简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is a disorder of lipid metabolism. The lipotoxic intermediates of lipid metabolism cause mitochondrial dysfunction and endoplasmic reticulum stress. Organelle-specific autophagy is responsible for the removal of dysfunctional organelles to maintain intracellular homeostasis. Lipophagy contributes to lipid turnover by degrading lipid droplets. The level of autophagy changes during the course of NAFLD, and the activation of hepatocyte autophagy might represent a method of treating NAFLD.

简介：AbstractBackground:Response to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.Methods:The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.Results:Forty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs. 15.5 months, P = 0.0005) and OS (11.1 months vs. not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs. 15.5 months, P = 0.0532) rather than OS (P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs. 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS (P = 0.0052) but not OS (P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[φ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4).Conclusions:Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

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简介：AbstractFor the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

简介：AbstractObjective:Amino acyl modification of lysine residues is an essential mechanism of nutrient sensing that regulates various biological functions including reproduction. At present, the lack of pan-specific antibodies for a recently identified lysine valylation hinders the characterization and detection of this modification. The objective of this study is to raise pan-specific antibodies that may facilitate the identification of novel expression patterns of lysine valylation.Methods:Chicken ovalbumin was valylated as an immunogen to raise polyclonal antibodies (PcAbs) in rabbits. The population of the pan-specific antibodies recognizing valylated lysine was purified using the chemically synthesized valylated peptides consisting of random amino acids. The specificity of the antibodies was evaluated using ELISA, dot blots, Western blots, and immunohistochemistry (IHC) staining in human epididymis as well.Results:A preliminary and simple strategy to make an anti-valylated lysine PcAb was developed. The recognition of the antibodies to valyllysine was evaluated as pan specific. This was useful for the detection of the newly identified valyl modification using ELISA, dot blots, and Western blots. The antibodies were also successfully utilized in IHC assays, which revealed novel valyllysine modification patterns in epididymis tissues of human.Conclusions:A new antibody tool was provided for the study of lysine valylation. The novel expression patterns of valyllysine in the epididymis suggest that this modification may be involved in sperm maturation.

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简介：AbstractObjective:It has recently been shown that the melanoma antigen gene (MAGE) family is expressed in various tumor cell lines but silent in normal tissues, except germ cell lines. Mageb4, a member of the MAGE family, is highly expressed in the testis and homologous in humans and mice. Whole-exome sequencing studies have identified Mageb4 as a possible X-linked cause of inherited male infertility. However, the function of Mageb4 protein remains largely unknown.Methods:Using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) 9 technology, we generated a Mageb4 knockout mouse model (Mageb4-/Y) to explore the role of this gene in spermatogenesis.Results:First, immunostaining of testicular cells showed that Mageb4 is localized in the cytoplasm of spermatogonia. Second, Mageb4-/Y male mice displayed significant increases in apoptosis. However, Mageb4-/Y male mice showed normal fertility, including normal sperm concentration, sperm motility, and testicular and epididymal histology.Conclusions:These findings suggest that, despite testis-exclusive expression, Mageb4 is dispensable for mouse spermatogenesis. Future research should focus on the role of this gene in apoptosis, aiming to provide clinical guidance regarding male infertility.

简介：AbstractMolecular imaging is of great significance for early diagnosis and timely treatment of cancer and disease, as well as basic medical and biological research. As personalized cancer treatment has become increasingly popular, the demand for more advanced imaging technologies has also significantly increased. Taking advantage of differences between the tumor microenvironment and normal tissue cells, tumor microenvironment-responsive or "turn-on" contrast agents have a higher signal-to-noise ratio and lower background interference compared with "turn-off" probes, which can remarkably improve the performance of tumor diagnostics. Thus, tumor microenvironment-responsive contrast agents can not only detect changes in the tumor microenvironment, but also have important significance for tumor diagnosis, prediction of invasion potential, evaluation of treatment effectiveness, planning of therapeutic regimens, and tumor prognosis. Herein, this review focuses on recent research progress of tumor microenvironment-responsive intelligent probes, and highlights future research directions of tumor microenvironment-responsive contrast agents for precision diagnostics.

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简介：AbstractPurpose:Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE.Methods:A systematic literature review searched "liver trauma" , "hepatic trauma" , "conservative management" , "non operative management" on MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials databases, EMBASE, and Google Scholar, to identify studies published on the conservative management of traumatic liver injuries between January 1990 and June 2020. Patients with traumatic liver injuries (blunt and penetrating) treated by NOM, described at least one outcome of interests and provided morbidity outcomes from NOM were included in this study. Studies reported the outcome of NOM without separating liver from other solid organs; studies reported NOM complications together with those post-intervention; case reports; studies including less than 5 cases; studies not written in English; and studies including patients who had NOM with AE as primary management were excluded. Efficacy of NOM and overall morbidity and mortality were assessed, the specific causes of morbidity were investigated, and the American Association for the Surgery of Trauma classification was used in all the studies analysed. Statistical significance has been calculated using the Chi-square test.Results:A total of 19 studies qualified for inclusion criteria were in this review. The NOM success rate ranged from 85% to 99%. The most commonly reported complications were hepatic collection (3.1%), followed by bile leak (1.5%), with variability between the studies. Other complications included hepatic haematoma, bleeding, fistula, pseudoaneurysm, compartment syndrome, peritonitis, and gallbladder ischemia, all with an incidence below 1%.Conclusion:NOM with simple clinical observation showed an overall low incidence of complications, but higher for bile leak and collections. In patients with grade III and above injuries, the incidence of bile leak, collections and compartment syndrome did not show a statistically significant difference with the AE group. However, the latter result is limited by the small number of studies available and it requires further investigations.

简介：AbstractWith the widespread adoption of advanced tourniquets, the mortality rate of limb wound hemorrhage has decreased significantly, and non-compressible torso hemorrhage has gradually occupied the leading position of potentially preventable death, both in military and civilian circumstances. With the emergence of novel hemostatic devices and materials, strategies for the management of non-compressible torso hemorrhage have changed significantly. This review summarizes the current treatment strategies and types of equipment for non-compressible torso hemorrhage and suggests future research directions, hoping to provide a comprehensive review for the medical personnel and researchers engaging in this field.

简介：AbstractObjective:There are few studies evaluating the impact of Aspirin-exacerbated respiratory disease (AERD) treatment on otologic symptoms. The aim of this study is to evaluate the effects of endoscopic sinus surgery (ESS) and aspirin desensitization (AD) on otologic symptoms in subjects with AERD.Methods:Retrospective chart review of adult patients diagnosed with AERD at our tertiary Care Academic Medical Center-Otorhinolaryngology Department. Charts of adult patients diagnosed with AERD who underwent ESS and ASA desensitization at our institution’s AERD Center from 2016 to 2019 were reviewed. Sino-Nasal Outcomes Test 22-item survey (SNOT-22) scores were evaluated for patients at various time points including: pre-surgery, post-surgery/pre-aspirin desensitization, and various times post-desensitization up to >12 months. Within the SNOT-22, otologic-specific subdomain scores were evaluated at similar time points. Patients on immunomodulatory medications other than corticosteroids were excluded from analysis.Results:SNOT-22 scores were analyzed for 121 patients. There was a significant improvement in overall SNOT scores from pre-surgery (44.62) to post surgery/pre-desensitization (23.34) (P < 0.0005). Similarly, SNOT-22 otologic-specific scores also improved after surgery prior to desensitization (3.19-2.04) (P = 0.005). Following AD, the improvement in the overall SNOT-22 continued to improve for up to 12 months (P < 0.005). While the otologic-specific SNOT-22 scores remained stable after surgery and ASA desensitization.Conclusion:ESS and AD reduce otologic-specific SNOT-22 scores and parallel trends in overall SNOT-22 scores. The effect of treatment is durable over the course of 12 months. Future work should aim to correlate otologic SNOT-22 scores with objective otologic data.

简介：AbstractIncreasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.

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简介：AbstractBackground:BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is an important cause of dysfunction and failure of renal transplants. This study aimed to assess the diagnostic performance of morning urine specific gravity (MUSG) in diagnosing BKPyVAN in kidney transplant recipients.Methods:A total of 87 patients, including 27 with BKPyVAN, 22 with isolated BKPyV viruria, 18 with T cell-mediated rejection(TCMR), and 20 with stable graft function, were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February 2017. MUSG at biopsy and during a follow-up period of 24 months after biopsy was collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of MUSG to discriminate BKPyVAN.Results:At biopsy, the MUSG of BKPyVAN group (1.008 ± 0.003) was significantly lower than that of isolated BK viruria group(1.013 ± 0.004, P < 0.001), TCMR group (1.011 ± 0.003, P = 0.027), and control group (1.014 ± 0.006, P < 0.001). There was no significant difference in MUSG among the isolated BK viruria group, TCMR group, and control group (P = 0.253). In BKPyVAN group, the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma, reaching a statistical difference at 3 months after treatment (1.012 ± 0.003, P < 0.001) compared with values at diagnosis. ROC analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009, with an area under the ROC curve (AUC) of 0.803 (95% confidence interval [CI]: 0.721–0.937). For differentiating BKPyVAN and TCMR, the optimal MUSG cut-off value was 1.010, with an AUC of 0.811 (95% CI: 0.687–0.934).Conclusion:Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.

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简介：AbstractThe philosophy of abdominal injury management is currently changing from mandatory exploration to selective non-operative management (NOM). The patient with hemodynamic stability and absence of peritonitis should be managed non-operatively. NOM has an overall success rate of 80%—90%. It also can reduce the rate of non-therapeutic abdominal exploration, preserve organ function, and has been defined as the safest choice in experienced centers. However, NOM carries a risk of missed injury such as hollow organ injury, diaphragm injury, and delayed hemorrhage. Adjunct therapies such as angiography with embolization, endoscopic retrograde cholangiopancreatography with stenting, and percutaneous drainage could increase the chances of successful NOM. This article aims to describe the evolution of NOM and define its place in specific abdominal solid organ injury for the practitioner who faces this problem.

简介：AbstractEndometriosis (EM) is a benign gynecological disease that affects the fertility and health of women of reproductive age; it is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Although several hypotheses have been proposed to explain the underlying cause of EM, its pathogenesis remains obscure. Recently, non-coding RNAs were reported to be involved in the occurrence and development of EM. MicroRNAs and long non-coding RNAs are the main members of the non-coding RNA family that contribute to EM progression in various aspects, such as cell proliferation, apoptosis, invasion, and angiogenesis. Angiogenesis plays a pivotal role in the initiation and development of EM and provides a substantial background for the invasion, proliferation, and long-term growth of endometriotic implants. This review aimed to investigate the role of microRNAs and long non-coding RNAs in regulating angiogenesis in EM and discuss how this mechanism can be used for diagnostic and therapeutic purposes in EM.

简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

简介：AbstractBackground:There is limited evidence of the effects of local anesthesia (LA) on outcomes of non-surgical periodontal treatment (NSPT), in particular among the Chinese. This retrospective cohort study aimed to evaluate the effects of LA on short-term treatment outcomes of NSPT and to determine under what circumstances LA should be prescribed to improve these outcomes.Methods:Data from periodontal examinations of 3980 patients were used. The data were from 3-month re-evaluation records of an electronic periodontal charting record system in the Department of Periodontology of Peking University School and Hospital of Stomatology from June 2008 to January 2015. Descriptive analyses included changes in probing depth (PD) and the Mazza bleeding index (BI). Two-level (patient and tooth) logistic regression models and three-level (patient, tooth, and site) linear regression models were constructed to analyze the influence of LA on PD for all teeth/sites and teeth/sites with an initial PD ≥ 5 mm. Decreases in PD and BI at sites under LA using the initial PD were also compared.Results:A significantly higher mean decrease in PD after NSPT was found in the LA group than in the no local anesthesia (NLA) group (0.98 vs. 0.54 mm, t = 24.12, P < 0.001). A significantly higher probability of decreases was found in the LA group in BI (percentages of teeth with BI > 1 and BI > 2) for all teeth (16.7% vs. 13.8%, t=3.75, P < 0.001; 34.7% vs. 28.1%, t = 6.73, P < 0.001) and PD for teeth with PD ≥ 5 mm (32.3% vs. 17.3%, t = 28.48, P < 0.001). The difference in PD between the LA and NLA groups increased as the initial PD increased. The difference between the two groups was 0.12 to 0.22 mm for sites with a baseline PD < 7 mm; however, it increased to 0.41 to 1.37 mm for sites with a baseline PD ≥ 7 mm.Conclusions:LA improved the decrease in PD after NSPT. Root debridement at sites with initial PD ≥ 7 mm should be performed under routine LA.