PTCH1 mutation as a potential predictive biomarker for immune checkpoint inhibitors in gastrointestinal cancer.

Immune checkpoint inhibitors (ICIs) have become prominent therapies for gastrointestinal cancer (GC). However, it is urgent to screen patients who can benefit from ICIs. Protein patched homolog 1 (PTCH1) is a frequently altered gene in GC. We attempt to explore the association between PTCH1 mutation and immunotherapy efficacy. The Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 236) with GC (esophageal, gastric and colorectal cancers) patients receiving ICIs was used for discovery and the Peking University Cancer Hospital (PUCH) GC cohort (n = 92) was used for validation. Overall survival (OS) and tumor mutational burden (TMB) of the PTCH1 mutant-type (PTCH1-MUT) and PTCH1 wild-type (PTCH1-WT) groups were compared. Furthermore, GC data were collected from The Cancer Genome Atlas to assess the potential mechanisms. In the MSKCC cohort, PTCH1-MUT group showed significantly better OS (P = 0.017) and higher TMB. Multivariate analysis showed that PTCH1 mutation was associated with better OS. In the PUCH cohort, PTCH1-MUT group showed significantly longer OS (P = 0.036) and progression-free survival, and higher durable clinical benefit and TMB. Immune cell infiltration analysis revealed that PTCH1-MUT group had significantly higher distributions of CD8 T cells, CD4 T cells, NK cells, mast cells and M1 cells. The PTCH1-MUT group showed significantly higher expression of most immune-related genes. Gene set enrichment analysis showed that the PTCH1-MUT group had enriched INF-γ response, INF-α response, glycolysis and reactive oxygen species pathway gene sets. PTCH1 mutation may represent a potential biomarker for predicting ICIs response in GC. Nevertheless, prospective cohort studies should be performed to further validate our results.

Anti-oncogenic mechanism of KLF17 in colon cancer by repressing cell migration and invasion via FHL1 upregulation.

Colon cancer is a disease with high prevalence worldwide. This study sought to investigate Kruppel-like factor 17 (KLF17) mechanism in the development of colon cancer through four-and-a-half-LIM domain protein 1 (FHL1). In colon cancer cells, KLF17 and FHL1 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. After gain- and loss-of-function experiments in colon cancer cells, cell proliferative, invasive, and migrating abilities were tested by cell counting kit-8, transwell, and scratch assays, respectively. The expression of epithelial-mesenchymal transition (EMT)-related genes, E-cadherin, N-cadherin, and Vimentin, was measured by RT-qPCR and Western blot. Chromatin immunoprecipitation and dual-luciferase reporter gene assays were performed to detect the binding of KLF17 and the FHL1 promoter. Finally, a transplantation tumor model in nude mice was established for in vivo validation. Mechanistically, KLF17 facilitated FHL1 transcription by binding to the FHL1 promoter. KLF17 or FHL1 upregulation suppressed the colon cancer cell proliferative, invasive, and migrating capacities, accompanied by elevated E-cadherin expression and diminished N-cadherin and Vimentin expression. Furthermore, FHL1 silencing abrogated the repressive impacts of KLF17 upregulation on colon cancer cell EMT, proliferative, invasive, and migrating capabilities. Furthermore, KLF17 augmented FHL1 expression and curtailed the growth of transplanted tumors in nude mice. Conclusively, KLF17 promoted FHL1 transcription, thereby impeding the invasion, migration, and EMT of colon cancer cells.

Evaluation and prediction method of railway passenger long-term vibration comfort under complex operating conditions.

Vibration contributes large increases in railway passenger discomfort during long-term sitting. Discomfort caused by vibration may differ in different operation conditions. This paper conducted field measurements to investigate the interrelationships between the three. Participants completed a 240-min train journey with their whole-body vibration, subjective comfort ratings and train operating parameters being recorded. A large correlation was observed between the estimated vibration dose value and subjective comfort. The relationship that vibration magnitude significantly increases with increasing the train speed and tunnel density was also found and quantified. A vibration exposure limit of 2.08 m/s1.75 corresponding to the boundary between subjective ratings of comfortable and discomfortable was obtained. Based on the exposure limit and the quantified relationship, a vibration comfort prediction method that can calculate the passenger's maximum tolerance time under a given operation condition was proposed and may help in determining the optimal operating speed and tunnels distribution to alleviate vibration discomfort. Practitioner summary: Similar to the guide to effect of vibration on health in current standard, a vibration exposure limit regarding comfort was provided for reference when assessing long-term vibration comfort. Meanwhile, a prediction method was proposed for determining the best train operating speed and tunnels distribution, thereby alleviating railway passengers' vibration discomfort.

Upregulated Solute Carrier SLC39A1 Promotes Gastric Cancer Proliferation and Indicates Unfavorable Prognosis.

Backgrounds: Solute carrier 39A1 (SLC39A1) is an indirect zinc transporter which showed diverse tumor-related functions in different malignancies. Here, we aimed to investigate its expression and role in gastric adenocarcinoma. Methods: A retrospective gastric adenocarcinoma cohort (n = 154) was collected from our hospital to test their tissue expression of SLC39A1 through immunohistochemical staining method. After SLC39A1 overexpression or knockdown, proliferation and invasion assays were conducted for proliferation and invasion estimation, respectively. Xenograft in nude mice was used as the in vivo strategy to validate in vitro findings. Results: Compared with adjacent stomach tissues, gastric adenocarcinoma tissues showed significantly higher SLC39A1 on both mRNA and protein levels. Higher SLC39A1 was observed in patients with larger tumor size (P=0.003) and advanced tumor stages (P < 0.001). Univariate (P=0.001) and multivariate analyses (P=0.035) confirmed the independent prognostic significance of SLC39A1 on gastric adenocarcinoma outcomes. The median survival time was 22.0 months in patients with high-SLC39A1 expression, while up to 57.0 months in those with low-SLC39A1 (P=0.001). In vitro and in vivo assays demonstrated that overexpressing SLC39A1 could promote gastric cancer growth and invasion, while silencing SLC39A1 led to opposite effects. Conclusions: Aberrant high-SLC39A1 expression can serve as an independent unfavorable prognostic factor for gastric adenocarcinoma. High SLC39A1 is critical for a more aggressive tumor phenotype by promoting cell proliferation and invasion. Therefore, targeting SLC39A1 may provide novel therapeutic insights.

Autonomous driving testing scenario generation based on in-depth vehicle-to-powered two-wheeler crash data in China.

A reliable critical-scenario-based safety assessment of autonomous vehicles in China requires a thorough understanding of complex crash scenarios in Chinese background traffic. Based on actual crashes between a vehicle and a powered two-wheeler (PTW) in China, this study generated the autonomous driving testing scenarios from functional, logical and concrete levels. First, 239 video-recorded crash cases were selected from the China In-depth mobility Safety Study - Traffic Accident (CIMSS-TA) database. Using the k-medoids clustering method, six functional scenarios were generalized according to seven crash characteristics (time of day, road type, road surface, obstruction, motion of vehicle, motion of PTW, relative moving direction and position of PTW with respect to vehicle), which contained two straight road scenarios, two T-junction scenarios and two intersection scenarios. Then, using a trajectory analysis program written by Python, the dangerous time instant of each crash was extracted based on the relative trajectory. According to five dynamic parameters of dangerous time instant, namely vehicle velocity (Vehicle_V), PTW X'-coordinate velocity (PTW_VX'), PTW Y'-coordinate velocity (PTW_VY'), PTW X'-coordinate relative position (PTW_LocX') and PTW Y'-coordinate relative position (PTW_LocY'), a crash trigger scheme was built to remain a case challenging when the involved vehicle is replaced by an autonomous vehicle with completely different maneuvers. Using the kernel density estimation (KDE), the logical scenarios were evolved by calculating the distribution of these dynamic parameters in each cluster. The results showed that there were differences in the distribution of dynamic parameters between six functional scenarios. For instance, the Vehicle_V in the scenario where a vehicle turning right impacts with a right/right rear PTW traveling straight ahead was higher than that in the scenario where a vehicle changing to the left lane impacts with a left/left rear PTW traveling straight ahead, with ranges of (10 km/h, 30 km/h) and (5 km/h, 15 km/h), respectively. Finally, considering the correlation of dynamic parameters, a virtual crash generation approach based on the independent component analysis (ICA) representing the original crashes with independent parameters was proposed to obtain sufficient concrete testing scenarios. The results showed that the statistical characteristics of virtual crashes were consistent with those of original crashes. Therefore, the virtual crash generation approach was effective. And a concrete crossing testing scenario with the crash trigger conditions of Vehicle_V = 26.272 km/h, PTW_VX' = 15.567 km/h, PTW_VY' = -1.670 km/h, PTW_LocX' = -27.265 m and PTW_LocY' = 52. 149 m was especially demonstrated. This study provides a theoretical basis for generating autonomous driving testing scenarios and data support for establishing relevant testing schemes tailored to the traffic environment in China.

Portulaca oleracea extract reduces gut microbiota imbalance and inhibits colorectal cancer progression via inactivation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: Portulaca oleracea is a known medicinal plant with antioxidant, anti-inflammatory, and anticancer activities, and it may also function an important role in colorectal cancer (CRC). PURPOSE: We probed into study the critical function of Portulaca oleracea extract (POE) in CRC and the related downstream factors. METHODS: Azoxymethane (AOM) and dextransodiumsulfate (DSS) were used to induce mouse models of CRC, which were then administered different doses of POE to evaluate the therapeutic effects of POE on CRC. Diversity, abundance, and function of gut microbiota were analyzed. Moreover, the potential molecular targets of POE inhibiting CRC development were determined. Expression of c-Myc and cyclin D1 as well as CRC cell proliferation and apoptosis was detected. RESULTS: POE treatment inhibited AOM/DSS-induced CRC development in mice and ameliorated gut microbial imbalance. Bioinformatic analysis revealed marked differences in the gut microbiota between CRC samples and normal samples and that 20 differential microbiota may be involved in CRC development through the Wnt signaling pathway. Additionally, c-Myc and cyclin D1 were identified to be the key downstream target genes of the Wnt/ß-catenin signaling pathway. In vitro data revealed that POE played a suppressive role in the proliferation of CRC cells by reducing the expression of c-Myc and cyclin D1 and inactivating the Wnt/ß-catenin signaling pathway. CONCLUSION: This study underlines that POE reduces gut microbiota imbalance and inhibits CRC development and progression via inactivation of the Wnt/ß-catenin signaling pathway and downregulation of c-Myc and cyclin D1 expression, which is expected to be a potential biomarker for CRC.

Long non-coding RNA SNHG1/microRNA-195-5p/Yes-associated protein axis affects the proliferation and metastasis of gastric cancer via the Hippo signaling pathway.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been found to be highly expressed in gastric cancer (GC). However, the study for exploring the effects of SNHG1 and microRNA (miR)-195-5p on GC is limited. This research commits to unravel the regulatory effects of SNHG1, miRNA-195-5p, and Yes-associated protein 1 (YAP1) on GC. SNHG1, miR-195-5p and YAP1 levels in GC tissues and GC cells were detected. The GC cells were treated with various constructs altering SNHG1 or miR-195-5p expression to determine the biological activities of GC cell in vitro. The effect of SNHG1 inhibition on subcutaneous tumorigenesis of GC cells in a nude mouse model in vivo was detected. The binding relation among SNHG1, miR-195-5p, and YAP1 was validated. SNHG1 and YAP1 levels were elevated and miR-195-5p level was reduced in GC. Reduction of SNHG1 or elevation of miR-195-5p retarded GC cell biological activity in vitro. Downregulated SNHG1 suppressed tumor growth in vivo. SNHG1 bound to miR-195-5p, and miR-195-5p directly targeted YAP1. The downregulated SNHG1 hinders the biological behaviors of GC cells via the modulation of the miR-195-5p/YAP1 axis.

Types, Risk Factors, Consequences, and Detection Methods of Train Driver Fatigue and Distraction.

Train drivers' inattention, including fatigue and distraction, impairs their ability to drive and is the major risk factor for human-caused train accidents. Many experts have undertaken numerous studies on train driver exhaustion and distraction, but a systematic study is still missing. Through a systematic review, this work aims to outline the types, risk factors, consequences, and detection methods of train driver fatigue and distraction. The effects of central nervous fatigue and cognitive distraction in train drivers during driving are caused by rest and sleep schedules, workload, automation levels, and mobile phones. Furthermore, train drivers' fatigue and distraction can cause loss of concentration and slow reaction, resulting in dangerous driving behaviour such as speeding and SPAD. Researchers have combined subjective reporting, physiological parameters, and physical factors to construct detection algorithms with good results to detect train driver fatigue and distraction. This review offers recommendations for researchers looking into train driver fatigue and distraction. And it can also make valuable recommendations for future studies about railway traffic safety.

Assessment of passenger long-term vibration discomfort: a field study in high-speed train environments.

This study revealed the mechanism of long-term passenger vibration discomfort in high-speed trains and proposed a novel evaluation model to assess it, while the most popular international standard ISO 2631-1 is unsuitable. Here, a field test was conducted to investigate the long-term passenger vibration comfort in high-speed trains under different operation environments by the measurement of the whole-body vibration (WBV) and the subjective ratings of passenger comfort. During the whole sitting period of high-speed train passengers, the phenomena 'compensatory degradation' and 'discomfort accumulation' were found, which meant that the brief termination of vibration cannot fundamentally alleviate passenger vibration comfort. And the vibration comfort can be evaluated by the product of exposure time and the novel vibration acceleration index we proposed. Meanwhile, high-speed trains with higher velocities or running in tunnel environments have higher frequency-weighted WBV amplitude than open-air and lower velocities, which caused more vibration discomfort of passengers. Practitioner Summary: This field study provided data support for ensuring the occupational health of train drivers whose work routes involve a large number of tunnels and improving passenger vibration comfort. Meanwhile, a novel idea was provided for evaluating the vibration comfort of passengers who prolonged exposure to low-amplitude environments.

Risky behaviors, psychological failures and kinematics in vehicle-to-powered two-wheeler accidents: Results from in-depth Chinese crash data.

As the use of powered two-wheeler (PTW) becomes increasingly prevalent, PTW accidents are emerging as a major threat to the people's life and property in China. Understanding the risky behaviors, psychological failures and kinematics in vehicle-to-PTW accidents is an important first step in addressing this issue. Here 69 vehicle-to-PTW accidents captured on video from the Traffic Accident Investigation and Research in China (TAIRC) database are selected and reconstructed. All accidents are categorized into different crash scenarios using a harmonized method. Accident causations are identified from the perspectives of praxeology and psychology. Kinematics characteristics, such as impact speed and relative position, are also analyzed. The results show the crossing accident bundle is the most frequent followed by rear, oncoming and run-up accident bundles, with proportions of 43.48 %, 27.54 %, 11.59 % and 17.39 % respectively. Accident causations of different crash scenarios have great differences whether in accident responsibilities or in psychological failures. For instance, the PTW riders who violate the traffic regulations need to be mainly responsible for most crossing accidents, whereas most rear accidents are blamed on drivers who fail to properly check their mirrors when they turn, turn around or change lanes. From the perspective of psychology, the perception failures encountered by both drivers and riders are a typical causation in crossing accidents, while it is a contributing factor in rear accidents that a failure of prognosis from the rider combined with a failure of perception from the driver. Visual obstruction exists widely in crossing and oncoming accident bundles. The impact speeds of vehicles and PTWs are often less than 40 km/h in all accident bundles. A wider sensing area (field of view = 90°, view detection range = 35 m) should be achieved to more effectively detect the conflict PTWs. These findings about vehicle-PTW accidents provide a stronger support for the development of prevention countermeasures and advanced driver assistance system.

circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis.

Pancreatic cancer (PC) is one of the most common and lethal cancers that affects millions of people around the world. The prognosis of PC is poor with very limited effective treatments. Here, we fully investigated the function and underlying mechanism of circSFMBT1 (hsa_circ_0066147) in PC. Real-time quantitative PCR, Western blotting, and immunohistochemistry were used to examine levels of circSFMBT1, miR-330-5p, PAK1 (p21-activated kinase 1), or proliferation/metastasis-related proteins. Colony formation assay, flow cytometry, and transwell assay detected the roles of circSFMBT1 and miR-330-5p in cell apoptosis, proliferation, migration, and invasion of PC cells, respectively. Dual luciferase assay and RNA immunoprecipitation were used to validate the interactions of circSFMBT1/miR-330-5p and miR-330-5p/PAK1. Fluorescence in situ hybridization was performed to examine the subcellular localization of circSFMBT1 and miR-330-5p. Subcutaneous tumor growth was monitored in nude mice and in vivo metastasis was examined as well following injection of PC cells into the tail vein. This study demonstrated that circSFMBT1 and PAK1 were up-regulated in PC tissues and cells, while miR-330-5p was down-regulated. circSFMBT1 directly bound miR-330-5p and inhibited its expression. In addition, circSFMBT1 promoted proliferation, migration, and invasion of PC cells through up-regulating proliferation-related proteins and down-regulating apoptosis-related proteins via miR-330-5p. miR-330-5p directly bound PAK1 mRNA and suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition process via targeting PAK1 in PC cells. Further, knockdown circSFMBT1 increased miR-330-5p level, but decreased PAK1 expression and repressed tumor growth and metastasis in vivo. Taken together, circSFMBT1 promotes proliferation and metastasis of PC via regulating miR-330-5p/PAK1 pathway as a miR-330-5p sponge.

Assessment of hearing loss induced by tympanic membrane perforations under blast environment.

PURPOSES: This study provides an approach to estimating tympanic membrane perforation-induced hearing loss (HL) using a human middle ear model. METHODS: Sixty-one cases of tympanic membrane perforation originating from fireworks were reported from the Ear-Nose-Throat Department. The otoscope, audiometry data and diagnosis records were organized, and gender, age, etiology, perforation size and diseased ear side were classified as independent variables. A multinomial regression model was used to analyze the potential effects of the variables on HL. Meanwhile, a human middle ear model was implemented to calculate the ensued HL resulting from different perforation areas and sites. In addition, linear regression models were used to establish functions between perforation size and HL. RESULTS: The audiometry data indicate that HL at high frequencies (f > 2 kHz) is much more profound than that at the speech frequency band (f < 1 kHz). Compared with mild HL (<15 dB), mediate HL (15-30 dB) was correlated with the perforation area (p < 0.05, 95% CI), while severe HL (>30 dB) was affected by both perforation size and age (p < 0.05, 95% CI). However, other factors, including gender and diseased ear side, do not show a statistically significant effect on HL. Furthermore, the Kruskal-Wallis test result reveals that HL at frequencies of 0.25 kHz ≤ f ≤ 8 kHz is strongly associated with the perforation size (p < 0.05, 95% CI). CONCLUSIONS: It is conclusive that HL is positively proportional to the perforation size. However, HL is not correlated with the perforation site for small perforation areas of < 10% (p > 0.05, 95% CI).

A study on the effect of ligament and tendon detachment on human middle ear sound transfer using mathematic model.

The objective of this study is to investigate the effects of ligament and tendon detachment on human middle ear sound transfer. For this purpose, a geometric human middle ear model was reconstructed based on the computed tomography scanning data of the temporal bones from healthy adult volunteers. For the ear model, pars tensa was assumed to be fit for a 5-parameter Maxwell model and inverse method was used to obtain the necessary coefficients. Furthermore, frequency response method was implemented to investigate the vibration behaviors of tympanic membrane umbo and stapes footplate under an acoustic stimulus of 90 dB within 0.2-8 kHz. Meanwhile, nine patterns of fractured ligaments and tendons, whose effects on the middle ear sound transfer function were simulated by setting free the nodes of the ligaments and tendons of interest. The results indicate that the displacement of tympanic membrane umbo and stapes footplate as well as the velocity transfer function lies within the bounds of the published experimental data. The detachments of ligaments or tendons except for lateral mallear ligament may incur both gains as much as 15 dB and losses of -8 dB in the velocity of stapes footplate at low frequencies (f≤ 1 kHz), while no significant changes were observed at high frequencies (f > 1 kHz). However, detachment of the ligaments or tendons induces tiny changes in the displacement of stapes footplate at the frequencies of 0.2-8 kHz.

Tunnel driving occupational environment and hearing loss in train drivers in China.

OBJECTIVE: Hearing loss caused by high levels of noise is a potential occupational health disorder among train drivers around the world. This study aims to investigate the relationship between tunnel driving occupational environment and hearing loss in train drivers, to provide some insights into helping reduce hearing loss among train drivers. METHODS: This study analysed cross-sectional data for 1214 train drivers who work at China Railway Guangzhou Group. Health examination was taken by physicians with professional licences, and audiometric testing was performed by health technicians in a sound-isolated room. T/R is defined as the ratio of the length of the tunnels to the length of the railway along drivers' work routes. Different multivariate models and stratified models were established for sensitivity analysis. A multivariable logistic regression model was used to estimate the ORs of hearing loss associated with tunnel driving occupational environment. RESULTS: The adjusted OR for high-frequency hearing loss in association with the highest T/R levels (30%-45%) versus the lowest T/R levels (<15%) was 3.72 (95% CI 1.43 to 9.69). The corresponding OR for speech-hearing loss was 1.75 (95% CI 0.38 to 8.06). The sensitivity analysis shows our results are suitable for various alternative models. CONCLUSIONS: This study found that there was a significant association between tunnel driving occupational environment and hearing loss. Train drivers who work in a higher T/R environment have worse hearing loss.

CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

Comparative analyses of bicyclists and motorcyclists in vehicle collisions focusing on head impact responses.

To investigate the differences of the head impact responses between bicyclists and motorcyclists in vehicle collisions. A series of vehicle-bicycle and vehicle-motorcycle lateral impact simulations on four vehicle types at seven vehicle speeds (30, 35, 40, 45, 50, 55 and 60 km/h) and three two-wheeler moving speeds (5, 7.5 and 10 km/h for bicycle, 10, 12.5 and 15 km/h for motorcycle) were established based on PC-Crash software. To further comprehensively explore the differences, additional impact scenes with other initial conditions, such as impact angle (0, π/3, 2π/3 and π) and impact position (left, middle and right part of vehicle front-end), also were supplemented. And then, extensive comparisons were accomplished with regard to average head peak linear acceleration, average head impact speed, average head peak angular acceleration, average head peak angular speed and head injury severity. The results showed there were prominent differences of kinematics and body postures for bicyclists and motorcyclists even under same impact conditions. The variations of bicyclist head impact responses with the changing of impact conditions were a far cry from that of motorcyclists. The average head peak linear acceleration, average head impact speed and average head peak angular acceleration values were higher for motorcyclists than for bicyclists in most cases, while the bicyclists received greater average head peak angular speed values. And the head injuries of motorcyclists worsened faster with increased vehicle speed. The results may provide even deeper understanding of two-wheeler safety and contribute to improve the public health affected by road traffic accidents.

Ursodeoxycholyl lysophosphatidylethanolamide protects against hepatic ischemia and reperfusion injury in mice.

The ischemia and reperfusion (I/R) injury that occurs during liver transplantation causes severe complications leading to transplantation failure. We have designed a cytoprotective agent, ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), which promotes the survival of cultured hepatocellular cell lines and inhibits apoptosis and inflammation in the in vivo models of liver injury. Here, we show that UDCA-LPE increased the viability of mouse hepatocytes by activating the Akt/glycogen synthase kinase 3ß survival signaling pathways. We further tested whether UDCA-LPE could protect hepatic I/R injury in mice by clamping liver lobes of C57/BL6 mice for 90 min of ischemia followed by unclamping and reperfusion for 2 h. Two regimens for UDCA-LPE treatment were carried out; with a single dose of 100 mg/kg UDCA-LPE intraperitoneally injected 30 min prior to ischemia and a double dose of 50 mg/kg UDCA-LPE given 30 min prior to ischemia and just prior to reperfusion. Using histology and liver enzyme determination, we observed that hepatic I/R caused significant hepatic necrosis, which was decreased in UDCA-LPE-treated mice undergoing I/R. Ursodeoxycholyl LPE concomitantly protected against I/R-induced apoptosis (cleaved caspase 3, cleaved poly[ADP-ribose] polymerase 1), inflammation (IL-1ß, CD11b, chemokine ligands 2 and 3, chemokine receptor 2), and portal fibrogenesis (α-smooth muscle actin, plasminogen activator inhibitor 1), as determined by Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses. The protection by UDCA-LPE was found to be better in the double-dose than in the single-dose regimen. Thus, UDCA-LPE promoted the survival of mouse hepatocytes and protected against hepatic I/R injury and thus may be of therapeutic use in liver transplantation settings.

N-cadherin and P-cadherin are biomarkers for invasion, metastasis, and poor prognosis of gallbladder carcinomas.

Gallbladder cancer (GBC) is a rare, but highly aggressive cancer. The most common type of gallbladder cancer is adenocarcinoma (AC), while squamous cell/adenosquamous carcinoma (SC/ASC) is a rare type of gallbladder cancer. The clinicopathologic and biological characteristics of SC/ASC have not been well documented. In this study, the protein expression of N-cadherin and P-cadherin in 46 SC/ASCs and 80 ACs was measured using immunohistochemistry. We demonstrated that positive N-cadherin and P-cadherin expression were significantly associated with large tumor size, invasion, and lymph node metastasis of both SC/ASC and AC. In contrast, positive N-cadherin and P-cadherin expression were significantly associated with differentiation and TNM stage in only AC. Univariate Kaplan-Meier analysis showed that positive N-cadherin and P-cadherin expression, differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and surgical curability were significantly associated with overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive N-cadherin and P-cadherin expression are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive N-cadherin and P-cadherin expression closely correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.