Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

OBJECTIVES: To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish. METHODS: The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression. RESULTS: After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells. CONCLUSIONS L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.
Animals ; Zebrafish/immunology* ; Acetic Acid/metabolism* ; Propionates/metabolism* ; Fatty Acids, Volatile/metabolism*

OBJECTIVES: To investigate the efficacy of Lactobacillus plantarum ZG03 (L. plantarum ZG03) for ameliorating oxidative stress in zebrafish. METHODS: We evaluated the growth pattern of L. plantarum ZG03, observed its morphology using field emission scanning electron microscopy, and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis. FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish. In a zebrafish model of 2% glucose-induced oxidative stress, the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue (CHT), superoxide dismutase (SOD) activity, reactive oxygen species (ROS) levels, and malondialdehyde (MDA) content. Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids (SCFAs) in the zebrafish, and the antioxidant effects of the key metabolites (acetate, propionate, and caproate) were tested. RESULTS: On MRS agar, L. plantarum ZG03 formed circular, smooth, moist, and milky-white colonies with a rod-shaped cell morphology. Genomic analysis revealed abundant sugar metabolism gene clusters. After inoculation of FITC-labeled L. plantarum ZG03 in zebrafish, green fluorescence was clearly observed in the intestinal bulb, mid-intestine, and hind intestine. In zebrafish with glucose-induced oxidative stress, L. plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity. L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid, propionic acid, and caproic acid in zebrafish metabolites. In addition, sodium acetate, sodium propionate, and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models. CONCLUSIONS L. plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites, particularly the SCFAs including acetic acid, propionic acid and caproic acid.
Animals ; Zebrafish/metabolism* ; Oxidative Stress ; Lactobacillus plantarum/metabolism* ; Fatty Acids, Volatile/metabolism* ; Probiotics ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/metabolism*

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To analyze the implementation and effectiveness of standardized training for medical aesthetic practitioners in Guangdong province from 2015 to 2023.Methods:Training data from 2015 to 2023 were retrospectively collected from programs organized by the Guangdong Medical Association, including sessions in aesthetic surgery, dermatology, dentistry, traditional Chinese medicine, laser aesthetics, and injectable aesthetics. The training implementation was summarized. A random sample of 120 trainees was selected to complete a questionnaire to assess training outcomes.Results:A total of 45 offline standardized training sessions were held, covering both theoretical and practical instruction. The total training duration reached 180 days, involving 6 776 participant attendances. Aesthetic surgery accounted for the highest number (1 701 attendances), followed by aesthetic dermatology (1 197 attendances). Among specialized technical programs, laser aesthetics (1 708 attendances) and injectable aesthetics (1 578 attendances) had the most participants. Most trainees (5 705 attendances) were physicians from tertiary public general hospitals. A total of 116 questionnaires were collected, with 115 participants expressing satisfaction with the course content, teaching arrangement, and training materials. All trainees passed the skills assessment and received training certificates.Conclusions:The standardized training for medical aesthetic practitioners in Guangdong province from 2015 to 2023 has been well implemented and shows favorable outcomes. It contributes to improving the technical competence of professionals in the medical aesthetics field.

Allergen immunotherapy（AIT）can alter the natural course of allergic diseases through immunomodulatory mechanisms and maintain the efficacy after completion. The induction of immune tolerance by AIT is considered to be effective treatment and the mechanism involves the participation of a variety of immune cells，including effector T cells，B cells，dendritic cells，innate lymphoid cells，mast cells and basophils. Studies have found that a variety of immune cells in peripheral blood changed during AIT treatment and the changes of some immune cells were related to the efficacy of AIT，which may provide some theoretical reference for practical clinical activities and may become potential biomarkers for predicting and evaluating the efficacy of AIT. This article reviews the changes of peripheral blood immune cells in the treatment of AIT.

Objective To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish.Methods The intestinal colonization of L.paracasei E6 labeled by fluorescein isothiocyanate(FITC)in zebrafish was observed under fluorescence microscope.In a zebrafish model of vinorelbine-induced immunosuppression,the immunomodulatory activity of L.paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue(CHT),the number of T-lymphocyte,and the expressions of interleukin-12(IL-12)and interferon-γ(IFN-γ).The contents of short-chain fatty acids(SCFAs)in L.paracasei E6 fermentation supernatant and the metabolites of L.paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics.The immunomodulatory effects of the SCFAs including sodium acetate,sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression.Results After inoculation,green fluorescence of FITC-labeled L.paracasei E6 was clearly observed in the intestinal ball,midgut and posterior gut regions of zebrafish.In the immunocompromised zebrafish model,L.paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT,increased the fluorescence intensity of T-lymphocytes,and promoted the expressions of IL-12 and IFN-γ.Compared with MRS medium,L.paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid,propionic acid and butyric acid,which were also detected in immunocompromised zebrafish following treatment with L.paracasei E6.Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells.Conclusion L.paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.

Objective To investigate the efficacy of Lactobacillus plantarum ZG03(L.plantarum ZG03)for ameliorating oxidative stress in zebrafish.Methods We evaluated the growth pattern of L.plantarum ZG03,observed its morphology using field emission scanning electron microscopy,and assessed its safety and potential efficacy with whole-genome sequencing for genetic analysis.FITC-labeled ZG03 was used to observe its intestinal colonization in zebrafish.In a zebrafish model of 2%glucose-induced oxidative stress,the effect of ZG03 was evaluated by assessing the changes in neutrophils in the caudal hematopoietic tissue(CHT),superoxide dismutase(SOD)activity,reactive oxygen species(ROS)levels,and malondialdehyde(MDA)content.Liquid chromatography-mass spectrometry-based targeted metabolomics was used for analyzing short-chain fatty acids(SCFAs)in the zebrafish,and the antioxidant effects of the key metabolites(acetate,propionate,and caproate)were tested.Results On MRS agar,L.plantarum ZG03 formed circular,smooth,moist,and milky-white colonies with a rod-shaped cell morphology.Genomic analysis revealed abundant sugar metabolism gene clusters.After inoculation of FITC-labeled L.plantarum ZG03 in zebrafish,green fluorescence was clearly observed in the intestinal bulb,mid-intestine,and hind intestine.In zebrafish with glucose-induced oxidative stress,L.plantarum ZG03 significantly reduced ROS levels and the number of neutrophils in the CHT with increased SOD activity.L.plantarum ZG03 significantly increased the content of SCFAs including acetic acid,propionic acid,and caproic acid in zebrafish metabolites.In addition,sodium acetate,sodium propionate,and sodium caproate in the SCFAs significantly increased SOD activity in the zebrafish models.Conclusion L.plantarum ZG03 ameliorates oxidative stress in a glucose-induced zebrafish model through its metabolites,particularly the SCFAs including acetic acid,propionic acid and caproic acid.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To analyze the implementation and effectiveness of standardized training for medical aesthetic practitioners in Guangdong province from 2015 to 2023.Methods:Training data from 2015 to 2023 were retrospectively collected from programs organized by the Guangdong Medical Association, including sessions in aesthetic surgery, dermatology, dentistry, traditional Chinese medicine, laser aesthetics, and injectable aesthetics. The training implementation was summarized. A random sample of 120 trainees was selected to complete a questionnaire to assess training outcomes.Results:A total of 45 offline standardized training sessions were held, covering both theoretical and practical instruction. The total training duration reached 180 days, involving 6 776 participant attendances. Aesthetic surgery accounted for the highest number (1 701 attendances), followed by aesthetic dermatology (1 197 attendances). Among specialized technical programs, laser aesthetics (1 708 attendances) and injectable aesthetics (1 578 attendances) had the most participants. Most trainees (5 705 attendances) were physicians from tertiary public general hospitals. A total of 116 questionnaires were collected, with 115 participants expressing satisfaction with the course content, teaching arrangement, and training materials. All trainees passed the skills assessment and received training certificates.Conclusions:The standardized training for medical aesthetic practitioners in Guangdong province from 2015 to 2023 has been well implemented and shows favorable outcomes. It contributes to improving the technical competence of professionals in the medical aesthetics field.