BACKGROUND:The diabetic microenvironment can cause excessive M1 polarization of macrophages,and this hyperglycemic inflammatory state can inhibit osteogenic differentiation of bone marrow mesenchymal stem cells,thus affecting the healing of diabetic bone defects.Studies have indicated that mogroside V possesses anti-inflammatory,antioxidant,and hypoglycemic properties.However,its potential to modulate M1 polarization of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition remains unclear. OBJECTIVE:To explore the effect of mogroside V on regulating M1 macrophage polarization and its effect on osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition. METHODS:Murine diabetic models were established using C57BL/6 mice.Bone marrow-derived macrophages were isolated from tibia and fibula of normal and diabetic mice,and cultured in low-glucose and high-glucose media.Then M1 polarization of bone marrow-derived macrophages was induced using lipopolysaccharide and interferon-γ.Bone marrow-derived macrophages were treated with 160,320,and 640 μmol/L mogroside V.Flow cytometry was employed to determine the proportion of F4/80+CD86+cells.qRT-PCR was utilized to assess mRNA expression levels of inducible nitric oxide synthase,interleukin 1β,and interleukin 6.ELISA was employed to evaluate tumor necrosis factor-α secretion in bone marrow-derived macrophage supernatants.Bone marrow mesenchymal stem cells were isolated from tibia and fibula of C57BL/6 suckling mice,and induced osteogenic differentiation using low-or high-glucose osteogenic induction medium.Bone marrow mesenchymal stem cells were treated with M1 macrophage-conditioned mediums with or without 320 μmol/L mogroside V in osteogenic differentiation process.qRT-PCR was employed to assess the mRNA expression of alkaline phosphatase,Runt-related factor 2,osteocalcin,and osteopontin on day 14 after osteogenic induction.Alizarin red staining and quantitative analysis were conducted to evaluate calcium deposition on day 21 after osteogenic induction. RESULTS AND CONCLUSION:(1)Flow cytometry results showed that with the treatment of 320 and 640 μmol/L mogroside V,the proportion of F4/80+CD86+bone marrow-derived macrophages was significantly lower than that in the high-glucose control group(P<0.05).(2)qRT-PCR results showed that with the treatment of 160,320,and 640 μmol/L mogroside V,the mRNA expression levels of inducible nitric oxide synthase and interleukin 6 were significantly lower than that in the high-glucose control group(P<0.05).With the treatment of 320 and 640 μmol/L mogroside V,the mRNA expression level of interleukin 1β was significantly lower than that in the high-glucose control group(P<0.05).(3)ELISA results exhibited that with the treatment of 160,320,and 640 μmol/L mogroside V,the tumor necrosis factor-α secretion level was significantly lower than that in the high-glucose control group(P<0.05).(4)With the treatment of 320 μmol/L mogroside V,calcium salt deposition was increased in bone marrow mesenchymal stem cells under high glucose and inflammatory conditions(P<0.05),and the mRNA relative expression levels of alkaline phosphatase,Runt-related factor 2,and osteopontin were increased(P<0.05).These findings indicate that mogroside V can promote osteogenic differentiation of bone marrow mesenchymal stem cells by inhibiting the M1 polarization of bone marrow-derived macrophages under high glucose and inflammatory conditions and reducing the generation of inflammatory factors.

The theory of "Yang transforming Qi while Yin constituting form" in the Huangdi's Internal Classic is derived from the application， transformation， movement， and balance of Tao. It is highly condensed， revealing the true meaning of Tao and guiding the changes and progress of all natural things， including diseases. Therefore， the appearance of various physical diseases is the manifestation of Yin-Yang Qi transformation. Sweat pore， formed by the Qi transformation of Yin and Yang， is the nourishing and regulating system. It serves as the hub and channel， assisting in the flow and transformation of Qi， facilitating the exchange of material， energy， and information with the outside world. With sweat pore as the hub and based on the macro-control and holistic thinking of "Yang transforming Qi while Yin constituting form"， this paper explores the microscopic mechanisms underlying chronic liver disease. In combination with the roles of mitochondria， exosomes， and the ultraliver sieve structure in the formation and progression of chronic liver disease， this paper elucidates the close internal relationship between the disease's initial quality， symptom signs， and its physiological and pathological functions under the guidance of this theory. Modern studies have shown that autophagy， intestinal flora disorders， glucose and lipid metabolism disturbances， activation of inflammatory factors， ferroptosis， and other microscopic pathological mechanisms are involved in the occurrence and development of chronic liver disease. The common connotation of the Yin-Yang concept in traditional Chinese medicine （TCM） and the pathological mechanisms in modern medicine is deeply analyzed. The corresponding relevant microscopic mechanisms and the guiding role of the theory of "Yang transforming Qi while Yin constituting form-sweat pore" in the management of chronic liver disease are summarized. Wind medicine promotes growth and transformation through sweat pore. The combination of pungent and sweet medicines facilitates Yang and disperse Yin. The formulas， combining the characteristics of wind medicine and pungent and sweet medicines， fit the principle of "Yang transforming Qi while Yin constituting form-sweat pore". This paper combines both macro and micro perspectives to explain the scientific connotation and microscopic mechanisms of chronic liver disease based on the theory of "Yang transforming Qi while Yin constituting form-sweat pore"， and explore the prevention and treatment of chronic liver disease through the principles， methods， prescriptions， and medicines featured by combination of pungent and sweet medicines， facilitating Yang， activating sweat pore， and dispersing Yin， providing new ideas and reference for the clinical treatment of chronic liver disease.

OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

Objective:To observe the signal intensity and homogeneity of subretinal hyperreflective material (SHRM) in neovascular age-related macular degeneration (nAMD) and preliminarily analyze its relationship with macular neovascularization (MNV) morphology.Methods:A prospective cross-sectional observational study. Forty-six eyes of 46 nAMD patients with SHRM who initially visited Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 2022 to March 31, 2023 were enrolled. Optical coherence tomography (OCT) examination was performed according to a standardized protocol, and 3D Slicer software was used for three-dimensional reconstruction of SHRM lesions. Signal intensity was represented by the mean gray value (mGV) of the three-dimensional lesion area, and homogeneity was represented by the standard deviation of gray values (GV-SD). OCT angiography (OCTA) was used to scan the 6 mm×6 mm area of the macula. FIJI and Angio Tool software were used to measure MNV vascular network total area, perimeter, maximum and minimum diameters, maximum vessel diameter, vascular component area, total number of vascular network junctions and endpoints, vessel dispersion, and mean lacunarity. The ratio of maximum to minimum diameter of the vascular network, average vessel length, vessel density, and vessel fractal index were calculated. Using the mean mGV of the total sample as the standard, the eyes were divided into low-density SHRM group (20 eyes) and high-density SHRM group (26 eyes); using the mean GV-SD of the total sample as the standard, the eyes were divided into homogeneous SHRM group (29 eyes) and non-homogeneous SHRM group (17 eyes). The morphological characteristics of MNV between groups were compared. Independent samples t-test or Mann-Whitney U test was used for between-group comparisons; a multivariate regression model was established to analyze independent factors affecting SHRM signal characteristics. Results:Among the 46 eyes of 46 patients, there were 26 eyes of 26 males (56.52%, 26/46) and 20 eyes of 20 females (43.48%, 20/26). The mean age was (65.61±7.50) years. The average vessel length and vessel dispersion in the high-density SHRM group and low-density SHRM group were (6.88±4.56), (11.30±6.31) mm ?1 and 41.30±67.26, 13.22±11.34, respectively. Compared with the low-density SHRM group, the high-density SHRM group had significantly lower average vessel length ( t=2.645) and higher vessel dispersion ( t=?2.090), with statistically significant differences ( P=0.012, 0.046). Compared with the homogeneous SHRM group, the non-homogeneous SHRM group had significantly higher total area ( t=?2.338), maximum diameter ( t=?3.137), and minimum diameter ( t=?2.173), with statistically significant differences ( P<0.05). The total number of vascular network junctions in the non-homogeneous SHRM group and homogeneous SHRM group were (90.71±67.34) and (49.34±41.91), respectively; the non-homogeneous SHRM group had significantly more junctions than the homogeneous SHRM group, with a statistically significant difference ( t=?2.286, P=0.032). Multivariate regression analysis showed that average vessel length was an independent factor affecting SHRM intensity (odds ratio=0.819, 95% confidence interval 0.705-0.951, P=0.009); there were no independent vascular indicators affecting SHRM reflectivity homogeneity ( P>0.05). Conclusion:In nAMD, compared with low-density SHRM, high-density SHRM has significantly lower average vessel length and higher vessel dispersion; compared with homogeneous SHRM, non-homogeneous SHRM has a larger spatial dimension of the vascular network.

Objective To investigate the therapeutic mechanism of Thesium chinense Turcz.(TCT)for antibiotic-associated diarrhea(AAD).Methods Network pharmacology,KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD,the key signaling pathways and the binding between the active components in TCT and the core protein targets.In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride,the effects of daily gavage of 1%carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg(n=10)on body weight and diarrhea were observed.HE staining,ELISA,16S rRNA sequencing,and Western blotting were used to examine pathologies,expression levels of IL-6 and TNF-α,changes in gut microbiota,and protein expressions of EGFR,p-EGFR,PI3K,p-PI3K,Akt,and p-Akt in the colon tissues of the mice.Results We identified a total of 66 active components of TCT and 68 core targets including EGFR,STAT3 and PIK3CA.KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway.Molecular docking showed that EGFR had the highest binding affinity with coniferin,and the EGFR-coniferin complex maintained a stable conformation at 10 ns,whose stability was also confirmed by Gibbs free energy analysis.In the mouse models of AAD,treatment with TCT significantly improved colonic tissue morphology,decreased colonic levels of TNF-α and IL-6,increased gut microbiota diversity,and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides.TCT treatment also markedly reduced protein expressions of p-EGFR,p-PI3K and p-Akt in the colon tissues of the mice.Conclusion TCT can alleviate AAD in mice by modulating gut microbiota composition,regulating the EGFR/PI3K/Akt signaling pathway,and reducing TNF-α and IL-6 expressions.

Aplastic anemia is a rare and life-threatening bone marrow failure that is becoming more common and tends to affect younger individuals.Traditional Chinese medicine has a long history of preventing and treating asthenia and blood syndrome.Its treatment of aplastic anemia involves coordinated regulation through multiple components,targets,and channels.The article classifies and elaborates on the therapeutic effects of traditional Chinese medicine compounds and their components on aplastic anemia.As well as the expression of related factors from three aspects:hematopoietic stem/progenitor cells,the immune system,and bone marrow microenvironmental abnormalities.It also analyzes the frequency and meridian of commonly used drugs in traditional Chinese medicine compounds.Deficiency tonifying drugs were found to be the most frequently used treatment for aplastic anemia,which is consistent with the deficiency-based nature of the disease.The related organs affected are the liver,spleen,and kidney.This paper reviews the mechanism of aplastic anemia and the preventive and therapeutic effects of traditional Chinese medicine.The study is of great significance for the follow-up research on traditional Chinese medicine in improving aplastic anemia.

Aplastic anemia is a rare and life-threatening bone marrow failure that is becoming more common and tends to affect younger individuals.Traditional Chinese medicine has a long history of preventing and treating asthenia and blood syndrome.Its treatment of aplastic anemia involves coordinated regulation through multiple components,targets,and channels.The article classifies and elaborates on the therapeutic effects of traditional Chinese medicine compounds and their components on aplastic anemia.As well as the expression of related factors from three aspects:hematopoietic stem/progenitor cells,the immune system,and bone marrow microenvironmental abnormalities.It also analyzes the frequency and meridian of commonly used drugs in traditional Chinese medicine compounds.Deficiency tonifying drugs were found to be the most frequently used treatment for aplastic anemia,which is consistent with the deficiency-based nature of the disease.The related organs affected are the liver,spleen,and kidney.This paper reviews the mechanism of aplastic anemia and the preventive and therapeutic effects of traditional Chinese medicine.The study is of great significance for the follow-up research on traditional Chinese medicine in improving aplastic anemia.

Objective:To observe the signal intensity and homogeneity of subretinal hyperreflective material (SHRM) in neovascular age-related macular degeneration (nAMD) and preliminarily analyze its relationship with macular neovascularization (MNV) morphology.Methods:A prospective cross-sectional observational study. Forty-six eyes of 46 nAMD patients with SHRM who initially visited Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 2022 to March 31, 2023 were enrolled. Optical coherence tomography (OCT) examination was performed according to a standardized protocol, and 3D Slicer software was used for three-dimensional reconstruction of SHRM lesions. Signal intensity was represented by the mean gray value (mGV) of the three-dimensional lesion area, and homogeneity was represented by the standard deviation of gray values (GV-SD). OCT angiography (OCTA) was used to scan the 6 mm×6 mm area of the macula. FIJI and Angio Tool software were used to measure MNV vascular network total area, perimeter, maximum and minimum diameters, maximum vessel diameter, vascular component area, total number of vascular network junctions and endpoints, vessel dispersion, and mean lacunarity. The ratio of maximum to minimum diameter of the vascular network, average vessel length, vessel density, and vessel fractal index were calculated. Using the mean mGV of the total sample as the standard, the eyes were divided into low-density SHRM group (20 eyes) and high-density SHRM group (26 eyes); using the mean GV-SD of the total sample as the standard, the eyes were divided into homogeneous SHRM group (29 eyes) and non-homogeneous SHRM group (17 eyes). The morphological characteristics of MNV between groups were compared. Independent samples t-test or Mann-Whitney U test was used for between-group comparisons; a multivariate regression model was established to analyze independent factors affecting SHRM signal characteristics. Results:Among the 46 eyes of 46 patients, there were 26 eyes of 26 males (56.52%, 26/46) and 20 eyes of 20 females (43.48%, 20/26). The mean age was (65.61±7.50) years. The average vessel length and vessel dispersion in the high-density SHRM group and low-density SHRM group were (6.88±4.56), (11.30±6.31) mm ?1 and 41.30±67.26, 13.22±11.34, respectively. Compared with the low-density SHRM group, the high-density SHRM group had significantly lower average vessel length ( t=2.645) and higher vessel dispersion ( t=?2.090), with statistically significant differences ( P=0.012, 0.046). Compared with the homogeneous SHRM group, the non-homogeneous SHRM group had significantly higher total area ( t=?2.338), maximum diameter ( t=?3.137), and minimum diameter ( t=?2.173), with statistically significant differences ( P<0.05). The total number of vascular network junctions in the non-homogeneous SHRM group and homogeneous SHRM group were (90.71±67.34) and (49.34±41.91), respectively; the non-homogeneous SHRM group had significantly more junctions than the homogeneous SHRM group, with a statistically significant difference ( t=?2.286, P=0.032). Multivariate regression analysis showed that average vessel length was an independent factor affecting SHRM intensity (odds ratio=0.819, 95% confidence interval 0.705-0.951, P=0.009); there were no independent vascular indicators affecting SHRM reflectivity homogeneity ( P>0.05). Conclusion:In nAMD, compared with low-density SHRM, high-density SHRM has significantly lower average vessel length and higher vessel dispersion; compared with homogeneous SHRM, non-homogeneous SHRM has a larger spatial dimension of the vascular network.

ObjectiveTo analyze the epidemic characteristics of measles and rubella in Pudong New Area of Shanghai from 2013 to 2022， and to provide data support for the elimination of measles and rubella. MethodsEnzyme linked immunosorbent assay was used to detect IgM antibodies in serum samples. The sequence of 630 nucleotides at the C-terminal of N gene of measles virus was amplified by reverse transcription-polymerase chain reaction and the phylogenic tree was constructed. ResultsA total of 1 529 suspected cases of measles were detected from 2013 to 2022， among which the positive rate of measles IgM antibody was 33.55% （513/1 529）. The highest positive rate （20.73%） was from March to May ， and the positive rate of rubella IgM antibody was 6.80% （104/1 529）. The positive rate of both IgM was higher in males than that in females （P<0.05）. The IgM against measles was mainly detected in 0‒ years old （63.16%， 96/152） and 20‒ years old （45.61%， 161/353）. The IgM against rubella was mainly detected in 10‒20 years old （27.27%， 18/66）. The IgM antibody could be detected more easily from 4 to 28 days after eruption， and the IgM antibody positive rate of measles/rubella from 2020 to 2022 was significantly lower than previous years （2013‒2019）. There were 2 D8 genotype strains， and the rest were H1a gene subtypes. ConclusionThe positive rate of IgM antibodies against measles/rubella in Pudong New Area of Shanghai decreased significantly. People aged 0‒ years and 20‒ years old are more susceptible to measles， and rubella is concentrated in 10‒ years old. It is necessary to strengthen the vaccination of school-age children， in order to achieve the goal of eliminating measles. The age group with high risk of exposure should be checked for vaccination status to ensure the enhanced immunization， and the surveillance of imported measles cases should be strengthened.