The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

[Construction of the Whole Process Management Model of Hospice and Palliative Care Outpatient Clinic].

Objective To construct a scientific and practical management model of the hospice and palliative care outpatient clinic and provide a reference for the operation and development of the outpatient clinic. Methods The basic framework of the whole process management model of hospice and palliative care outpatient clinic was determined preliminarily by literature analysis,qualitative interviews and experts group meetings.Two rounds of consultation were conducted among 18 experts in hospice and palliative care and medical-nursing combined outpatient service by the Delphi method. Results The questionnaire response rates of the two rounds of expert consultation were both 100% and the authority coefficients of the two rounds of expert consultation were 0.88 and 0.91,respectively.Finally,the whole process management model of hospice and palliative care outpatient clinic was constructed,which was composed of three first-level indicators including staff composition,work structure and effect evaluation,5 second-level indicators and 62 third-level indicators. Conclusion The constructed whole process management model is scientific,innovative and continuous,which can provide a reference for the operation and development of the hospice and palliative care outpatient clinic.

Heme oxygenase-1 inhibits the cytotoxicity of natural killer cells to acute myeloid leukemia by downregulating human leukocyte antigen-C.

BACKGROUND AIMS: Recently, immune escape has been considered as a factor leading to relapse of acute myeloid leukemia (AML). In our previous study, heme oxygenase 1 (HO-1) proved to play an essential role in the proliferation and drug resistance of AML cells. In addition, recent studies by our group have shown that HO-1 is involved in immune escape in AML. Nevertheless, the specific mechanism by which HO-1 mediates immune escape in AML remains unclear. METHODS: In this study, we found that patients with AML and an overexpression of HO-1 had a high rate of recurrence. In vitro, overexpression of HO-1 attenuated the toxicity of natural killer (NK) cells to AML cells. Further study indicated that HO-1 overexpression inhibited human leukocyte antigen-C and reduced the cytotoxicity of NK cells to AML cells, leading to AML relapse. Mechanistically, HO-1 inhibited human leukocyte antigen-C expression by activating the JNK/C-Jun signaling pathway. RESULTS: In AML, HO-1 inhibits cytotoxicity of NK cells by inhibiting the expression of HLA-C, thus causing immune escape of AML cells. CONCLUSIONS: NK cell-mediated innate immunity is important for the fight against tumors, especially when acquired immunity is depleted and dysfunctional, and the HO-1/HLA-C axis can induce functional changes in NK cells in AML. Anti-HO-1 treatment can promote the antitumor effect of NK cells and may play an important role in the treatment of AML.

General Anesthesia Versus Regional Anesthesia in the Elderly Patients Undergoing Hip Fracture Surgeries: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Surgery is the preferred treatment option for the elderly patients with hip fractures. However, the choice of general anesthesia (GA) or regional anesthesia (RA) remains controversial. The quality of evidence has further improved with the advent of several high-quality randomized clinical trials (RCTs) in the last two years. The purpose of this study was to compare the clinical outcomes of two anesthetic techniques in elderly patients undergoing hip fracture surgeries. METHODS: Eligible studies were identified from PubMed/MEDLINE, Web of Science, Scopus, EMBASE and reference lists from January 2000 to June 2022 in this current systematic review and meta-analysis. The outcomes included the surgery-related outcomes (duration of surgery, duration of anesthesia, intraoperative blood loss and number of transfusions) and postoperative outcomes (30-day mortality, postoperative delirium,cardiovascular events and other complications). RESULTS: A total of 10 RCTs were included, and a total of 3594 patients were analyzed. RA was associated with shorter duration of surgery, shorter length of hospital stays and less intraoperative blood loss compared to GA. There were no significant differences between the two groups in the number of blood transfusions, duration of anesthesia, 30-day mortality or postoperative delirium. CONCLUSIONS: Our pooled analysis identified no significant differences in terms of the safety between RA and GA, while RA reduces intraoperative blood loss, length of hospital stays and duration of surgery. These results suggest that RA appears to be preferable for the elderly patients with hip fractures.

A novel technique of penetrating keratoplasty to prevent intraocular contents extrusion for infectious keratitis.

PURPOSE: To evaluate the safety and the effectiveness of our novel penetrating keratoplasty for infectious keratitis. METHODS: Retrospective, noncomparative, interventional case series of patients with infectious keratitis who received the novel penetrating keratoplasty technique were analyzed. A prepared plastic sheet was located between the diseased cornea and iris-lens diaphragm. After the diseased lesions were removed, the graft was positioned on the plastic sheet and sutured to the recipient bed. The plastic sheet was pulled out from the anterior chamber before the all interrupted sutures were placed. The intra- and post-operative complications, the outcome of the graft and the number of corneal endothelial cells were analyzed. RESULTS: A total of 82 eyes of 82 patients was included. The mean follow-up period was 29 ± 16 months (range from 13 to 45 months). No intraocular content extrusion, simultaneous cataract extraction and suprachoroidal hemorrhage occurred. Direct contact between the infectious cornea and the graft was successfully avoided. Greater than expected endothelial cell reduction or complications were not found. CONCLUSIONS: This modified technique effectively prevents the extrusion of intraocular contents while avoiding the direct contact with donor endothelium during the procedure. The occurrence rate of complications such as endothelial cell loss is not higher than the conventional methods.

A novel pupilloplasty in crescent-shaped suturing pattern for coloboma and traumatic iris defects.

OBJECTIVE: PURPOSE: To observe the safety and effect of the C-pupilloplasty for the treatment of iris coloboma and traumatic iris defects. METHODS: A total of 21 cases (21 eyes) with iris coloboma or traumatic iris defects who underwent C-pupilloplasty (a single-pass three-throw technique) from Feb. 2016 to Mar. 2020 were analyzed retrospectively. Uncorrected visual acuity, refraction, corneal topographic keratometry and endothelial cell density were examined. RESULTS: All the patients were successfully treated, and a central and round pupil was restored. The mean follow-up duration was 8.76 ± 3.58 months (ranging from 2 to 14 months). All patients had round or round-like pupils with a diameter less than or equal to 3 mm after the C-pupilloplasty. Very slightly endothelial loss, negligible symptoms such as glare, distortion, dizziness and photophobia were observed. CONCLUSION: We introduced a new technique of pupilloplasty (C-pupilloplasty) which could be a more straight forward and more effective treatment for iris coloboma and traumatic iris defect.

Fatal, non-fatal burden of cancer in the elderly in China, 2005-2016: a nationwide registry-based study.

BACKGROUND: As populations age, cancer burden becomes increasingly conspicuous. This study quantified the cancer burden of the elderly (≥ 60 years) in China, based on the China Cancer Registry Annual Report to provide epidemiological evidence for cancer prevention and control. METHODS: Data on cancer cases and deaths among the elderly aged ≥ 60 years were collected from the China Cancer Registry Annual Report, 2008-2019. Potential years of life lost (PYLL) and disability-adjusted life years (DALY) were calculated to analyze fatalities and the non-fatal burden. The time trend was analyzed using the Joinpoint model. RESULTS: From 2005 to 2016, the PYLL rate of cancer in the elderly was stable between 45.34‰ and 47.62‰, but the DALY rate for cancer decreased at an average annual rate of 1.18% (95% CI: 0.84-1.52%). The non-fatal cancer burden in the rural elderly was higher than that of the urban elderly. Lung, gastric, liver, esophageal, and colorectal cancers were the main cancers causing the cancer burden in the elderly, and accounted for 74.3% of DALYs. The DALY rate of lung cancer in females in the 60-64 age group increased (annual percentage change [APC] = 1.14%, 95% CI: 0.10-1.82%). Female breast cancer was one of the top five cancers in the 60-64 age group, with DALY rates that also increased (APC = 2.17%, 95% CI: 1.35-3.01%). With increasing age, the burden of liver cancer decreased, while that of colorectal cancer rose. CONCLUSIONS: From 2005 to 2016, the cancer burden in the elderly in China decreased, mainly reflected in the non-fatal burden. Female breast and liver cancer were a more serious burden in the younger elderly, while colorectal cancer burden was mainly observed in the older elderly.

[Difference in liver injury induced by dictamnine between males and females: based on untargeted metabolomics].

In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered "non-toxic" TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P<0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

[Molecular mechanism of sleep deprivation-induced body injury and traditional Chinese medicine prevention and treatment: a review].

Sleep occupies one-third of a person's lifetime and is a necessary condition for maintaining physiological function and health. With the increase in social and economic pressures, the growing use of electronic devices and the accelerated aging process of the population, insufficient sleep and its hazards have drawn widespread attention from researchers in China and abroad. Sleep deprivation refers to a decrease in sleep or a severe lack of sleep due to various reasons. Previous studies have found that sleep deprivation can cause extensive damage to the body, including an increased incidence and mortality rate of neuropathic diseases in the brain, cardiovascular diseases, imbalances in the gut microbiota, and other multi-organ diseases. The mechanisms underlying the occurrence of multi-system and multi-organ diseases due to sleep deprivation mainly involve oxidative stress, inflammatory responses, and impaired immune function in the body. According to traditional Chinese medicine(TCM), sleep deprivation falls into the category of sleepiness, and long-term sleepiness leads to Yin-Yang imbalance, resulting in the consumption of Qi and damage to the five Zang-organs. The appropriate treatment should focus on tonifying deficiency, reinforcing healthy Qi, and harmonizing Yin and Yang. TCM is characterized by a wide variety and abundant resources, and it has minimal side effects and a broad range of applications. Numerous studies have shown that TCM drugs and prescriptions not only improve sleep but also have beneficial effects on liver nourishment, intelligence enhancement, and kidney tonification, effectively preventing and treating the body injury caused by sleep deprivation. Given the increasing prevalence of sleep deprivation and its significant impact on body health, this article reviewed sleep deprivation-mediated body injury and its mechanism, summarized and categorized TCM compound prescriptions and single drugs for preventing and treating body injury, with the aim of laying the foundation for researchers to develop effective drugs for preventing and treating body injury caused by sleep deprivation and providing references for further exploration of the molecular mechanisms underlying the body injury caused by sleep deprivation.

Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation.

This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71-610) days and 284.5 (95% CI: 81-610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

Immunomodulatory effects of fentanyl and morphine on DSS- and TNBS-induced colitis.

BACKGROUND: Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even death, in IBD patients. This study aimed to define the role of fentanyl and morphine, two representative strong opioids, in the pathogenesis of dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis. METHOD: DSS and TNBS models were induced in C57BL/6J and Balb/c mice, respectively. Disease activity index (DAI), histopathology, enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry were performed to evaluate the effects of fentanyl and morphine. RESULT: Fentanyl exacerbated DSS- and TNBS-induced colitis, while morphine exhibited no significant immunomodulatory effect. Fentanyl and morphine had no obvious effects on the serum levels of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), and prostaglandin E2 (PGE-2) in DSS and TNBS models. Fentanyl elevated the proportions of Th1 cells, µ-opioid receptor (MOR) + Th1 cells, and MOR + macrophages in the colonic mucosa of DSS-treated mice, and enhanced the proportions of Th1 cells, macrophages, MOR + Th1 cells, and MOR + macrophages in the colonic mucosa of TNBS-treated mice. We found that fentanyl upregulated the levels of inflammatory cytokines/chemokines in MOR + macrophages of the colonic lamina propria mononuclear cells (LPMCs) from DSS-treated mice, whereas it had no effect on the expression of most inflammatory cytokines/chemokines in MOR + macrophages in the colonic LPMCs from TNBS-treated mice. CONCLUSION: Our findings suggest that fentanyl exacerbates murine colitis via Th1 cell- and macrophage-mediated mechanisms, while morphine exhibits no significant immunomodulatory effect.

Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication.

Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.

Antibacterial Prenylated p-Hydroxybenzoic Acid Derivatives from Oberonia myosurus and Identification of Putative Prenyltransferases.

Twelve hitherto unknown tandem prenylated p-hydroxybenzoic acid derivatives, namely, oberoniamyosurusins A-L, together with five known derivatives, were isolated from an EtOH extract of the whole parts of the plant Oberonia myosurus. Compounds 10, 13, and 17 exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213 with MIC50 values ranging from 7.6 to 23 µg/mL. To determine the biosynthetic pathway of this class of tandem prenyl-substituted compounds, the full-length transcriptome of O. myosurus was sequenced, yielding 19.09 Gb of clean data and 10 949 nonredundant sequences. Two isoforms of p-hydroxybenzoic acid prenyltransferases were annotated and functionally characterized as the enzymes that might be involved in the biosynthesis of nervogenic acid (13) in Pichia pastoris.

Reviewing the thermo-chemical recycling of waste polyurethane foam.

The worldwide production of polymeric foam materials is growing due to their advantageous properties of light weight, high thermal insulation, good strength, resistance and rigidity. Society creates ever increasing amounts of poly-urethane (PU) waste. A major part of this waste can be recycled or recovered in order to be put into further use. The PU industry is committed to assist and play its part in the process. The recycling and recovery of PU foam cover a range of mechanical, physical, chemical and thermo-chemical processes. In addition to the well-documented mechanical and chemical processing options, thermo-chemical treatments are important either as ultimate disposal (incineration) or towards feedstock recovery, leading to different products according to the thermal conditions of the treatment. The review focuses on these thermo-chemical and thermal processes. As far as pyrolysis is concerned, TDI and mostly polyol can be recovered. The highest recovery yields of TDI and polyols occur at low temperatures (150-200 °C). It is however clear from literature that pure feedstock will not be produced, and that a further upgrading of the condensate will be needed, together with a thermal or alternative treatment of the non-condensables. Gasification towards syngas has been studied on a larger and industrial scale. Its application would need the location of the PU treatment plant close to a chemical plant, if the syngas is to be valorized or considered in conjunction with a gas-fired CHP plant. Incineration has been studied mostly in a co-firing scheme. Potentially toxic emissions from PU combustion can be catered for by the common flue gas cleaning behind the incineration itself, making this solution less evident as a stand-alone option: the combination with other wastes (such as municipal solid waste) in MSWI's seems the indicated route to go.

Magnetic resonance spectroscopy features of the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder: a prospective study. / å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥ä¸˜è„‘å’Œå°è„‘ç£å ±æŒ¯æ³¢è°±ç‰¹å¾å’Œä¸´åºŠå ³ç³»çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the changes in biochemical metabolites in the thalamus and the cerebellum and their association with clinical features in children with autism spectrum disorder (ASD). METHODS: In this prospective study, magnetic resonance spectroscopy (MRS) with point-resolved spatial selection was used to analyze the thalamus and the cerebellum at both sides in 50 children with ASD aged 2-6 years. Creatine (Cr) was as the internal standard to measure the relative values of N-acetylaspartate (NAA)/Cr, choline (Cho)/Cr, myoinositol (MI)/Cr, and glutamine and glutamate complex (Glx)/Cr, and the differences in metabolites and their association with clinical symptoms were compared. RESULTS: In the children with ASD, NAA/Cr in the left thalamus was positively correlated with the scores of hearing-language and hand-eye coordination in the Griffiths Development Scales-Chinese (P<0.05). Cho/Cr in the right cerebellum was positively correlated with the scores of personal-social competence, hearing-language, and hand-eye coordination (P<0.05). NAA/Cr and Glx/Cr in the left thalamus were positively correlated with those in the left cerebellum (P<0.05). There was no significant difference in metabolites between the left and right sides of the thalamus and the cerebellum in the children with ASD (P>0.05). CONCLUSIONS: There are metabolic disorders in the cerebellum and the thalamus in children with ASD, and there is a correlation between the changes of metabolites in the left cerebellum and the left thalamus. Some metabolic indexes are related to the clinical symptoms of ASD. MRS may reveal the pathological basis of ASD and provide a basis for diagnosis and prognosis assessment of ASD as a noninvasive and quantitative detection method.

Hepatitis B virus pregenomic RNA status can reveal the long-term prognoses of chronic hepatitis B patients treated with nucleos(t)ide analogues.

We examined whether the hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after nucleos(t)ide (NA) treatment can predict the long-time prognoses of chronic hepatitis B patients. Patients with chronic hepatitis B (98) who were treatment-naïve and had begun a 7-year NA therapy regimen were enrolled in this study. Biochemical indicators and serological markers of HBV infection were performed during therapy. HBV pgRNA was quantified by real-time quantitative PCR with specific primers. During treatment, HBV DNA undetectable rates increased. The aminotransferase (ALT) normalization (ALT < 50 IU/L) and HBeAg-negative rates also increased. After 48 weeks' NA treatment, 48.28% (28/58) of HBV DNA undetectable patients still had HBV pgRNA-positive. After 7 years of treatment, more HBV pgRNA-negative patients (n = 35) achieved HBeAg clearance than the patients who were HBV pgRNA-positive (n = 63) (19/23 vs 19/56, P < .00). HBV pgRNA-positive patients also had an increased risk of failing to achieve HBeAg clearance (OR = 9.25, 95% CI: 2.75-31.08). The median time to HBeAg clearance in the HBV pgRNA-positive patients was longer than that of the HBV pgRNA-negative patients (152 weeks vs 72 weeks). The HBV pgRNA-positive patients also required more time to achieve HBV DNA undetectable (124 weeks, 95% CI: 103.33-144.67 vs 48 weeks, 95% CI: 34.80-61.20). The HBV pgRNA status after NA treatment can predict the long-term prognoses of patients with chronic HBV. Patients who remain HBV pgRNA-positive after 48 weeks of NA treatment have an increased risk of not achieving HBeAg clearance, need more time to achieve HBeAg clearance and undetectable HBV DNA load.

Circular RNA hsa_circ_0000517 modulates hepatocellular carcinoma advancement via the miR-326/SMAD6 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant heterogeneous disease in primary liver tumors. Circular RNA hsa_circ_0000517 (hsa_circ_0000517) is connected with HCC prognosis. Nevertheless, there are few studies on the role and mechanism of hsa_circ_0000517 in HCC. METHODS: Expression of hsa_circ_0000517, miR-326, and SMAD family member 6 (SMAD6) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, colony formation, cell cycle, migration, and invasion were determined though Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound healing, or transwell assays. Protein levels of Cyclin D1, matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), SMAD6, and proliferating cell nuclear antigen (PCNA) were examined with western blot analysis. The relationship between hsa_circ_0000517 or SMAD6 and miR-326 was determined via dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The role of hsa_circ_0000517 in vivo was confirmed via xenograft assay. RESULTS: Hsa_circ_0000517 and SMAD6 were up-regulated while miR-326 was down-regulated in HCC tissues and cells. Hsa_circ_0000517 down-regulation repressed cell proliferation, colony formation, migration, and invasion, and induced cell cycle arrest in HCC cells in vitro, and constrained tumor growth in vivo. Notably, hsa_circ_0000517 regulated SMAD6 expression via acting as a competing endogenous RNA (ceRNA) for miR-326. And the repressive influence on malignant behaviors of HCC cells mediated by hsa_circ_0000517 inhibition was reversed by miR-326 inhibitors. Moreover, SMAD6 elevation overturned the inhibitory impacts of miR-326 mimics on malignant behaviors of HCC cells. CONCLUSIONS: Hsa_circ_0000517 depletion repressed HCC advancement via regulating the miR-326/SMAD6 axis.

High-density lipoprotein cholesterol is a predictor of survival in cirrhotic patients with acute gastrointestinal bleeding: a retrospective study.

BACKGROUND: Lipid profiles are declined in patients with viral liver cirrhosis and correlated with severity of liver disease. Hepatitis B virus (HBV) is the leading cause of liver cirrhosis in China. Our primary aim was to investigate whether serum lipids and lipoproteins associate with survival in patients with HBV-related cirrhosis and acute gastrointestinal bleeding, and develop a 6-week mortality risk score that incorporates it. METHODS: From January 2008 to December 2015, consecutive cirrhotic patients with acute gastrointestinal bleeding admitted to our hospital were evaluated and randomly divided into the derivation (n = 629) and validation (n = 314) cohorts. A logistic regression model was established to confirm the association between lipoprotein cholesterol and mortality. Accuracy to predict mortality were assessed by area under the receiver operating characteristic curves (AUROCs) and compared using the Hanley and McNeil test. RESULTS: Among study subjects, the 6-week mortality rate was 10.6%. High-density lipoprotein cholesterol (HDL-C) level was found to correlate most strongly with prognostic scores. On ROC analysis, HDL-C showed excellent diagnostic accuracy for 6-week mortality. Logistic regression analysis provided a simple algorithm based on the combined use of 4 variables (total bilirubin (TBIL), HDL-C, International normalized ratio, and hemoglobin), allowing accurate discrimination of 3 distinct prognostic subgroups with 1.7% (low risk), 12.3% (intermediate risk), and 56.9% (high risk) mortality. Its accuracy was significantly better than that of Child-Pugh, model of end-stage liver disease, albumin-bilirubin score, D'Amico model, Augustin model, AIMS65 score and Glasgow-Blatchford score. Baseline HDL-C values ≤ 0.54 mmol/L were associated with markedly lower 6-week survival. Comparable results were found in the validation set. CONCLUSION: HDL-C is a potential indicator for the prognosis of patients with cirrhosis and acute gastrointestinal bleeding. The new algorithm based on HDL-C allowed an accurate predictive assessment of 6-week mortality after bleeding attack.

Principle and potential applications of the non-classical protein secretory pathway in bacteria.

In addition to the extracellular proteins secreted by known secretory pathways, a number of cytoplasmic proteins without predicable or known signal sequences or secretory motifs have been found in the extracellular milieu, and were consequently classified as non-classically secreted proteins. Non-classical protein secretion is considered to be a general, conserved cellular phenomenon in both eukaryotes and prokaryotes. There are several research hotspots on the non-classical protein secretory pathway, and the most important two of them are the recognition principle of substrate proteins and possible secretory mechanisms. To date, researchers have made some progress in understanding the characteristics of these proteins. For example, it was discovered that many non-classically secreted proteins exist and are secreted in multimeric form. Some of these proteins prefer to be clustered and exported at the poles and the septum of the cell. The majority of these proteins play different functions when they are in the intra- and extracellular environments, and several of their functions are related to survival and pathogenicity. Furthermore, non-classically secreted proteins can be used as leading proteins to guide a POI (protein of interest) out of the cells, which provides a novel strategy for protein secretion with potential applications in the industry. Summarizing these findings, this review emphasizes the hot spots related to non-classically secreted proteins in bacteria, lists the most important hypotheses on the selection and secretion mechanisms of non-classically secreted proteins, and put forward their potential applications.

Clinical characterization and mutation spectrum in patients with familial adenomatous polyposis in China.

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is the most common adenomatous polyposis syndrome. Patients with FAP are screened for germline mutations of two genes, APC and MUTYH. However, limited data exist on the clinical characterization and genotypic spectrum of FAP in China. This study was aimed to determine APC and MUTYH mutational status in a small cohort of FAP probands in China and to characterize the genotype-phenotype correlation in mutated patients. METHODS: Mutation screening of 46 unrelated probands was performed using multigene panels by next-generation sequencing. Clinical data of the index were used to assess genotype-phenotype correlations. RESULTS: Overall, 42 out of 46 (91.30%) unrelated probands found mutations, including 35 (76.09%) with APC mutations, 3 (6.52%) with MUTYH mutations, and 4 (8.70%) with both APC and MUTYH mutations. Ten APC genetic alterations variants were novel. The hereditary pattern of the family with both APC and MUTYH mutations was autosomal dominant inheritance. Upper gastrointestinal polyp was the most common extracolonic manifestations. The onset time for patients with both APC and MUTYH mutations was earlier than MUTYH mutation carriers and similar to APC mutation carriers. But the age of carcinogenesis for patients with both APC and MUTYH mutations was later than APC mutation carriers and similar to MUTYH mutation carriers. CONCLUSION: In this study, we show the importance of using multigene panels that allow for a parallel comprehensive screening. We suggest that genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analyses simultaneously.