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Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400[~]480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with [≥] 50% decrease in MN titers when comparing the available peak and current MN titers ([≥] 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.
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BackgroundSARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed. MethodsEpidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines. Results40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. ConclusionCOVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.
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The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.
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BackgroundThe outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidating the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this disease. MethodsRespiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information. FindingsExcept for BALF, the sputum possessed the highest positive rate (74.4%[~]88.9%), followed by nasal swabs (53.6%[~]73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected [≥] 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%[~]61.1%. The positive rate of throat swabs collected [≥] 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground-glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples. InterpretationSputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP. FundingNational Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.
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Objective To explore the clinical and pathological characterizations of single progesterone receptor positive breast cancer,and identify the prognostic factors.Methods Obtained from SEER database,the author selected female patients diagnosed with invasive ductal breast cancer between January 1,2010,and December 31,2013.Seven hundred and seventy-five cases were single progesterone receptor positive breast cancer and 12 075 cases were triple negative breast cancers.Patient characteristics were compared using a Chi-square test or Fisher's exact test as appropriate.The Kaplan-Meier method was used to construct survival curves.The multivariate COX regression models were built to assess the independent association of all the variables.Results There was no significant difference between the two groups in terms of race (P =0.711),tumor location (P =0.325),marital status (P =0.255),Grade (P =0.773),tumor size (P =0.949),lymph node status (P =0.821),stage (P =0.567) or radiation treatment (P =0.434).Compared with triple negative breast cancer,patients with single progesterone receptor positive breast cancer tended to be younger(P =0.001),however no significant difference was found in breast cancer-specific survival(P =0.481)between the two groups.Larger tumor size [HR =2.777 (95％ CI:1.295-5.955),P =0.009],and lymph node invasion [HR =3.669 (95％ CI:1.881-7.154),P ＜ 0.001] could significantly increase the risk of dying from cancer in single progesterone receptor positive breast cancer patients.Conclusions Single progesterone receptor positive breast cancer presented with an early onset of disease,and experienced similar cancer-specific survival as triple negative breast cancer.Tumor size and lymph node status were independent prognostic factors.
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Objective To investigate the anatomical relation between Zuckerkandl's tubercle and recurrent laryngeal nerve and the superior parathyroid glands anatomy in endoscopic thyroidectomy.Methods From Jul.2012 to Jun.2014 implementation of the 120 cases of endoscopic thyroid surgery (at least one side of the line lobectomy) intraoperative Zuckerkandl tubercle of the presence, all the patients from Subei People's Hospital and location of the relationship between anatomy recurrent laryngeal nerve and superior parathyroid glands.Zuckerkandl tubercle identified by intraoperative recunent laryngeal nerve to expose and superior parathyroid glands.Results Zuckerkandl tubercle appear in the vast majority of cases: on the left is 86％ (51/59), 88％ in the right side (65/74), most of superior parathyroid glands were located on the top of Zuckerkandl tubercle.Looking for recurrent laryngeal nerve by Zuckerkandl tubercle method is more direct, can reduce surgical bleeding and shmten the operation time.Conclusion Recurrent laryngeal nerve and superior parathyroid glands and have close anatomical relationship with Zuckerkandl tubercle.In endoscopic thyroidectomy by intraoperative discern Zuckerkandl tubercle can better avoid injury recurrent laryngeal nerve and superior parathyroid glands.
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Long non-coding RNAs are RNA transcripts longer than 200 nt without any function of coding protein,and gradually become a new focus of cancer research because of their important roles in regulating genes expression at the epigenetic,transcriptional and post-transcriptional levels.Recently,more researches show that are closely related to the occurrence of breast cancer and other tumors.Therefore,in this review,we summarize the developing understanding of LncRNAs associated with breast cancer.
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Background and purpose:Aberrant DNA methylation that leads to the inactivation of tumor suppressor genes plays important roles in development and progression of breast cancer. Clinically, related gene methylation is considered to be a promising biomarker for tumor diagnosis and prognosis. This study aimed to investigate the methylation status ofSox17 gene in breast cancer tissue and its corresponding plasma circulating DNA, as well as to investigate its value in breast cancer early diagnosis and prognosis.Methods:TheSox17 gene promoter methylation status was detected by MSP in 86 cases of breast cancer, 36 normal breast tissues and its paired plasma DNA, the results were analyzed with corresponding clinical and pathological features.Results:The frequency ofSox17 gene methylation rate among 86 breast cancer tissues was 77.9%(67/86), and was 61.6%(53/86)in plasma circulating DNA, however, noSox17 gene methylation was found in normal breast tissues.Sox17 gene promoter methylation in plasma circulating DNA was signiifcantly associated with the methylation status in tumor tissues (r=0.502,P=0.000). In breast cancer tissue specimens,Sox17 methylation status was significantly correlated with tumor stage (χ2=6.18,P=0.041) and lymph node metastasis (χ2=13.54,P=0.001);Sox17 gene methylation rate was signiifcantly correlated with tumor stage (χ2=27.06,P=0.000), tumor size (χ2=9.65,P=0.007) and lymph node metastasis (χ2=20.80,P=0.000) in plasma samples, and there was no signiifcant difference ofSox17 gene methylation between patient age, histological grade and ER, PR, HER-2/neu status.Conclusion:Sox17 gene promoter methylation plays an important role in the carcinogenesis and development of breast cancer, and may be associated with the prognosis of breast cancer. Furthermore, methylatedSox17 gene may be a useful tumor biomarker in plasma circulating DNA for breast cancer detection and disease monitoring.
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Background and purpose: DNA methylation is an important mechanism for regulating gene expression, and plays an important role in the tumorigenesis. Study shows that DNA methylation is a potentially promising biomarker in tumor diagnosis, prognosis as well as treatment selection. This study aimed to analyze the methylation status and assessed possible clinical value of 3 DNA repair genes BRCA1, GSTP1 and MGMT in breast cancer samples of Chinese women. Methods:Using methylation speciifc PCR (MSP), we analyzed the methylation status of 3 DNA repair genes BRCA1, GSTP1 and MGMT in 106 paired breast tumors and corresponding normal tissues. Results: The methylation rates of BRCA1, GSTP1 and MGMT were 24.5% (26/106), 29.2% (31/106) and 18.9%(20/106) in breast cancer tissues, which were higher than those (7.5%, 11.3%and 4.7%) in paired normal breast tissues, respectively (P<0.01). Methylation in at least one of the genes was found in 50.9%(54/106) of the breast cancer and 19.8%(21/106) in paired normal breast tissues. And the mean number of genes hypermethylated in each tumor and paired normal breast tissues were 0.73 and 0.24, respectively (P<0.000 1). The methylation status of BRCA1 was more frequent in the younger patients than in the older patients (P=0.007) and most BRCA1 methylated patients were ER negative (P=0.020). Methylation status of GSTP1 was signiifcantly correlated with tumor size, lymph node metastasis (P=0.028 and 0.033, respectively). MGMT methylation was significantly correlated with tumor stage, higher tumor grade and lymph node metastasis (P=0.016, 0.025 and 0.030, respectively). High frequency simultaneous methylation of these 3 genes was more often in those with higher tumor stage and lymph node metastasis (P=0.028 and 0.007, respectively). Conclusion:Hypermethylation of BRCA1, GSTP1 and MGMT genes may be linked to various known clinicopathological features of breast cancer in Chinese women, and the increasing multiple gene methylation in tumors may indicate an aggressive phenotype for breast cancer. Detection of the methylation status of these genes may be useful for identifying patients at high risk for breast cancer.
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Objective To investigate the reliability and feasibility of sentinel lymph node biopsy (SLNB) in papillary thyroid carcinoma ( PTC ) using methylene blue staining techniques.Methods Nineteen patients,older than 45,with PTC were included in the study.No case had clinical evidence of cervical lymph node involvement(cNO).Methylene blue was injected around the tumor during surgery.The stained lymph nodes were dissected.Subtotal thyroidectomy and modified radical neck dissection were performed.Both the bulk specimen and SLN were submitted for routine histology.Results The sentinel lymph nodes( SLN )were identified in 18 cases,with SLN positive in 13 cases.The sensitivity and specificity of SLNB were 86.6％ and 94.4％ respectively.There was 1 case with SLN metastasis in the lateral neck,and 1 case with positive lymph node and negative SLN.Conclusion SLNB is sensitive in detecting cervical lymph node metastasis and has clinical significance in making operative plans for cN0 PTC.
