Epigallocatechin Gallate from Green Tea Effectively Blocks Infection of SARS-CoV-2 and New Variants by Inhibiting Spike Binding to ACE2 Receptor

As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Here, we demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

CAR-NK Cells Effectively Target the D614 and G614 SARS-CoV-2-infected Cells

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious presenting a significant public health issue. Current therapies used to treat coronavirus disease 2019 (COVID-19) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants, though the current therapeutic options remain limited and expensive. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of SARS-CoV-2 infection. However, their long-term side effects are not yet to be documented, and populations with immunocompromised conditions (e.g., organ-transplantation and immunodeficient patients) may not be able to mount an effective immune response. In addition, there are concerns that wide-scale immunity to SARS-CoV-2 may introduce immune pressure that could select for escape mutants to the existing vaccines and monoclonal antibody therapies. Emerging evidence has shown that chimeric antigen receptor (CAR)- natural killer (NK) immunotherapy has potent antitumor response in hematologic cancers with minimal adverse effects in recent studies, however, the potentials of CAR-NK cells in preventing and treating severe cases of COVID-19 has not yet been fully exploited. Here, we improve upon a novel approach for the generation of CAR-NK cells for targeting SARS-CoV-2 and its D614G mutant. CAR-NK cells were generated using the scFv domain of S309 (henceforward, S309-CAR-NK), a SARS-CoV and SARS-CoV-2 neutralizing antibody that targets the highly conserved region of SARS-CoV-2 spike (S) glycoprotein, therefore would be more likely to recognize different variants of SARS-CoV-2 isolates. S309-CAR-NK cells can specifically bind to pseudotyped SARS-CoV-2 virus and its D614G mutant. Furthermore, S309-CAR-NK cells can specifically kill target cells expressing SARS-CoV-2 S protein in vitro and show superior killing activity and cytokine production, compared to that of the recently published CR3022-CAR-NK cells. Thus, these results pave the way for generating off-the-shelf S309-CAR-NK cells for treatment in high-risk individuals as well as provide an alternative strategy for patients unresponsive to current vaccines.

A meta-analysis of the association between Caipain-10 gene polymorphism and T2DM in Chinese population / 中国糖尿病杂志

Objective To evaluate the association between calpain-10 gene polymorphism and type 2 diabetes mellitus(T2DM) by system assessment method.Methods CNKI,CBM and WangFang Data were searched for studies assessing the genetic association between calpain-10 gene polymorphism and T2DM.The data from included studies were extracted to calculate for odds ratio (OR).The simplified version of STREGA list was used to evaluate the quality of researches.Review Manger 5.3.1 software was used to analyze the heterogeneity (I2 values) among the studies,α=0.05.Results A total of 21 randomized controlled studies were analyzed.3062 T2DM patients were involved in SNP43 loci polymorphism evaluation.The highest score of STREGA list was 6 points and the lowest score was 3 points.The proportions of 6 points,5 points,4 points and 3 points were 38.10％,33.33％,9.52％ and 19.05％,respectively.Both scores of "whether having description of genotyping method" item and "whether having sufficient data" item were 0 point.Meta analysis results showed that SNP 43 mutation type "A" of Calpain-10 gene was related to T2DM (OR 0.60,95％CI 0.52,0.68,P＜0.05).The ORs of SNP 19,44 and 63 for T2DM were 0.92,1.50 and 0.84,with P values 0.50,0.11 and 0.08,respectively.The sensitivity analysis showed the similar results,with a small publication bias.Conclusion SNP43 loci of Calpain-10 gene has a genetic association with T2DM.

Clinical application of the third dorsal metacarpal artery island flap with the dorsal metacarpal superficial vein / 中华创伤骨科杂志

Objective To explore the surgical technique of applying the third retrograde 3rd dorsal metacarpal artery island flap with d orsal metacarpal superficial vein i n order to expand the repairing range of the3rd dorsal metacarpal artery island flap and increase the survival of the flap.Methods After 1999,13cases of the dorsal and pulp soft tissue defect of the 3rd and 4th fingers were designed to be repaired with the third dorsal metacarpal artery island fla p with dorsal metacarpal superficia l vein.The flap pedicle carried the 3rd dorsal cutaneous nerve and superficial metacarpal vein.The flap axis extended proximally 6cm along the original axis.The flap was harvested according to t he axis of the superficial vein.Results All flaps survived completely and2cases seemed survived as vein flaps.Consclusions This surgical technique can be used t o expand the re-pairing range of the 3rd dorsal metac arpal artery island flap,and be suitable to repair the dorsal and pulp soft tissue defcts of the 3rd and 4th finge rs.The one stage operation is simple,practical and effective.

The improvement of living quality for the patient with carcinoma of esophagus: Reconstruction for the defect of pharynx and cervical esophagus with inferior antebrachial skin flap on the basis of retaining the laryngeal function / 中国组织工程研究

Objective To investigate the effect of reconstruction for inferior pharyngeal and cervical esophagus defect with inferior antebrachial skin flaps on the living quality of patients after surgery. Method Perform radical operation of the tumor, but retain larynx and trachea. Free antebrchial skin flaps were used to reconstruct the defect of inferior pharynx and cervical esophagus. Roll the skin flap to form a skin tube, and then carry out anastomosis with floor of mouth and cervical esophagus. Result The laryngeal function was retained after surgery. And permanent orifice of trachea was unnecessary. The effect was satisfying. The vocalization wasn't affected and food- intake through oral was normal in the 2 patients followed up. Conclusion It is a feasible way to reconstruct the inferior pharynx and cervical esophagus defect caused by radical operation of the tumor at pharynx and cervical esophagus. It can improve the living quality of patients effectively.

Application of Forearm Flap in Tongue Reconstrution / 中国医师杂志

Objective To sum up the experiences of tongue repair after radical operation of tongue carcinoma with free forearm flap in the last two years. Methods The clinical data of 26 patients underwent forearm free flap transfer for tongue repair from February 2002 to February 2004 were retrospectively analysed . Results Among the 26 grafted forearm flaps, 25 survived. Only one flap occurred arterial thrombosis and necrosis after the second operation.All the patients were followed up for 6 months to 2 years. Reconstruction tongues had suitable volume and shape as well as perfect movement ability. Conclusion Free forearm flap was suitable to repair the tongue defect after radical operation of tongue caicinoma. The rate of operation success was high, and reconstructed tongues could basically meet patient's normal life.

Experimental study of Radix Saposhnikoviae and Feutus Trbuli on antagonizing type Ⅰ allergy / 中成药

AIM: To study the effects of Radix Saposhnikoviae(RL) and Feutus Trbuli(FI) used singly and combinedly on antagonizing type Ⅰ allergy,such as passive cutaneous anaphylaxis(PCA),released model from mast cell granules,Schulz-Dale respond. METHODS: Mouse and rat models mainly induced by IgE were used in experiments. RESULTS: RL and FI used singly and combinedly could significantly inhibit PCA of same species of mice,the degranulation of mast cells of skull in rats and Schulz-Dale response. CONCLUSION: Both RL and FI respectively have antagonistic effect on type Ⅰ allergy and RL in combination with FI will possess more satisactory effect

Pharmacodynamics study on Radix saposhnikoviae(RL) and Feutus tribuli (FI) / 中成药

Objective: To study the pharmacological effects of Radix Saposhnikoviae (RL) and Fruetus Tribuli (FI) used singly and combinedly. Methods: The effect of the tested drugs on the animal itching models induced by dextran 40 and Histanmine, skin capillary permeability induced by Histamine and experimental nettle rash induced by dimethylsulfoxide (DMSO) were observed. Results: RL and FI used singly and combinedly could obviously relieve the itch, inhibit the increase of skin capillary permeability induced by Histamine and resist experimental nettle rash induced by dimethylsulfoxide (DMSO) in different degree. Conclusion:RL and FI used singly and combinedly have anti allergic effect and the effect of RL and FI used combinedly is the same as used respectively.