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The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus . Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers.AimsIn this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes.MethodFrom 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country.ResultsA total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries.ConclusionsThis study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

In this study, we aimed to identify an immune-related signature for predicting prognosis in cutaneous melanoma (CM). Sample data from The Cancer Genome Atlas (TCGA; n = 460) were used to develop a prognostic signature with 23 immune-related gene pairs (23 IRGPs) for CM. Patients were divided into high- and low-risk groups using the TCGA and validation datasets GSE65904 (n = 214), GSE59455 (n = 141), and GSE22153 (n = 79). The ability of the 23-IRGP signature to predict CM was precise, with the stratified high-risk groups showing a poor prognosis, and it had a significant predictive power when used for immune microenvironment and biological analyses. We subsequently established a novel promising prognostic model in CM to determine the association between the immune microenvironment and CM patient results. This approach may be used to discover signatures in other diseases while avoiding the technical biases associated with other platforms.

Aberrant scar formation, which includes keloid and hypertrophic scars, is associated with a pathological disorganized wound healing process with chronic inflammation. The TGF-β/Smad signaling pathway is the most canonical pathway through which the formation of collagen in the fibroblasts and myofibroblasts is regulated. Sustained activation of the TGF-β/Smad signaling pathway results in the long-term overactivation of fibroblasts and myofibroblasts, which is necessary for the excessive collagen formation in aberrant scars. There are two categories of therapeutic strategies that aim to target the TGF-β/Smad signaling pathway in fibroblasts and myofibroblasts to interfere with their cellular functions and reduce cell proliferation. The first therapeutic strategy includes medications, and the second strategy is composed of genetic and cellular therapeutics. Therefore, the focus of this review is to critically evaluate these two main therapeutic strategies that target the TGF-β/Smad pathway to attenuate abnormal skin scar formation.

Wound scarring remains a major challenge for plastic surgeons. Transforming growth factor (TGF)-β plays a key role in the process of scar formation. Previous studies have demonstrated that truncated TGF-β type II receptor (t-TGF-βRII) is unable to continue signal transduction but is still capable of binding to TGF-β, thereby blocking the TGF-β signaling pathway. Hepatocyte growth factor (HGF) is a multifunctional growth factor that promotes tissue regeneration and wound healing. Theoretically, the combination of HGF and t-TGF-βRII would be expected to exert a synergistic effect on promoting wound healing and reducing collagen formation. In the present study, lentivirus-mediated transfection of the two genes (t-TGF-βRII/HGF) into fibroblasts in vitro and in a rat model in vivo was used. The results demonstrated that the expression of t-TGF-βRII and HGF in NIH-3T3 cells was successfully induced. The expression of both molecules significantly reduced collagen I and III expression, and also inhibited fibroblast proliferation. Furthermore, histological examination and scar quantification revealed less scarring in the experimental wound in a rat model. Moreover, on macroscopic inspection, the experimental wound exhibited less visible scarring compared with the control. Therefore, the present study demonstrated that the combination gene therapy of t-TGF-βRII and HGF promoted wound healing, with less scarring and more epithelial tissue formation, not only by suppressing the overgrowth of collagen due to its antifibrotic effect, but also by promoting tissue regeneration.

Summary: When the core body temperature is higher than 40°C, life is threatened due to heatstroke. Tumor repressor p53 is required for heat-induced apoptosis at hyperthermia conditions (>41°C). However, its role in sub-heatstroke conditions (≤40°C) remains unclear. Here, we reveal that both zebrafish and human p53 promote survival at 40°C, the heatstroke threshold temperature, by preventing a hyperreactive heat shock response (HSR). At 40°C, both Hsf1 and Hsp90 are activated. Hsf1 upregulates the expression of Hsc70 to trigger Hsc70-mediated protein degradation, whereas Hsp90 stabilizes p53 to repress the expression of Hsf1 and Hsc70, which prevents excessive HSR to maintain cell homeostasis. Under hyperthermia conditions, ATM is activated to phosphorylate p53 at S37, which increases BAX expression to induce apoptosis. Furthermore, growth of p53-deficient tumor xenografts, but not that of their p53+/+ counterparts, was inhibited by 40°C treatment. Our findings may provide a strategy for individualized therapy for p53-deficient cancers. : Gong et al. report that in contrast to promoting apoptosis in hyperthermia conditions, both zebrafish and human tumor repressor p53 protect cells from death by preventing a hyperreactive heat shock response at 40°C, the heatstroke threshold temperature (HTT). They may provide a strategy for individualized therapy for p53-deficient cancers. Keywords: p53, heatstroke threshold temperature, hyperthermia temperature, cell death, Hsf1, Hsc70, Hsp90, ATM, zebrafish, human cell

The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn’t directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-β 1 (TGF-β1). This may provide new insight on scar treatment in clinic.

Epigallocatechin gallate (EGCG) is associated with various health benefits. In this review, we searched current work about the effects of EGCG and its wound dressings on skin for wound healing. Hydrogels, nanoparticles, micro/nanofiber networks and microneedles are the major types of EGCG-containing wound dressings. The beneficial effects of EGCG and its wound dressings at different stages of skin wound healing (hemostasis, inflammation, proliferation and tissue remodeling) were summarized based on the underlying mechanisms of antioxidant, anti-inflammatory, antimicrobial, angiogenesis and antifibrotic properties. This review expatiates on the rationale of using EGCG to promote skin wound healing and prevent scar formation, which provides a future clinical application direction of EGCG.

Background: Long noncoding RNA (lncRNA) LUADT1 is a known oncogenic lncRNA in lung cancer. This study aimed to explore the roles of LUADT1 in melanoma. Materials and Methods: Sixty pairs of melanoma and nontumor tissues were obtained from 60 melanoma patients (37 men and 23 women, 38-68 years, 52.1 ± 4.9 years) at the First Affiliated Hospital of Zhejiang University School of Medicine. Gene expression was analyzed by quantitative polymerase chain reaction and western blot. Cell transfections were performed to analyze gene expression. Results: We found that LUADT1 was upregulated in melanoma and high levels of LUADT1 predicted poor survival. RNA interaction prediction showed that LUADT1 can form base pairing with miR-28-5p. In melanoma cells, LUADT1 overexpression mediated the upregulated Ras-related protein Rap-1b (RAP1B). Cell proliferation assay showed that LUADT1 and RAP1B overexpression mediated the increased proliferation rate of melanoma cells. In addition, miR-28-5p overexpression played opposite roles attenuating the effects of LUADT1 overexpression on both RAP1B expression and cancer cell proliferation. Conclusions: LUADT1 in melanoma and may sponge miR-28-5p to upregulate RAP1B, thereby promoting cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Background Prior studies have demonstrated the association of air pollution with cardiovascular deaths. Singapore experiences seasonal transboundary haze. We investigated the association between air pollution and acute myocardial infarction (AMI) incidence in Singapore. Methods and Results We performed a time‐stratified case‐crossover study on all AMI cases in the Singapore Myocardial Infarction Registry (2010–2015). Exposure on days where AMI occurred (case days) were compared with the exposure on days where AMI did not occur (control days). Control days were chosen on the same day of the week earlier and later in the same month and year. We fitted conditional Poisson regression models to daily AMI incidence to include confounders such as ambient temperature, rainfall, wind‐speed, and Pollutant Standards Index. We assessed relationships between AMI incidence and Pollutant Standards Index in the entire cohort and subgroups of individual‐level characteristics. There were 53 948 cases. Each 30‐unit increase in Pollutant Standards Index was association with AMI incidence (incidence risk ratio [IRR] 1.04, 95% CI 1.03–1.06). In the subgroup of ST‐segment–elevation myocardial infarction the IRR was 1.00, 95% CI 0.98 to 1.03, while for non–ST‐segment–elevation myocardial infarction, the IRR was 1.08, 95% CI 1.05 to 1.10. Subgroup analyses showed generally significant. Moderate/unhealthy Pollutant Standards Index showed association with AMI occurrence with IRR 1.08, 95% CI 1.05 to 1.11 and IRR 1.09, 95% CI 1.01 to 1.18, respectively. Excess risk remained elevated through the day of exposure and for >2 years after. Conclusions We found an effect of short‐term air pollution on AMI incidence, especially non–ST‐segment–elevation myocardial infarction and inpatient AMI. These findings have public health implications for primary prevention and emergency health services during haze.

The elementary research of spray and combustion is of great significance to the development of compactness of modern diesel engines. In this paper, three injectors with different nozzle orifice diameters (0.23 mm, 0.27 mm and 0.31 mm) were used to study the diesel spray, ignition and flame-wall impingement visualization experiment. This paper studied the influence of different nozzle sizes on the trends of spray, ignition and flame diffusion under the flame-wall impinging combustion and used the flame luminosity to characterize the soot generation in combustion. By analyzing the quantitative data, such as spray penetration, ignition delay, flame area and flame luminosity systematically, it was shown that the smaller nozzle benefitted diesel combustion to some extent. The 0.23 mm nozzle injector in these experiments had the best fuel-air mixing effect under 800 K. The length of the spray liquid under the 0.23 mm nozzle condition was 19% and 23% shorter than that of 0.27 and 0.31 mm, respectively. Smaller orifice size of the nozzle can help to reach the gas ignition conditions more effectively. Without liquid fuel impingement, the simple flame-wall impingement will not change the trend of the nozzle influence on combustion. The total amount of accumulated soot according to the approximate luminosity spatial integral calculation in the combustion process was reduced by 37% and 43% under 0.27 mm and 0.23 mm nozzles, respectively, which is favorable for the clean combustion of diesel engines.

The applications of magnetron sputtering technology on the surface coating of fabrics have attracted more and more attention from researchers. Over the past 15 years, researches on magnetron sputtering coated fabrics have been mainly focused on electromagnetic shielding, bacterial resistance, hydrophilic and hydrophobic properties and structural color etc. In this review, recent progress of the technology is discussed in detail, and the common target materials, technologies and functions and characterization of coated fabrics are summarized and analyzed. Finally, the existing problems and future prospects of this developing field are briefly proposed and discussed.

Reduction mammoplasty (RM) is a proven method of treating macromastia, but the risk factors for postoperative complications have not been clearly identified. Through this meta-analysis, the authors aimed to identify the risk factors of RM complications.An extensive search of the literature describing complications after RM was performed using the PubMed Central, Embase, and Cochrane databases. The following risk factors were extracted: age, body mass index (BMI), tissue resection weight per breast (TRW), smoking and radiation therapy. Odds ratios (OR) were pooled with 95% confidence intervals (CI) to evaluate the relationship between these risk factors and complications after RM.A total of 16 unique studies including 10 593 patients were included in the final analysis. It showed that there was a significant difference in complications in BMI ≥30 kg/m2 (OR 0.73; 95% CI: 0.61-0.89, p = 0.001) and smoking (OR 1.56; 95% CI: 0.98-2.49, p = 0.06). Infection in those with BMI ≥30 kg/m2 showed a significant difference (OR 0.68; 95% CI: 0.52-0.89, p = 0.004), as well as wound dehiscence in smokers (OR 2.73; 95% CI: 1.60-4.67, p = 0.0002) and infection in irradiated breasts (OR 20.38; 95% CI: 3.42-121.35, p = 0.0009). However, there was no significant difference in age ≥50 years (OR 0.96; 95% CI: 0.71-1.29, p = 0.78), combined TRW ≥1000 g (OR 1.04; 95% CI: 0.43-2.50, p = 0.93).BMI ≥30 kg/m2 and smoking increase the risk of complications. Persons who are obese or irradiated are more likely to develop infections, and smokers experienced a higher incidence of wound dehiscence than did nonsmokers. However, patients aged ≥50 years and TRW ≥1000 g are not associated with complications from RM.

AIM: To compare the curative effects of two surgical treatment methods for open angle glaucoma and cataract patients.METHODS: Totally 69 patients with primary open angle glaucoma and cataract were divided into two groups: group A and group B. Thirty-four patients(34 eyes)in group A underwent small incision non-phacoemulsification cataract surgery combined with trabeculectomy, just combined operations, 35 patients(35 eyes)in group B underwent small incision non-phacoemulsification cataract surgery beyond 6mo after trabeculectomy, just two stage operations. Postoperative intraocular pressure at 1wk and 3mo, postoperative corrected visual acuity and filtering bleb at 3mo were observed, and intraoperative and postoperative complications were compared. All the patients were followed up for 3-6mo.RESULTS: All the visual acuity were increased compared with that before surgery in two groups, the difference was not statistically significant. All the intraocular pressure was controlled in two groups, the difference was not statistically significant, and the difference about the filtering bleb was neither statistically significant(P>0.05). There were no serious intraoperative and postoperative complications in two groups.CONCLUSION: The two stage operations and the combined operations both can control theintraocular pressure and improved visual acuity of open angle glaucoma and cataract. The two stage operations may prevent a second operation for post trabeculectomy cataract, allowing earlier visual rehabilitation.

AIM: To evaluate the safety and effectiveness of 23G micro-invasion vitrectomy combined surgery for proliferative diabetic retinopathy(PDR). METHODS: Forty cases(40 eyes)with PDR of fibrovascular membrane range >5PD were randomly treated with 20G and 23G vitrectomy combined surgery. The medical records of patients were reviewed, and the visual acuity of postoperation, intraocular pressure, complications in preoperation or postoperation were analyzed.RESULTS:After 1, 3 and 6mo of surgery, the best corrected visual acuity(BCVA)were LogMAR(0.88±0.43),(0.69±0.23),(0.45±0.17)in group 23G, and LogMAR(0.57±0.32),(0.41±0.21),(0.30±0.17)in group 20G. Compared with each other, the differences were not statistically significant. The patients were followed up 6-23mo after surgery. CONCLUSION: 23G vitrectomy issafe and effective for complicated PDR.

AIM: To study the clinical effectiveness of trabeculectomy combined with small incision extracapsular cataract extraction and intraocular lens(IOL)implantation for the treatment of primary open angle glaucoma coexisting with cataract.METHODS: A total of 34 eyes of 34 patients with primary open angle glaucoma and cataract had trabeculectomy combined with small incision extracapsular cataract extraction and intraocular lens implantation from January 2011 to January 2013. The postoperative visual acuity, intraocular pressure(IOP), filtering bleb and complications were observed.RESULTS: The follow up duration was 6-24 months. The best corrected visual acuity(BCVA)was 0.1～CONCLUSION: Trabeculectomy combined with small incision extracapsular cataract extraction and IOL implantation are effective as an initial surgical treatment for open angle glaucoma patients coexisting with cataract.

AIM: To evaluate the therapeutic effect of modified amnion and lmibal stem cell(LSC)comnined with mitomycin C(MMC)on recurrent pterygium. METHODS: Sixty-two patients(73 eyes)with recurrent pterygium in our hospital during January 2010 and May 2012 were divided into two groups. Thirty patients(35 eyes)in control group were treated with conventional amniotic membrane transplantation and 32 patients(38 eyes)in trial group were treated with modified amnion and LSC comnined with MMC. Postoperative amniotic fit, corneal epithelial healing, ocular surface and recurrence rates were observed in two groups.RESULTS: During the follow-up of 3-6 months(average 5 months), Tear film function were affected at early postoperative stage in control group, but in trial group, it was influenced slightly. Six months after operation, tear film function was recovered. Pterygium was recurrent in 8 eyes(22.9%)in control group and 2 eyes(5.3%)in trail group. CONCLUSION: The method of modified amnion and LSC combined with MMC can achieve a good therapeutic effect with fewer complications in recurrent pterygium treatment.

Tea (Camellia sinensis L.) is a popular world beverage, and propagation of tea plants chiefly depends on the formation of adventitious roots in cuttings. To better understand potential mechanisms involved in adventitious root formation, we performed transcriptome analysis of single nodal cuttings of C. sinensis treated with or without indole-3-butyric acid (IBA) using the Illumina sequencing method. Totally 42.5 million RNA-Seq reads were obtained and these were assembled into 59,931 unigenes, with an average length of 732 bp and an N50 of 1292 bp. In addition, 1091 differentially expressed unigenes were identified in the tea cuttings treated with IBA compared to controls, including 656 up- and 435 down-regulated genes. Further real time RT-PCR analysis confirmed RNA-Seq data. Functional annotation analysis showed that many genes were involved in plant hormone signal transduction, secondary metabolism, cell wall organization and glutathione metabolism, indicating potential contributions to adventitious rooting. Our study presents a global view of transcriptome profiles of tea cuttings in response to IBA treatment and provides new insights into the fundamental mechanisms associated with auxin-induced adventitious rooting. Our data will be a valuable resource for genomic research about adventitious root formation in tea cuttings, which can be used to improve rooting for difficult-to-root varieties.

Despite the worldwide consumption and high economic importance of tea, the plant (Camellia sinensis) is not well studied in molecular biology. Under the few circumstances in which the plant is studied, C. sinensis flowers, which are important for reproduction and cross-breeding, receive less emphasis than investigation of its leaves or roots. Using high-throughput Illumina RNA sequencing, we analyzed a C. sinensis floral transcriptome, and 26.9 million clean reads were assembled into 75,531 unigenes averaging 402 bp. Among them, 50,792 (67.2%) unigenes were annotated with a BLAST search against the NCBI Non-Redundant (NR) database and 10,290 (16.67%) were detected that contained one or more simple sequence repeats (SSRs). From these SSR-containing sequences, 2,439 candidate SSR markers were developed and 720 were experimentally tested, validating 431 (59.9%) novel polymorphic SSR markers for C. sinensis. Then, a consensus SSR-based linkage map was constructed that covered 1,156.9 cM with 237 SSR markers distributed in 15 linkage groups. Both transcriptome information and the genetic map of C. sinensis presented here offer a valuable foundation for molecular biology investigations such as functional gene isolation, quantitative trait loci mapping, and marker-assisted selection breeding in this important species.

Purpose: Little is known about catheter-based endovascular treatment of vertebrobasilar artery branch occlusion (VEBABO) in acute ischemic stroke (AIS). Nonetheless, the experience of mechanical thrombectomy (MT) in distal small sized arteries of the anterior circulation seems promising in AIS. In this multicenter study, we report the feasibility, efficacy and safety of MT in VEBABO., Methods: Retrospective analysis of consecutive AIS patients treated with MT due to VEBABO including posterior and anterior inferior cerebellar artery (PICA, AICA) and superior cerebellar artery (SCA) occlusions at seven tertiary care centers between January 2013 and May 2020. Baseline demographics and angiographic outcomes including recanalization success of the affected cerebellar arteries and procedural complications were recorded. Clinical outcomes were evaluated by the modified Rankin scale (mRS) at discharge and 90 days., Results: Out of 668 endovascularly treated posterior circulation strokes we identified 16 (0.02%) cases with MT for VEBABO. Most frequently, MT of the SCA was done (13/16, 81%). Most VEBABOs occurred after MT of initial basilar/posterior cerebral artery occlusion (9/16, 56%). In 10/16 (63%) procedures, the affected VEBABO was successfully recanalized. Out of four patients three (75%) with isolated VEBABO had benefited from endovascular therapy. Subarachnoid hemorrhage was observed in 3/16 (19%) procedures. The rate of favorable outcome (mRS ≤2) was 40% at discharge and 47% at 90-day follow-up. Mortality was 13% (2/15)., Conclusion: The use of MT for VEBABO is rare but appears to be feasible and effective; however, the comparatively high rate of procedure-related hemorrhage highlights that the indications for MT in these occlusion sites should be carefully weighed up., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Food and Drug Administration (FDA) approved crizotinib for advanced ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) patients due to a single-arm study PROFILE 1001. However, there is no direct comparison between crizotinib and platinum-pemetrexed chemotherapy., Materials and Methods: Clinical data of advanced ROS1+NSCLC patients treated with first-line crizotinib or platinum-pemetrexed chemotherapy between August 2010 and December 2017 were analyzed., Results: Seventy-seven patients were eligible, including 30 (39.0%) in the crizotinib group and 47 (61.0%) in the platinum-pemetrexed chemotherapy group. The median follow-up was 28.1 months (95% confidence interval [CI]: 19.2-39.0). The objective response rate (ORR) of crizotinib (86.7%, 95% CI: 73.3-96.7) was higher than that of platinum-pemetrexed chemotherapy (44.7%, 95% CI: 29.8-57.4, P < .001). The disease control rate (DCR) was 96.7% (95% CI: 90.0-100) in the crizotinib group and 85.1% (95% CI: 74.5-95.7) in the chemotherapy group (P = .140). Significantly longer progression-free survival (PFS) was observed in the patients treated with crizotinib (18.4 months, 95% CI: 6.4-30.3) versus platinum-pemetrexed chemotherapy (8.6 months, 95% CI: 6.9-10.3, P < .001). Overall survival (OS) was also compared between the two groups and no significant difference was seen (Not reach vs 28.4 months [95% CI: 20.7-36.0], P = .176). Notably, a total of 37 patients have treatment crossover after the failure of first-line treatment. Among those patients, difference in OS was not statistically significant between seven patients who have given first-line crizotinib (38.6 months, 95% CI: 0-81.0) and 30 patients who have given platinum-pemetrexed chemotherapy initially (32.8 months, 95% CI: 11.9-53.8, P = .805)., Conclusions: Our results suggested that first-line crizotinib had higher ORR and longer PFS than platinum-pemetrexed chemotherapy in patients with advanced ROS1+NSCLC, but the differences were not observed for OS., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The cannabinoid receptor-2 (CB2R) was initially thought to be the "peripheral cannabinoid receptor." Recent studies, however, have documented CB2R expression in the brain in both glial and neuronal cells, and increasing evidence suggests an important role for CB2R in the central nervous system inflammatory response. Intracerebral hemorrhage (ICH), which occurs when a diseased cerebral vessel ruptures, accounts for 10-15% of all strokes. Although surgical techniques have significantly advanced in the past two decades, ICH continues to have a high mortality rate. The aim of this study was to investigate the therapeutic effects of CB2R stimulation in acute phase after experimental ICH in rats and its related mechanisms. Data showed that stimulation of CB2R using a selective agonist, JWH133, ameliorated brain edema, brain damage, and neuron death and improved neurobehavioral outcomes in acute phase after ICH. The neuroprotective effects were prevented by SR144528, a selective CB2R inhibitor. Additionally, JWH133 suppressed neuroinflammation and upregulated the expression of microglial M2-associated marker in both gene and protein level. Furthermore, the expression of phosphorylated cAMP-dependent protein kinase (pPKA) and its downstream effector, cAMP-response element binding protein (CREB), were facilitated. Knockdown of CREB significantly inversed the increase of M2 polarization in microglia, indicating that the JWH133-mediated anti-inflammatory effects are closely associated with PKA/CREB signaling pathway. These findings demonstrated that CB2R stimulation significantly protected the brain damage and suppressed neuroinflammation by promoting the acquisition of microglial M2 phenotype in acute stage after ICH. Taken together, this study provided mechanism insight into neuroprotective effects by CB2R stimulation after ICH.