The current epidemic situation of coronavirus disease 2019 (COVID-19) still remains severe. As the National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital of the Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang Province. Based on the present expert consensus carried out by the National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on “Four-Anti and Two-Balance” for clinical practice. The “Four-Anti and Two-Balance” strategy includes antivirus, anti-shock, anti-hypoxemia, and anti-secondary infection, and maintaining of water, electrolyte and acid/base balance and microecological balance. Simultaneously, an integrated multidisciplinary personalized treatment is recommended to improve therapeutic effects. The importance of early viral detection, dynamic monitoring of inflammatory indexes, and chest radiographs has been emphasized in clinical decision-making. Sputum was observed with the highest positive rate by reverse transcription-polymerase chain reaction (RT-PRC). Viral nucleic acids could be detected in 10% of the patients’ blood samples at the acute phase and 50% of patients had positive RT-PCR results in their feces. We also isolated live viral strains from feces, indicating potential infectiousness of feces. Dynamic cytokine detection was necessary to timely identify cytokine storms and for the application of the artificial liver blood purification system. The “Four-Anti and Two-Balance” strategy effectively increased cure rates and reduced mortality. Early antiviral treatment alleviated disease severity and prevented illness progression. We found that lopinavir/ritonavir combined with abidol showed antiviral effects against COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system was able to rapidly remove inflammatory mediators and block the cytokine storm. Moreover, it also contributed to the balance of fluids, electrolytes, and acids/bases and thus improved treatment efficacy during critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid administration was supported. Patients with an oxygenation index below 200 mm Hg were transferred to the intensive care unit. Conservative oxygen therapy was preferred and noninvasive ventilation (NIV) was not recommended. Patients with mechanical ventilation were strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was prescribed rationally and was not recommended, except for patients with a long course of disease, repeated fever, and elevated procalcitonin, similarly secondary fungal infections were of concern. Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased genus such as Lactobacillus and Bifidobacterium. Nutritional and gastrointestinal function should; therefore, be assessed for all patients. Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infections due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established a dynamic assessment and warning for psychological crises. We also integrated Chinese medicine in the treatment to promote rehabilitation. We optimized nursing processes for severe patients to promote their rehabilitation. Since viral clearance patterns after severe acute respiratory syndrome coronavirus 2 infections remained unclear, 2 weeks quarantine for discharged patients was required, and a regular following-up was also needed. These Zhejiang experiences and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work is warranted to further improve strategies of prevention, diagnosis, and treatment for COVID-19.

Although several features of apoptosis and autophagy have been reported in the larval organs of Lepidoptera during metamorphosis, solid experimental evidence for autophagy is still lacking. Moreover, the role of the two processes and the nature of their relationship are still cryptic. In this study, we perform a cellular, biochemical and molecular analysis of the degeneration process that occurs in the larval midgut of Bombyx mori during larval-adult transformation, with the aim to analyze autophagy and apoptosis in cells that die under physiological conditions. We demonstrate that larval midgut degradation is due to the concerted action of the two mechanisms, which occur at different times and have different functions. Autophagy is activated from the wandering stage and reaches a high level of activity during the spinning and prepupal stages, as demonstrated by specific autophagic markers. Our data show that the process of autophagy can recycle molecules from the degenerating cells and supply nutrients to the animal during the non-feeding period. Apoptosis intervenes later. In fact, although genes encoding caspases are transcribed at the end of the larval period, the activity of these proteases is not appreciable until the second day of spinning and apoptotic features are observable from prepupal phase. The abundance of apoptotic features during the pupal phase, when the majority of the cells die, indicates that apoptosis is actually responsible for cell death and for the disappearance of larval midgut cells.

Two currently licensed live oral rotavirus vaccines (Rotarix® and RotaTeq®) are highly efficacious against severe rotavirus diarrhea. However, the efficacy of such vaccines in selected low-income African and Asian countries is much lower than that in middle or high-income countries. Additionally, these two vaccines have recently been associated with rare case of intussusception in vaccinated infants. We developed a novel recombinant subunit parenteral rotavirus vaccine which may be more effective in low-income countries and also avert the potential problem of intussusception. Truncated recombinant VP8* (ΔVP8*) protein of human rotavirus strain Wa P[8], DS-1 P[4] or 1076 P[6] expressed in E. coli was highly soluble and was generated in high yield. Guinea pigs hyperimmunized intramuscularly with each of the ΔVP8* proteins (i.e., (P[8], P[4] or P[6]) developed high levels of homotypic as well as variable levels of heterotypic neutralizing antibodies. Moreover, the selected ΔVP8* proteins when administered to mice at a clinically relevant dosage, route and schedule, elicited high levels of serum anti-VP8* IgG and/or neutralizing antibodies. Our data indicated that the ΔVP8* proteins may be a plausible additional candidate as new parenteral rotavirus vaccines.

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.