1.Natural products for the treatment of age-related macular degeneration:New insights focusing on mitochondrial quality control and cGAS/STING pathway
Xuelu XIE ; Shan LIAN ; Wenyong YANG ; Sheng HE ; Jingqiu HE ; Yuke WANG ; Yan ZENG ; Fang LU ; Jingwen JIANG
Journal of Pharmaceutical Analysis 2025;15(5):956-973
Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
2.Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway.
Xuelu XIE ; Shan LIAN ; Wenyong YANG ; Sheng HE ; Jingqiu HE ; Yuke WANG ; Yan ZENG ; Fang LU ; Jingwen JIANG
Journal of Pharmaceutical Analysis 2025;15(5):101145-101145
Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.
3.The effect of cytomegalovirus and EB virus activation on hematopoietic reconstitution after intensive immunosuppressive therapy for severe aplastic anemia
Qian ZHANG ; Hong WANG ; Xiaoli LI ; Miao MIAO ; Hongxia MA ; Yaoyao SHEN ; Nan WEI ; Kai ZOU ; Wanxiu SU ; Jingqiu YU ; Depei WU ; Limin LIU
Chinese Journal of Internal Medicine 2025;64(6):514-521
Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.
4.Clinical and genetic characteristics of fibrocalculous pancreatic diabetes associated with SPINK1 gene mutations in a patient with type 1 diabetes
Wanxia ZHAO ; Hao WANG ; Bo HUANG ; Shiwei LI ; Kailei FENG ; Jingqiu CUI ; Ming LIU
Chinese Journal of Internal Medicine 2025;64(7):675-679
To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.
5.The effect of cytomegalovirus and EB virus activation on hematopoietic reconstitution after intensive immunosuppressive therapy for severe aplastic anemia
Qian ZHANG ; Hong WANG ; Xiaoli LI ; Miao MIAO ; Hongxia MA ; Yaoyao SHEN ; Nan WEI ; Kai ZOU ; Wanxiu SU ; Jingqiu YU ; Depei WU ; Limin LIU
Chinese Journal of Internal Medicine 2025;64(6):514-521
Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.
6.Clinical and genetic characteristics of fibrocalculous pancreatic diabetes associated with SPINK1 gene mutations in a patient with type 1 diabetes
Wanxia ZHAO ; Hao WANG ; Bo HUANG ; Shiwei LI ; Kailei FENG ; Jingqiu CUI ; Ming LIU
Chinese Journal of Internal Medicine 2025;64(7):675-679
To investigate the pathogenic mechanisms of a patient with type 1 diabetes mellitus (T1DM) complicated with fibrocalculous pancreatic diabetes at Tianjin Medical University General Hospital Airport Site in June 2024, clinical and genetic characteristic analyses were performed. Potential pathogenic genes were screened by whole-exome sequencing (WES), and Sanger sequencing validated the identified genetic variants within the family. The proband exhibited elevated blood glucose levels and positivity for tyrosine phosphatase antibodies, suggesting a diagnosis of T1DM. Multiple calcifications in the pancreas were observed in the proband. Genetic testing revealed that the proband carried two variants in the serine peptidase inhibitor Kazal type 1 (SPINK1) gene, namely, c.194+2T>C and c.-215G>A. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.194+2T>C mutation is preliminarily classified as pathogenic, while the c.-215G>A variant is classified as a variant of uncertain significance (VUS). Bioinformatics analysis indicated that the c.194+2T>C variant in the SPINK1 gene results in a truncated protein, affecting the three-dimensional structure and activity of the protein. This mutation is in complete linkage disequilibrium with the c.-215G>A variant, which may have a protective function and influence the clinical phenotype. Given that the patient also has T1DM and FCPD, there should be increased awareness of the co-occurrence of both types of diabetes to prevent misdiagnosis and underdiagnosis.
7.Retrospect on seventy years of Chinese stomatology history research:focusing on papers issued by Chinese Journal of Stomatology
Jingqiu ZHANG ; Rongxia ZHANG ; Qian YU ; Songling WANG ; Jian ZHOU
Chinese Journal of Stomatology 2024;59(12):1185-1192
Chinese Journalof Stomatology has issued eighty papers on Chinese stomatology history in seventy years. According to three stages of the journal,statistics of the quantity and themes of the issued papers are compiled: the number of issued papers increased while the theme shifted from Chinese stomatology history before 1912 to Chinese contemporary stomatology history. Research methods shifted from the comparatively scanty summary or induction on literature and cultural relics materials to multidisciplinary approaches. Early researches testified the achievments of senior scholars such as Zhou Dacheng and Mao Xiejun in the field while research teams represented by colleges and research institutions have published varied research topics in recent years. As the research deepens, platforms for issuing stomatology papers have been expanded and more subjects have been cross-disciplined. Varieties of academic monographs on stomatology history and stomatology education history have been published, among which Zhou Dacheng's Historic textual research of Chinese stomatology can be regarded as a milestone in the field. Comparing with other fields of stomatology, current research on stomatology history still has much more gaps to fill. The academic community should put more emphasis on talent training, discipline construction, research approaches, museum construction, as well as the cooperation between Chinese and western medical sciences so that to assist in the long-term development of the research.
8.Literature review and prospect on oral cognition and disease diagnosis and treatment between Han and Tang dynasties.
Qin GAO ; Mengdi ZHU ; Jiabo WANG ; Songling WANG ; Jian ZHOU ; Jingqiu ZHANG
West China Journal of Stomatology 2023;41(5):604-612
Chinese medicine entered a significant period from foundation to maturity between Han and Tang dynasties when the Chinese traditional stomatology was a key stage. Sorting and analysis of existing literature and research outcomes have showed that current research on stomatology between Han and Tang dynasties focuses on oral physiology, pathology, diagnosis and treatment, and health care. It also involves stomatology history and explanation of termino-logies related to mouth and teeth recorded in medical books, use of simple methods, and thinking with citation and analysis of literature simply listed and reasoning preliminarily deducted. From the macro perspective, current research has not unveiled the whole picture of stomatology between the two dynasties and left a series of key issues unresolved. Thus, new methods should be developed and employed to carry out medical research on stomatology between Han and Tang dynasties given that is has a prosperous future.
Mouth
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Oral Medicine
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Cognition
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China
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Medicine, Chinese Traditional
9.Study on related factors and effect relationship of hyperuricemia in health check-up participants
Lin ZHUO ; Siting CHEN ; Yihuan GAO ; Hang LU ; Xiuying WANG ; Lang ZHUO ; Jingqiu CUI
Chinese Journal of Endocrinology and Metabolism 2022;38(10):880-886
Objective:To investigate the influencing factors of hyperuricemia(HUA) and explore early intervention of metabolic diseases.Methods:A total of 70 523 participants were selected from the database of check-ups in 2016. Univariate analysis and logistic regression analysis were used to identify related factors of HUA. Correspondence analysis was performed for the aggregation of different levels of uric acid(UA) and related factors. The mediating effect of mean blood pressure(MBP) between abnormal metabolic indicators and abnormal renal function was tested.Results:The age, sex, occupation, body mass index(BMI), systolic blood pressure, diastolic blood pressure, blood urea nitrogen(BUN), creatinine(Cr), estimated glomerular filtration rate(eGFR), fasting plasma glucose(FPG), total cholesterol(TC), triacylglycerol(TG), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol, plasma viscosity were significantly related to HUA( P<0.001). Logistic regression analysis showed that youth, male, hypertension, TC, TG, and Cr were risk factors for HUA, while HDL-C was a protective factor for HUA( P<0.001). Correspondence analysis showed that during the gradual increase of UA, TC was the first to appear abnormal, followed by hypertension and TG, and the increase of Cr appeared last. Mediating effect showed that in changes of UA, the mediating effects of MBP on TC, TG, and HDL-C were 36.35%, 12.63%, and 9.41%, respectively. In changes of eGFR, the mediating effects of MBP on TC, TG and HDL-C were 30.20%, 27.70%, and 6.13%, respectively. Conclusions:UA is positively correlated with blood pressure, TC, and TG, and inversely with HDL-C. TC and TG have an impact on renal impairment, in which MBP plays a mediating role.
10.Comparison on Skin Permeability of Corydalis Rhizoma Total Alkaloid Patches at Shenque Acupoint and Non-acupoint Administration
Mingrui JIANG ; Zhicheng WANG ; Zhuzhu YUE ; Jingqiu ZHANG ; Peihua WANG ; Guimei ZHANG ; Huinan WANG ; Ziye YANG ; Mengyu CHEN ; Yingzi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(19):148-153
ObjectiveTo compare the differences in resistance and structure of skin between acupoints and non-acupoints, and to study the difference in skin permeability characteristics of Corydalis Rhizoma total alkaloid patches (CTTP) after administration at Shenque acupoint and non-acupoint, so as to provide experimental support for its clinical acupoint application to prevent and treat chronic pain. MethodTaking corydaline (CD), tetrahydropalmatine (THP) and corydalis L (CDL) as evaluation indexes, and the quantitative analysis was carried out by high performance liquid chromatography (HPLC). The mobile phase was methanol-0.04 mol·L-1 phosphoric acid aqueous solution (70∶30, pH 6.0 adjusted with triethylamine), the detection wavelength was 281 nm. In vitro transdermal test in Franz diffusion cell and in vivo transdermal test were used to study the skin permeability characteristics of CTTP through Shenque acupoint and non-acupoint administration. At the same time, the skin resistance between Shenque acupoint and non-acupoint was measured before and after the administration, and the distribution of the drug in each layer of the skin was compared by freezing sectioning, and visual verification was performed with fluorescence inverted microscope. ResultAfter 24 h of administration, the results of in vivo and in vitro experiments showed that the cumulative permeation and retention of CD, THP and CDL at Shenque acupoint skin were higher than those at non-acupoint skin (P<0.05, P<0.01), the skin resistance of Shenque acupoint was lower than that of non-acupoint at all time points. The fluorescence microscopic observation results showed that the drug content of each layer of the skin was all Shenque acupoint>non-acupoint, indicating that the skin of Shenque acupoint had better effect on drug penetration and storage than non-acupoint. ConclusionThe 24 h cumulative permeation and retention of CTTP in Shenque acupoint skin are higher than those in non-acupoint skin, and the mechanism may be related to the thin skin, low electrical resistance and large number of hair follicle bodies at Shenque acupoint.

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