Association of neutralizing breadth against SARS-CoV-2 with inoculation orders of heterologous prime-boost vaccines.

BACKGROUND: Emerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear. METHODS: We conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA. FINDINGS: We observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders. CONCLUSIONS: Our data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism. FUNDING: National Key R&D Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.

The role of katanin p60 in breast cancer bone metastasis.

p60 is a subunit of katanin involved in microtubule-severing. Previous studies of p60 were primarily focused on microtubule regulation and cell cycle regulation. More recent research has demonstrated that katanin p60 possesses a function in prostate cancer bone metastasis; however, its role in breast cancer bone metastasis remains unclear. In the present study, immunohistochemistry was used to analyze the expression of katanin p60 in primary and bone metastatic breast cancer. The role of up- and downregulated katanin p60 was investigated using cell proliferation, and migration experiments. Overall, katanin p60 was highly expressed in breast cancer bone metastatic tissue compared with primary tumor tissue. In breast cancer cells, overexpression of katanin p60 inhibited cell proliferation, but promoted cell migration, whereas silencing katanin p60 expression promoted cell proliferation but inhibited cell migration. Overall, the present study indicated that katanin p60 serves a role in cell proliferation and migration, and thus may be a novel therapeutic target for prevention of breast cancer metastasis.

Association of mRNA expression level of IP-10 in peripheral blood mononuclear cells with HBV-associated acute-on-chronic liver failure and its prognosis.

HBV-associated acute-on-chronic liver failure is prevalent in mainland China. The prognosis of HBV-ACLF is poor. The mortality of HBV-ACLF is approximately 80%. Therefore, a prognostic indicator was needed in order to allow us to intervene as soon as possible. The model for end-stage liver disease (MELD) scoring system is widely used to predict the prognosis of liver failure. However, the assessment is too complex to restrict its application. This study aimed to investigate the expression of IP-10 in peripheral blood mononuclear cells (PBMC), in order to explore the relationship between the expression and prognosis of patients with HBV-ACLF. The mRNA level of IP-10 in PBMCs were analyzed in 80 patients with HBV-ACLF, 40 patients with chronic hepatitis B (CHB) and 40 healthy people by fluorescent quantitative PCR. IP-10 mRNA level was significantly higher in the HBV-ACLF group than in the other two groups (P<0.01). Group with MELD score below 30 had lower IP-10 mRNA level than group with MELD score over 30 (P<0.05). The IP-10 mRNA level in PBMCs in positive group was higher than that in negative group (P<0.01). With a threshold of 0.925, the area under the receiver operating characteristic (ROC) curves was 0.815. These findings suggest that assessment of IP-10 mRNA level in the PBMCs would be helpful for evaluating the disease severity and prognosis in patients with HBV-ACLF.

Association of mRNA Expression Level of IP-10 in Peripheral Blood Mononuclear Cells with HBV-associated Acute-on-chronic Liver Failure and Its Prognosis / 华中科技大学学报（医学）（英德文版）

HBV-associated acute-on-chronic liver failure is prevalent in mainland China.The prognosis of HBV-ACLF is poor.The mortality of HBV-ACLF is approximately 80％.Therefore,a prognostic indicator was needed in order to allow us to intervene as soon as possible.The model for end-stage liver disease (MELD) scoring system is widely used to predict the prognosis of liver failure.However,the assessment is too complex to restrict its application.This study aimed to investigate the expression ofIP-10 in peripheral blood mononuclear cells (PBMC),in order to explore the relationship between the expression and prognosis of patients with HBV-ACLF.The mRNA level of IP-10 in PBMCs were analyzed in 80 patients with HBV-ACLF,40 patients with chronic hepatitis B (CHB)and 40 healthy people by fluorescent quantitative PCR.IP-10 mRNA level was significantly higher in the HBV-ACLF group than in the other two groups (P＜0.01).Group with MELD score below 30 had lower IP-10 mRNA level than group with MELD score over 30 (P＜0.05).The IP-10 mRNA level in PBMCs in positive group was higher than that in negative group (P＜0.01).With a threshold of 0.925,the area under the receiver operating characteristic (ROC) curves was 0.815.These findings suggest that assessment of IP-10 mRNA level in the PBMCs would be helpful for evaluating the disease severity and prognosis in patients with HBV-ACLF.

[Correlation of -31G/C polymorphisms of survivin promoter to tumorigenesis of gastric carcinoma].

BACKGROUND & OBJECTIVE: Survivin, a bifunctional protein that regulates cell division and suppresses apoptosis, may play an important role in tumorigenesis. This study was to determine the correlations of survivin gene 31-GC polymorphisms to the occurrence of gastric carcinoma and survivin mRNA expression. METHODS: The -31G/C single nucleotide polymorphism (SNP) of survivin promoter in peripheral blood samples from 96 gastric carcinoma patients and 67 healthy subjects was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing. Survivin mRNA expression in gastric carcinoma tissues was detected by real-time quantitative reverse transcription-polymerase chain reaction (RQ-RT-PCR). RESULTS: The genotype frequencies for -31G/G, -31G/C and -31C/C were 20.84%, 39.58% and 39.58% in gastric carcinoma patients, and 46.26%, 41.80% and 11.94% in healthy subjects, respectively. The frequencies of survivin-31C allele and C/C genotype were significantly higher in gastric carcinoma patients than in healthy subjects [59.37% vs. 32.84%, Chi2 = 22.26, P<0.005, odds ratio (OR)=2.98, 95% confidence interval (CI)=1.96-4.51; 39.58% vs. 11.94%, Chi2 =14.88, P<0.005, OR=4.83, 95% CI=2.91-8.03], but survivin mRNA was overexpressed with no significant difference in gastric cancer tissues subgrouped by genotypes. CONCLUSION: The -31C genotype of survivin promoter is associated with gastric cancer, and may be a risk factor of gastric carcinoma.

Expression of survivin and its splice variants in gastric cancer.

Survivin variants specific real time quantitative RT-PCR was developed to analyze their expression in 53 paired cancer and para-cancerous tissues, and the expression of the wild-type survivin protein was detected by immunohistochemistry. The results showed that survivin mRNA and protein were expressed in gastric cancer and para-cancerous tissues. The survivin-2B was dominantly expressed in para-cancerous tissues, whereas the survivin-DeltaEx3 was more frequently detected in cancer tissues. The positive rate of survivin-2a was 100% in both cancer and para-cancerous tissues, but its relative transcript expression level was not significantly increased in cancer tissues in comparison with para-cancerous tissues. The correlation analysis revealed that the expression of survivin-2a mRNA was significantly associated with that of total survivin (r (s)=0.4178, P=0.0018), whereas inversely to that of survivin-DeltaEX3 (r (s)=-0.4506, P=0.0007). It was suggested that survivin-2a may act as an antagonist of survivin-DeltaEX3. The balance between antiapoptotic survivin iso-forms and nonantiapoptotic ones may play an important role in tumorigenesis and tumor progression. Promising value is hinted to analyze survivin and its variants in tumor early diagnosis and distinguishing malignant tumors from benign ones.

Rapid quantification of hepatitis B virus DNA by direct real-time PCR from serum without DNA extraction.

The purpose of this study was to quantify hepatitis B virus DNA by direct real-time PCR from serum without the need for DNA extraction. Crossing point (Cp) values were determined automatically using the second derivative maximum mode. Since serum samples from patients are inevitably haemolysed, lipaemic or icteric, the interference of endogenous substances from the serum in real-time PCR was evaluated. The result showed that, although serum protein quenched the intensity of fluorescence, the Cp value adopted to calculate the quantity of DNA copies remained unchanged. Importantly, real-time PCR from serum with or without DNA extraction reached a high level of concordance. This direct serum PCR method without the DNA extraction and gel electrophoresis allows for substantial labour and cost savings. In addition, it is also suitable for rapid DNA quantification during clinical diagnosis.