Antiviral Efficacy and Mechanism of BD-77 Against Novel Coronavirus SARS-CoV-2 / 中国实验方剂学杂志

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC50） of 526.3 mg·L-1 and 653.0 mg·L-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

SERPINE1 as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Objectives@#. Nicotine is an ingredient of tobacco, and exposure to nicotine increases the risks of various cancers, including oral cancer. Previous studies have focused on the addictive properties of nicotine, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process through which nicotine promotes the occurrence and development of oral cancer via data mining and experimental verification. @*Methods@#. This study involved three parts. First, key genes related to nicotine-related oral cancer were screened through data mining; second, the expression and clinical significance of a key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed. @*Results@#. SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways, such as the tumor necrosis factor and apelin pathways, and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to bleomycin and docetaxel. @*Conclusion@#. This study revealed SERPINE1 as a key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

SARS-CoV-2 activates lung epithelia cell proinflammatory signaling and leads to immune dysregulation in COVID-19 patients by single-cell sequencing

ObjectiveThe outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in the lung of COVID-19 patients. DesignWe analyzed single-cell RNA sequencing (scRNA-seq) data of lung samples from 17 subjects (6 severe COVID-19 patients, 3 mild patients who recovered and 8 healthy controls). The expression of SARS-CoV-2 receptors (ACE2 and TMPRSS2) was examined among different cell types in the lung. The immune cells infiltration patterns, their gene expression profiles, and the interplay of immune cells and SARS-CoV-2 target cells were further investigated. ResultsCompared to healthy controls, the overall ACE2 (receptor of SARS-CoV-2) expression was significantly higher in lung epithelial cells of COVID-19 patients, in particular in ciliated cell, club cell and basal cell. Comparative transcriptome analysis of these lung epithelial cells of COVID-19 patients and healthy controls identified that SARS-CoV-2 infection activated pro-inflammatory signaling including interferon pathway and cytokine signaling. Moreover, we identified dysregulation of immune response in patients with COVID-19. In severe COVID-19 patients, significantly higher neutrophil, but lower T and NK cells in lung were observed along with markedly increased cytokines (CCL2, CCL3, CCL4, CCL7, CCL3L1 and CCL4L2) compared with healthy controls as well as mild patients who recovered. The cytotoxic phenotypes were shown in lung T and NK cells of severe patients as evidenced by enhanced O_SCPLOWIFNC_SCPLOW{gamma}, Granulysin, Granzyme B and Perforin expression. Moreover, SARS-CoV-2 infection altered the community interplay of lung epithelial cells and immune cells: the interaction between epithelial cells with macrophage, T and NK cell was stronger, but their interaction with neutrophils was lost in COVID-19 patients compared to healthy controls. ConclusionsSARS-CoV-2 infection activates pro-inflammatory signaling in lung epithelial cells expressing ACE2 and causes dysregulation of immune response to release more pro-inflammatory cytokines. Moreover, SARS-CoV-2 infection breaks the interplay of lung epithelial cells and immune cells.

Significance of diagnosis of tympanosclerosis by HRCT combined with pure tone audiometry / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the significance of diagnosis of tempanosclerosis by HRCT combined with pure tone audiometry. METHODS 176 patients(181 ears) with chronic suppurative otitis media in stationary phase were recruited in Guizhou Medical University Affiliated Hospital between January 2014 to December 2015. Temporal bone HRCT combined with pure tone audiometry were applied to all patients before operation to diagnose tempanosclerosis. Intraoperative exploration results was the gold standard to observe sensitivity, specificity, positive likelihood ratio and the difference of accuracy of two diagnostic methods. RESULTS 1. The sensitivity, specificity, positive likelihood, negative likelihood ratio and accuracy of tympanosclerosis diagnosed only by temporal bone HRCT were 58.55%, 93.10%, 8.49, 0.46 and 64.09% respectively. 2. The sensitivity, specificity, positive likelihood, negative likelihood ratio and accuracy of tympanosclerosis diagnosed by HRCT combined with pure tone audiometry were caculated as 94.08%, 89.66%, 9.09, 0.01 and 93.37% respectively. Type I diagnostic accordance rate was 89.66%, type II was 87.50%, type III was 84.62%and type IV was 82.14%. The total diagnosis coincidence rate was 86.18%. The diagnostic efficacy increased significantly by the combined method than by the temporal bone HRCT alone. CONCLUSION Temporal bone HRCT combined with pure tone audiometry is valuable in diagnosis of tympanosclerosis. It can provide theoretical basis for making optimal operation scheme in suspect tympanosclerosis patients.

Injectable nano/chitosan/bone morphogenetic protein-2 induces periodontal tissue regeneration / 中国组织工程研究

BACKGROUND:Chitosan hydrogel has good biocompatibility, biodegradability and antibacterial property, which can promote tissue healing and induce bone formation. As a scaffold carrying growth factors, it can ensure the efficient and slow release of exogenous growth factors. OBJECTIVE: To observe the effect of injectable nano/chitosan/bone morphogenetic protein-2 composite to promote periodontal tissue regeneration in rats. METHODS:Fifty-four Wistar rats were randomized into three groups, and then chronic periodontitis model of the second molar was established. After modeling, injectable nano/chitosan/bone morphogenetic protein-2 composite was implanted into the periodontal tissue of the second molar in the experimental group; injectable nano/chitosan hydrogel was implanted in the control grouop; and nothing was implanted in the blank group. At 3, 6, 9 weeks after surgery, gingival bleeding index, probing depth, and tooth mobility were detected. X-ray and histopathological observations were carried out. RESULTS AND CONCLUSION:At 9 weeks after surgery, the probing depth and tooth mobility were both lower in the experimental group than the other two groups (P < 0.05). In the experimental group, the alveolar bone height was restored at the root bifurcations, bone trabeculae were arranged densely and evenly, the newly formed periodontal ligament and alveolar bone tissues were dense and equaly distributed in the bone defect area at 9 weeks after surgery, indicating a better restoration effect than the control and blank groups. These findings suggest that the injectable nano/chitosan/bone morphogenetic protein-2 composite has an anti-inflammatory role and can guide periodontal tissue regeneration.

Nursing of patients with Grave's opththalmopathy undergoing endoscopic trans - ethmoid orbital decompression / 中国实用护理杂志

Objective To introduce an effective nursing practice for patients with Grave's ophthalmopathy(GO) undergoing endoscopic trans-ethmoid orbital decompression(ETOD). Methods The treatment and nursing experience of 31 cases (57 eyes) undergoing orbital decompression through endoscopic trans-ethmoid approach were reviewed and analyzed. Results Three months after operation, exophthalmos was corrected in all 31 cases (57 eyes) with satisfying result, and the visual acuity was improved in all 9 cases (16 eyes),who complained of visual loss preoperatively. At the 3-months' review, 2 patients presented diplopia on the primary eye position due to newly on-set global displacement. Conclusions Advanced treatment and careful nursing are very important to improve the surgical safety and decrease the complications.

Mechanism and targeted therapy of liver metastases of colorectal cancer / 国际肿瘤学杂志

The process of liver metastasis of colorectal cancer includes tumor cells invasion,survival in blood stream,extravasation to the liver and proliferation. It is involved in series of molecular markers,among which vascular endothelial growth factor and endothelial growth factor receptor are the major targets.

The curative effect of different dose of calcitriol on uremic hemodialysis patients with second dary hyperparathyroidism / 中国基层医药

Objective To compare the therapeutic effect of routine dose of calcitriol and large dose impulsion therapy on hemodialysis patients with secondary hyperparathyroidism(SHPT). Methods 48 uremic hemodialysis patients were divided into group A(routine group, n = 22) and group B(control group, n = 21 ). In group A,22 pa-tients were administered with calcitriol for 6 months at the dosage of 0.25～0.5μg/d,adding calcium agents simul-taneously;the patients in group B were not given calcitriol for economic reason. In group C,21 patients were given calcitriol twice a week at the dosage of 2μg/time after hemodialysis for 3 months. Results Comparing to group B,serum PTH,AKP in group A had no significant difference,but serum hypocalcium and hyperphasphate were partly corrected,symptoms of bone pain, muscular convulsion and akin pruriter were improved. Comparing to group A,serum hypocalcium and hyperphasphate in group C were corrected, serum PTH, AKP were significantly decreased( t=2.031,P<0.05;t =3.317,P<0.001),and no hypercalcium oecurred. Conelosion Routine dose of calcitriol can not control uremic-SHirr,while impulsion therapy with lower dose oral calcitriol is effective and safe.