Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

A temporary-sustainable team: A new multidisciplinary team model for severe trauma.

The treatment of severe trauma, especially multiple injuries, requires multidisciplinary collaboration. The current study aims to highlight the challenges of consultation mode for severe trauma in general hospitals and emphasizes the need to create a new temporary-sustainable team. It suggests developing an information consultation mode and enforcing the fine management to improve the quality and safety of the medical treatment. The management mode of a temporary-sustainable team will reduce the cost and improve the treatment efficiency. Overall, a temporary-sustainable team has significant advantages over a traditional multidisciplinary team for severe trauma treatment.

Current trauma care system and trauma care training in China.

Trauma is a life-threatening "modern disease". The outcomes could only be optimized by cost-efficient and prompt trauma care, which embarks on the improvement of essential capacities and conceptual revolution in addition to the disruptive innovation of the trauma care system. According to experiences from the developed countries, systematic trauma care training is the cornerstone of the generalization and the improvement on the trauma care, such as the Advance Trauma Life Support (ATLS). Currently, the pre-hospital emergency medical services (EMS) has been one of the essential elements of infrastructure of health services in China, which is also fundamental to the trauma care system. Hereby, the China Trauma Care Training (CTCT) with independent intellectual property rights has been initiated and launched by the Chinese Trauma Surgeon Association to extend the up-to-date concepts and techniques in the field of trauma care as well to reinforce the generally well-accepted standardized protocols in the practices. This article reviews the current status of the trauma care system as well as the trauma care training.

Retraction: Origin of colossal permittivity in (In1/2Nb1/2)TiO2via broadband dielectric spectroscopy.

Retraction of 'Origin of colossal permittivity in (In1/2Nb1/2)TiO2via broadband dielectric spectroscopy' by Xiao-gang Zhao et al., Phys. Chem. Chem. Phys., 2015, 17, 23132-23139.

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

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

Correction: Origin of colossal permittivity in (In1/2Nb1/2)TiO2via broadband dielectric spectroscopy.

Correction for 'Origin of colossal permittivity in (In1/2Nb1/2)TiO2via broadband dielectric spectroscopy' by Xiao-gang Zhao et al., Phys. Chem. Chem. Phys., 2015, 17, 23132-23139.

Origin of colossal permittivity in (In1/2Nb1/2)TiO2via broadband dielectric spectroscopy.

(In1/2Nb1/2)TiO2 (IN-T) ceramics were prepared via a solid-state reaction route. X-ray diffraction (XRD) and Raman spectroscopy were used for the structural and compositional characterization of the synthesized compounds. The results indicated that the sintered ceramics have a single phase of rutile TiO2. Dielectric spectroscopy (frequency range from 20 Hz to 1 MHz and temperature range from 10 K to 270 K) was performed on these ceramics. The IN-T ceramics showed extremely high permittivities of up to ∼10(3), which can be referred to as colossal permittivity, with relatively low dielectric losses of ∼0.05. Most importantly, detailed impedance data analyses of IN-T demonstrated that electron-pinned defect-dipoles, interfacial polarization and polaron hopping polarization contribute to the colossal permittivity at high temperatures (270 K); however, only the complexes (pinned electron) and polaron hopping polarization are active at low temperatures (below 180 K), which is consistent with UDR analysis.

Potential role of therapeutic hypothermia in the salvage of traumatic hemorrhagic shock.

Although therapeutic hypothermia could serve as a potential therapeutic strategy for treatment of traumatic hemorrhagic shock, significant controversy exists regarding its safety and feasibility. The current resuscitation strategy in traumatic hemorrhagic shock may also require updating. In this article, we have carried out an extensive literature search in this field and propose an initial algorithm for use of therapeutic hypothermia in traumatic hemorrhagic shock. This work lays essential groundwork for future investigations in this field.

[Study of the expression and function of Syk and VEGF-C in the development of non-small cell lung cancer].

OBJECTIVE: To explore the role of Syk and VEGF-C in the development of NSCLC. METHODS: Transfered these genes(eukaryotic expression vector pcDNA3.1-VEGF-C and pLNCX-syk)into A549 cells with the liposomes. Tested the expression of VEGF-C mRNA and Syk mRNA with RT-PCR.Investigated the cell invasion assay with transwell chamber in vitro. Analysis the expression of VEGF-C proteins in A549 cells and detect Syk and VEGF-C proteins of 81 NSCLC tissue samples with immunohistochemical staining. RESULTS: Higher expression of VEGF-C was revealed in VEGF-C-construct-transfected A549 cell than that in controls through RT-PCR (P < 0.05) and immunohistochemistry(P < 0.01).RT-PCR also revealed that Syk expression was higher in Syk-construct-transfected cells than in controls (P < 0.05). The cell invading experiments showed that there was more invaded cells in both transfected terms than in controls (P < 0.05). The expression of Syk protein in NSCLC tissue were significantly lower than that in the normal lung tissue (P < 0.05), while the expression of VEGF-C protein in NSCLC tissue were significantly higher than that in the normal lung tissue(P < 0.05). The expression of Syk and VEGF-C has a negative correlationship (r = -1.000, P = 0.019). CONCLUSION: The expression of Syk and VEGF-C has a negative correlationship in NSCLC tissue, VEGF-C-construct-transfected A549 cells are more aggressive than Syk-construct-transfected cells. And they may cooperated with each other in the development of NSCLC.

Emergency management of hemodynamically unstable pelvic fractures.

Pelvic fractures are serious injuries. Death within 24 hours is most often a result of acute blood loss. The emergency management of these patients is challenging and controversial. The key issues in its management are identifying the site(s) of hemorrhage and then controlling the bleeding. Management of hemodynamically unstable patients with pelvic fracture requires a multidisci- plinary team. The issues addressed in this management algorithm are diagnostic evaluation, damage control resuscitation, indications for noninvasive pelvic stabilization, preperitoneal pelvic packing and the critical decisions concerning surgical options and angiography. This review article focuses on the recent body of know- ledge on those determinations.

An in vitro model for studying neutrophil activation during cardiopulmonary bypass by using a polymerase chain reaction thermocycler.

The accurate temperature control of a polymerase chain reaction (PCR) thermocycler was exploited in developing an in vitro model to study neutrophil activation during cardiopulmonary bypass. Neutrophils from 12 volunteers underwent temperature changes in a PCR thermocycler (37 degrees C for 30 minutes, 28 degrees C for 60 minutes, and then 37 degrees C for 90 minutes). Different co-incubates were applied to neutrophils, as follows: Group A: phosphate-buffered saline solution; Group B: platelet activating factor (PAF) ; Group C: platelet-depleted plasma; Group D: platelet-depleted plasma + PAF; and Group E: platelet-rich plasma. Membrane-bound elastase (MBE) activity was measured every 30 minutes throughout the experiment. MBE activity decreased significantly after hypothermia, compared with the baseline level (p < 0.001), and it resumed an increase after re-warming. Among all co-incubates, platelet-rich plasma was the most potent pro-inflammatory stimulus to neutrophils. A linear correlation was found between MBE and platelet count in platelet-rich plasma (p = 0.004). A novel in vitro model involving a PCR thermocycler has been proved to be reliable in the study of neutrophil activation during cardiopulmonary bypass. The model could possibly be used as an alternative to animals in the development of new drugs to combat neutrophil damage to tissues and organs during cardiopulmonary bypass in cardiac surgery.

Risk factors for urban road traffic injuries in Hangzhou, China.

OBJECTIVE: To investigate factors that most influence urban road traffic injuries (RTI) mortality and morbidity. METHODS: The study used linked police and hospital records of RTI patients in the city of Hangzhou during the 3-year period 2004-2006. Three RTI outcome groups were included: (1) fatally injured; (2) severely injured; and (3) mildly injured persons. RESULTS: High risks for fatal road traffic accidents (RTA) were found on urban links, over weekend, during night hours, in male drivers who drove old vehicles without using seat belts, and at exceeding speeds, or with night time accidents and bad weather condition. In case of higher risk for all urban road users on urban junctions, the numbers on mildly injury cases were increasing. The highest combined risk for dying or being severely injured was found in male drivers driving at excessive speed, on urban links, and with night time accidents. CONCLUSIONS: Intensifying safety education of motor vehicle drivers, enhancing traffic management and keeping balance of "person-vehicle-road" system will greatly reduce the urban traffic accidents and casualties.

A nomogram prediction model for recurrent laryngeal nerve lymph node metastasis in thoracic oesophageal squamous cell carcinoma.

BACKGROUND: The metastasis rate to the recurrent laryngeal nerve lymph node (RLN LN) is high, but resection of it is challenging and increases complications. This study explored the risk factors for the RLN LN metastasis in thoracic oesophageal squamous cell carcinoma and developed a novel scoring system to predict it. METHODS: We retrospectively analysed the clinicopathological data of 265 patients between 2015 and 2018. Univariate and multivariate analyses were performed to screen for risk factors and establish a logistic regression model to predict the risk of RLN LN metastasis. A nomogram was constructed accordingly. Further analyses were conducted regarding right and left RLN LN metastasis alone. RESULTS: (I) The metastatic rates of the left and right RLN LN were 15.1% and 20.4%, respectively. (II) Multivariate logistic regression analysis showed that the short axis diameter of the left RLN LN, short axis diameter of the right RLN LN, maximum diameter of the tumor, tumor location, subcarinal lymph node status and paraoesophageal lymph node status were all independent risk factors for RLN LN metastasis. (III) Multivariate logistic regression analysis showed that the short axis diameter of right RLN LN, tumor location and subcarinal lymph node status were independent risk factors for right RLN LN metastasis. (IV) Multivariate logistic regression analysis showed that short axis diameter of left RLN LN was an independent risk factor for left RLN LN metastasis. CONCLUSIONS: The metastatic rates of the left and right RLN LNs were high and can be predicted according to these nomograms.

Risk factors of mortality in road traffic injury patients with acute respiratory distress syndrome.

BACKGROUND: Among the deaths due to trauma, about one half of the patients suffer from road traffic injury (RTI). Most of RTI patients complicate acute respiratory distress syndrome (ARDS) and severe multiple injuries. ARDS is a major contributor to morbidity and mortality in trauma patients. Although many injuries and conditions are believed to be associated with ARDS independent risk factors in trauma patients, their relative importance in development of the syndrome are undefined. We hypothesize that not all of the traditional risk factors impacting mortality are independently associated with patients strictly identified by traffic injury. This study aimed to sieve distinctive risk factors in our RTI population, meanwhile, we also hypothesize that there may exist significantly different risk factors in these patients. METHODS: This was a retrospective cohort study regarding RTI as a single cause for emergency intensive care unit (EICU) admission. Patients identified as severe RTI with post-traumatic ARDS were enrolled in a prospectively maintained database between May 2002 and April 2007 and observed. Twenty-three items of potential risk impacting mortality were calculated by univariate and multivariate Logistic analyses in order to find distinctive items in these severe RTI patients. RESULTS: There were 247 RTI patients with post-traumatic ARDS admitted to EICU during the study period. The unadjusted odds ratio (OR) and 95% confidence intervals (CI) of mortality were associated with six risk factors out of 23: APACHE II score, duration of trauma factor, pulmonary contusion, aspiration of gastric contents, sepsis and duration of mechanical ventilation. The adjusted ORs with 95% CI were denoted with respect to surviving beyond 96 hours EICU admission (APACHE II score, duration of trauma factor, aspiration of gastric contents), APACHE II score beyond 20 EICU admission (duration of trauma factor, sepsis, duration of mechanical ventilation) and mechanical ventilation beyond 7 days EICU admission (duration of trauma factor and sepsis). CONCLUSIONS: We have retrospectively demonstrated an adverse effect of six different risk factors out of 23 items in mortality of post-traumatic ARDS within severe RTI patients and, moreover, gained distinct outcomes in stratified patients under real emergency trauma circumstance. An impact of APACHE II score and pulmonary contusion contributing to prediction of mortality may exist in prophase after traffic injury. Sepsis is still a vital risk factor referring to systemic inflammatory response syndrome, infection, and secondary multiple organs dysfunction. Eliminating trauma factors as early as possible becomes the critical therapeutic measure. Aspiration of gastric contents could lead to incremental mortality due to severe ventilation associated pneumonia. Long-standing mechanical ventilation should be constrained on account of severe refractory complications.

Comparison of the new injury severity score and the injury severity score in multiple trauma patients.

OBJECTIVE: To assess whether these characteristics of less misclassification and greater area under receiver operator characteristic (ROC) curve of the new injury severity score (NISS) are better than the injury severity score (ISS) as applying it to our multiple trauma patients registered into the emergency intensive care unit (EICU). METHODS: This was a retrospective review of registry data from 2 286 multiple trauma patients consecutively registered into the EICU from January 1,1997 to December 31, 2006 in the Second Affiliated Hospital, Medical School of Zhejiang University in China. Comparisons between ISS and NISS were made using misclassification rates, ROC curve analysis, and the H-L statistics by univariate and multivariate logistic progression model. RESULTS: Among the 2 286 patients, 176 (7.7%) were excluded because of deaths on arrival or patients less than 16 years of age. The study population therefore comprised 2 110 patients. Mean EICU length of stay (LOS) was 7.8 days ?2.4 days. Compared with the blunt injury group, the penetrating injury group had a higher percentage of male, lower mean EICU LOS and age. The most frequently injured body regions were extremities and head/neck, followed by thorax, face and abdomen in the blunt injury group; whereas, thorax and abdomen were more frequently seen in the penetrating injury group. The minimum misclassification rate for NISS was slightly less than ISS in all groups (4.01% versus 4.49%). However, NISS had more tendency to misclassify in the penetrating injury group. This, we noted, was attributed mainly to a higher false-positive rate (21.04% versus 15.55% for ISS, t equal to 3.310, P less than 0.001), resulting in an overall misclassification rate of 23.57% for NISS versus 18.79% for ISS (t equal to 3.290, P less than 0.001). In the whole sample, NISS presented equivalent discrimination (area under ROC curve: NISS equal to 0.938 versus ISS equal to 0.943). The H-L statistics showed poorer calibration (48.64 versus 32.11, t equal to 3.305, P less than 0.001) in the penetrating injury group. CONCLUSIONS: NISS should not replace ISS because they share similar accuracy and calibration in predicting multiple blunt trauma patients. NISS may be more sensitive but less specific than ISS in predicting mortality in certain penetrating injury patients.

[Relation of vascular endothelial growth factor-D expression to microvessel density, microlymphatic vessel density, and lymph-node metastasis of lung adenocarcinoma].

OBJECTIVE: To investigate the relationship of expression of vascular endothelial growth factor (VEGF)-D to microvessel density (MVD), microlymphatic vessel density (MLVD), and lymph node metastasis in lung adenocarcinoma. METHODS: Fresh specimens of lung adenocarcinoma were collected form 48 patients with lung adenocarcinoma, 28 males and 20 females, aged 35 - 78, during operation. Semi-quantitative RT-PCR was used to detect the mRNA expression of VEGF-D, and immunohistochemistry was used to detect the protein expression of VEGF-D, CD34 (marker of MVD), and VEGF receptor (VEGFR)-3 (marker of MLV). RESULTS: The expression of VEGF-D mRNA in the lung cancer was significantly higher than that in the normal lung tissue, and the expression of VEGF-D protein in the cancerous invasive edge was significantly higher than that in the center of cancerous tissues. Twenty-one of the 29 lung adenocarcinoma patients at stages III - IV were VEGF-D positive, a proportion significantly higher than that of the patients at stages I - II (7/19, P = 0.015). The MLVD of the VEGF-D positive group was 10.25 +/- 2.50, significantly higher than that of the VEGF-D negative group (6.8 +/- 2.2, P < 0.01). Twenty-three of the 28 VEGF-D positive patients showed lymph node metastasis, a proportion significantly higher than that of the VEGF-D negative group (9/20, P = 0.012). CONCLUSION: VEGF-D is related with the lymphangiogenesis and lymph node metastasis in lung adenocarcinoma, but not with angiogenesis.

Efficacy of betahistine plus cognitive behavioral therapy on residual dizziness after successful canalith repositioning procedure for benign paroxysmal positional vertigo.

BACKGROUND: Some patients still complain of residual dizziness after successful canalith repositioning procedure (CRP) for benign paroxysmal positional vertigo (BPPV). Previous study found that compared to the low-dose betahistine, the high-dose betahistine could yield better efficacy in treating residual dizziness. Therefore, this study was conducted to assess whether the addition of cognitive behavioral therapy (CBT) could make low-dose betahistine produce similar results to high-dose betahistine in treating residual dizziness. METHODS: The recruited patients were randomly assigned to receive either low-dose betahistine (6 mg/time, three times/day) or high-dose betahistine (12 mg/time, three times/day). Patients in the low-dose group also received CBT (twice a week, 1 hour per time). The treatment was continued for 4 weeks. The duration of residual dizziness, 25-item Dizziness Handicap Inventory (DHI), Hamilton Anxiety Rating Scale (HARS), and Hamilton Depression Rating Scale (HDRS) were recorded and analyzed. The duration of residual dizziness and DHI score were the primary outcomes, and the HARS and HDRS scores were the secondary outcomes. RESULTS: Each group had 50 patients. After treatment, the average DHI scores, HDRS scores, and HARS scores were significantly decreased in both groups. The duration of residual dizziness and average DHI score were nonsignificantly different (P=0.08; P=0.06) between the two groups, although they were lower in the low-dose group. Compared to the high-dose group, the low-dose group had the significantly lower average HDRS score (P=0.007) and HARS score (P=0.02). Meanwhile, four patients in the high-dose group experienced intolerable stomach upset. CONCLUSION: These results demonstrated that the addition of CBT could make low-dose beta-histine produce similar results to high-dose betahistine in treating residual dizziness. Moreover, the low-dose betahistine plus CBT showed some advantages over high-dose betahistine in relieving depressive and anxiety symptoms and should be further explored.

Effect of spleen tyrosine kinase on nonsmall cell lung cancer.

AIM OF STUDY: To investigate the anti.tumor effect of spleen tyrosine kinase. (Syk) on the human nonsmall cell lung cancer cells in vitro and its mechanism. MATERIALS AND METHODS: In this study, we constructed a eukaryotic expression vector pcDNA3.1D/V5-His-TOPO/Syk and transfected it into human nonsmall cell lung cancer cells A549. Then, we not only analyzed the expression of Syk in transfected cells and its invasion but also the expression of matrix metalloproteinase-9 (MMP-9). RESULTS: The results showed that overexpressed Syk significantly inhibited A549 cell invasive ability by decreasing the expression of MMP-9. CONCLUSION: The overexpressed Syk plays an important role in tumor invasion and metastasis, and a negative role in human nonsmall cell lung cancer cells.