Comparison of diagnostic efficacy between 99mTc-methylene diphosphate SPECT/CT and MRI for bone and joint infections: a multicenter retrospective analysis.

Objective: There is currently no non-invasive examination that can fully determine the diagnosis of osteomyelitis. SPECT/CT tomographic fusion imaging can provide both local metabolic activity and anatomical information to determine the condition and location. This study evaluates the diagnostic efficacy of 99mTc-MDP SPECT/CT in bone infections, compared to MRI. Methods: In this multicenter retrospective study, 363 patients with suspected bone and joint infections or osteomyelitis were included. Participants underwent 99mTc-MDP SPECT/CT and/or MRI examinations, supplemented by pathogenic bacterial cultures and histopathological analysis. Results: Only SPECT/CT was tested in 169 patients, and only MRI was used in 116. 78 people have implemented both inspections and have detailed information. The diagnostic sensitivity and specificity of SPECT/CT for infection were 96% and 92% respectively, with an accuracy of 96%. For MRI, these figures were 88%, 84%, and 87% respectively. Conclusion: This represents the largest global study to date evaluating osteomyelitis and bone infection diagnosis using 99mTc-MDP SPECT/CT tomographic fusion imaging. The findings indicate that 99mTc-MDP SPECT/CT fusion imaging offers superior diagnostic accuracy compared to MRI. This is particularly evident in cases involving metallic implants and chronic infections. 99mTc-MDP SPECT/CT fusion imaging emerges as a highly suitable non-invasive diagnostic modality, facilitating enhanced clinical follow-up and treatment.

[Electrocardiogram classification algorithm based on CvT-13 and multimodal image fusion].

Electrocardiogram (ECG) signal is an important basis for the diagnosis of arrhythmia and myocardial infarction. In order to further improve the classification effect of arrhythmia and myocardial infarction, an ECG classification algorithm based on Convolutional vision Transformer (CvT) and multimodal image fusion was proposed. Through Gramian summation angular field (GASF), Gramian difference angular field (GADF) and recurrence plot (RP), the one-dimensional ECG signal was converted into three different modes of two-dimensional images, and fused into a multimodal fusion image containing more features. The CvT-13 model could take into account local and global information when processing the fused image, thus effectively improving the classification performance. On the MIT-BIH arrhythmia dataset and the PTB myocardial infarction dataset, the algorithm achieved a combined accuracy of 99.9% for the classification of five arrhythmias and 99.8% for the classification of myocardial infarction. The experiments show that the high-precision computer-assisted intelligent classification method is superior and can effectively improve the diagnostic efficiency of arrhythmia as well as myocardial infarction and other cardiac diseases.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy.

OBJECTIVE: This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy (SBRT) cases, and evaluate the required planning target volume (PTV) margins. METHODS: A total of 11 liver tumor patients with a total of 57 fractions, who underwent SBRT with synchronous fiducial tracking, were enrolled for the present study. The correlation/prediction model error, geometric error, and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties. The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment. RESULTS: The correlation model error-related uncertainty was 4.3±1.8, 1.4±0.5 and 1.8±0.7 mm in the superior-inferior (SI), left-right, and anterior-posterior directions, respectively. These were the primary contributors among all uncertainty sources. The geometric error significantly increased for treatments without rotation correction. The fraction-level composite uncertainties had a long tail distribution. Furthermore, the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions, and only 75% of uncertainties in the SI direction. In order to cover 90% of uncertainties in the SI direction, an 8-mm margin would be needed. For scenarios without rotation correction, additional safety margins should be added, especially in the superior-inferior and anterior-posterior directions. CONCLUSION: The present study revealed that the correlation model error contributes to most of the uncertainties in the results. Most patients/fractions can be covered by a 5-mm margin. Patients with large treatment uncertainties might need a patient-specific margin.

Case Report: Long-term survival of a patient with advanced rectal cancer and multiple pelvic recurrences after seven surgeries.

Background: Rectal cancer has a high risk of recurrence and metastasis, with median survival ranging from 24 months to 36 months. K-RAS mutation is a predictor of poor prognosis in rectal cancer. Advanced rectal cancer can be stopped in its tracks by pelvic exenteration. Case summary: A 51-year-old woman was diagnosed with advanced rectal cancer (pT4bN2aM1b, stage IV) with the KRAS G12D mutation due to a change in bowel habits. The patient had experienced repeated recurrences of rectal cancer after initial radical resection, and the tumor had invaded the ovaries, sacrum, bladder, vagina and anus. Since the onset of the disease, the patient had undergone a total of seven surgeries and long-term FOLFIRI- or XELOX-based chemotherapy regimens, with the targeted agents bevacizumab and regorafenib. Fortunately, the patient was able to achieve intraoperative R0 resection in almost all surgical procedures and achieve tumor-free survival after pelvic exenteration. The patient has been alive for 86 months since her diagnosis. Conclusions: Patients with advanced rectal cancer can achieve long-term survival through active multidisciplinary management and R0 surgery.

A Simple Kit Formulation for Preparation and Exploratory Human Studies of a Novel 99mTc-Labeled Fibroblast Activation Protein Inhibitor Tracer for Imaging of the Fibroblast Activation Protein in Cancers.

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a 99mTc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic 99mTc-labeled complex ([99mTc]Tc-DP-FAPI) was obtained by kit formulation. In vitro cellular uptake and saturation binding assays were performed in FAP-transfected HT-1080 cells (FAP-HT-1080). The biodistribution was characterized, and micro-single-photon emission computed tomography (SPECT) imaging was performed in BALB/c nude mice bearing U87 MG tumors. Furthermore, a first-in-man application was performed in four healthy volunteers and three patients with gastrointestinal tumors. In vitro, the nanomolar Kd values of [99mTc]Tc-DP-FAPI indicated that it had significantly high target affinity for FAP. Biodistribution and micro-SPECT imaging studies showed that [99mTc]Tc-DP-FAPI exhibited high uptake and high tumor-to-nontargeted ratios. The calculated effective dose for [99mTc]Tc-DP-FAPI was approximately <5 mSv in four healthy volunteers. In three patients with gastrointestinal tumors, [99mTc]Tc-DP-FAPI quantitative SPECT/CT revealed high and reliable uptake. [99mTc]Tc-DP-FAPI exhibited high selectivity and affinity for FAP in vitro. The safety and effectiveness of [99mTc]Tc-DP-FAPI in primary tumor imaging have been confirmed by animal and clinical studies, revealing the potential clinical application value of this tracer.

Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with 131I-Labeling and SPECT Imaging.

Coronavirus disease 2019 (COVID-19) is a serious threat to public health and is in urgent need of specific drugs. Meplazumab, a humanized monoclonal antibody targeting CD147, was confirmed to competitively block the binding between the spike of syndrome coronavirus 2 (SARS-CoV-2) and CD147, making meplazumab a promising candidate drug for COVID-19. In this study, biodistribution and dosimetry of 131I-labeled meplazumab were performed to further evaluate its potential as a therapeutic drug for COVID-19. 131I-meplazumab was both safe and tolerant in mice and healthy volunteers. A biodistribution study was performed in normal mice, and blood samples were used for pharmacokinetic analysis. Three healthy volunteers were included and subjected to single-photon-emission computed tomography (SPECT) imaging of 131I-meplazumab within 2 weeks. The distribution in mice and humans was consistent with the in vivo distribution of CD147. Biodistribution and SPECT imaging results exhibited that the liver was the organ with the highest uptake for both mice and humans. Deiodination of 131I-meplazumab can be observed in vivo, and taking Lugol's solution can protect the thyroid gland effectively. The pharmacokinetic characteristics of 131I-meplazumab in mice and humans best fit the two-compartment model. The clearance half-life (T1/2ß) in mice and humans was 117.4 and 223.5 h, respectively. The results indicated that its pharmacokinetic properties in vivo were ideal. The effective dose calculated from healthy volunteers was 0.811 ± 0.260 mSv·MBq-1, which was twice the value calculated from mice. It was safe and feasible to perform human clinical imaging experiments using a diagnostic dose of 131I-meplazumab after thyroid closure by Lugol's solution. This study will provide more experimental basis for advancing the clinical translation of meplazumab and will be valuable in evaluating therapeutic interventions for patients with COVID-19, as well as providing a reference for clinical translation studies of other antibody drugs.

Immune-related keratitis is a rare complication associated with nivolumab treatment in a patient with advanced colorectal cancer: A case report.

Background: Immunotherapy has been widely used to treat Colorectal cancer but has also observe some immune-related adverse effects. With proper treatment, most irAE can be solved and the effect of immunotherapy will not be affected by temporary immunosuppression. However, there are few reports about corneal irAE, and the current understanding of irAE is incomplete. Here we report a metastatic colorectal cancer case of immune-related keratitis caused by nivolumab and to explore the occurrence of immune-related keratitis. Case description: Here we report the case of a 49-year-old man with mCRC who had no previous ocular disease but developed immune-related ulcerative keratitis after treatment with nivolumab. We summarize a large amount of literature to discuss the mechanism of immune-related keratitis. In addition, we conclude a method that may be used to detect the occurrence of immune keratitis, by monitoring MMPs and maspin in patients treated with nivolumab. We believe immune-related keratitis may be a rare complication of nivolumab in the treatment of mCRC. The effect of simple anti-infective therapy and repair-promoting drugs was not obvious, but the effect of glucocorticoid combined with autologous serum was significant. Conclusion: The mechanism of immune-related keratitis is that nivolumab destroys the immune microenvironment and ACAID, and affects corneal healing. Patients who use nivolumab can prevent immune keratitis by testing MMPs and maspin. The occurrence of immune keratitis may be a good indicator of the efficacy of ICI, and further study can be done in the follow-up.

Development of novel gene signatures for the risk stratification of prognosis and diagnostic prediction of osteosarcoma patients using bioinformatics analysis.

Background: Osteosarcoma (OS) is a common malignant bone cancer in children and teenagers that originates from osteoblast cells. Although many biomarkers have been reported in OS, they have not improved the prognosis of this disease. This study sought to identify effective biomarkers for the early diagnosis and prognosis of OS using a comprehensive bioinformatics analysis. Methods: OS-associated microRNAs (miRNAs) were screened in the Human microRNA Disease Database (HMDD). The differentially expressed genes (DEGs) related to OS were screened using 3 data sets (GSE16088, GSE36001, and GSE56001) from the Gene Expression Omnibus (GEO) database. By comparing the targets of these miRNAs with DEGs in response to OS, we identified OS-associated candidate genes. The gene expression and clinical data of 96 OS samples with complete clinical information was downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Comprehensive bioinformatics analyses, including univariate, multivariate Cox, and Kaplan-Meier (KM) analyses were conducted based on these data to identify the prognostic genes and construct prognostic signature for OS survival and recurrence. Logistic regression analysis was performed based on the GSE42352 data set (including 103 OS and 15 normal samples) to develop a diagnostic model for OS. Results: By comparing the DEGs and predicted targets of the 28 OS survival-associated miRNAs, we identified 267 OS-associated candidate genes. Additionally, 14 genes were found to be significantly associated with the survival of OS patients. Finally, 3 genes [i.e., signal transducer and activators of transcription factor 4 (STAT4), heat shock protein family E member 1 (HSPE1), and actin-related protein 2/3 complex subunit 5 (ARPC5)] were integrated into a prognostic index. The 3-gene signature was an independent factor for OS survival [hazard ratio (HR) =1.699; P<0.001] and recurrence (HR =2.532; P=0.004) and was found to have an excellent predictive performance [area under the receiver operating characteristic (ROC) curve (AUC) >0.7]. Additionally, 2 genes (i.e., STAT4 and HSPE1) were identified to be associated with OS diagnosis (P<0.05). This 2-gene diagnostic signature for OS presented a good discriminative power (AUC =0.981) and the error between the predicted and actual value was 0.029. Conclusions: We constructed a 3-gene prognostic signature and a 2-gene diagnostic signature that have the potential to assist in prognosis predicting and diagnosis of OS in clinic.

CircNRIP1 Exerts Oncogenic Functions in Papillary Thyroid Carcinoma by Sponging miR-653-5p and Regulating PBX3 Expression.

Background: Circular RNA circ_0004771 (termed circNRIP1) was identified by RNA-Seq previously and was elevated in papillary thyroid carcinoma (PTC) tissues. A series of studies also showed that circNRIP1 was upregulated in some tumors and could promote the malignant progression of tumors. This research intended to focus on the role of circNRIP1 in PTC progression and explore the mechanisms underlying circNRIP1 functions. Methods: RT-PCR or western blot determined circNRIP1, miR-653-5p, and pre-B-cell leukemia homeobox 3 (PBX3) expression. EdU, CCK-8, Tunel, and transwell assays determined cell proliferation, apoptosis, invasion, and migration, respectively. Luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down assays clarified the target relation between miR-653-5p and circNRIP1 or PBX3. Xenograft models were applied to explore the role of circNRIP1 in vivo. Results: circNRIP1 significantly increased in PTC tissues and PTC cell lines than that in normal ones. Higher circNRIP1 expression was associated with the TNM stage and poorer overall survival. circNRIP1 knockdown attenuated the malignant progression of PTC, specifically by inhibiting proliferation and invasion/migration and promoting apoptosis. circNRIP1 was a miR-653-5p sponge; miR-653-5p knockdown reversed the suppressive role of circNRIP1 silence in PTC progression. PBX3, a target of miR-653-5p, was positively medicated through circNRIP1 via competitively sponging miR-653-5p. Knockdown of circNRIP1 attenuated the PTC tumor progression via miR-653-5p/PBX3 axis. Conclusion: Silencing of circNRIP1 suppressed PTC development via miR-653-5p elevation and PBX3 reduction, providing a novel perspective for understanding PTC pathogenesis.

FTO Prevents Thyroid Cancer Progression by SLC7A11 m6A Methylation in a Ferroptosis-Dependent Manner.

N6 methyladenosine (m6A) modification serves as a novel epigenetic regulatory mechanism that is heavily implicated in the heredity of tumors. Meanwhile, fat mass and obesity-associated protein (FTO) has the potential to affect the regulation of m6A modification in the mRNA of key oncogenes as well as tumor suppressor genes that facilitate tumor progression. In our study, FTO was downregulated in papillary thyroid carcinoma (PTC) tissues. The role of FTO in PTC was assessed by Cell Counting Kit-8 analysis, cell scratch, migration, invasion experiment, flow cytometry apoptosis analysis, and nude mouse experiment. In addition to RNA-Seq and meRIP-Seq, luciferase reporting and mutation analysis have also identified SLC7A11 as the potential FTO regulatory gene. Moreover, X-ray electron microscopy, glutathione (GSH)/oxidized GSH, GPX, malondialdehyde determination, and western blot helped confirmed that FTO inhibited the development of PTC by downregulating the expression of SLC7A11 through ferroptosis. Finally, a rescue experiment was employed to clarify the relationship between FTO and its specific target gene SLC7A11. FTO is able to inhibit the occurrence of PTC by downregulating SLC7A11 in m6A independently, and it functions as a tumor suppressor gene in PTC. These findings could contribute to our understanding of the tumor malignancy regulated by m6A and might lead to new insights for potential biomarkers and therapeutic targets for the treatment of thyroid papillary carcinoma.

Clinical Efficacy of Gandakang Tablets plus Methylprednisolone in Patients with Systemic Lupus Erythematosus.

Objective: To evaluate the clinical efficacy of Gandakang tablets plus methylprednisolone in patients with systemic lupus erythematosus (SLE). Methods: From February 2015 to February 2019, 60 eligible patients with SLE were recruited and assigned via the random number table method at a ratio of 1 : 1 to receive either methylprednisolone (control group) or Gandakang tablets plus methylprednisolone (observation group). The primary endpoint was clinical efficacy, and the secondary endpoints included Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, immunoglobulin (Ig), inflammatory factor levels, and adverse events. Results: Gandakang tablets plus methylprednisolone were associated with a significantly higher treatment efficacy versus methylprednisolone alone (P < 0.05). Gandakang tablets plus methylprednisolone resulted in significantly lower SLEDAI scores and lower levels of IgG, IgM, IgA, tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-6 (IL-6) versus single medication of methylprednisolone (P < 0.05). The two groups showed a similar incidence of adverse events (P > 0.05). Patients given Gandakang tablets plus methylprednisolone had higher mental health, emotional role, physical role, social functioning, and bodily pain scores versus those receiving the monotherapy of methylprednisolone (P < 0.05). Conclusion: Gandakang tablets plus methylprednisolone is effective in the treatment of SLE by enhancing the patients' immunity, mitigating the inflammatory response, eliminating negative emotions, and improving their quality of life.

Clinical analysis of multi-target treatment for complex lupus nephritis.

OBJECTIVE: To observe the efficacy and safety of multi-target (tacrolimus + mycophenolate mofetil + prednisone) therapy for type III + V and IV + V type lupus nephritis. METHODS: A total of 56 patients with lupus nephritis were randomly divided into a treatment group receiving multi-target treatment and a control group receiving intravenous cyclophosphamide combined with prednisone treatment, with 28 patients in each group. Clinical indicators and adverse reactions were observed before and 4, 12, 24, 48 and 72 weeks after treatment. RESULTS: One patient withdrew from the treatment group and two patients from the control group due to adverse reactions within 72 weeks of treatment. Compared with those before treatment, urine protein quantification, ds-DNA antibody titer and systemic lupus erythematosus disease activity index (SLEDAI) scores were significantly decreased at 24 h after 72 weeks of treatment in both groups (P < 0.05). The total remission rate was 85.2% in the treatment group and 57.7% in the control group (P < 0.05) and dte total response rate was 59.3% and 30.8%, respectively (P < 0.05). CONCLUSION: Multiple target treatment of type III + V or IV + V type lupus nephritis has a higher total remission rate, a shorter treatment time, and a lower incidence of adverse reactions than cyclophosphamide and prednisone combined therapy.

Using the Diaphragm as a Tracking Surrogate in CyberKnife Synchrony Treatment.

BACKGROUND In this study, we assessed the usefulness of diaphragm surrogate tracking in the design of a respiratory model for CyberKnife Synchrony treatment of lung tumors. MATERIAL AND METHODS Twenty-four patients with lung cancer who underwent stereotactic body radiotherapy with CyberKnife between April and November 2019 were enrolled. Simulation plans for each patient were designed using Xsight lung tracking (XLT) and diaphragm tracking (DT) methods, and tumor visualization tests were performed. The offset consistency at each respiratory phase was analyzed. The relative distance along the alignment center of the superior-inferior (SI) axis in the 2 projections (dxAB), uncertainty (%), and average standard error (AvgStdErr)/maximum standard error (MAXStdErr) were also analyzed. RESULTS Bland-Altman analyses revealed that the average differences±standard deviation (SD) between XLT and DT tracking methods were 0.4±2.9 mm, 0.3±4.35 mm, and -1.8±6.8 mm for the SI, left-right (LR), and anterior-posterior (AP) directions, respectively. These results indicated high consistency in the SI and LR directions and poor consistency in the AP direction. Uncertainty differed significantly between XLT and DT (22.813±5.721% vs 9.384±3.799%; t=-5.236; P=0.0008), but we found no significant differences in dxAB, AvgStdErr, or MAXStdErr. CONCLUSIONS In the majority of cases, motion tracking by XLT and DT was consistent and synchronized in the SI directions, but not in the LR and AP directions. With a boundary margin of 0.3±4.35 mm and 1.8±6.8 mm for the LR and AP directions, DT may contribute to better implementation of CyberKnife Synchrony treatment in patients with lung tumors near the diaphragm that cannot be seen in tumor visualization tests.

Identification of prognostic biomarkers related to the tumor microenvironment in thyroid carcinoma.

Thyroid Carcinoma (THCA) is the most common endocrine tumor that is mainly treated using surgery and radiotherapy. In addition, immunotherapy is a recently developed treatment option that has played an essential role in the management of several types of tumors. However, few reports exist on the use of immunotherapy to treat THCA. The study downloaded the miRNA, mRNA and lncRNA data for THCA patients from the TCGA database ( https://portal.gdc.cancer.gov/ ). Thereafter, the tumor samples were divided into cold and hot tumors, based on the immune score of the tumor microenvironment. Moreover, the differentially expressed lncRNAs and miRNAs were obtained. Finally, the study jointly constructed a ceRNA network through differential analysis of the mRNA data for cold and hot tumors. The study first assessed the level of immune infiltration in the THCA tumor microenvironment then divided the samples into cold and hot tumors, based on the immune score. Additionally, a total of 568 up-regulated and 412 down-regulated DEGs were screened by analyzing the differences between hot and cold tumors. Thereafter, the study examined the differentially expressed genes for lncRNA and miRNA. The results revealed 629 differentially expressed genes related to lncRNA and 114 associated with miRNA. Finally, a ceRNA network of the differentially expressed genes was constructed. The results showed a five-miRNA hubnet, i.e., hsa-mir-204, hsa-mir-128, hsa-mir-214, hsa-mir-150 and hsa-mir-338. The present study identified the immune-related mRNA, lncRNA and miRNA in THCA then constructed a ceRNA network. These results are therefore important as they provide more insights on the immune mechanisms in THCA. The findings also provides additional information for possible THCA immunotherapy.

Depicting the molecular responses of adventitious rooting to waterlogging in melon hypocotyls by transcriptome profiling.

Waterlogging is a severe abiotic stressor that inhibits crop growth and productivity owing to the decline in the amount of oxygen available to the waterlogged organs. Although melon (Cucumis melo L.) is sensitive to waterlogging, its ability to form adventitious roots facilitates the diffusion of oxygen and allows the plant to survive waterlogging. To provide comprehensive insight into the adventitious rooting in response to waterlogging of melon, global transcriptome changes during this process were investigated. Of the 17,146 genes expressed during waterlogging, 7363 of them were differentially expressed in the pairwise comparisons between different waterlogging treatment time points. A further analysis suggested that the genes involved in sugar cleavage, glycolysis, fermentation, reactive oxygen species scavenging, cell wall modification, cell cycle governing, microtubule remodeling, hormone signals and transcription factors could play crucial roles in the adventitious root production induced by waterlogging. Additionally, ethylene and ERFs were found to be vital factors that function in melon during adventitious rooting. This study broadens our understanding of the mechanisms that underlie adventitious rooting induced by waterlogging and lays the theoretical foundation for further molecular breeding of waterlogging-tolerant melon. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02866-w.

Current Advancements in Sactipeptide Natural Products.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products that benefited from genome sequencing technology in the past two decades. RiPPs are widely distributed in nature and show diverse chemical structures and rich biological activities. Despite the various structural characteristic of RiPPs, they follow a common biosynthetic logic: a precursor peptide containing an N-terminal leader peptide and a C-terminal core peptide; in some cases,a follower peptide is after the core peptide. The precursor peptide undergoes a series of modification, transport, and cleavage steps to form a mature natural product with specific activities. Sactipeptides (Sulfur-to-alpha carbon thioether cross-linked peptides) belong to RiPPs that show various biological activities such as antibacterial, spermicidal and hemolytic properties. Their common hallmark is an intramolecular thioether bond that crosslinks the sulfur atom of a cysteine residue to the α-carbon of an acceptor amino acid, which is catalyzed by a rSAM enzyme. This review summarizes recent achievements concerning the discovery, distribution, structural elucidation, biosynthesis and application prospects of sactipeptides.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Hengshun Aromatic Vinegar Improves Glycolipid Metabolism in Type 2 Diabetes Mellitus via Regulating PGC-1α/PGC-1ß Pathway.

Hengshun aromatic vinegar (HSAV), produced by typical solid-state or liquid-state fermentation techniques, is consumed worldwide as a food condiment. HSAV shows multiple bioactivities, but its activity in type 2 diabetes mellitus (T2DM) and possible mechanisms have not been reported. In this study, the effects of HSAV against T2DM were evaluated in insulin-induced HepG2 cells and high-fat diet (HFD) and streptozotocin (STZ) induced T2DM rats. Then, the mechanisms of HSAV against T2DM were explored by Real-time PCR, Western blot, immunofluorescence assays, siRNA transfection and gene overexpression experiments. Results indicated that HSAV significantly improved glucose consumption and reduced triglycerides (TG) contents in metabolic disordered HepG2 cells. Meanwhile, HSAV obviously alleviated general status, liver and kidney functions of T2DM rats, and decreased hyperglycemia and hyperlipidemia, improved insulin resistance, and reduced lipid accumulation in liver. Mechanism studies indicated that HSAV markedly down-regulated the expression of proliferator-activated receptor γ coactivator-1α (PGC-1α), then regulated peroxisome proliferators-activated receptor α (PPAR-α)/protein kinase B (AKT) signal pathway mediated gluconeogenesis and glycogen synthesis. Meanwhile, HSAV significantly up-regulated proliferator-activated receptor γ coactivator-1ß (PGC-1ß), and subsequently decreased sterol regulatory element binding protein-1c (SREBP-1c) pathway mediated lipogenesis. In conclusion, HSAV showed potent anti-T2DM activity in ameliorating dysfunction of glycolipid metabolism through regulating PGC-1α/PGC-1ß pathway, which has a certain application prospect as an effective diet supplement for T2DM therapy in the future.

Lateral meniscus "PASTA injury": Partial-thickness radial tear of the lateral meniscus: A case report.

INTRODUCTION: We report a relatively rare case of partial-thickness radial tear in the inferior surface of lateral meniscus, while the superior surface is intact. This situation was similar to PASTA rotator cuff tear. Meanwhile, there is a full-thickness radial tear in the edge. CASE PRESENTATION: A 17-year-old boy twisted the left knee while playing basketball. Magnetic resonance imaging (MRI) revealed radial tear of the lateral meniscus. During arthroscopy, it was found that there was a full-thickness radial tear of about 2 mm located in the edge. Partial meniscectomy was performed to treat radial meniscal tear located in the white area. After that, we found that the superior surface of the lateral meniscus was intact. However, in the inferior surface of the lateral meniscus, partial-thickness radial tear was found extending to red zone. We used FASTFIX (Smith & Nephew) for all-inside suture. As of three months after this surgery, the patient recovered smoothly. DISCUSSION: Suspect that the force acts on a special position of meniscus and the thickness of the meniscus is uneven. Thus, it leads to partial-thickness radial tear in the inferior-surface, while the superior surface is intact. CONCLUSION: Partial-thickness radial tears in the inferior surface of lateral meniscus are relatively rare. This situation was similar to PASTA rotator cuff tear. Because the superior surface of the meniscus is intact, it may results in misdiagnosis. It's easy to ignore the inferior surface injury.