Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Objective:To analyze mortality risk factors in patients with severe pneumonia and investigate their varying influences across different time periods.Methods:A total of 134 patients with severe pneumonia admitted to the Emergency Department of Xiang’an Hospital, Xiamen University, between June 2019 and February 2020 were enrolled. All patients were treated in the EICU and followed up for four years. Based on outcomes, they were categorized into a death group ( n=77) and a survival group ( n=57). COX regression analysis was employed to identify mortality risk factors at different time points, while logistic regression analysis was used to assess risk factors influencing mortality during hospitalization, ICU stay, 1-month, and 1-year follow-up periods. Results:Mortality rates were 11.9% ( n=16) during ICU admission, 20.8% ( n=28) during hospitalization, 16.4% ( n=22) within 1 month, and 31.3% ( n=42) within 1 year. By the end of the follow-up, 57.4% ( n=77) of patients had died. Ten mortality risk factors were identified, with the number increasing over time. During ICU admission and hospitalization, significant risk factors included total bilirubin levels, APACHE-II score, invasive ventilation, ARDS, and vasopressor use in the ICU. One-month mortality risk additionally involved bacterial infection. One-year mortality risk further incorporated advanced age and chronic heart failure. By the end of follow-up, acute kidney injury (AKI) during ICU admission also emerged as a contributing factor, while higher body weight was identified as a protective factor. Conclusions:The number of mortality risk factors in severe pneumonia patients increases progressively over time. Early-stage factors during hospitalization and ICU admission exert a stronger impact on short-term mortality, whereas bacterial infection, advanced age, and chronic heart failure become increasingly significant in later stages. These findings highlight the dynamic nature of risk factors and underscore the importance of tailored monitoring and intervention strategies at different disease phases.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Objective:To develop a scientific and practical questionnaire for general practice residents, and to conduct multidimensional and comprehensive evaluation of the quality of general practice teaching clinics.Methods:A preliminary draft of the questionnaire items was formulated based on a literature review and in-depth interviews. The Delphi method was employed to conduct two rounds of consultation with 14 experts. Following revisions, a convenience sampling method was used to invite general practice residents from three standardized residency training bases to test the reliability and validity of the questionnaire.Results:The questionnaire consisted of 23 items, covering the three dimensions of preparation, implementation process, and comprehensive evaluation of the teaching clinics. The response rates for the two rounds of the expert consultation were both 100.00%, with expert authority coefficients of 0.89 and 0.90, respectively. The overall Cronbach's α coefficient of the questionnaire was 0.93, and the correlation coefficients between each item score and the total score were all >0.30. Structural validity analysis revealed that three common factors were extracted from the questionnaire, with a cumulative variance contribution rate of 77.89%. Conclusions:The General Practice Teaching Clinic Quality Evaluation Questionnaire for Residents developed in this study demonstrates high reliability and validity. The questionnaire provides a scientific basis for the standardized assessment of teaching quality in general practice clinics. By incorporating resident feedback on the teaching process, the questionnaire promotes the development of a teaching clinic quality improvement mechanism focused on residents and plays a significant role in enhancing the teaching capabilities of supervising physicians in clinics.

Objective:To develop a scientific and practical questionnaire for general practice residents, and to conduct multidimensional and comprehensive evaluation of the quality of general practice teaching clinics.Methods:A preliminary draft of the questionnaire items was formulated based on a literature review and in-depth interviews. The Delphi method was employed to conduct two rounds of consultation with 14 experts. Following revisions, a convenience sampling method was used to invite general practice residents from three standardized residency training bases to test the reliability and validity of the questionnaire.Results:The questionnaire consisted of 23 items, covering the three dimensions of preparation, implementation process, and comprehensive evaluation of the teaching clinics. The response rates for the two rounds of the expert consultation were both 100.00%, with expert authority coefficients of 0.89 and 0.90, respectively. The overall Cronbach's α coefficient of the questionnaire was 0.93, and the correlation coefficients between each item score and the total score were all >0.30. Structural validity analysis revealed that three common factors were extracted from the questionnaire, with a cumulative variance contribution rate of 77.89%. Conclusions:The General Practice Teaching Clinic Quality Evaluation Questionnaire for Residents developed in this study demonstrates high reliability and validity. The questionnaire provides a scientific basis for the standardized assessment of teaching quality in general practice clinics. By incorporating resident feedback on the teaching process, the questionnaire promotes the development of a teaching clinic quality improvement mechanism focused on residents and plays a significant role in enhancing the teaching capabilities of supervising physicians in clinics.

Teaching clinics represent a unique form of outpatient training of resident physicians and serve as a crucial instrument and core component of standardized training of general practice residents. This article reviews the common model and innovations of teaching clinics of general practice in China, and analyzes their reported effectiveness in enhancing the capabilities of consultation of resident physicians, the teaching capabilities of general practice trainers, as well as satisfaction levels of involved participants. It outlines the challenges encountered in implementing teaching clinics, including inadequate teaching facilities and equipment, incomplete incentive system for teaching, difficulties in patient recruitment, and weaknesses in the teaching capabilities of trainers. To address these challenges, this article proposes corresponding strategies based on realistic needs, including the improvement of facilities and equipment in teaching clinics, the establishment of incentive systems for teaching clinics, the expansion of patient recruitment channels for teaching clinics, and the enhancement of training for trainers' teaching capabilities. This is envisaged to provide both theoretical bases and practical guidance for the effective execution and standardized development of teaching clinics in general practice residency training bases.

Objective To investigate the effect of the long non-coding RNA FGD5 antisense RNA1(lncRNA FGD5-AS1)on myocar-dial cell injury induced by high glucose levels through regulation of the miR-195-5p/Pim-1 proto-oncogene(PIM1)axis.Methods The rat myocardial cell line H9c2 and human myocardial cells were randomly allocated to the control,model,lncRNA FGD5-AS1 overex-pression,miR-195-5p inhibitor,negative control,and lncRNA FGD5-AS1 overexpression+miR-195-5p mimic groups to determine the expression of lncRNA FGD5-AS1,miR-195-5p,and PIM1.In addition,cell proliferation,apoptosis,and pro-inflammatory cytokine levels of the cells in each group were analyzed.Results Compared with the control group,the protein and mRNA expressions of lncRNA FGD5-AS1 and PIM1 and the survival and proliferation rates in H9c2 and human myocardial cells in the model group decreased(P<0.05),and the expression of miR-195-5p,apoptosis rate,and production levels of tumor necrosis factorα(TNF-α)and interleukin-6(IL-6)increased(P<0.05).Overexpression of the lncRNA FGD5-AS1 reversed these pathological changes in model group cells,whereas upregulation of miR-195-5p could weaken the effects of overexpression of lncRNA FGD5-AS1.Conclusion Overexpression of lncRNA FGD5-AS1 enhances the expression of PIM1 by downregulating miR-195-5p,thereby inhibiting high glucose-induced myocyte inflamma-tion,promoting survival and growth,and alleviating apoptotic injury.