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BackgroundNucleos(t)ide analogues (NAs) cessation is not widely practiced and remains a controversial, but highly relevant subject in patients infected with hepatitis B virus (HBV). We aimed to explore the related factors for safe NAs cessation. MethodsThis is a multicenter prospective cohort study. Overall, 139 initially HBV e antigen (HBeAg)-positive patients meeting the stopping criteria were included in 12 hospitals in China. Enrolled patients ceased NAs and were followed up every 3 months for 24 months or until clinical relapse (CR).ResultsThe 24 month cumulative rates of virological relapse (VR), CR, HBeAg reversion and HBV surface antigen (HBsAg) loss were 50.4, 24.5, 11.5 and 9.4%, respectively. Patients with end of treatment (EOT) HBsAg  < 100 IU/mL plus negative HBV RNA had the lowest 24 month cumulative VR rate (5 vs 58%, p < 0.001). EOT HBsAg  ≥ 2 log10 IU/mL [odds ratio (OR) = 6.686, p = 0.006], EOT positive HBV RNA (OR = 3.453, p = 0.008) and EOT hepatitis B core-related antigen (HBcrAg)  ≥ 4log U/mL (OR = 3.702, p = 0.002) were found to independently predict the risk of VR. To predict VR, the area under the receiver-operating characteristic (AUROC) value of the EOT HBsAg  < 100 IU/mL plus EOT HBV RNA negative was 0.698 (p < 0.001), which was higher than other parameters alone or combinations.ConclusionsNAs cessation is suitable only for a small and selected patients. An EOT HBsAg  < 100 IU/mL and EOT negative HBV RNA identified a patient with low risk of off-treatment VR.

The controversial history of Indian subduction beneath Asia is crucial to understand the Himalayan orogeny and more in general the geodynamic process of continental subduction. New key information is here presented from the Oligocene‐Pliocene Shiquanhe Basin located in the southwestern Tibetan Plateau. The alluvial‐fan, lacustrine, and braided‐river sediments of the Oligocene Rigongla Formation were non‐conformably deposited onto the Upper Cretaceous Gangdese granitoid rocks and fed from erosion of the batholith itself and of associated Paleogene Linzizong volcanic rocks. Stratigraphic evidence testifies to the development of an orogen‐parallel intracontinental rift along the retro‐side of the Gangdese arc in the Oligocene, at the same time as the Kailas basin formed along the pro‐side of the Gangdese arc. The subsidence of these twin basins may have been caused by steepening of the subducting Indian continental slab or by the passage of a wave of dynamic topography during continuing subduction. Plain Language Summary The convergence and collision of India and Asia leading to the formation of the Himalayan Mountains and Tibetan Plateau (“the roof of the world”) is one of the most significant geological events of the Cenozoic Era. Geophysical data show that rocks of the Indian continent lie beneath southern Tibet, but the early subduction history of India related to the initial topographic grow of the Himalaya remains unclear. We studied the Shiquanhe Basin in southwestern Tibet to investigate the continent's subduction history using stratigraphic, sedimentological, and provenance analyses. Our results indicate that an orogen‐parallel rift developed in southern Tibet during the Oligocene Epoch. Challenging earlier beliefs, we propose two alternative models to explain such event of tectonic extension: steepening of subduction angle or passage of a topographic wave across the subducting plate. The latter hypothesis would also explain the widespread uplift and lack of Oligocene sedimentary deposits recorded all across the front of the Himalayan range. Key Points Oligocene Rigongla Fm. testifies to orogen‐parallel extension along retro‐side of Gangdese arc Shiquanhe Basin passed from extension to compression in Oligocene to Miocene times Oligocene extension was caused by change of Indian subduction angle or wave of dynamic topography

As a hot topic in Earth sciences, the Qinghai‐Tibet Plateau has accumulated a large amount of sedimentary‐related data. We constructed a dataset of detrital components for Qinghai‐Tibet Plateau from 63 peer‐reviewed publications. The dataset thus comprises 1813 Late Proterozoic to Pleistocene sandstones from 84 stratigraphic units. For each sample, we present details on reference, detrital composition, GPS, geographic location, depositional age, tectonic setting and depositional environment. It becomes a high‐quality dataset after the information on each sandstone sample was standardized and reviewed by sedimentary experts. The dataset can be used for regional geoscience studies, exploring the general laws of the source‐to‐sink process. The dataset may also be useful in the field of utilities, such as assisting in finding suitable building stones, helping oil and gas and mineral exploration, and so forth.

Our previous studies unexpectedly indicated that the level of serum hepatitis B core antibody (anti-HBc) was positively correlated with the serum alanine aminotransferase (ALT) level. The aim of this study was to determine whether anti-HBc could serve as a potential biomarker for the detection of liver inflammation in chronic hepatitis B (CHB) patients, especially in patients with normal ALT levels. Serum anti-HBc levels were quantified in 655 treatment-naïve CHB patients, including 45 patients who underwent two liver biopsies (baseline phase and the 78 th weeks of antiviral-treatment). Serum anti-HBc levels increased significantly along with the increasing histology activity index (HAI) score. After antiviral-treatment, patients with HAI score reduction had significant decline in serum anti-HBc level. Multivariate analysis showed that anti-HBc was independently associated with moderate-to-severe hepatic inflammation in patients with normal ALT level. Furthermore, serum anti-HBc showed a high diagnostic accuracy for predicting moderate-to-severe inflammation in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients with normal ALT levels (area under the curve, AUC = 0.87 and 0.75; respectively). Thus, anti-HBc may be a strong indicator for assessing the hepatic inflammatory degree and used for antiviral treatment decisions in CHB patients with normal ALT levels.

Background Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation. Methods This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred. Results Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P  < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P  = 0.001) were associated with HBsAg loss. The areas under the receiver operating characteristic curves for EOT HBsAg and HBcrAg levels were 0.952 ( P  < 0.001) and 0.765 ( P  < 0.001), respectively. Patients with EOT HBsAg ≤ 135 IU/mL (59.2% vs. 1.3%, P  < 0.001) or HBcrAg ≤ 3.6 logU/mL (17% vs. 5.4%, P =  0.027) had a higher 24-month cumulative HBsAg loss rate. In Group B, none of the patients experienced virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion. Conclusions EOT HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL can be used to identify patients with a higher likelihood of HBsAg loss after NA cessation. Patients with HBsAg negativity after NA cessation have favorable clinical outcomes, and HBsAg loss was durable in most cases.

Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT).Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test.Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis.Conclusions: The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

De novo combination of lamivudine (Lam) and adefovir (Adv) was not rarely used in clinical practice. However, head-to-head comparisons of entecavir (Etv) monotherapy with this combination in hepatitis B virus (HBV)-related compensated cirrhosis patients are unavailable. This study aimed to compare the efficacy and safety of Etv monotherapy with combination therapy in patients with HBV-related compensated liver cirrhosis. Treatment-naïve patients with HBV-related compensated liver cirrhosis were recruited to receive either Etv monotherapy or a de novo combination of Lam and Adv. Data were collected at baseline and every 6 months thereafter. A total of 578 patients (485 in Etv group, 93 in combination group) were included. Baseline characteristics were comparable between the two groups. At the end of 1, 2, and 3 years, HBV DNA was undetectable in 82.7%, 96.2%, and 94.3% of patients in the Etv group and 88.9%, 81.7%, and 84.6% in the combination group, respectively (all >0.05). The cumulative virological breakthrough rate at 1, 2, and 3 years was 2.7%, 6.7%, and 9.8% in the Etv group and 2.9%, 13.3%, and 32.2% in the combination group, respectively ( =0.003). After propensity-score adjustment for age, sex, and baseline HBeAg, ALT, and total bilirubin, virological breakthrough was higher in the de novo combination of Lam and Adv (HR 2.83, 95% CI 1.37-5.86; <0.01). The cumulative rate of liver-related events, including decompensation and hepatocellular carcinoma, at 1, 2, and 3 years was 2.9%, 4.2%, and 6.1% in the Etv group and 2.2%, 2.2%, and 6.7% in combination group, respectively ( =0.83). Biochemical response and serological response were similar between the groups. Etv treatment had less virological breakthrough and potentially higher HBV-DNA suppression than de novo combination of Lam and Adv during 3 years in treatment-naïve HBV-related compensated liver cirrhosis.

Mélange records a series of geological processes associated with oceanic subduction and continental collision. This paper reports for the first time the presence of Early Jurassic mélange from NW Nagqu in the southern margin of the Bangong–Nujiang suture zone, termed as the Gajia mélange. It shows typically blocks-in-matrix structure with matrix of black shale and siliceous mudstone, and several centimeters to several meters sized blocks of sandstone, silicalite, limestone and basalt. The sandstone blocks consist of homologous sandstone and two types of exotic sandstone, with different modal compositions. The Group 1 of exotic sandstone blocks consists of mainly of feldspar and quartz, whereas the Group 2 is rich in volcanic detritus. The Group 3 of homologous sandstone blocks is rich in feldspar and volcanic detritus with rare occurrence of quartz. U–Pb age data and in situ Hf isotopic compositions of detrital zircons from sandstone blocks are similar to those from the Lhasa terrane, suggesting that the sandstone blocks in the Gajia mélange most probably came from the Lhasa terrane. The YC1σ(2+) age of homologous sandstone blocks is 177 ± 2.4 Ma, suggesting an Early Jurassic depositional age for the sandstones within the Gajia mélange. The Gajia mélange likely records the southward subduction of the Bangong–Nujiang Ocean during the Early Jurassic.

Suraxavir marboxil (GP681) is an antiviral drug inhibiting the polymerase acidic protein (PA) of RNA polymerase, of influenza. It has shown therapeutic activity against influenza A and B virus infections in preclinical studies. In this multicenter randomized, double-blind, placebo-controlled, phase 3 trial, we aimed to investigate the efficacy and safety of single-dose suraxavir marboxil (40-mg oral dose) in otherwise healthy outpatients aged 5–65 years with uncomplicated influenza unaccompanied by severe issues. From 28 July 2022 to 31 October 2023, 591 outpatients aged 5–65 years with uncomplicated influenza underwent randomization in 46 research centers in China and were randomly assigned in a 2:1 ratio to receive suraxavir marboxil (40 mg) or placebo within 2 days of symptom onset. The primary outcome was time to alleviation of influenza symptoms (TTAS) (from the start of treatment until body temperature returned to 37.2 °C or less and all seven influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) resolved for at least 21.5 h) within 15 days by treatment. The secondary endpoints included virological indicators, system and respiratory symptoms, PA variant mutation and adverse events. The median TTAS was significantly shorter in the group that received suraxavir marboxil compared to the placebo group (42.0 h versus 63.0 h, P  = 0.002). Suraxavir marboxil was associated with more rapid decrease in viral load from baseline than placebo by 1 day after administration, with a mean change of −2.2 ± 1.3 compared to −1.3 ± 1.7 log 10 copies per ml ( P  < 0.001) in the placebo group. Adverse events were reported in 28.4% (112 of 395) of suraxavir marboxil recipients and 23.3% (45 of 193) of placebo recipients, most of which were mild or moderate. The incidences of PA variants with the I38T mutation in the H1N1pdm and H3N2 subtypes were 0.7% (1 of 138) and 0.9% (2 of 213), respectively. Low acquired drug resistance was observed. In this trial, timely single-dose suraxavir marboxil was effective in shortening TTAS and reducing the influenza viral load in patients aged 5–65 years with uncomplicated influenza safely. ClinicalTrials.gov registration: NCT05474755 . Suraxavir marboxil, an antiviral drug designed to inhibit the polymerase acidic protein of influenza, alleviates symptoms in individuals with influenza faster than placebo in a phase 3 trial conducted in China.

Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation. This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred. Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P = 0.001) were associated with HBsAg loss. The areas under the receiver operating characteristic curves for EOT HBsAg and HBcrAg levels were 0.952 (P < 0.001) and 0.765 (P < 0.001), respectively. Patients with EOT HBsAg [less than or equai to] 135 IU/mL (59.2% vs. 1.3%, P < 0.001) or HBcrAg [less than or equai to] 3.6 logU/mL (17% vs. 5.4%, P = 0.027) had a higher 24-month cumulative HBsAg loss rate. In Group B, none of the patients experienced virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion. EOT HBsAg [less than or equai to] 135 IU/mL or HBcrAg [less than or equai to] 3.6 logU/mL can be used to identify patients with a higher likelihood of HBsAg loss after NA cessation. Patients with HBsAg negativity after NA cessation have favorable clinical outcomes, and HBsAg loss was durable in most cases.