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The Huashi Baidu Formula (HSBDF), a key Chinese medical drug, has a remarkable clinical efficacy in treating acute lung injury (ALI), and it has been officially approved by the National Medical Products Administration of China for drug clinical trials. Nevertheless, the regulated mechanisms of HSBDF and its active compounds in plasma against ALI were rarely studied. Based on these considerations, the key anti-inflammatory compounds of HSBDF were screened by molecular docking and binding free energy. The key compounds were further identified in plasma by LC/MS. Network pharmacology was employed to identify the potential regulatory mechanism of the key compounds in plasma. Next, the network pharmacological prediction was validated by a series of experimental assays, including CCK-8, EdU staining, test of TNF-α, IL-6, MDA, and T-SOD, and flow cytometry, to identify active compounds. Molecular dynamic simulation and binding interaction patterns were used to evaluate the stability and affinity between active compounds and target. Finally, the active compounds were subjected to predict pharmacokinetic properties. Molecular docking revealed that HSBDF had potential effects of inhibiting inflammation by acting on IL-6R and TNF-α. Piceatannol, emodin, aloe-emodin, rhein, physcion, luteolin, and quercetin were key compounds that may ameliorate ALI, and among which, there were five compounds (emodin, aloe-emodin, rhein, luteolin, and quercetin) in plasma. Network pharmacology results suggested that five key compounds in plasma likely inhibited ALI by regulating inflammation and oxidative damage. Test performed in vitro suggested that HSBDF (0.03125 mg/ml), quercetin (1.5625 μM), emodin (3.125 μM), and rhein (1.5625 μM) have anti-inflammatory function against oxidative damage and decrease apoptosis in an inflammatory environment by LPS-stimulation. In addition, active compounds (quercetin, emodin, and rhein) had good development prospects, fine affinity, and stable conformations with the target protein. In summary, this study suggested that HSBDF and its key active components in plasma (quercetin, emodin, and rhein) can decrease levels of pro-inflammatory factors (IL-6 and TNF-α), decrease expression of MDA, increase expression of T-SOD, and decrease cell apoptosis in an inflammatory environment. These data suggest that HSBDF has significant effect on anti-inflammation and anti-oxidative stress and also can decrease cell apoptosis in treating ALI. These findings provided an important strategy for developing new agents and facilitated clinical use of HSBDF against ALI. [ABSTRACT FROM AUTHOR]

Patients with urothelial carcinoma (UC) of the bladder have a high risk of death in China. However, a lack of comprehensive molecular profiling in Chinese Han population hinders the development of targeted therapies for bladder cancer. In our present study, we collected fresh bladder tumors from low-grade (T1, N0, M0, G1) non-muscle invasive bladder cancer (NMIBC) patients (n = 16) and high-grade (T2-4, N0, M0, Gx) muscle-invasive bladder cancer (MIBC) patients (n = 16) with their paired normal bladder tissues, and subjected the total genomic DNAs to targeted next-generation sequencing (NGS) for 94 cancer-associated genes. NGS results showed that 30.9% of detected genes (29/94) was mutated in 32 urothelial carcinoma bladder tissues. Furthermore, our results and ICGC database showed that FGFR3, KMT2D, TP53, KDM6A, and ARID1A were the most frequently mutated genes in UC patients. Of note, NMIBC and MIBC displayed distinguishable genomic alterations. FGFR3, KMT2D, AKT1, ARID1A, and STAG2 were the most frequently mutated genes in NMIBC patients, whereas mutations of TP53, CREBBP, FGFR3, KDM6A, KMT2D, and ARID1A were frequently detected in MIBC. Intriguingly, gene ontology and clustering analysis revealed that these frequently mutated genes were highly enriched in signaling pathways responsible for cancer development. Taken together, the mutation frequency of genes associated with UC development in NMIBC and MIBC was screened out in Chinese Han population and elucidation of the related mechanisms provides theoretical basis and technical support for the development of early diagnosis and therapeutic strategies in UC. [ABSTRACT FROM AUTHOR]

Erythropsis kwangsiensis (Sterculiaceae), a wild endangered tree that grows in South China, is an economically important species. There is scant information available on the chloroplast (cp) genome of this species. The present study is the first to analyze the cp genome of E. kwangsiensis using genome skimming. The whole cp genome is 160,836 bp long with 131 genes, including 84 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The GC content is 37.0%. Phylogenetic analysis revealed a close relationship to Firmiana colorata. This data will be useful for future investigations of conservation genetics and potential applications in breeding new varieties of this endangered and economically important tree. [ABSTRACT FROM AUTHOR]

Carbonate melts play an essential role in the deep carbon cycle between Earth's surface and interior. Most previous studies proposed that the source of carbonate melt resulted from the recycling of subducted oceanic slabs. Recent studies on orogenic rocks show that continental subduction may also deliver carbonate sediments into the deep mantle. However, these rocks usually have undergone complex geological processes and strong modifications during exhumation. Here we report evidence of continental subduction-triggered carbonate metasomatism of the lithospheric mantle from a suite of mantle xenoliths entrained by the Cenozoic Qixia basalts from the southeastern North China Craton (NCC). Both petrological (the same variation of mineral modal content as in carbonate melt-peridotite reaction experiments, the replacement of olivine and orthopyroxene by clinopyroxene, and the presence of apatite) and geochemical (high Ca/Al, La N /Yb N , and low Ti/Eu ratios in clinopyroxene) evidence show mantle xenoliths record obvious signals of carbonated silicate melt metasomatism. The high 87Sr/86Sr ratios of 0.7094–0.7100 in clinopyroxene of these xenoliths indicate that the carbonated silicate melt was derived from subducted continental crust rather than oceanic crust and asthenosphere mantle. The carbonated silicate melt could be produced by carbonate dissolution during continental subduction or resulted from the partial melting of the diapiric carbonate-rich sediments. An estimation suggests a carbon input flux of 14 ± 7 Mt yr−1 associated with the Yangtze continental subduction, approximately 20–50% of the estimated total carbon input flux of the global oceanic subduction. It is therefore important to include the contribution of continental subduction when deciphering deep carbon recycling and its effects. • Qixia mantle xenoliths from North China Craton suffered carbonate metasomatism. • Carbonated silicate melt was derived from the subducted Yangtze Block. • Continental subduction plays an essential role in the deep carbon cycle. • Input flux of 14 ± 7 Mt. C yr−1 is estimated during Yangtze continental subduction. [ABSTRACT FROM AUTHOR]

Abstract: Craton destruction is a complex process involving both chemical and physical interactions between the crust and the mantle. Several mechanisms, including thermo-chemical erosion, delamination, lithosphere extension and subducting slab dehydration, have been proposed to explain the destruction of the North China Craton (NCC). We present constraints extrapolated directly from laboratory melt–peridotite reaction experiments, which demonstrate that the reaction between eclogite-derived melt and peridotite can lead to crystallization of low-Mg# pyroxenite and generation of high Mg# andesite, which is consistent with natural observations of the melt–peridotite reactions in the NCC. However, this reaction is a sluggish process under dry and hydrostatic conditions. It can be promoted significantly on a relatively large scale by the formation of melt-filled cracks/veins (melt+clinopyroxene) in peridotite under axial compression conditions or by the production of shear enhanced reaction zones (low Mg# olivine+orthopyroxene) under simple shear conditions. Our results also reveal that the lower crust of the NCC has a viscosity much lower than the upper crust and the unaltered dry upper mantle. These results suggest that 1) vertical tectonic deformation can facilitate large-scale melt–peridotite reaction and mantle refertilization; 2) weakening of the upper mantle by water is a prerequisite for eclogitilized lower crust to sink down through the otherwise strong lithospheric upper mantle. We propose a long-period, small-scale delamination model as a possible mechanism for the destruction of the interior of the North China Craton. [Copyright &y& Elsevier]

• Malan loess is anisotropic and it behaves strongly in vertical direction. • Malan loess under in-situ situation tends to fail at high rupture angles. • The anisotropy is in good agreement with the vertiloess structure. • The anisotropy favors deep vertical cracks which mobilize toppling and falling failures. • These failures shape the loess mass into columns and walls. Loess is widely distributed in China, with the Loess Plateau having the largest global bulk accumulation. The micro-scale loess landforms are featured by loess walls and loess columns, which can stand vertically for many years. The main failure modes of loess to form these vertical features are toppling and falling along a rupture surface of high angles. These failure modes are attributed to loess strength behavior, which in turn are dominated by the inner structure of loess soil. Bearing this in mind, we sought to conduct a series of mechanical tests on both vertical and horizontal loess samples. These included tension as well as uniaxial and triaxial compression tests. It is found that Malan loess had strong anisotropy in terms of failure pattern and strength. The vertical specimens possess strengths 1.3 times greater than those of horizontal specimens, and tend to fail at high rupture angles of approximately 85° under uniaxial and triaxial compression conditions. These findings were in good agreement with the vertiloess structure, where the vertically aligned strong units resulting from inter-particle bonding and close compaction make the loess behave strongly in the vertical direction, while the vertically aligned weak segments are responsible for the high rupture angles. These findings explain the formation of deep vertical cracks which mobilize loess toppling and falling and shape the loess mass into columns and walls. [ABSTRACT FROM AUTHOR]

Multi-phase deepwater fan systems have formed in the Baiyun Sag of the Pearl River Mouth Basin on the northern margin of the South China Sea since the beginning of the Miocene. Integrated analysis of 2D/3D seismic, well log, core, and biostratigraphic data shows that the early Miocene Pearl River deepwater fan deposits consist of four 3rd-order sequences, SQ23.8, SQ21, SQ17.5 and SQ16.5. Each of them is bounded by regional discontinuity surfaces (3rd-order sequence boundaries). Of particular interest are the sandy deepwater fan deposits in the HST of SQ23.8 and LST of SQ21, which are absent in SQ17.5 and SQ16.5. The SQ23.8 deepwater deposits are relatively thin sheets, densely spaced sandy debris flow channels and MTDs, whereas in SQ21 they manifest as thicker sheets and larger channels. In terms of lithofacies, SQ23.8 deepwater deposits are massive sandstones, in contrast to SQ21 deposits of massive sandstones, normally graded sandstones, inversely graded sandstones, and locally interbedded ripple laminated siltstones. It is interpreted that SQ23.8 deepwater sands result from homochronous slumping of the shelf margin delta front, while SQ21 deepwater sands result from the erosion and re-deposition of the ancient SQ23.8 highstand shelf margin delta. The Paleocene-Early Oligocene rift stage (57.5 Ma ∼ 32 Ma) was characterized by extensive development of half-grabens and normal faults. Since 32 Ma, the drift stage has been characterized by thermal subsidence and weak tectonic activity. The distributions of deepwater sands in SQ23.8 and SQ21 are interpreted to have been controlled by seabed topography that was inherited from buried rift-related tectonic features. We propose that the primary controlling factor for the development of the early Miocene Pearl River Deepwater Fan System was likely sediment supply of the Pearl River influenced by the Baiyun Event and the uplift of Qinghai-Tibet Plateau. The specific location of the sandy deepwater fan was due to tectonic influence on paleotopography of the shelf. The interpreted two depositional models can help predict the types of deepwater depositional elements are in the Baiyun Sag of the Pearl River Mouth Basin and where deepwater sands are likely to occur. [ABSTRACT FROM AUTHOR]

Background: To determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics., Methods: In the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N = 301), 7.5 mg/day tolvaptan group (N = 153) and placebo group (N = 76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint., Results: The administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P = 0.026; P = 0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P 7.5  = 0.05, P 15.0  = 0.002 and P 7.5  = 0.037, P 15.0  = 0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P = 0.002, P < 0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P = 0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P = 0.543)., Conclusions: Tolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic., Trial Registration: NCT01349348. Retrospectively registered May 2011.

The potential association between coal-burning arsenic exposure and type 2 diabetes (T2D) was examined through a case control study, conducted in coal-burning arsenic poisoning areas in the Guizhou Province. This study included patients diagnosed with type 2 diabetes. Control subjects without type 2 diabetes were recruited randomly after gender and age 1:1 matching. All subjects completed questionnaire surveys and underwent physical examination and whole blood arsenic level testing. The whole blood arsenic level was associated with a significant increase in the risk of type 2 diabetes (75th versus 25th, adjusted OR = 1.76, 95% CI: 1.03-3.01). However, a nonlinear relationship was observed between the blood arsenic level and type 2 diabetes. The risk of type 2 diabetes increased with blood arsenic levels above 3.69 μg/L (Log As ≥0.57). The subgroup analysis revealed that blood arsenic levels were associated with significantly increased risk of type 2 diabetes in people who ever smoked (P < .05), particularly those who smoked ≥15 years (adjusted OR = 3.15, 95% CI: 1.9-7.28). Therefore, prolonged arsenic exposure, even at a low level, is associated with a higher prevalence of type 2 diabetes in a nonlinear pattern. Blood arsenic levels less than 3.69 μg/L may be considered safe with respect to the risk of T2D. However, smoking, particularly smoking ≥15 years, may be associated with the development of diabetes in patients with arsenic exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

More than 80% of maturity-onset diabetes of the young (MODY) in Chinese is genetically unexplained. To investigate whether the insulin gene (INS) mutation is responsible for some Chinese MODY, we screened INS mutations causing MODY10 in MODY pedigrees and explored the potential pathogenic mechanisms. INS mutations were screened in 56 MODY familial probands. Structure-function characterization and clinical profiling of identified INS mutations were conducted. An INS mutation, at the position 2 alanine-to-threonine substitution (A2T), was identified and co-segregated with hyperglycemia in a MODY pedigree. The A2T mutation converted an α-helix into a β-sheet at the N-terminal of the signal peptide (SP) of preproinsulin. The A2T mutation did not affect preproinsulin translocation across endoplasmic reticulum (ER) membrane, but impaired its SP cleavage within the ER. In INS-1 cells transfected with an A2T mutant, glucose-stimulated insulin secretion (GSIS) was significantly decreased, while BiP luciferase activities were significantly increased compared to that of wild type (WT). We identified an INS-A2T mutation cosegregating with diabetes in a Chinese MODY pedigree. This mutation severely impaired SP cleavage and thus blocked the formation of proinsulin, resulting in enhanced ER stress, which may be responsible for decreased insulin secretion and subsequently, the onset of MODY10.

Background: Drug-induced liver injury (DILI) is the most common reason for a drug to be withdrawn from the market. Apart from stopping the offending drug, no regimens are available for treating idiosyncratic DILI in clinical practice., Methods: We carried out a randomized, double-blind, multidoses, active drug controlled, multicentre phase II trial to assess the safety and efficacy of the study drug, magnesium isoglycyrrhizinate (MgIG), as compared to tiopronin, a standard therapy for DILI in China. The primary outcome was the proportion of alanine aminotransferase (ALT) normalization at week 4 after study drug administration. Logistic regression was used to examine the odds of ALT normalization between low dose (Group A) and high dose (Group B) vs active control (Group C)., Results: One hundred and seventy-four eligible subjects were randomized and enrolled into three groups: 59 in group A, 56 in group B and 59 in group C. It was shown that group A and group B lowered ALT level even at early stage of study drug administration; when compared with Group C (61.02%), the proportions of ALT normalization at week 4 were significantly greater in Group A (84.75%, P = .0029) and Group B (85.71%, P = .0037) respectively. The results from the univariate logistic model showed that the odds of ALT normalized among subjects in Group A were about 3.6 times greater (OR = 3.55, 95% CI: 1.47-8.57, P = .0049) than subjects in Group C. Similar effect was observed among subjects in Group B (OR = 3.83, 95% CI: 1.54-9.55, P = .0039)., Conclusions: This trial provided preliminary evidence that MgIG is an effective and safe treatment for patients with acute DILI., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this study, we evaluated the performance of three blood culture systems in a Chinese tertiary-care hospital. Samples of simulated bacteremia were prepared using 10 mL of fresh blood from healthy humans and bacterial suspensions of known cell density. Portions of the specimens were treated with an antibiotic or antifungal drug at specified concentrations to simulate antibacterial drug treatment. We analyzed three blood culture systems: BACTEC Plus, BacT/Alert, and VersaTREK. Both time-to-detection (TTD) of 10 types of bacteria and five types of yeasts in samples without antibiotic treatment and positive detection rate of samples treated with different concentrations of antibiotic or antifungal drugs were compared among the culture systems. We also retrospectively analyzed the use of the culture systems in our hospital from 2015 to 2018. In the simulated study, in the absence of antibiotics, the VersaTREK REDOX 1 displayed the shortest TTD for Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Candida albicans , and Candida glabrata ( P < 0.001). Among the anaerobically cultured samples, BACTEC lytic/10 anaerobic/F displayed the shortest TTD for Escherichia coli, S. aureus, Enterococcus faecalis, S. pneumoniae, Bacteroides fragilis , and Bacteroides vulgatus ( P < 0.001). Comparatively, BacT/Alert FA/FN showed no advantages. In antibiotic-treated samples, overall recovery rates for the BACTEC, BacT/Alert, and VersaTREK systems were, were 70.2, 43.7, and 27.4%, respectively. BACTEC facilitated higher recovery rate than the other two systems ( P < 0.001). In antifungal treatment, the overall recovery rates for the BACTEC, BacT/Alert, and VersaTREK systems were 93.9, 98.3, and 69.4%, respectively. BACTEC Plus showed a recovery rate comparable to that of BacT/Alert ( P = 0.835), and the recovery rate of both these systems was higher than that of VersaTREK ( P < 0.001). The TTD values and positive rates determined in the retrospective study were consistent with those obtained in the simulated study. The combination of BACTEC PLUS Aerobic/F and BACTEC lytic/10 anaerobic/F culture systems displayed the best clinical performance. Furthermore, the BacT/Alert FAN culture system was found to be more resistant to antifungal drugs and levofloxacin, whereas the VersaTREK system is considered more suitable for primary blood cultures without antibiotic supplementation.