Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine.

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled 122 infected adults and 50 uninfected controls who had been unvaccinated or vaccinated with two or three doses of COVID-19 inactive vaccines and performed integrative analysis of 41-plex CyTOF, RNA-seq, and Olink on their peripheral blood samples. The frequencies of HLA-DRhi classical monocytes, non-classical monocytes, and Th1-like Tem tended to increase, whereas the frequency of Treg was reduced by booster vaccine, and they influenced symptom occurrence in a vaccine dose-dependent manner. Intercorrelation and mechanistic analysis suggested that the booster vaccination induced monocytic training, which would prime monocytic activation and maturation rather than differentiating into myeloid-derived suppressive cells upon Omicron infections. Overall, our study provides insights into how booster vaccination elaborates protective immunity across SARS-CoV-2 variants.

Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer.

Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that exhibit marked resistance to cisplatin with association with glycolysis metabolism. Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa. These findings enhance our understanding of the mechanisms underlying cisplatin resistance, offering valuable insights for identifying novel intervention targets to overcome drug resistance in Bca.

The m6 A modification of Il17a in CD4+ T cells promotes inflammation in psoriasis.

Psoriasis is a chronic inflammatory skin disorder. The mechanism of psoriasis pathogenesis is not entirely clear. Here, we reported that the level of the N6-methyladenosine (m6 A) modification was increased in psoriatic CD4+ T cells compared with healthy controls. In the psoriasis mouse model, depletion of the RNA demethylase, Alkbh5, from CD4+ T cells promoted the psoriasis-like phenotype and inflammation. Intriguingly, this phenotype and inflammation were alleviated by the ablation of the m6 A methyltransferase Mettl3 in CD4+ T cells. Mechanistically, we found that the m6 A modification of IL17A mRNA increased the expression of IL-17A (an important pro-inflammatory factor in psoriasis) and promoted psoriasis. Thus, our study provided evidence that the m6 A modification of IL17A in CD4+ T cells regulates inflammation in psoriasis.

Using unsupervised learning to classify inlet water for more stable design of water reuse in industrial parks.

The water reuse facilities of industrial parks face the challenge of managing a growing variety of wastewater sources as their inlet water. Typically, this clustering outcome is designed by engineers with extensive expertise. This paper presents an innovative application of unsupervised learning methods to classify inlet water in Chinese water reuse stations, aiming to reduce reliance on engineer experience. The concept of 'water quality distance' was incorporated into three unsupervised learning clustering algorithms (K-means, DBSCAN, and AGNES), which were validated through six case studies. Of the six cases, three were employed to illustrate the feasibility of the unsupervised learning clustering algorithm. The results indicated that the clustering algorithm exhibited greater stability and excellence compared to both artificial clustering and ChatGPT-based clustering. The remaining three cases were utilized to showcase the reliability of the three clustering algorithms. The findings revealed that the AGNES algorithm demonstrated superior potential application ability. The average purity in six cases of K-means, DBSCAN, and AGNES were 0.947, 0.852, and 0.955, respectively.

Impact of nonalcoholic fatty liver disease status change on antiviral efficacy of nucleos(t)ide analogues in HBeAg-positive chronic hepatitis B.

Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.

Urbanization alters soil bacterial communities in southern China coastal cities.

Urbanization carries essential influences to ecosystem of soil bacteria in coastal cities. Comprehending the patterns and drivers of bacterial diversity are essential to understanding how soil ecosystems respond to environmental change. This study aimed to explore how soil bacterial community (SBC) response to distinct urbanization of coastal cities on composition, assembly process and potential function in Guangdong province, south China. 72 samples from 24 sample sites within 3 cities were included in the study. Soil chemical properties were analyzed, and the bacterial community were investigated by high-throughout sequencing. Proteobacteria and Acidobacteria were the main phyla. Assembly processes remained in stochastic processes and co-occurrence network of SBC kept stable, while urbanization altered SBC by influencing the dominant phyla. The indicators of communities in coastal city soils were the genera gamma_proteobacterium and beta_proteobacterium. Urbanized extent was the non-negligible factor which affected soil bacterial community, despite the total carbon was still the most vital. The impact of urbanization on bacterial communities might follow a non-linear pattern. Faprotax function prediction showed different urbanized coastal city soils share similar metabolic potential. Our study improved our understanding of the response of soil bacterial communities to urbanization in subtropical coastal cities and offered a useful strategy to monitor the ecology risk toward the soil under urbanization.

Vulnerability assessment of strait/canals in maritime transportation using fuzzy evidential reasoning approach.

The safety and security of straits and canals have been playing an important role in maritime transportation. The disruption of a strait or canal will lead to increased transportation costs and world trade problems. Therefore, an advanced approach incorporating fuzzy logic and an evidential reasoning (ER) algorithm is developed to conduct the vulnerability assessment of straits or canals in this paper. A hierarchical structure is first developed taking into account both qualitative and quantitative factors. The fuzzy rule-based transformation technique is applied to convert quantitative factors into qualitative ones, which enables the application of a fuzzy ER method to synthesize all the information from the bottom to the top along the developed hierarchical structure. The software of intelligent decision system (IDS) is used to facilitate the process of vulnerability assessment. The developed framework then is validated and demonstrated in a case study for vulnerability prioritization which can be used as a reference to ensure the safety and security of straits and canals for decision-makers.

Role of myo-inositol supplementation against toxicity of excessive dietary copper in Pacific white shrimp Litopenaeus vannamei.

Raw materials for making dried shrimp (a type of foodstuff) are mostly from farmed shrimp and preliminary findings indicated that head copper (Cu) concentrations in some commercial dried shrimp products exceeded the safe limit specified in pollution-free aquatic products (50 mg/kg), which may influence food safety. Therefore, a 63-day feeding trial was conducted to explore effects of dietary Cu concentrations on accumulation of Cu in tissues, growth performance, immune response and antioxidant status of Pacific white shrimp (Litopenaeus vannamei). Moderating effect of myo-inositol (MI, adding 200 mg/kg diet) on the adverse impacts caused by excessive dietary Cu was also investigated. 600 shrimp (initial weight: 0.89 ± 0.00 g) were divided into five groups: 37.08 mg Cu/kg diet group (control group), 62.57 mg Cu/kg diet group, 125.99 mg Cu/kg diet group, 63.41 mg Cu/kg diet group (supplemented with MI) and 119.19 mg Cu/kg diet group (supplemented with MI). The results showed that dietary Cu concentrations increased from 37.08 to over 62.57 mg/kg, hepatopancreas Cu concentrations raised from 29.04 to 233.43-263.65 mg/kg, and muscle Cu concentrations only increased from 6.22 to 6.99-8.39 mg/kg. Report to control group, excessive Cu concentration (125.99 mg/kg) didn't significantly affect growth performance, but it notably reduced whole body lipid content and immune response, induced oxidative stress and damaged the hepatopancreas structure, which was ameliorated by MI supplementation. The results suggested that consuming shrimp head and its processed products weren't recommended. Cu concentrations of commercial feeds for Pacific white shrimp should be controlled below 62.57 mg/kg. Additionally, MI supplementation mitigated the negative impacts induced by excessive dietary Cu.

CSN6 inhibition suppresses pancreatic adenocarcinoma metastasis via destabilizing the c-Fos protein.

Deubiquitinase (DUB) can reverse the ubiquitin signal, and participate in virtually all aspects of cancer progression. Thus, DUB represents an attractive target for development of anticancer drugs. However, little is known about DUB which can be used as drug targets. Here, we found that the constitutive photomorphogenic 9 (COP9) signalosome complex subunit 6 (COPS6/CSN6), a DUB belongs to JAMM/MPN domain-associated metallopeptidases(JAMMs) class, was highly expressed in pancreatic adenocarcinoma(PAAD) tissues. High expression of CSN6 was associated with tumor TNM stage and metastasis in PAAD patients. Moreover, we demonstrated that CSN6 promoted invasion and metastasis through regulating forkhead box protein A1 (FOXA1) in PAAD cells. Re-expression of FOXA1 rescued the decreased invasion and metastasis caused by CSN6 knockdown, whereas inhibition of FOXA1 alleviated the pro-metastasis effect induced by CSN6 overexpression. Further, CSN6 regulated the expression of FOXA1 via c-Fos in PAAD cells. Mechanistically, CSN6 stabilized c-Fos protein by binding to it and decreasing its ubiquitination. Our work identified CSN6 as a targeting-permissible deubiquitinase, and CSN6 inhibition maybe a potential treatment strategy for PAAD.

Circular RNA hsa_circ_001895 serves as a sponge of microRNA-296-5p to promote clear cell renal cell carcinoma progression by regulating SOX12.

There is an urgent need to find novel potential therapeutic targets for the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) due to its highly invasive ability as a common urological malignant tumor. Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression. We first used qRT-PCR analysis to find dysregulated circRNAs in ccRCC. A novel circRNA, hsa_circ_001895, was upregulated in ccRCC specimens and associated with metastatic properties of ccRCC. However, the tumorigenic mechanism of hsa_circ_001895 on ccRCC is yet to be found. We first indicated that hsa_circ_001895 predicted a poor prognosis in ccRCC patients. Additionally, overexpression of hsa_circ_001895 not only promoted cell proliferation, invasion and migration of ccRCC, but also inhibited cell apoptosis, whereas hsa_circ_001895 knockdown reversed the effect on ccRCC progression. In vivo s.c. xenotransplanted tumor model also showed that silencing hsa_circ_001895 could suppress in vivo ccRCC growth. Mechanistically, hsa_circ_001895 directly binds with microRNA (miR)-296-5p and inhibits its expression. Moreover, sex determining region Y (SRY)-box 12 (SOX12) was identified as a target of miR-296-5p, the expression of which was suppressed by miR-296-5p. Notably, the inhibitory effect of hsa_circ_001895 on ccRCC progression was reversed by miR-296-5p inhibitor. In general, our findings indicated that hsa_circ_001895 may sponge miR-296-5p and promote SOX12 expression, which is the underlying mechanism of hsa_circ_001895-induced ccRCC progression.

Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries.

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

Effect and mechanism of lentivirus-mediated silencing of TPX2 gene on proliferation and apoptosis of human hepatoma cells.

This study aimed to investigate the role and mechanism of action of targeting protein for Xklp2 (TPX2) in liver cancer, we compared TPX messenger RNA (mRNA) expression in liver cancer tissue samples and adjacent normal liver tissue samples as well as in human liver cancer cell lines and nonmalignant cell line by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TPX2 gene was silenced in HepG2 cells by transfection with the lentiviral vector expressing TPX2-targeting short hairpin RNA (shRNA), and the knockdown efficiency was evaluated by RT-qPCR. Cell proliferation, apoptosis as well as protein level of c-Myc, cyclin D1, caspase-3, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin in HepG2 cells were evaluated before and after the TPX2 knockdown. Wnt/ß-catenin signaling pathway was inhibited by treatment with 20 µM of XAV-939 or activated by treatment with 20 mM of LiCl. We found that TPX2 mRNA level was significantly increased in liver cancer tissue samples and cell lines comparing to noncancerous counterparts (P < 0.05). TPX2 knockdown significantly reduces TPX2 expression (P < 0.01), cell proliferation (P < 0.05), protein level of c-Myc and cyclin D1 (P < 0.01), activation of Wnt/ß-catenin signaling in HepG2 cells (P < 0.01) while increasing cell apoptosis (P < 0.01). Treatment with XAV-939 significantly reduced HepG2 cell proliferation (P < 0.05) while increasing cell apoptosis (P < 0.01). Treatment with LiCl significantly attenuated the antiproliferative and apoptosis-promoting effect of TPX2 knockdown on HepG2 cells (P < 0.05). Lentivirus-mediated silencing of TPX2 gene could inhibit proliferation and induce apoptosis in hepatoma cells by inhibiting Wnt signaling pathway and regulating cyclin and apoptosis-related proteins.

Exposure to acute ammonia stress influences survival, immune response and antioxidant status of pacific white shrimp (Litopenaeus vannamei) pretreated with diverse levels of inositol.

The effect of acute ammonia challenge on survival, immune response and antioxidant status of Litopenaeus vannamei pretreated with diets containing different inositol levels was investigated. Shrimp (initial mean weight 0.40 ±â€¯0.00 g) were randomly allocated in 18 tanks (30 shrimp per tank) and triplicate tanks were fed with a control diet without myo-inositol (MI) supplementation (242.6 mg inositol kg-1 diet) or diets containing diverse levels of inositol (368.8, 459.7, 673.1, 993.8 and 1674.4  mg kg-1 diet) as treatment groups for 8-week. Randomly selected 10 shrimp per tank (final mean weight approximately 11.1-13.8g) were exposed to ammonia stress (total ammonia-nitrogen, 60.21  mg L-1) for 24 h after feeding trial. The results showed that after exposed to ammonia stress, survival rates of MI-supplemented groups were enhanced by 31-77% when compared with the control group. MI supplementation increased activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in plasma, and reduced its activities in hepatopancreas. It also enhanced activities of total antioxidant capacity (T-AOC), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and content of reduced glutathione (GSH), and lowered malondialdehyde (MDA) and protein carbonyl (PC) content in plasma or hepatopancreas. In addition, mRNA expression levels of ferritin (FT), arginine kinase (AK), thioredoxin (Trx), heat shock protein 70 (Hsp70), catalase (CAT) and peroxiredoxin (Prx) were significantly differentially regulated in hepatopancreas owing to MI supplementation. Therefore, it suggested that L. vannamei pretreated with higher dietary inositol content may have better ammonia stress tolerance and antioxidant status after ammonia stress, and the optimum levels ranged from 459.7 to 993.8 mg inositol kg-1 when total ammonia-nitrogen concentration was 60.21  mg L-1.

Changes in growth performance, haematological parameters, hepatopancreas histopathology and antioxidant status of pacific white shrimp (Litopenaeus vannamei) fed oxidized fish oil: Regulation by dietary myo-inositol.

A 58-day feeding trial was conducted to evaluate the effects of dietary myo-inositol (MI) supplementation on growth performance, haematological parameters, hepatopancreas histopathology and antioxidant status of Litopenaeus vannamei fed with oxidized fish oil (OFO). Control diet contained fresh fish oil (FFO) without MI supplementation. The other four diets contained two oxidation levels of OFO (peroxide value: 133.2 and 268.7 meq kg-1) with or without 200 mg MI kg-1 diets (MI0+L, MI0+H, MI200 + L and MI200 + H). Results showed that OFO-supplemented groups (without MI supplementation) showed better growth performance and lower whole-body inositol content when opposed to control group. MI supplementation significantly improved whole-body inositol content in high-oxidized fish oil (HOFO) groups, and also reduced whole-body lipid in low-oxidized fish oil (LOFO) groups. Moreover, Supplementation of OFO and MI markedly hit the fatty acid profile of muscle. HOFO caused severe histopathological changes in hepatopancreas of shrimp, which slightly alleviated by MI supplementation. MI supplementation also grew the total protein (TP) content and alkaline phosphatase (AKP) activity and decreased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of serum in OFO-supplemented groups. Ingestion of OFO increased levels of lipid peroxidation and protein oxidation in serum or hepatopancreas, which partly ameliorated by MI supplementation. Activities of antioxidant enzymes exhibited different expression patterns because of OFO and MI. In addition, HOFO markedly increased mRNA expression levels of antioxidant genes including ferritin (FT), thioredoxin (Trx), GPX, glutathione S-transferase (GST) and catalase (CAT) and decreased peroxiredoxin (Prx) expression, in which expression of GPX and Prx were increased owing to MI supplementation. Therefore, it suggested that dietary OFO stimulated growth performance, but also induced oxidative stress and caused impairment to hepatopancreas in L. vannamei. The negative impact brought about by OFO was partially mitigated by dietary MI supplementation.

Sustained serological and complete responses in HBeAg-positive patients treated with Peginterferon alfa-2b: a 6-year long-term follow-up of a multicenter, randomized, controlled trial in China.

BACKGROUND: Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. METHODS: Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 µg/kg/wk. 24 weeks or 1.5 µg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA < 2000 IU/mL. RESULTS: The proportions of patients achieving sustained SR among patients who had SR at EOS were high in three treatment groups (61.9, 65.5, 76.5%, respectively, p = 0.46); treatment with PEG-IFN alfa-2b 1.5 µg/kg/wk. 48 weeks had the highest proportion of a sustained CR among patients who had CR at EOS (75.0%, p = 0.05). A considerable number of patients achieved sustained SR (18.2-29.9%) and sustained CR (14.8-18.3%) after EOS despite no further NA treatment. At the LTFU, rates of SR and CR were less than 70.0 and 50.0%, respectively, among all enrolled patients regardless of additional nucleos(t)ide analogs before the LTFU. CONCLUSIONS: PEG IFN alfa-2b therapy had considerable off-treatment sustainability in Chinese HBeAg positive chronic hepatitis B patients with serological and complete responses.

Inhibitory Effects of Antimicrobial Peptide JH-3 on Salmonella enterica Serovar Typhimurium Strain CVCC541 Infection-Induced Inflammatory Cytokine Release and Apoptosis in RAW264.7 Cells.

The antibiotic resistance of Salmonella has become increasingly serious due to the increased use of antibiotics, and antimicrobial peptides have been considered as an ideal antibiotic alternative. Salmonella can induce macrophage apoptosis and thus further damage the immune system. The antimicrobial peptide JH-3 has been shown to have a satisfactory anti-Salmonella effect in previous research, but its mechanism of action remains unknown. In this study, the effects of JH-3 on macrophages infected with Salmonella Typhimurium CVCC541 were evaluated at the cellular level. The results showed that JH-3 significantly alleviated the damage to macrophages caused by S. Typhi infection, reduced the release of lactic dehydrogenase (LDH), and killed the bacteria in macrophages. In addition, JH-3 decreased the phosphorylation level of p65 and the expression and secretion of interleukin 2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α) by inhibiting the activation of the mitogen-activated protein kinase (MAPK) (p38) signaling pathway and alleviating the cellular inflammatory response. From confocal laser scanning microscopy and flow cytometry assays, JH-3 was observed to inhibit the release of cytochrome c in the cytoplasm; the expression of TNF-αR2, caspase-9, and caspase-8; to further weaken caspase-3 activation; and to reduce the S.-Typhi-induced apoptosis of macrophages. In summary, the mechanism by which JH-3 inhibits Salmonella infection was systematically explored at the cellular level, laying the foundation for the development and utilization of JH-3 as a therapeutic alternative to antibiotics.

Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B.

AIM: The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. METHODS: Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. RESULTS: The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. CONCLUSIONS: Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization.

Clinical values of circular RNA 0000181 in the screening of gastric cancer.

BACKGROUND: Circular RNAs (circRNAs) are recently found involved in cancer occurrence and development. However, their values in the diagnosis of gastric cancers are largely unknown. In this study, we analyzed the values of hsa_circ_0000181 in the diagnosis of gastric cancer. METHODS: Using divergent primers, hsa_circ_0000181 expression levels in fresh gastric cancer tissues and paired adjacent non-tumorous tissues, and plasmas from patient with gastric cancer and health people were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between hsa_circ_0000181 levels and the clinicopathologic features of patients with gastric cancer was further analyzed. Finally, to evaluate the diagnostic value, receiver operating characteristic (ROC) curve was established. RESULTS: Hsa_circ_0000181 levels in gastric cancer tissues and plasma from gastric cancer patients were significantly decreased than those in paired adjacent non-tumorous tissues (P < .001) and healthy people (P < .001), respectively. Furthermore, hsa_circ_0000181 expression in gastric cancer tissues was significantly correlated with tumor diameter (P = .027), lymphatic metastasis (P = .044), distal metastasis (P = .023), and carbohydrate antigen 19-9 (P = .031). Its decreased levels in patients' plasma were significantly associated with differentiation (P = .038) and carcinoembryonic antigen (P = .037). The areas under ROC curve were 0.756. The specificity of tissue hsa_circ_0000181 and sensitivity of plasma hsa_circ_0000181 were 85.2% and 99.0%, respectively. CONCLUSIONS: Thanks to the high stability, tissue and plasma hsa_circ_0000181 may be a novel biomarker for the diagnosis of gastric cancer.

Femtosecond-level timing fluctuation suppression in atmospheric frequency transfer with passive phase conjunction correction.

We demonstrate femtosecond-level timing fluctuation suppression in indoor atmospheric comb-based frequency transfer with a passive phase conjunction correction technique. Timing fluctuations and Allan deviations are both measured to characterize the excess frequency instability incurred during the frequency transfer process. By transferring a 2 GHz microwave over a 52-m long free-space link in 5000 s, the total root-mean-square (RMS) timing fluctuation was measured to be about 280 fs with a fractional frequency instability on the order of 3 × 10-13 at 1 s and 6 × 10-17 at 1000 s. This atmospheric comb-based frequency transfer with passive phase conjunction correction can be used to build an atomic clock-based free-space frequency transmission link because its instability is less than that of a commercial Cs or H-master clock.

[ABCC8 gene analysis, treatment and follow-up of an infant with neonatal diabetes mellitus].

OBJECTIVE: To analyze the clinical characteristics of an infant with neonatal diabetes mellitus (NDM) and to sequence the ABCC8 gene of this family in order to provide a theoretical basis for the diagnosis and treatment. METHODS: The clinical data of the patient was collected, and the proband and his direct relatives within three generations were sequenced. RESULTS: The patient was 1-month-old, random blood glucose was more than 27.8 mmol/L, C-peptide was 33.8 pmol/L, blood gas analysis was pH 7.16, HCO3- 3.9 mmol/L and urine alkone was 3+. Genetic testing revealed that the patient, his father, elder brother and grandmother have carried heterozygous mutation c.2690A>T(p.D897V) of the ABCC8 gene. Fluid infusion, intravenous administration of insulin and other supportive therapies were provided. After the correction of acidosis, subcutaneous insulin injection were uesd to control the blood glucose. Eight months later, blood glucose was pooly controlled. After combined with glibenclamide, blood glucose was under control. CONCLUSION: The patient carries a heterozygous mutation c.2690A>T(p.D897V) of ABCC8 gene, which is a novel mutation. Glibenclamide was partly effective for the patient.