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Background: Cancer cachexia significantly contributes to morbidity and mortality in patients with non-small-cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin-6 (IL-6) play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab in the management of NSCLC with coexisting IL-6-elevated cachexia., Methods: In this retrospective study, data were collected from patients with NSCLC and concurrent IL-6-elevated cachexia who received either tocilizumab plus antitumour therapy or antitumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at Week 12. The secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C-reactive protein (CRP) and mGPS. Qualitative improvements in patient self-rated appetite and fatigue were reported as exploratory analysis., Results: The study included 49 patients diagnosed with NSCLC and IL-6-elevated cachexia, Eastern Cooperative Oncology Group performance status of 2-4. Of these, 26 received tocilizumab in combination with antitumour therapy, and 23 received antitumour therapy alone. The majority of these patients were male (87.8%). Baseline characteristics were almost identical between the two groups. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08-0.38; p < 0.001). The rate of patients surviving with mGPS improvement at Week 12 was significantly higher in the tocilizumab group than in the control group (risk difference 0.88, 95% confidence interval 0.75-1.00; p < 0.001). Over the 12-week period, significant improvements were observed in body weight, albumin, CRP and mGPS in the tocilizumab group compared to the control group (body weight: 5.15 ± 0.53 kg vs. -5.69 ± 0.76 kg, p = 0.041; albumin: 5.89 ± 0.70 g/L vs. -2.97 ± 0.71 g/L, p < 0.001; CRP: -91.50 ± 7.15 mg/L vs. 9.47 ± 13.69 mg/L, p < 0.001; mGPS: -1.61 ± 0.15 vs. 0.03 ± 0.08, p < 0.001). The tocilizumab group also displayed significantly higher rates of improvement in appetite and fatigue (both p < 0.001). The incidence of Grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab-related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection., Conclusion: Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, CRP, mGPS and symptom burden in patients with NSCLC and concurrent IL-6-elevated cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Small cell lung cancer (SCLC) presents considerable challenges regarding the availability of second-line treatment options, which remain limited. The paucity of effective therapeutic choices at this setting emphasizes the urgent requirement for rigorous research and investigation into novel treatment strategies. To address this clinical gap, the current study aimed to compare the efficacy and safety of anlotinib with the standard second-line treatment, topotecan, in patients with relapsed SCLC., Methods: This retrospective collected data from SCLC patients who received either anlotinib or topotecan as second-line treatment. The primary endpoints were progression-free survival (PFS), while the secondary endpoints included the overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety assessment., Results: The study included 46 SCLC patients, with 20 receiving anlotinib and 26 receiving topotecan as second-line treatment. The anlotinib group showed a significantly longer median PFS compared to the topotecan group [5.6 vs. 2.2 months; hazard ratio (HR) =0.50; 95% confidence interval (CI): 0.27-0.92; P=0.02]. However, there was no statistically significant difference in OS between the two groups (9.1 vs. 7.7 months; HR =0.88; 95% CI: 0.46-1.70; P=0.71). The ORRs were 20.0% and 7.7% (P=0.48), and the DCRs were 70.0% and 23.1% (P=0.007) for the anlotinib and topotecan groups, respectively. Treatment-related adverse events (TRAEs) occurred in 13 patients (65.0%) in the anlotinib group and 20 (76.9%) in the topotecan group (P=0.49)., Conclusions: Anlotinib shows the potential to extend PFS and manageable adverse events (AEs) compared to topotecan in the second-line setting for relapsed SCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-274/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Background: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV., Results: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined., Conclusion: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology., (© 2024. The Author(s).)

To assess the value of parameters of myocardial work for dynamic monitoring of myocardial injury after neonatal asphyxia. Fifty-three neonates with asphyxia admitted within 24 h after delivery were divided into a mild asphyxia group (n = 40) and severe asphyxia group (n = 13). Echocardiography was performed within 24 h post-birth, within 72 h post-birth (48 h after first echo), and during recovery. The left ventricular ejection fraction on M-mode echocardiography and by Simpson's biplane method (LVEF and Bi-EF, respectively), stroke volume (SV), cardiac output (CO), cardiac index (CI), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and other parameters were measured. Echocardiographic indicators were compared between groups and over time. GWI was significantly increased at 72 h in the mild asphyxia group (P < 0.05) but showed no significant change over time in the severe asphyxia group (P > 0.05). While GCW increased significantly over time in both groups (P < 0.05), it increased earlier in the mild asphyxia group. Time and grouping factors had independent effects on GWI and GCW (P > 0.05). The characteristics of differences in GWI and GCW between the two groups were different from those for LVEF, Bi-EF, SV, CO, CI, and GLS and their change characteristics with improvement from treatment. GWI and GCW changed significantly during recovery from neonatal asphyxia, and their change characteristics differed between mild and severe asphyxia cases. Myocardial work parameters can be used as valuable supplements to traditional indicators of left ventricular function to dynamically monitor the recovery from myocardial injury after neonatal asphyxia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Walnut blight is a serious bacterial disease that affects the yield and quality of walnuts. Pantoea agglomerans is one of the main causative agents of walnut blight. However, there have been few studies on the response of walnuts to P. agglomerans infection., Methods: In this study, the soluble sugar, photosynthesis, antioxidant enzyme activities, and secondary metabolites were measured, and the transcriptomic analysis was performed to determine the response of walnut tissue cultures to P. agglomerans infection., Results: After pathogen inoculation, the soluble sugar content decreased, and photosynthesis was inhibited. Antioxidant enzyme (superoxide dismutase and peroxidase) activities and secondary metabolites (phenol and flavonoid) contents increased, especially in the early stages of inoculation. Transcriptomic analysis revealed that the phenylpropanoid biosynthesis pathway is induced after infection, and pathogen infection promotes ABA and ethylene signal transduction and inhibits auxin signaling. In addition, SA and JA-related gene expression was altered after inoculation with P. agglomerans , and the FLS- and calcium-mediated disease resistance signaling pathways were activated. Furthermore, our results suggested an involvement of the R-protein RPM-mediated disease resistance pathway in the response of walnuts to bacterial infections., Discussion: Our findings indicated that phenylpropanoid biosynthesis, hormone signal transduction, and plant-pathogen interaction have key roles in pathogenic inoculation, which provide insights into the molecular mechanisms in the response of walnuts to P. agglomerans infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 An, Wang, Wang, Li, Si, Zhao and Tian.)

Background: During the early stages of Trichinella spiralis infection, macrophages predominantly undergo polarization to the M1-like phenotype, causing the host's inflammatory response and resistance against T. spiralis infection. As the disease progresses, the number of M2-type macrophages gradually increases, contributing to tissue repair processes within the host. While cysteine protease overexpression is typically associated with inflammation, the specific role of T. spiralis cathepsin L (TsCatL) in mediating macrophage polarization remains unknown. The aim of this study was to assess the killing effect of macrophage polarization mediated by recombinant T. spiralis cathepsin L domains (rTsCatL2) on newborn larvae (NBL)., Methods: rTsCatL2 was expressed in Escherichia coli strain BL21. Polarization of the rTsCatL2-induced RAW264.7 cells was analyzed by enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR), western blot, immunofluorescence and flow cytometry. The effect of JSH-23, an inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), on rTsCatL2-induced M1 polarization investigated. Cytotoxic effects of polarized macrophages on NBL were observed using in vitro killing assays., Results: Following the co-incubation of rTsCatL2 with RAW264.7 murine macrophage cells, qPCR and ELISA revealed increased transcription and secretion levels of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, IL-1β and tumor necrosis factor alpha (TNF-α) in macrophages. Western blot analysis showed a significant increase in iNOS protein expression, while the expression level of arginase-1 protein remained unchanged. Flow cytometry revealed a substantial increase in the number of CD86-labeled macrophages. The western blot results also indicated that rTsCatL2 increased the expression levels of phospho-NF-κB and phospho-nuclear factor-κB inhibitor alpha (IκB-α) proteins in a dose-dependent manner, while immunofluorescence revealed that rTsCatL2 induced nuclear translocation of the p65 subunit of NF-κB (NF-κB p65) protein in macrophages. The inhibitory effect of JSH-23 suppressed and abrogated the effect of rTsCatL2 in promoting M1 macrophage polarization. rTsCatL2 mediated polarization of macrophages to the M1-like phenotype and enhanced macrophage adhesion and antibody-dependent cell-mediated cytotoxicity (ADCC) killing of NBL., Conclusions: The results indicated that rTsCatL2 induces macrophage M1 polarization via the NF-κB pathway and enhances the ADCC killing of NBL. This study provides a further understanding of the interaction mechanism between T. spiralis and the host., (© 2023. The Author(s).)

Non-suicidal self-injury (NSSI) is becoming increasingly common in adolescents and seriously affects their physical and mental health, and it is also a major risk factor for suicide among adolescents. NSSI has now become a public health issue of general concern; however, the identification of cognitive dysfunction in NSSI is still based on neuropsychological cognitive assessment and subjective questionnaire assessment, with a lack of objective evaluation indicators. As a method for studying the cognitive neural mechanism of NSSI, electroencephalography is a reliable tool for finding objective biomarkers of NSSI. This article reviews the recent research on electrophysiology associated with cognitive dysfunction in adolescents with NSSI.

Background: The genus Rickettsia contains the lineages spotted fever group (SFG), typhus group (TG), and transitional group (TRG). The spotted fever group Rickettsia (SFGR) is transmitted by ticks. The tick species Dermacentor nuttalli is considered the main vector carrying SFGR in Inner Mongolia. Studying the genetic diversity and population structure of Rickettsia is essential for developing effective control strategies and predicting evolutionary trends of Rickettsia., Methods: In 2019 we collected 408 D. nuttalli in the Inner Mongolia Autonomous Region, detected the percentage of Rickettsia-positive specimens, and characterized the haplotypes. From the Rickettsia-positive ticks, the gltA and ompA genes were extracted, amplified, and sequenced., Results: Ten haplotypes of the gltA gene and 22 haplotypes of the ompA gene were obtained. The phylogenetic analysis showed that the haplotypes G1-G7 and G9 of the gltA gene cluster with Rickettsia raoultii, while G8 and G10 cluster with Rickettsia sibirica. Haplotypes O1-O15, O18 and O20-O22 of the ompA gene cluster with R. raoultii, while O16 and O19 cluster with R. sibirica. The average haplotype diversity was 0.3 for gltA and 0.7 for ompA. The average nucleotide diversity was greater than 0.05. Neutrality tests were nonsignificant for Tajima's D results and Fu's Fs results. The fixation index values (F ST ) showed that the degree of genetic differentiation between most sampled populations was small (F ST  < 0.05), whereas some populations showed a medium (F ST  > 0.05) or large (F ST  > 0.15) degree of differentiation. Analysis of molecular variance (AMOVA) revealed that the variation within populations was greater than that between populations. The mismatch analysis of Rickettsia showed double peaks., Conclusions: We found two Rickettsia spp. (R. raoultii and R. sibirica). The high genetic disparity of Rickettsia allows for easy adaption to different environments. Genetic differentiation between populations is small, and Rickettsia populations do not show a geographically differentiated structure. The high rates of retention and infection of Rickettsia in D. nuttalli together with the animal husbandry exchange in Inner Mongolia gradually led to the harmonization of genetic characteristics of Rickettsia across various regions. Overall, the significant genetic diversity and geographical structure of Rickettsia in D. nuttalli are critical for SFGR control., (© 2022. The Author(s).)

1. The aim of this study was to explore the effects of acute heat stress on serum hormone levels and the expression of genes and proteins related to the unfolded protein response (UPR) pathway and apoptotic process in the liver of broilers.2. A total of 144 Arbor Acres broilers (35-d-old) were randomly allocated to 4 different environmental-controlled chambers for acute heat exposure. The temperature of the 4 environmental chambers was adjusted to 26°C (control), 29°C, 32°C, and 35°C within 1 h, respectively. The blood and liver samples were collected after 6 h of constant heat exposure at set temperatures.3. The results showed that 6 h of acute heat stress increased serum hormone levels and up-regulated the expression of heat shock protein. The endoplasmic reticulum (ER) stress markers, GRP78 and GRP94, in the liver of broilers were significantly upregulated at the mRNA and protein levels. The PERK, IRE1 , and XBP1 genes, which are involved in the unfolded protein response signalling, were significantly up-regulated at the mRNA levels. However, other pro-apoptotic genes showed no significant changes in the liver of broiler chickens in all groups except for upregulation of the anti-apoptotic gene BCL-xl .4. The results suggested that broilers have tolerance to acute heat stress to a certain extent. The UPR activation can alleviate ER stress and further prevent apoptosis in the liver of broilers under short-term exposure to high ambient temperatures.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Tyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of erb-b2 receptor tyrosine kinase 2 (ERBB2/HER2) have been extensively reported in non-small cell lung cancer (NSCLC). Nevertheless, the clinical significance of non-TKD mutations remains unknown. To date, no clinical trials have revealed that tyrosine kinase inhibitors are effective in NSCLC patients with non-TKD ERBB2 mutations. Here we report a patient with advanced lung adenocarcinoma harboring non-TKD mutation of ERBB2, S335C, without other actionable alterations benefited from pyrotinib. After first-line treatment of pyrotinib monotherapy, a pan-HER inhibitor, the patient achieved a durable partial response with good tolerance. This case powerfully illustrates that pyrotinib might be a promising first-line treatment strategy for NSCLC patients with non-TKD mutation of ERBB2., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Ticks (Arthropoda, Ixodida), after mosquitoes, are the second most prevalent vector of infectious diseases. They are responsible for spreading a multitude of pathogens and threatening the health and welfare of animals and human beings. However, given the history of tick-borne pathogen infections in the Inner Mongolia Autonomous Region of China, surprisingly, neither the genetic diversity nor the spatial distribution of haplotypes within ticks has been studied., Methods: We characterized the haplotype distribution of Dermacentor nuttalli in four main pastoral areas of the Inner Mongolia Autonomous Region, by sampling 109 individuals (recovered from sheep) in April-August 2019. The 16S rRNA gene, cytochrome c oxidase subunit I (COI), and the internal transcribed spacer 2 region (ITS2) were amplified and sequenced from extracted DNA., Results: Twenty-six haplotypes were identified using 16S rRNA sequences, 57 haplotypes were identified with COI sequences, and 75 haplotypes were identified with ITS2 sequences. Among the three genes, total haplotype diversity was greater than 0.7, while total nucleotide diversity was greater than 0.06. Neutrality tests revealed a significantly negative Tajima's D result, while Fu's Fs was not significantly positive. Fixation index values (F ST ) indicated that the degree of genetic differentiation among some sampled populations was small, while for others it was moderate. Analysis of molecular variance (AMOVA) revealed that the variation within populations was greater than that among populations. The mismatch analysis of D. nuttalli exhibited double peaks., Conclusion: The genetic diversity of D. nuttalli populations in our region can likely adapt to different geographical environments, thereby leading to genetic diversity, and creating genetic differentiation among different populations. However, genetic differentiation is cryptic and does not form a pedigree geographical structure.

This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = -0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.

Objective: To investigate the types and distribution of blood-sucking insects and arboviruses in Inner Mongolia autonomous region, and provide basic data for the prevention of arbovirus transmitted disease. Methods: Blood-sucking insects were collected by lamp trapping method in nature. Mosquito samples were classified according to morphologic characteristics and then stored at liquid nitrogen. Viruses were isolated in cell culture and characterized, using molecular biological methods. Results: A total of 24 240 mosquitoes and 17 110 aphids were collected from 2 sites of 5 counties (Flags) in Inner Mongolia in 2014 and during 2017-2018. Among them, Japanese encephalitis virus gene was detected in Culex pipiens pallens, and 4 virus strains isolates which could be stably passaged. The isolates were identified as Getah virus and densonucleosis virus by molecular biology identification. Phylogenetic analysis on the E2 gene of the Getah virus (NMDK1813-1) showed that it belonged to the same evolutionary branch of the Gansu isolates (GS10-2) and having six common amino acid variation sites. Conclusions: The emergence of Japanese encephalitis virus and Getah virus from specimen of mosquitoes in Inner Mongolia indicated the new challenges on the prevention and control of arbovirus and related diseases. The results pf this study provided basic data for the prevention and control stretagies of arbovirus transmitted diseases in Inner Mongolia.

Background: Frequent recurrent hepatic metastasis after hepatic metastasectomy is a major obstacle in the treatment of colorectal liver metastasis (CRLM). We performed the present systematic review to evaluate the short- and long-term outcomes after repeat hepatectomy for recurrent CRLM and determine factors associated with survival in these patients., Data Sources: An electronic search of PubMed database was undertaken to identify all relevant peer-reviewed papers published in English between January 2000 and July 2018. Hazard ratios (HR) with 95% confidence interval (95% CI) were calculated for prognostic factors of overall survival (OS)., Results: The search yielded 34 studies comprising 3039 patients, with a median overall morbidity of 23% (range 8%-71%), mortality of 0 (range 0-6%), and 5-year OS of 42% (range 17%-73%). Pooled analysis showed that primary T3/T4 stage tumor (HR = 1.94; 95% CI: 1.04-3.63), multiple tumors (HR = 1.49; 95% CI: 1.10-2.01), largest liver lesion ≥5 cm (HR = 1.89; 95% CI: 1.11-3.23) and positive surgical margin (HR = 1.80; 95% CI: 1.09-2.97) at initial hepatectomy, and high serum level of carcinoembryonic antigen (HR = 1.87; 95% CI: 1.27-2.74), disease-free interval ≤12 months (HR = 1.34; 95% CI: 1.10-1.62), multiple tumors (HR = 1.64; 95% CI: 1.32-2.02), largest liver lesion ≥5 cm (HR = 1.85; 95% CI: 1.34-2.56), positive surgical margin (HR = 2.25; 95% CI: 1.39-3.65), presence of bilobar disease (HR = 1.62; 95% CI: 1.19-2.20), and extrahepatic metastases (HR = 1.60; 95% CI: 1.23-2.09) at repeat hepatectomy were significantly associated with poor OS., Conclusions: Repeat hepatectomy is a safe and effective therapy for recurrent CRLM. Long-term outcome is predicted mainly by factors related to repeat hepatectomy., (Copyright © 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy. We conducted a systematic review and meta-analysis to assess the evidence available on the long-term outcomes of cHCC-CC patients after either hepatectomy or liver transplantation (LT)., Data Sources: Relevant studies published between January 2000 and January 2018 were identified by searching PubMed and Embase and reviewed systematically. Data were pooled using a random-effects model., Results: A total of 42 observational studies involving 1691 patients (1390 for partial hepatectomy and 301 for LT) were included in the analysis. The median tumor recurrence and 5-year overall survival (OS) rates were 65% (range 38%-100%) and 29% (range 0-63%) after hepatectomy versus 54% (range 14%-93%) and 41% (range 16%-73%) after LT, respectively. Meta-analysis found no significant difference in OS and tumor recurrence between LT and hepatectomy groups., Conclusion: Hepatectomy rather than LT should be considered as the prior treatment option for cHCC-CC., (Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy and safety of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with stage ⅢB/Ⅳ NSCLC who progressed after two lines or more regimens were randomized into anlotinib group (12 mg daily from day 1 to 14 of a 21-day cycle) or placebo group with ratio of 2∶1. Study drugs or placebo were given until disease progression or intolerable toxicity. The primary endpoint was overall survival (OS), and the second endpoints were progression free survival (PFS), objective response rate, and disease control rate. Results: Between April 2015 and December 2015, twenty-four patients were assigned at Peking Union Medical College Hospital. The baseline characteristics of the anlotinib group ( n= 16) and placebo group ( n= 8) were fairly comparable. The median OS was 12.7 months in anlotinib group and 11.1 months in placebo group ( P= 0.460).The median PFS was 4.0 months in anlotinib group and 1.4 months in placebo group ( P= 0.065).The common adverse events were manageable such as hypertension, hand-foot syndrome, thyroiddy sfunction. No drug-related mortality occurred. Conclusions: Anlotinib had a trend of improvement in OS and PFS as third-line treatment or beyond in advanced NSCLC compared with placebo with manageable toxicity. ClinicalTrials:: NCT02388919.

Background: Hepatic angiosarcoma is a rare malignant vascular tumor presenting unique treatment challenges. The aim of the present study was to determine the treatment and prognosis of this entity., Data Sources: A systematic literature search was conducted using PubMed, Embase and Chinese Biomedical Literature database, to identify articles published from January 1980 to July 2017. Search terms were "hepatic angiosarcoma" and "liver angiosarcoma". Additional articles were retrieved through manual search of bibliographies of the relevant articles. Pooled individual data concerning the prognosis following various therapeutic modalities were analyzed., Results: A total of 75 articles involving 186 patients were eligible for inclusion. The median overall survival (OS) was 8 months, with 1-, 3-, and 5-year OS rates of 36.6%, 22.3%, and 12.0%, respectively. The median OS after partial hepatectomy (n = 86), chemotherapy (n = 36), liver transplantation (n = 17), and supportive care (n = 46) were 15, 10, 5 and 1.3 months, respectively. Small tumor size (<10 cm) was the only significant favorable factor for OS after partial hepatectomy (P = 0.012)., Conclusions: Despite the dismal prognosis, partial hepatectomy could prolong the survival of hepatic angiosarcoma patients, particularly those with tumors <10 cm. Chemotherapy could be an option for unresectable disease. Liver transplantation is not a recommendable option for the management of this malignancy., (Copyright © 2018. Published by Elsevier B.V.)

Background and Objective: To assess the safety and therapeutic outcome of different surgical interventions for severe pancreatic fistula after pancreatoduodenectomy., Methods: A systematic literature search was performed in PubMed database for relevant articles published between 1990 and March 2017. Descriptive statistics were performed and data are expressed as mean., Results: Twenty-four studies involving 370 patients undergoing surgical interventions for severe pancreatic fistula after pancreatoduodenectomy were included. Rates of further relaparotomy, in-hospital mortality, and long-term endocrine insufficiency were reported for completion pancreatectomy (31.8%, 42% and 100% respectively), disconnection of anastomosis with preservation of a pancreatic remnant (25%, 21.3% and 17.8% respectively), internal or external wirsungostomy (10.4%, 14.9%, and 12.3% respectively), salvage pancreaticogastrostomy (12.5%, 0% and 25%, respectively), and simple peripancreatic drainage (30%, 47.9% and 12.5%, respectively)., Conclusions: The pancreas-preserving strategy of disconnection of anastomosis with preservation of a pancreatic remnant, internal or external wirsungostomy, and salvage pancreatogastrostomy seems to be the preferred option for the treatment of severe pancreatic fistula after pancreatoduodenectomy. As completion pancreatectomy is a very aggressive treatment, it should only be reserved for specific instances in which organ-preserving resection is technically unfeasible., (Copyright © 2017 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

Inflammatory bowel disease (IBD) is a chronic relapsing disease in gastrointestinal tract. Conventional medications lack the efficacy to offer complete remission in IBD therapy, and usually associate with serious side effects. Recent studies indicated that nanoparticle-based nanotherapeutics may offer precise and safe alternative to conventional medications via enhanced targeting, sustained drug release, and decreased adverse effects. Here, we reviewed orally cell-specific nanotherapeutics developed in recent years. In addition, the various obstacles for oral drug delivery are also reviewed in this manuscript. Orally administrated cell-specific nanotherapeutics is expected to become a novel therapeutic approach for IBD treatment., Competing Interests: Conflict-of-interest statement: The authors declared no conflict of interest related to this study.

Integrating droplet-based microfluidics with mass spectrometry is essential to high-throughput and multiple analysis of single cells. Nevertheless, matrix effects such as the interference of culture medium and intracellular components influence the sensitivity and the accuracy of results in single-cell analysis. To resolve this problem, we developed a method that integrated droplet-based microextraction with single-cell mass spectrometry. Specific extraction solvent was used to selectively obtain intracellular components of interest and remove interference of other components. Using this method, UDP-Glc-NAc, GSH, GSSG, AMP, ADP and ATP were successfully detected in single MCF-7 cells. We also applied the method to study the change of unicellular metabolites in the biological process of dysfunctional oxidative phosphorylation. The method could not only realize matrix-free, selective and sensitive detection of metabolites in single cells, but also have the capability for reliable and high-throughput single-cell analysis.

Background/objective: Postoperative nausea and vomiting (PONV) is one of the most common and distressing adverse events after laparoscopic cholecystectomy (LC). A meta-analysis of randomized clinical trials (RCTs) was performed to determine the efficacy and safety of dexamethasone combined with other antiemetic in the prevention of PONV in patients undergoing LC., Methods: A systematic literature search was conducted to identify all relevant RCTs. The primary outcome was PONV in the early period (0-3 hours, 0-4 hours, or 0-6 hours), late period (>6 hours), and the overall period (0-24 hours)., Results: Nine RCTs with a total of 1089 patients were included in the analysis. Pooled analysis showed that dexamethasone combined with other antiemetics provided significantly better prophylaxis than single antiemetics in the early period [odds ratio (OR): 0.34; 95% confidence interval (CI): 0.21-0.55; p < 0.001], late period (OR: 0.35; 95% CI: 0.22-0.57; p < 0.001), and the overall period (OR: 0.36; 95% CI: 0.27-0.49; p < 0.001). Correspondingly, rescue antiemetic usage was significantly less in the combination therapy group (OR: 0.22; 95% CI: 0.12-0.41; p < 0.001). The most frequently reported adverse events were headache, dizziness, and itching. The incidence of adverse events did not differ between the two groups., Conclusion: Dexamethasone combined with other antiemetics was significantly better than single antiemetics for prophylaxis of PONV in patients undergoing LC, without apparent side effects., (Copyright © 2014. Published by Elsevier Taiwan.)

Acute renal failure is one of the most common complications observed in hospitals. Although extensive studies have been carried out to search for therapeutic treatments, no effective cure has been established. In recent years, stem cell therapy for tissue engineering and repair has become a key area of study. Bone marrow mesenchymal stem cells (MSCs) have been demonstrated to exhibit a reparative role in ischemia reperfusion-injured kidney tissue, and the stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis has been found to play an important role in the migration and homing of MSCs. In the present study, transforming growth factor-β1 (TGF-β1) in the homogenate of the acute ischemia reperfusion-injured renal tissue was found to markedly increase the CXCR4 surface expression of MSCs, which contributes to the migration of MSCs to SDF-1. Neutralization of TGF-β1 inhibited the migration in an antibody concentration-dependent manner, through downregulation of CXCR4 localized to the membrane. These observations suggest a potential mechanism for MSC migration to the kidney which may provide a possible therapeutic target for curing acute renal failure.

As a barrier to metastasis of cancer, cells that lost contact with the neighbouring cells or extracellular matrix(Extracellular matrix, ECM) will be subjected to apoptosis. This cell death process has been termed "anoikis". When normal epithelial cells or solid tumor cells without metastatic potential detach from the primary site, and then enter into the circulatory system, the anoikis mechanism will be activated. The significance of anoikis is to prevent the shedding cells from growing and implanting into other inappropriate sites. Tumor cells, especially several malignant cells that is prone to transfer to distant sites, have properties of anti-anoikis, which facilitates metastasis as well as invasion of tumor cells. The studies found that tumor cells can resist anoikis through multiple mechanisms: the pro-survival pathways are activated by cells autocrine growth factors and paracrine factors derived from neighboring cells; cells change the pattern of integrin expression so that they can receive survival signals from new environment; reactive oxygen species (ROS) activates growth factor receptors in a ligand-independent way to avoid apoptosis; and epithelial-mesenchymal transformation(EMT) is activated etc.. All of these mechanisms lead to activation of survival signals and inhibition of apoptotic pathways, and ultimately cause resistance to anoikis as well as metastasis. This paper summarizes the key mechanisms of the current studies on metastasis, which also suggest important targets for cancer therapy.

Aspirin is an important antithrombotic agent. However, its clinical benefit is impaired by aspirin resistance. The term of "aspirin resistance" usually refers to laboratory resistance. It can be identified by measuring thromboxane A2 or thromboxane-dependent platelet function. Clinical trials have shown that laboratory aspirin resistance is correlated with vascular events.

Objective: To evaluate the effect of Valeriana officinalis var latifolia(VOL) on expression of transforming growth factor beta 1 (TGF-beta 1) in hypercholesterolemic rats and study its possible mechanisms., Method: Dietary-induced hypercholesterolemia was induced in male Wistar rats by given 4% cholesterol and 1% cholic acid diet for 16 weeks. Changes of serum lipid, urinary albumin, renal function and Mesangial matrix index were assessed. Moreover, immunohistochemical stain for TGF-beta 1 and type IV collagen were performed., Result: VOL could reduce the serum levels of total cholesterol, low density lipoprotein, urinary albumin and serum creatinine. Light microscopy and immunohistochemical stain revealed that in the same time of lowing serum lipid, Mesangial matrix index was significantly reduced, accompanied by decreased expression of TGF-beta 1 and type IV collagen., Conclusion: VOL has the protective effect on lipid-induced nephropathy, and the inhibition of TGF-beta 1 expression might be the mechanism of VOL on renal protection.