Risk Factors for Contralateral Occult Papillary Thyroid Carcinoma in Patients with Clinical Unilateral Papillary Thyroid Carcinoma: A Case-Control Study.

Introduction: Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies that has increased in recent decades around the world. Although the indicator for navigating the surgical extent in PTC patients is still in debate, a key issue is how to predict that there are undetected preoperative tumors in the contralateral thyroid lobe. This study aims to find risk factors for contralateral occult papillary thyroid cancer (COPTC) to facilitate more accurate surgical decisions made for patients with PTC. Materials and Methods: In our study, we included 229 patients who underwent total thyroidectomy plus central and ipsilateral lateral lymph nodes dissection from January 1, 2019, to September 1, 2021. Univariate and multivariate logistic regression analyses were conducted to assess the association between COPTC and clinical-pathological characteristics, as well as the relation between the diameter of the occult lesions and predictors. The forest plot was plotted to visualize the prediction factors from the output of the multivariate regression analysis. A ROC curve was used to evaluate the combining potency of all the risk factors. Results: Of the 229 patients included in our study, 46 with COPTC were assigned to the case group, representing 20.1% in this study. Multifocality in one lobe (OR = 2.21, P=0.03), intact capsule (OR = 2.54, P=0.01), central lymph node metastasis (OR = 3.00, P=0.02), and Hashimoto's thyroiditis (OR = 2.08, P = 0.04) are more prone to present contralateral occult papillary thyroid carcinoma. The ROC curve of the aggregate potency of the risk factors presents AUC = 0.701 (P < 0.001), and the best cutoff value was 2.02, with a sensitivity of 78.3% and specificity of 55.2%. Furthermore, there was no statistical correlation between the diameter of the occult tumor and the four obtained variables. Conclusion: Patients with multifocality in one lobe, intact capsule, central lymph node metastasis, and HT may harbor contralateral papillary thyroid carcinoma. It is essential to be prudent to make a surgical or follow-up decision on these patients. In addition, more clinical rather than postoperative pathological indicators need to be revealed in the future.

Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain

A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a "turning point". The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

Robust induction of B cell and T cell responses by a third dose of inactivated SARS-CoV-2 vaccine

SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 AU/ml to 8.8 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly "non-responders" but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.

Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study

BackgroundSystemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. MethodsFrom December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. ResultsCorticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p<0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. ConclusionsCorticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.

Accuracy evaluation for 3D bone reconstruction based on medical 3D reconstruction software / 中华创伤骨科杂志

Objective To investigate the feasibility of an accuracy evaluation method for 3D reconstructed bone model based on 3D reconstruction software Arigin3D Pro.Methods Pig femurs were used as solid models which were scanned by CT and MRI respectively.The scan data were imported into software Arigin3D Pro for 3D model reconstruction by 3 operators with different reconstruction experience (≤1 year,2 to 3 years,and ≥4 years,respectively).Each operator reconstructed the femurs 3 times and in each reconstruction measured the diameter of the femoral head,the length of the femur and the width of the knee joint at the distal end of the femur 3 times respectively using software Geomagic Wrap.The above parameters of the solid models were measured using a vernier caliper.The parameter values of reconstructed models and solid models were compared and the differences were analyzed.Results The measurements by Geomagic Wrap showed deviations between the CT and MRI reconstruction models and the solid models,and the maximum deviation percentages were 1.47％ and 1.08％,respectively.The percentages of intra-operater difference ranged from 0.29％ to 1.53％;the 3D models reconstructed by operators with different reconstruction experience were not identical.Conclusions It is a feasible accuracy evaluation method to compare key parameters between the 3D bone model reconstructed by software Arigin3D Pro and the real animal bone.The deviations of 3D reconstructed bone model based on CT and MR1 images are acceptable.The accuracy of 3D bone construction is related to the difference in operators.

Accuracy evaluation for 3D bone reconstruction based on medical 3D reconstruction software / 中华创伤骨科杂志

Objective@#To investigate the feasibility of an accuracy evaluation method for 3D reconstructed bone model based on 3D reconstruction software Arigin3D Pro.@*Methods@#Pig femurs were used as solid models which were scanned by CT and MRI respectively. The scan data were imported into software Arigin3D Pro for 3D model reconstruction by 3 operators with different reconstruction experience (≤1 year, 2 to 3 years, and ≥4 years, respectively). Each operator reconstructed the femurs 3 times and in each reconstruction measured the diameter of the femoral head, the length of the femur and the width of the knee joint at the distal end of the femur 3 times respectively using software Geomagic Wrap. The above parameters of the solid models were measured using a vernier caliper. The parameter values of reconstructed models and solid models were compared and the differences were analyzed.@*Results@#The measurements by Geomagic Wrap showed deviations between the CT and MRI reconstruction models and the solid models, and the maximum deviation percentages were 1.47% and 1.08%, respectively. The percentages of intra-operater difference ranged from 0.29% to 1.53%; the 3D models reconstructed by operators with different reconstruction experience were not identical.@*Conclusions@#It is a feasible accuracy evaluation method to compare key parameters between the 3D bone model reconstructed by software Arigin3D Pro and the real animal bone. The deviations of 3D reconstructed bone model based on CT and MRI images are acceptable. The accuracy of 3D bone construction is related to the difference in operators.

Cotton Leaf Curl Multan virus C4 protein suppresses both transcriptional and post-transcriptional gene silencing by interacting with SAM synthetase.

Gene silencing is a natural antiviral defense mechanism in plants. For effective infection, plant viruses encode viral silencing suppressors to counter this plant antiviral response. The geminivirus-encoded C4 protein has been identified as a gene silencing suppressor, but the underlying mechanism of action has not been characterized. Here, we report that Cotton Leaf Curl Multan virus (CLCuMuV) C4 protein interacts with S-adenosyl methionine synthetase (SAMS), a core enzyme in the methyl cycle, and inhibits SAMS enzymatic activity. By contrast, an R13A mutation in C4 abolished its capacity to interact with SAMS and to suppress SAMS enzymatic activity. Overexpression of wild-type C4, but not mutant C4R13A, suppresses both transcriptional gene silencing (TGS) and post-transcriptional gene silencing (PTGS). Plants infected with CLCuMuV carrying C4R13A show decreased levels of symptoms and viral DNA accumulation associated with enhanced viral DNA methylation. Furthermore, silencing of NbSAMS2 reduces both TGS and PTGS, but enhanced plant susceptibility to two geminiviruses CLCuMuV and Tomato yellow leaf curl China virus. These data suggest that CLCuMuV C4 suppresses both TGS and PTGS by inhibiting SAMS activity to enhance CLCuMuV infection in plants.

Comparison between curved and unipedicular approach vertebroplasty for treatment of osteoporotic vertebral compression fractures / 中华创伤杂志

Objective To evaluate the safety and effectiveness of a curved vertebroplasty (CVP) compared with traditional unipedicular approach vertebroplasty (UVP) in treating osteoporotic vertebral compression fractures (OVCF).Methods This was a retrospective case control study on the clinical data of 77 OVCF patients (12 males,65 females;aged 55-86 years,mean 70.8 years) admitted between July 2013 and December 2016.There were 6 injured vertebrae at T1 10,73 at T11 L2,and 12 at L3 5.The patients were divided into CVP group (36 patients,44 vertebrae) and UVP group (41 patients,47 vertebrae) with no significant difference in baseline clinical variables.Intraoperative and postoperative complications including neurovascular injury were recorded.Operation duration,fluoroscopy frequency,volume of cement per level,cement leakage rate per level treated,cement distribution,and refracture rate were compared between the two groups.Preoperative and postoperative visual analog scale (VAS) and Oswestry disability index (ODI) were compared both within the group and between the groups.Results No severe complications related to puncture were observed.No significant difference was observed for operation duration,fluoroscopy frequency,and cement leakage rate per level treated between the two groups (P ＞ 0.05).Compared with UVP group,CVP group had larger volume of cement per level [(5.0 ± 1.4) ml vs.(4.3 ± 1.6) ml],more uniform cement distribution (none vs.10 cases),and lower refracture rate (0 vs.10％) (P ＜ 0.05).The two groups were followed up for 6-49 months (mean,25.9 months).Significant improvements on the VAS and ODI were noted within each group (P ＜0.01),but there was no significant difference between the two groups (P ＞ 0.05).Conclusions Both CVP and UVP are safe and effective treatments for OVCF.Compared with UVP,CVP entails more uniform cement distribution and lower refracture rate.