differences with respect to the causes of severe spinal deformity and the corrective rate of scoliosis and kyphosis. Changes in intraoperative evoked potentials were different in these three types according to this new classification, and the recovery rates of changes in the three groups were 71.1, 50.0, and 14.1 %, respectively. Postoperative spinal cord injury was positively related to intraoperative changes of evoked potentials. CONCLUSION: The classification system may be useful for guiding surgical decisions in patients with severe spinal deformities to minimize the risk of neurological complications.