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.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Osteoscarcopenia (OS) is a common degenerative syndrome in the elderly, which is caused by a decrease in both bone and muscle mass during the aging process, leading to osteoporosis and sarcopenia, a decrease in body balance, and a risk of falls and fractures, posing a serious threat to the quality of life and lifespan of the elderly. Osteoskeletal dystrophy increases with age, and its occurrence is higher in females than that in males. At present, there is no unified diagnostic standard, making it impossible to achieve early detection and intervention. The commonly used diagnostic methods include quantitative computed tomography (CT), magnetic resonance imaging (MRI), dual energy X-ray absorptiometry (DXA), muscle mass bioelectrical impedance analysis (BIA), as well as daily gait speed (UGS), short physical performance battery (SPPB), timed start test (TUG), and biochemical evaluation indicators to improve early diagnosis and screening. Due to the fact that both bones and muscles belong to the motor system, osteoporosis and sarcopenia share common pathogenic factors in genetics, endocrine, paracrine, and fat infiltration, which interact and regulate each other, inducing the occurrence of osteoscarcopenia. Osteoporosis and sarcopenia, two age-related diseases, share the same pathogenesis and regulatory pathways, as well as common drug targets. For example: somatostatin α‑actin-3, peroxisome proliferator activated receptor γ coactivation factor-1α (PGC-1α), myocyte enhancer factor-2 (MEF2C), sterol regulatory element binding transcription factor 1 (SREBF1), protoadhesion 7 (PCDH7) and methyltransferase like 21C (METTL21C), osteocalcin and bone derived bone factor gap junction connexin 43 (Cx43), growth hormone (GH), sex hormones, and diseases (such as tumors, diabetes, polycystic ovary syndrome, cardiovascular disease, anemia, disability, inflammatory disease), aging, nutrition, and poor living habits are closely related to osteosarcopenia. Osteoporosis is characterized by low bone mass and microstructural degeneration of bone tissue, while sarcopenia is characterized by loss of muscle mass, strength, and function, both of which often coexist in the elderly population. Exercise regulates muscle and skeletal cytokines such as myostatin (MSTN) and irisinβ‑aminoisobutyric acid (BAIBA), brain derived neutrophil factor (BDNF), interleukin, prostaglandin E2, Wnt, osteocalcin (OCN), and transforming growth factor‑β (TGF‑β) and receptor activator of NF-κB ligand (RANKL) interfere with each other to prevent and treat osteoscarcopenia. Wnt/β‑catenin signaling pathway can simultaneously regulate the growth and metabolism of bones and muscles, and promote osteoblast proliferation, maturation, and mineralization by increasing OPG/RANKL, which is beneficial for bone mass increase and induces proliferation of muscle satellite cells, stimulating and promoting increased muscle synthesis. NF‑κB pathway is the main regulatory factor for inflammation mediated muscle atrophy. Meanwhile, NF‑κB DNA can participate in RANKL inducing osteoclast differentiation in bone tissue, thereby reducing bone mass. Although exercise and nutrition can improve the symptoms of osteoporosis, they cannot be completely cured, and there are no specific drugs in clinical practice that can cure sarcopenia. Because osteoscarcopenia has a common crosstalk mechanism in the aging process, it is of great significance to prevent osteoscarcopenia by improving bone mass and muscle content through exercise, nutrition, and medication.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective: Recent studies indicate that 3 morphological types of atlanto-occipital joint (AOJ) exist in the craniovertebral junction and are associated with type II basilar invagination (BI) and atlanto-occipital instability. However, the actual biomechanical effects remain unclear. This study aims to investigate biomechanical differences among AOJ types I, II, and III, and provide further evidence of atlanto-occipital instability in type II BI. Methods: Models of bilateral AOJ containing various AOJ types were created, including I-I, I-II, II-II, II-III, and III-III models, with increasing AOJ dysplasia across models. Then, 1.5 Nm torque simulated cervical motions. The range of motion (ROM), ligament and joint stress, and basion-dental interval (BDI) were analyzed. Results: The C0–1 ROM and accompanying rotational ROM increased progressively from model I-I to model III-III, with the ROM of model III-III showing increases between 27.3% and 123.8% indicating ultra-mobility and instability. In contrast, the C1–2 ROM changes were minimal. Meanwhile, the stress distribution pattern was disrupted; in particular, the C1 superior facet stress was concentrated centrally and decreased substantially across the models. The stress on the C0–1 capsule ligament decreased during cervical flexion and increased during bending and rotating loading. In addition, BDI gradually decreased across the models. Further analysis revealed that the dens showed an increase of 110.1% superiorly and 11.4% posteriorly, indicating an increased risk of spinal cord impingement. Conclusion Progressive AOJ incongruity critically disrupts supportive tissue loading, enabling incremental atlanto-occipital instability. AOJ dysplasia plays a key biomechanical role in the pathogenesis of type II BI.

Objective:This paper aims to analyze the current status,characteristics,and problems of the policy text of China's chronic disease from the perspective of full-cycle,and provide a reference for subsequent policy optimization.Methods:The author selected 104 policy documents on chronic disease published at the national level from 2009 to 2023,used content analysis method,constructed a two-dimensional analysis framework of"policy tools-full-cycle management",and carried out one-dimensional quantitative analysis and two-dimensional cross-analysis.Results:The application of policy tools is obviously unbalanced,with supply-type policy tools accounting for as much as 63.23％,and demand-type policy tools used the least,only 10.51％.In the dimension of full-cycle management,the proportions of prevention,prevention and treatment,treatment,treatment and rehabilitation,health care,and full-cycle stages are 21.01％,24.58％,28.89％,7.32％,4.69％and 13.51％respectively.It is noteworthy that the proportions of the treatment and rehabilitation,and health care stages are relatively low.All stages of chronic disease health management interact frequently with supply-type policies,and the treatment and rehabilitation,health care and full-cycle stages cross less with demand-type policy tools.Conclusion:It is necessary to adjust the proportion of policy tools,strengthen their internal coordination,improve the top-level design of treatment and rehabilitation and health care,enhance the synergistic interaction between various types of policy tools and full-cycle management,and improve the overall effectiveness of policies.

Aim To investigate the effect of safflower yellow on the learning and memory of scopolamine hydrobromide-induced memory impairment model mice.Methods 6-month-old C57BL/6J mice were randomly divided into the control group,model group,SY high-dose group,SY medium-dose group,SY low-dose group,and Huperzine-A group(12 mice in each group).SCOP was used to establish a memory impair-ment model,the spatial learning,memory and cognitive ability of mice with memory impairment were evaluated by behavioral experiments,the function of the choliner-gic nervous system in the cortex of mice was measured by ELISA kit,the pathological changes of brain tissue were observed by Nissl staining,and the expression of synaptic plasticity and BDNF/TrkB/CREB pathway re-lated proteins in the cortical and hippocampus of mice in each group was detected by Western blot.Results Compared with the model group,the learning and mem-ory ability of the mice in each administration group was improved.The neurons in the hippocampus and corti-cal were neatly arranged,the cell morphology tended to be complete,and the number of normal neurons in-creased.The function of the cortical cholinergic nerv-ous system was significantly improved,the expression of synaptic plasticity-related proteins in brain tissue was increased,and the BDNF/TrkB/CREB signaling path-way was activated.Conclusions SY can significantly improve the learning and memory ability of mice with SCOP-induced memory impairment,and its mechanism may play a neuroprotective role by improving choliner-gic nervous system function,activating BDNF/TrkB/CREB signaling pathway,regulating synaptic plasticity,and reduces neuronal damage.