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 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.

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.

In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance， Innovation， and Development of traditional Chinese medicine（TCM） and the spirit of the National Conference on TCM， Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis （AR） and they reached a basic consensus. In recent years， the prevalence of AR has been on the rise， threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity， and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease， western medicine features rapid onset. However， it is cost-intensive and causes severe surgical trauma， and the recurrence is common. TCM boasts diverse methods for AR， which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion， runny nose， or dysosmia in the attack stage， preventing recurrence in the remission stage， and treating refractory AR or steroid-resistant AR. In particular， acupuncture enjoys a reputation in treatment of AR， which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR， TCM regulates the psychosomatic conditions， which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine， give full play to the unique nonnegligible and irreplaceable advantages of TCM， formulate a comprehensive diagnosis and treatment scheme for learning and promotion， and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.

Objective:To investigate difficult-to-treat sites in patients with psoriasis receiving biological therapy.Methods:Clinical data were retrospectively collected from 73 adult patients with psoriasis in the database of Psoriasis Center, National Clinical Research Center for Skin and Immune Diseases from June 2020 to September 2021, who had received sufficient and standardized treatment with biological agents for ≥ 24 weeks, and were still treated with biological agents at the time of enrolment into this study with the psoriasis area and severity index (PASI) score being 1 - 5 at the time of enrolment into the database of Psoriasis Center. Distribution of psoriatic lesions resistant to biological therapy were analyzed, and differences in refractory sites were compared between different biologics. Chi-square test or Fisher′s exact test was used to analyze differences in the anatomical distribution of residual skin lesions after treatment with different biologics, McNemar test to compare the anatomical distribution of skin lesions before and after biological therapy, and Kruskal-Wallis H test to analyze the association between PASI scores for residual skin lesions and dermatology life quality index (DLQI) scores. Results:After ≥ 24 weeks of sufficient and standardized biological therapy in the 73 patients, refractory skin lesions mostly involved the lower limbs (46 cases, 63.01%) , followed by the scalp (36 cases, 49.32%) and upper limbs (27 cases, 36.99%) ; proportions of patients with residual skin lesions on the face and neck, trunk, upper limbs, lower limbs, hands and feet significantly decreased after biological therapy compared with those before treatment (paired χ2 = 5.14, 7.69, 9.90, 4.17 and 6.13, P = 0.016, 0.003, 0.001, 0.031 and 0.008, respectively) , while there was no significant difference in the proportions of patients with skin lesions on the scalp and genital areas before and after treatment (both P > 0.05) . No significant difference in the anatomical distribution of residual skin lesions was observed between the 13 patients receiving treatment with tumor necrosis factor inhibitors (adalimumab, infliximab, or tumor necrosis factor receptor-antibody fusion protein) and 59 receiving treatment with interleukin-17 (IL-17) inhibitors (secukinumab or ixekizumab) (all P > 0.05) . There was no significant difference in the anatomical distribution of residual skin lesions in the 13 patients before and after the treatment with tumor necrosis factor inhibitors (all P > 0.05) ; in the 59 patients treated with IL-17 inhibitors, the proportions of patients with residual skin lesions on the trunk, upper limbs, hands and feet significantly decreased after treatment (paired χ2 = 4.90, 9.09 and 7.11, P = 0.021, 0.001 and 0.004, respectively) , while there was no significant difference in the distribution of skin lesions on the scalp, face and neck, lower limbs and genital area before and after treatment (all P > 0.05) . Among the 73 patients, the PASI scores for lesions on the upper and lower limbs and the total PASI scores were all associated with the DLQI scores ( H = 7.52, 12.61, 6.75, respectively, all P < 0.05) , and were significantly higher in the patients with DLQI scores of > 10 points than in those with DLQI scores of ≤ 5 points (all P < 0.05) . Conclusions:Biological therapy-resistant psoriatic lesions were mostly located on the scalp, and refractory skin lesions mostly involved the lower limbs, scalp and upper limbs. No significant difference in the anatomical distribution of residual skin lesions was observed between patients treated with tumor necrosis factor inhibitors and IL-17 inhibitors, but IL-17 inhibitors may result in lesion clearance at more anatomical sites compared with tumor necrosis factor inhibitors.

Objective : To assess the safety and feasibility of incision in the retroauricular sulcus for removal of benign tumors in the lower pole of the parotid gland and to provide some ideas for aesthetic consideration of parotidectomy. Methods: In total, 18 cases with benign tumors of the lower pole regions of the parotid gland were included in this study, including 9 pleomorphic adenomas, 2 myoepitheliomas, 5 Warthin tumors, 1 basal cell adenoma and 1 oncocytoma. Three months after the operation, facial paralysis and salivary fistula were assessed. A visual analog scale was used to score the cosmetic satisfaction of the surgical incision. Tumor recurrence was followed up 6 ~ 12 months after operation. Results: In 18 patients with benign tumors the lower pole regions of the parotid gland, the tumor diameter ranges from 1.0 to 3.1 cm, with an average value of 2.5 cm. All patients experienced successful complete removal of the parotid mass with the minimally invasive retroauricular approach, and all wounds healed in one stage after operation. No serious complications, such as permanent facial paralysis and tumor recurrence, occurred 3 months after the operation. The patients were satisfied with the appearance of the surgical incision (aesthetic score 9.3 ± 0.4), achieving the expected aesthetic effect. Conclusion This approach is feasible and safe for most small benign parotid tumors located in the lower pole region of the parotid gland and in the posterior region of the jaw. The scar is located in the retroauricular sulcus, which significantly meets the aesthetic needs of the concealed incision for patients.

Objective To compare the sonographic features as well as clinical histopathological features of follicular variant papillary thyroid carcinoma(FVPTC) and conventional papillary thyroid carcinoma (CPTC) in pediatric patients.Methods From Jan.2006 to Dec.2017,26 FVPTC patients and 82 CPTC patients were enrolled in this study.The clinical histopathological findings and the sonographic features were compared between the two groups.FVPTCs and CPTCs were divided into PTC-like and follicular neoplasm(FN)-like based on sonographic characteristics.Results The mean nodule size of FVPTCs was larger than that of conventional PTCs.Extrathyroid invasion and cervical lymph node metastasis did not have significant difference between CPTC and FVPTC patients(53.8％ vs 62.2％ and 76.9％ vs 82.9％,respectively).Multiple nodules(P=0.000)and distant pulmonary metastases(P=0.024) were more frequent in CPTCs than in FVPTCs(P＜0.05).The rate of an ill-defined margin (P=0.000) and calcification (P=0.003)in terms of sonographic features were lower in FVPTCs than conventional PTCs(P＜0.05).A Ⅴ+Ⅵ diagnosis of PTC on FNAC of FVPTCs was less common than that of conventional PTCs (P=0.014).Multifocality(P=0.000),extrathyroidal invasion (P=0.000),and lymph node metastasis (P=0.000) were significantly different between PTC-like FVPTCs and FN-like FVPTCs.Conclusion FVPTC in children and adolescents shows a relatively larger size,more benign sonographic features,and a lower diagnostic rate of PTC by FNAC compared with conventional PTCs in pediatric patients.