Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

BACKGROUND:Traditional scoliosis orthosis has some disadvantages,such as complex manufacturing process,long processing cycle,poor fit and so on.Three-dimensional printed scoliosis orthosis has the advantages of high manufacturing precision and personalization. OBJECTIVE:To evaluate the efficacy of three-dimensional printed scoliosis orthosis for scoliosis based on multi-criteria decision model. METHODS:Clinical data of 72 patients with scoliosis admitted to Chen Xinghai Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to October 2022 were retrospectively collected and divided into two groups according to the treatment of orthosis.Study group(n=23)received three-dimensional printed scoliosis orthosis.Traditional group(n=49)received the traditional polypropylene spine brace treatment.The clinical efficacy and complications were compared between the two groups.A multi-criteria decision model for the treatment of scoliosis with three-dimensional printed scoliosis orthosis was established,and the stability of the benefit value,risk value and decision model of the two groups were evaluated. RESULTS AND CONCLUSION:(1)Compared with the traditional group,there were significant differences in the top vertebral offset distance,Cobb angle,top vertebral rotation,Functional Movement Screen score,visual analog scale score and total effective rate in the study group at 6 months after surgery(P<0.05).(2)Among the benefit indexes,Cobb angle had the greatest impact on the condition of patients,while the risk indexes had the greatest impact on dyspnea.(3)The benefit values of the study group and the traditional group for scoliosis were 79 and 64,and the risk values were 74 and 57,respectively.The combined benefit and risk values found that the benefit-risk value of the study group was 16 higher than that of the traditional group.(4)In the range of 0-100%relative risk weight,the benefit-risk value of the study group was always higher than that of the traditional group,which proved that the multi-criteria decision-making model had good stability.(5)It is indicated that three-dimensional printed scoliosis orthosis can better restore the physiological curvature of scoliosis and improve the efficiency of treatment.

Objective To evaluate the effect of extracorporeal membrane oxygenation (ECMO) on early allograft dysfunction (EAD) after heart transplantation. Methods Clinical data of 614 heart transplant recipients were retrospectively analyzed. All recipients were divided into the ECMO group (n=43) and non-ECMO group (n=571) according to postoperative application of ECMO. In the ECMO group, the conditions of recipients undergoing ECMO after heart transplantation were summarized. Perioperative status and long-term prognosis of recipients were compared between two groups. Results Among 43 recipients undergoing ECMO, 17 cases underwent thoracotomy due to bleeding, 10 cases of infection, 4 cases of venous thrombosis of the lower limbs, and 1 case of stroke, respectively. Twenty-six recipients were recovered and discharged after successful weaning from ECMO, six died during ECMO support, six died after weaning from ECMO, five received retransplantation due to unsuccessful weaning from ECMO, and only one survived after retransplantation. Compared with the non-ECMO group, intraoperative cardiopulmonary bypass duration was significantly longer, the proportion of recipients requiring postoperative intra-aortic balloon pump (IABP), dialysis due to renal insufficiency, reoperation for hemostasis, infection, mechanical ventilation time≥96 h and tracheotomy was significantly higher, and the length of postoperative intensive care unit (ICU) stay was significantly longer in the ECMO group (all P < 0.05). The survival rate after discharge and 90-d survival rate in the ECMO group were 63% and 96%, significantly lower than 97% and 100% in the non-ECMO group (both P < 0.05). Survival analysis showed that the long-term survival rate in the ECMO group was significantly lower than that in the non-ECMO group (P < 0.05). After excluding the recipients who died within 90 d after heart transplantation, no significant difference was observed in the long-term survival rate (P > 0.05). Conclusions ECMO is an effective treatment of EAD after heart transplantation. The short-term survival rate of recipients using ECMO after heart transplantation is lower than that of those who do not use ECMO, and there is no significant difference in long-term survival of recipients surviving 90 d after heart transplantation.

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.
Humans ; Pluripotent Stem Cells/metabolism* ; Embryo, Mammalian/metabolism* ; Cell Differentiation ; Blastocyst ; Cell Lineage ; Embryonic Development

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.

In this article, a case for random signal interference in resolver (or encoder) of carousel on Varian VitalBeam medical linear accelerator was illustrated. This case was considered as a rare failure of the technology platform (including TrueBeam) by Chinese, European and American technical experts in Varian. In this article, the differences of the carousel in the structure and control system between VitalBeam and traditional accelerator were comparatively analyzed to enable the peers to have a deeper understanding of resolver. The logic and methods to solve the fault were summarized, providing reference experience for analyzing the problems related to carousel. It is found that the interlocking system is imperfect, which provides a factual and technological basis for Varian to optimize the system.

Objective:To evaluate the relationship between the mechanism of promoting wound healing by modified autologous blood transfusion and metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) in diabetic mice. Methods:Twenty SPF ICR mice, weighing 21-25 g, in which the diabetic model was successfully established, were divided into 2 groups ( n=10 each) using a random number table method: modified preservation group (group I) and ordinary preservation group (group O). Peripheral venous blood samples were collected and stored in the corresponding preservation solution for 7 days.The platelet aggregation rate, blood glucose, serum glycosylated hemoglobin (GHB) and phosphodiesterase (DPG) concentrations and WBC were measured.Autologous blood was transfused back immediately after the wound model was established.The percentage of wound healing area was calculated at 7, 10 and 14 days after autologous blood transfusion.The expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, matrix metalloproteinase-9, β-actin, type Ⅰ collagen (Col Ⅰ), Col Ⅲ protein and mRNA and MALAT1 was determined by Western blot, immunohistochemistry and quantitative real-time polymerase chain reaction respectively, at 14 days after transfusion. Results:Compared with group O, the blood glucose, serum concentrations of GHB and DPG, and WBC were significantly decreased, platelet aggregation rate was increased, the percentage of wound healing area was increased, the positive staining rate of Col Ⅰ and Col Ⅲ was increased, and the expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, matrix metalloproteinase-9, ColⅠ, Col Ⅲ and β-actin protein and mRNA and MALAT1 was up-regulated in group I ( P<0.05). Conclusion:The mechanism by which modified autologous blood transfusion promotes wound healing may be related to up-regulating MALAT1 expression in diabetic mice.

Objective To analyze the early outcomes of heart transplantation in critical patients and its significance in donor allocation decision. Methods Clinical data of 449 recipients undergoing heart transplantation were retrospectively analyzed. According to preoperative status, all patients were divided into the critical status group (n=64) and general status group (n=385). The incidence of critical status was summarized. Clinical data of recipients were statistically compared between two groups. Postoperative survival and causes of death in recipients between two groups were analyzed. Perioperative results of critical recipients undergoing different mechanical circulation support as a bridge to heart transplantation were compared. Results Critical patients accounted for 14.3% of the total number of transplant recipients. The proportion of critical patients gradually increased in recent 5 years. Compared with the general status group, the recipients in critical status group had a lower proportion of smoking history, a higher proportion of cardiac surgery history, a higher serum level of creatinine, and a higher proportion of primary diseases of heart failure before heart transplantation(all P≤0.01). The proportion of undergoing mechanical circulation support was higher, the incidence of complications was higher, the stay time in intensive care unit (ICU) was longer and the in-hospital fatality was higher after heart transplantation in the critical status group (all P≤0.01). The 1-year survival rate of recipients in critical status group was significantly lower than that in general status group (83% vs. 95%, P < 0.01). The fatality of recipients due to infection and multiple organ failure in critical status group was higher than that in general status group. Among 64 critical recipients, 1 recipient received ventilator alone, and 63 recipients underwent mechanical circulation support devices as a bridge to heart transplantation. Among them, intra-aortic balloon pump (IABP) alone was applied in 49 cases (77%), 8 cases (13%) of extracorporeal membrane oxygenation (ECMO) combined with IABP, 4 cases (6%) of ECMO alone, and 2 cases (3%) of left ventricular assist device (LVAD) alone. Critical patients who received preoperative ECMO and ECMO combined with IABP bridging to heart transplantation have a higher proportion of postoperative complications, a longer ICU stay time, a longer mechanical ventilation time, and a higher proportion of hospital deaths. Conclusions The overall prognosis of critical patients undergoing heart transplantation is relatively poor. Effective preoperative management may reverse the high-risk status of critical patients in a certain extent. The limited quantity of donor heart should be allocated to the most urgent patients who can obtain the greatest benefit from heart transplantation.

ObjectiveTo analyze the mental health status of non-psychiatric inpatients in a general hospital， and to explore the relevant influencing factors， so as to provide references for the screening of mental health problems and the construction of intervention models among non-psychiatric inpatients. MethodsA cross-sectional study was conducted among 916 non-psychiatric inpatients in a third grade class A general hospital in Guangzhou， and all the inpatients were assessed using Patient Health Questionnaire-9 item （PHQ-9）， Generalized Anxiety Disorder-7 item （GAD-7）， Athens Insomnia Scale （AIS） and Columbia-Suicide Severity Rating Scale （C-SSRS） to detect their depression， anxiety， insomnia and suicide risk status. Thereafter， univariate and multivariate Logistic regression analysis were used to screen the risk factors affecting the mental health of inpatients. ResultsA total of 339 （37.0%） inpatients with positive mental health problems were screened， and the screening results for each dimension revealed 218 cases （23.8%） of depression， 141 cases （15.4%） of anxiety， 257 cases （28.1%） of insomnia， 42 cases （4.6%） of suicidal ideation and 7 cases （0.8%） of suicidal behavior. Binary Logistic regression analysis showed that female （OR=1.379， P<0.05） was a risk factor for positive screening of mental health problems. Ordinal Logistic regression analysis denoted that age above 60 years old （OR=1.542， P<0.05） and singlehood （OR=2.055， P<0.05） were risk factors affecting the severity of depression， while senior high school to junior college education （OR=0.524， P<0.05） was a protective factor of depression， meantime， female （OR=1.472， P<0.05） was a risk factor affecting the severity of insomnia. ConclusionMental health problems are quite common among non-psychiatric inpatients in general hospitals， and are mainly affected by factors such as gender， age， marital status and educational background.

Objective:To detect the infection and subtype status of human papilloma virus (HPV) for patients with head and neck squamous cell carcinoma (HNSCC) treated in a single center in Chaoshan area of Guangdong Province.Methods:The primary lesion samples from 167 HNSCC patients in Cancer Hospital of Shantou University Medical College between December 2014 and December 2016 were collected. The expression of p16 protein in tumor tissues was detected by using immunohistochemistry (IHC), and the positive rate of tumor cell p16 protein≥ 76% was used as a diagnostic standard to judge HPV in HNSCC; the relationship between p16 protein and the clinicopathological factors was analyzed. The status of HPV 16/18 DNA in tumor tissues was tested by using in situ hybridization(ISH). RNA scope was used to detect the RNA expression of 18 kinds of common high-risk HPV subtype (HPV HR 18), and the positive status of HPV HR 18 in tumor tissues with the positive cell proportion ≥ 50% of p16 protein was analyzed.Results:The strong expression rate of p16 protein was 7.2% (12/167). The strong expression rate of p16 protein in the younger group (< 50 years old) was higher than that in the older group (≥ 50 years old) [17.2% (5/29) vs. 5.1% (7/138), χ 2=5.321, P=0.021]. The strong expression rate of p16 protein in the oropharyngeal carcinoma group was higher than that in the non-oropharyngeal carcinoma group [29.4% (5/17) vs. 4.7% (7/150), χ 2=14.019, P < 0.01]. The strong expression rate of p16 protein in the gender, smoking and alcohol consumption, tumor staging and stratification among different patients was not statistically different (all P > 0.05). HPV 16/18 DNA was not found in all HNSCC primary lesions by using ISH, which showed the same result after repeated examination. RNAscope method showed that 3 cases (15.8%) out of the 19 patients with p16 protein positive rate≥50% were HPV HR 18 RNA positive. Conclusions:The positive rate of HPV for HNSCC patients in Chaoshan area is low, while the patients with oropharyngeal carcinoma have the highest rate and tend to be younger. The main carcinogenic viruses of HPV for HNSCC patients in Chaoshan area are other subtypes of HPV including HPV HR 18 rather than HPV 16/18.