The coronavirus disease 2019 (COVID‐19) is a highly infectious disease caused by SARS‐CoV‐2. Since its first report in December 2019, COVID‐19 has evolved into a global pandemic causing massive healthcare and socioeconomic challenges. HLA system is critical in mediating anti‐viral immunity and recent studies have suggested preferential involvement of HLA‐B in COVID‐19 susceptibility. Here, by investigating the HLA‐B genotypes in 190 unrelated Chinese patients with confirmed COVID‐19, we identified a significant positive association between the B22 serotype and SARS‐CoV‐2 infection (p = 0.002, Bonferroni‐corrected p = 0.032). Notably, the B22 serotype has been consistently linked to susceptibility to other viral infections. These data not only shed new insights into SARS‐CoV‐2 pathogenesis and vaccine development but also guide better infection prevention/control.

17beta-Estradiol and progesterone were found to relax various vascular beds through multiple mechanisms. However, the exact ionic mechanisms underlying the acute relaxant responses to both hormones are incompletely understood. This study was aimed to examine the possible role of K channel activation in the relaxation induced by both hormones in isolated rat mesenteric artery rings. Isometric tension of each ring was measured with Grass force displacement transducers. In rat endothelium-denuded rings preconstricted by 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F (U46619), the relaxation induced by 17beta-estradiol was partially inhibited by tetrapentylammonium, 4-aminopyridine, iberiotoxin, BaCl, and tertiapin-Q but not by tetraethylammonium, charybdotoxin, apamin, or glibenclamide. In contrast, these putative K channel blockers, except for glibenclamide, did not affect the relaxant response to progesterone. In 4 x 10(-2) K -preconstricted rings, the K channel blockers lost their inhibitory effects on 17beta-estradiol-induced relaxation. Endothelium did not seem to be involved in the effects of K channel blockers on 17beta-estradiol-mediated relaxation. Nifedipine-induced relaxation was not inhibited but was instead enhanced by tetrapentylammonium, iberiotoxin, 4-aminopyridine, and BaCl2. The above results indicate that in rat mesenteric artery rings, nonselective activation of K channels contributes partially to the relaxation induced by 17beta-estradiol. These K channels involved in the estrogen response appeared to be sensitive to inhibition by K(Ca), K, and K(IR) channel blockers. Lack of effect of K channel blockers on progesterone-induced relaxation suggests that these K channels play little or no role. The present findings provide pharmacological evidence for an additional mechanism contributing to acute vasorelaxation induced by 17beta-estradiol.

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In endothelium-intact rat mesenteric arteries pretreatment with low concentrations of isoproterenol enhanced the acute relaxant response to 17 beta-estradiol. This enhancement was dependent on the presence of endothelium and abolished by L-NAME via a beta(2)-adrenoceptor-mediated cyclic AMP-dependent mechanism.

17β-Estradiol has been shown to relax blood vessels partly through inhibition of Ca²⁺ channels at supraphysiological concentrations; however, it is unknown whether acute exposure of the isolated artery rings to near physiological concentrations of sex steroid hormones could modulate the ionic channels that are involved in regulation of vascular tone. Brief incubation (20 min) with 17β-estradiol (1–3 nmol/l) did not alter the relaxant response to three blocking agents of L-type voltage-sensitive Ca²⁺ channels, nifedipine, diltiazem and verapamil in either endothelium-intact or endothelium-denuded rat mesenteric artery rings. In contrast, 17β-estradiol at 3 nmol/l significantly attenuated the relaxation induced by K⁺ channel openers, cromakalim and pinacidil in endothelium-denuded rings. Similarly, preincubation with progesterone (3 nmol/l) inhibited pinacidil-induced relaxation with much less effect on cromakalim-induced relaxation. It appears that 17β-estradiol and progesterone attenuated the cromakalim- and pinacidil-induced relaxation in a different manner. These results suggest that acute exposure to female sex steroid hormones at near physiological levels may reduce the activity of ATP-sensitive K⁺ channels in the rat arteries.

Background/aims Treatment of chronic hepatitis B (CHB) with lamivudine (3TC) is limited by development of drug-resistant mutants at the YMDD motif. We aimed to validate the use of mass spectrometry to detect YMDD mutants and quantify viral subpopulations. Methods A total of 21 Chinese patients with severe acute exacerbation of CHB treated with 3TC were studied. Serial serum samples were tested for wild-type and YMDD mutants using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. INNO-LiPA assay was performed for comparison. Results At a median follow-up of 192 weeks, 11 patients developed YMDD mutants (six had YIDD, four had YVDD and one had YV/IDD). Mass spectrometry was concordant with INNO-LiPA in all but one patient, in which INNO-LiPA detected coexistence of YIDD and YVDD but mass spectrometry and direct sequencing detected YVDD only. Mass spectrometry was able to reliably detect a minor hepatitis B virus (HBV) subtype at 5% or above. By serial quantitative measurement, several patterns of viral dynamics were observed. In some cases, YMDD mutants dominated the whole viral population. In other cases, the proportion of YMDD mutants fluctuated with time. When more than one mutant was present (that is, YIDD and YVDD), the different mutants might dominate during different time periods. Conclusions Mass spectrometry is an accurate and cheap method for the detection of YMDD mutants, even in the presence of overwhelming wild-type HBV. We observed some intriguing mutant viral dynamics during 3TC treatment. Further studies are needed to clarify whether they have any clinical significance.

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