Waning immune responses against SARS-CoV-2 among vaccinees in Hong Kong

BackgroundNearly 4 billion doses of the BioNTech-mRNA and Sinovac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. MethodsWe compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. FindingsStandard BioNTech and Sinovac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC50 and median frequencies of reactive CD4 subsets were consistently lower among Sinovac-vaccinees than BioNTech-vaccinees. Against VOCs, NAb response rate and geometric mean IC50 against B1.351 and B.1.617.2 were significantly lower for Sinovac (14.3%, 15 and 50%, 23.2) than BioNTech (79.4%, 107 and 94.1%, 131). Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among Sinovac-vaccinees. InterpretationOur results indicate that Sinovac-vaccinees may face higher risk to pandemic VOCs breakthrough infection. FundingThis study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF to Z.C and C1134-20GF); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

Posttransplant Management of Recipients Undergoing Liver Transplantation for Hepatocellular Carcinoma. Working Group Report From the ILTS Transplant Oncology Consensus Conference.

Although liver transplantation (LT) is the best treatment for patients with localized hepatocellular carcinoma (HCC), recurrence occurs in 6%-18% of patients. Several factors, particularly morphological criteria combined with dynamic parameters, known before LT modify this risk and combined in prediction models may be used to stratify patients at need of variable surveillance strategies. Additional variables though likely explain differences in recurrence rates in patients with the same pre-LT HCC status. One of these variables is possibly immunosuppression (IS). Once recurrence takes place, management is highly heterogenous. Within the International Liver Transplantation Society Consensus Conference on Liver Transplant Oncology, working group 4 aim was to analyze the data regarding posttransplant management of recipients undergoing LT for HCC. Three areas of research were considered: (1) cancer prediction models and surveillance strategies; (2) tailored IS for cancer recipients; and (3) new adjuvant therapies for HCC recurrence. Following formulation of several questions, a literature search was undertaken with abstract review followed by article retrieval and full-data extraction. The grading of recommendations assessment, development and evaluation (GRADE) system was used for evidence rating incorporating strength of recommendation and quality of evidence.

{2,6-Bis[(2,6-diisopropyl-phosphan-yl)-oxy]-4-fluoro-phenyl-κ(3)P,C(1),P'}(1H-pyrazole-κN(2))nickel(II) hexa-fluoro-phosphate.

The title compound, [Ni(C(18)H(30)FO(2)P(2))(C(3)H(4)N(2))]PF(6), was prepared by halide abstraction with TlPF(6) in the presence of CH(3)CN in CDCl(3) from the respective neutral pincer chlorido analogue followed by addition of pyrazole. The PO-C-OP pincer ligand acts in typical trans-P(2) tridentate fashion to generate a distorted square-planar nickel structure. The Ni-N(pyrazole) distance is 1.925 (2) Šand the plane of the pyrazole ligand is rotated 56.2 (1)° relative to the approximate square plane surrounding the Ni(II) center in which the pyrazole is bound to the Ni(II) atom through its sp(2)-hybridized N atom. This Ni-N distance is similar to bond lengths in the other reported Ni(II) pincer-ligand square-planar pyrazole complex structures; however, its dihedral angle is significantly larger than any of those for the latter set of pyrazole complexes.

Reduced CRYL1 expression in hepatocellular carcinoma confers cell growth advantages and correlates with adverse patient prognosis.

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p < 0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and promoter hypermethylation to be likely inactivating mechanisms as well. Re-expression of CRYL1 in the SK-Hep1 cell line, where biallelic loss of CRYL1 was found, induced profound inhibition of cellular proliferation and cell growth (p < 0.0015). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of PARP cleavage. Flow cytometry further revealed that CRYL1 could prolong the G(2)-M phase, possibly through interruption of the Cdc2/cyclin B pathway. Given that regional chromosome 13q12-q14 loss is a causal genomic event in HCC tumourigenesis, our finding may have implications for identifying a novel TSG CRYL1 within this important locus.

Is gliomatosis peritonei derived from the associated ovarian teratoma?

Gliomatosis peritonei, a rare condition that occurs almost exclusively in the setting of ovarian immature teratoma, is characterized by the occurrence of nodules of mature glial tissues in the peritoneum. It is controversial whether glial tissues are derived from maturation of the associated teratomatous tissue that has implanted in the peritoneum, or glial differentiation of subperitoneal stem cells. In this study, we employed the unique genetic characteristics of ovarian teratomas (often with a duplicated set of maternal chromosomes and thus homozygous at many polymorphic microsatellite loci) versus normal tissues (heterozygous pattern due to presence of maternal and paternal genetic materials) to investigate the origin of gliomatosis peritonei. DNA samples were extracted from microdissected paraffin-embedded tissues, including the glial implants, the associated ovarian teratomas, and normal tissues, to determine their patterns of microsatellite loci in a multiplex polymerase chain reaction system. Two cases were not informative because the ovarian teratoma showed a heterozygous microsatellite pattern. In the 5 informative cases, the normal tissues showed a heterozygous pattern in the microsatellite loci, the associated teratomas showed a homozygous pattern, and the glial tissues showed a heterozygous pattern. Thus, gliomatosis peritonei is genetically unrelated to the associated teratoma but is probably derived from nonteratomatous cells, such as through metaplasia of submesothelial cells.

Comparison of noninvasive tear break-up time measurements from black and white background instruments.

PURPOSE: To compare noninvasive tear break-up time (NITBUT) measured using a black background instrument (NITBUTb) and that measured using a white background instrument (NITBUTw). METHODS: The NITBUTb and NITBUTw of the right eye of 58 asymptomatic subjects aged 16 to 23 years were measured by the same examiner on the same day and compared. NITBUT measurement was terminated at 45 s to minimize ocular discomfort and reflex tearing. RESULTS: Three subjects had reflex tearing during the NITBUT measurement, and nine subjects had either NITBUTb or NITBUTw values > 45 s, so their data were excluded. For the 46 subjects with NITBUT < or = 45 s, no significant difference between NITBUTb and NITBUTw was found (Wilcoxon test p = 0.156). No statistically significant relationship was found between NITBUTb and NITBUTw (Spearman r = 0.217, p = 0.147). The agreement between NITBUTb and NITBUTw was poor, with a mean difference of 1.3 s and 95% limits of agreement of -20.0 to +22.6 s. CONCLUSIONS: There was no significant difference in NITBUT made from instruments of different backgrounds if the procedures and endpoint criterion were the same. The poor agreement between NITBUTb and NITBUTw was due to the large variations in NITBUT rather than the difference in the background color of the instrument used. However, use of the black background instrument for subjects with dark irides is recommended, as it is relatively easier to see the grid image on the eye and > 50% of our subjects complained of discomfort from glare with the white background instrument.

Recombinant human bone morphogenetic protein-4 (rhBMP-4) enhanced posterior spinal fusion without decortication.

In posterior spinal fusion, insufficient decortication may decrease the number of bone marrow derived ostoprogenitor stem cells and affect the success of bony fusion. The finding of bone formation through interaction between rhBMP-4 and non-marrow derived mesenchymal cells constituted the basis of the current study. The aim is to investigate the possibility of molecular enhancement of posterior spinal fusion by site-specific application of rhBMP-4 with or without surgical decortication. Eighteen adult rabbits underwent single level bilateral posterior intertransverse process spinal fusion at L5-L6. one side with decortication, and the other side without decortication. Two animals underwent sham operation without bone grafts, the other 16 animals were randomly allocated into three groups, using hydroxyapatite-tricalcium phosphate (HA-TCP) ceramic blocks augmented with 0, 125 and 5 micromg [corrected] of rhBMP-4 respectively. Spinal fusion morphology was evaluated with sequential X-ray, microradiography and histomorphology. At week 7, complete bony fusion was achieved in none of the groups without rhBMP-4 irrespective of whether the bony contact surface was decorticated or not. In the groups with low dose rhBMP-4, complete fusion occurred in two of six un-decorticated sites (33%) and in three of six (50%) decorticated sites. 100% complete fusion was found in the high dose rhBMP-4 group independent of surgical decortication. The dorsal cortices of the un-decorticated transverse processes were replaced by newly formed trabecular bone through biological remodeling. This study suggested that rhBMP-4 can induce non-marrow derived mesenchymal cells to differentiate into osteogenic cells and thus enhance the high success rate of pesterior spinal fusion in both the decorticated and un-decorticated model.

Hepatic stress genes expression and ultrastructural feature under intermittent Pringle manoeuvre in hepatectomy patients / 中国普通外科杂志

ObjectiveTo evaluate the expression of heat shock genes and acute phase genes and to examine the hepatic ultrastracture under the stress of intermittent Pringle manoeuvre. MethodsRT-PCR was used to detect the expression of HSP70A, HSC70, TNF-? and IL-6,and electronic microscopy examination was taken to document the ultrastructural change in patients with hepatocellular carcinoma, with or without, Pringle manoeuvre, during the operations. ResultsHeat shock gene family-HSP70A and HSC70, which is related to intracellular repair and cell protection, was on higer expression after liver transection in Pringle manoenvre group than that of control group. Normal ultrastructure were also found in liver parenchymal cells and nonparenchymal cells in Pringle manoeuvre group after liver resection. ConclusionIntermittent Pringle manoeuvre induced relatively higher expression of heat shock genes, which are related to intracellular homestasis, and was consistent with the well maintenance of liver ultrastructure.