The relationship between shear wave elastography and pathological classification in nephrotic syndrome / 中国医师杂志

Objective:To explore the clinical value of shear wave elastography in the diagnosis and pathological classification of nephrotic syndrome.Methods:A retrospective analysis was conducted on the clinical data of 43 patients with primary nephrotic syndrome (primary nephrotic syndrome group) diagnosed through renal biopsy at the Yongchuan Hospital Affiliated to Chongqing Medical University from June 2022 to March 2023. They were further divided into three subgroups: mesangial proliferative glomerulonephritis group, membranous nephropathy group, and minimal change nephropathy group. Another 30 healthy individuals were selected as the control group. We applied shear wave elastography to measure the shear wave velocity of the right renal lower pole parenchyma and statistically analyzed the differences in shear wave velocity between each group.Results:There was a statistically significant difference in shear wave velocity between the primary nephrotic syndrome group [(1.76±0.41)m/s] and the control group [(1.55±0.34)m/s] ( P<0.05); The shear wave velocity in the membranous nephropathy group [(1.97±0.36)m/s] was the highest, and there was a statistically significant difference ( P<0.05) compared to the small lesion nephropathy group [(1.54±0.42)m/s]; There was no statistically significant difference in shear wave velocity between the membranous nephropathy group and the mesangial proliferative glomerulonephritis group [(1.74±0.38)m/s], as well as between the mesangial proliferative glomerulonephritis group and the small lesion nephropathy group (all P>0.05). Conclusions:Shear wave elastography is a non-invasive examination that provides valuable clinical clues for the diagnosis and pathological classification of nephrotic syndrome by detecting the shear wave velocity of the kidney.

Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

Single-dose AAV-based vaccine induces a high level of neutralizing antibodies and provides long-term protection against SARS-CoV-2 in rhesus macaques

Coronavirus disease 2019 (COVID-19), which is triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, continues to threaten global public health. Developing a vaccine that only requires single immunization but provides long-term protection for the prevention and control of COVID-19 is important. Here, we developed an adeno-associated virus (AAV)-based vaccine expressing a stable receptor-binding domain (SRBD) protein. The vaccine requires only a single shot but provides effective neutralizing antibodies (NAbs) over 598 days in rhesus macaques (Macaca mulatta). Importantly, our results showed that the NAbs were kept in high level and long lasting against authentic wild-type SARS-CoV-2, Beta, Delta and Omicron variants using plaque reduction neutralization test. Of note, although we detected pre-existing AAV2/9 antibodies before immunization, the vaccine still induced high and effective NAbs against COVID-19 in rhesus macaques. AAV-SRBD immune serum also efficiently inhibited the binding of ACE2 with RBD in the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1/P.2 (Gamma), B.1.617.2 (Delta), B.1.617.1/3(Kappa), and C.37 (Lambda) variants. Thus, these data suggest that the vaccine has great potential to prevent the spread of SARS-CoV-2.

A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10µg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity). Additionally, according to the enzyme-linked immunospot, intracellular cytokine staining, and cytometric bead array assays, significant and functional T-cell immunity was induced by 10µg of the rNTD vaccination with aluminum and CpG adjuvant. Furthermore, rNTD-immunized mice showed reduced lung abnormalities in a MERS-CoV-challenge mouse model transfected with an adenoviral vector expressing human DPP4, showing protection consistent with that found with rRBD vaccination. These data show that rNTD induced potent cellular immunity and antigen-specific neutralizing antibodies in mice and that it demonstrated protective capacity against a viral challenge, indicating that rNTD is a vaccine candidate against MERS-CoV infection.

Correlative analysis between plasma BNP,CRP levels and computed tomographic manifestations in acute moderate or severe traumatic brain injury / 中国基层医药

Objective To investigate correlative analysis between plasma BNP,CRP levels and computed tomographic manifestations in acute moderate or severe traumatic brain injury.Methods According to the severe traumatic brain injury and mild traumatic brain injury criteria that onset within 24h,patients were devided into the observation group A (73 cases with moderate or severe traumatic brain injury)and observation group B(20 cases with mild traumatic brain injury ).All patients received CT scan,CT image characteristics and Rotterdam CT grading were recorded.,Plasma BNP and CRP levels were detected at the same time,healthy persons with matched age and gender within same period were selected (control group),relationships of plasma BNP and CRP levels with CT manifestations were analyzed.Results Plasma BNP and CRP levels of the observation group were obviously higher than those of the control group (P 5mm,ventricular pressure≤0.2,Rotterdam CT score >3, the BNP and CRP levels were higher than the corresponding patnents (P 3 points.Conclusion Plasma BNP and CRP levels of patients with acute moderate or severe traumatic brain injury are closely related to various characteristics of CT,and are independent predictors of Rotterdam CT scores,they can be used as a biological marker assisting to evaluate degree of severe craniocerebral injury patients.

Clinical and Biological Character in Mouse Models for Middle East Respiratory Syndrome Generated by Transduction with Different Doses of DPP4 Molecule / 病毒学报

In this study, we evaluated the difference ot biological characteristics in the MERS-CoV infected mice model in prior to transduction with different dosage of human DPP4. Firstly, we transduced different dosage of DPP4 (high or low) into mice, and then challenged them with MERS-CoV in order to establish the model. After establishment of mice model, we observed the clinical signs of disease, virus replication, immunopathogenesis and antibody response. The results indicated that the infected mice showed typical pneumonia, virus replication, histological lesions, and neutralizing antibody production. Moreover, the high dosage group was superior to the low dosage group. Fourteen days after infection, the specific antibody to virus structural protein and neutralizing antibody were analyzed, the high dosage group induced higher level antibody. In summary, the MERS-CoV infected mice model were established prior transduction with DPP4, and the level of DPP4 influenced the clinical signs of disease, virus replication and antibody response in this model.

Value of real time shear wave elastography in differential diagnosis of benign and malignant breast lesions / 重庆医学

Objective To use the real-time shear wave elastography(SWE)to detect the elasticmodulus values of different breast lesions,and to assess its application value in differential diagnosis of benign and malignant breast lesions.Methods SWE was per-formed in 71 breast lesions from 63 pathologically confirmed patients.The maximum,minimum and mean elasticmodulus values in breast lesions were detected and the ROC curves were used to determine the optimal diagnostic cut off value.Results Among 7 1 le-sions,48 cases were benign lesions and 23 cases were malignant lesions.The diagnostic accuracy and Youden index of the ordinary ultrasound were 77.5% and 0.55 respectively.The maximum,minimum and mean elasticity values for malignant lesions were (106.7±37.9),(23.7±6.4),(44.8±6.6)kPa respectively,whereas which for benign lesions were(42.7±14.6),(17.2±6.3), (29.4±8.0)kPa respectively.The maximum,minimum and mean elastic values had statistically significant differences between be-nign and malignant lesions(P<0.05).The areas under the curve(AUC)of the maximum,minimum and mean elastic values were 0.963,0.798 and 0.914 respectively.Taking 78.1 kPa as the threshold of the maximum elasticity value,the sensitivity was 82.6%and the specificity was 95.8%.Taking 37.6 kPa as the threshold of the mean elasticity value,the sensitivity was 87.0% and the specificity was 83.3%.Conclusion SWE provides a new way for the differential diagnosis of benign and malignant breast lesions, and the maximum and mean elastic value can be used as the diagnostic evidence for differentiating benign and malignant breast le-sions.

Histopathological changes in EV71-infected mouse model:a transmission electron microscopic study / 中华病理学杂志

<p><b>OBJECTIVE</b>To document ultrastructural changes of brain, spinal cord, skeletal muscle, jejunum and lung of EV71 infection mouse model, and to explore the myotropism and pathogenesis of EV71 in nervous system.</p><p><b>METHODS</b>Ten-day-old suckling mice were infected with EV71 strain via the intraperitoneal route. Mice with paralysis were scarified on day 4 post infection and the brain, spinal cord, skeletal muscle, jejunum and lung were sampled for transmission electron microscopy and light microscopy.</p><p><b>RESULTS</b>Lesions in brain were generally mild with inner chamber swelling in some of mitochondria. Myelin sheaths of medullated fibers were split with vacuolated changes. The Nissl bodies in anterior motor neurons disappeared along with mitochondria swelling, rough endoplasmic reticulum swelling and degranulation. Cytoplasm of anterior motor neurons showed cribriform appearance accompanied by neuronophagia. The bands of skeletal muscle in the infected group disappeared with degeneration and karyopyknosis in myocytes, in addition to mitochondrial swelling. Microvilli of epithelium in jejunum became loosely arranged along with formation of spiral medullary sheath structure and mitochondria swelling. Interstitial pneumonia was observed in lungs with type II pneumocyte proliferation and evacuation of the multilamellar bodies.</p><p><b>CONCLUSIONS</b>EV71 infection causes severe myositis in the mouse model suggesting a strong myotropism of EV71 virus. The presence of lesions of various degrees in central nervous system and changes in anterior motor neurons may be associated with limb paralysis.</p>