1.Research Progress on the Correlation Between Mitophagy and Vascular Cognitive Impairment
Yan LIU ; Xingang DONG ; Xiaoyuan WANG ; Gege QI ; Yiqin REN ; Lianpeng ZHOU ; Hui LI ; Suqing ZHANG ; Weifeng LI
Medical Journal of Peking Union Medical College Hospital 2025;16(2):338-349
Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.
2.Preliminary study on the biological characteristics of heat shock cognate protein 20 of Schistosoma japonicum
Xingang YU ; Kaijian YUAN ; Yilong LI ; Xuanru MU ; Hui XU ; Qiaoyu LI ; Wenjing ZENG ; Zhiqiang FU ; Yang HONG
Chinese Journal of Schistosomiasis Control 2025;37(3):294-303
Objective To clone and express the heat shock cognate protein 20 (SjHsc20) of Schistosoma japonicum, and to preliminarily investigate its biological characteristics. Methods The target fragment of the SjHsc20 gene was amplified using PCR assay and cloned into the pET-28a(+) expression plasmid to generate the recombinant expression vector pET-28a(+)-SjH-sc20, which was then transformed into Escherichia coli BL21 (DE3) competent cells. The recombinant SjHsc20 (rSjHsc20) protein was induced with isopropyl β-D-thiogalactopyranoside (IPTG) and purified, and the expression of the rSjHsc20 protein was checked with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The immunogenicity of the rSjHsc20 protein was detected using Western blotting, and the transcriptional levels of SjHsc20 were quantified in S. japonicum worms at different developmental stages and in male and female adult worms using real-time quantitative PCR (RT-qPCR) assay. Thirty female BALB/c mice at ages 6 to 8 weeks were divided into three groups, including the rSjHsc20 immunization group, the PBS control group, and the ISA 206 adjuvant group, of 10 mice in each group. Mice in the rSjHsc20 immunization group were subcutaneously immunized with 20 μg rSjHsc20 on days 1, 15 and 31, and animals in the PBS control group were subcutaneously injected with the same volume of PBS on days 1, 15 and 31, while mice in the ISA 206 adjuvant group were subcutaneously immunized with the same volume of ISA 206 adjuvant on days 1, 15 and 31, respectively. All mice in each group were infected with (40 ± 2) S. japonicum cercariae via the abdomen 14 day following the last immunization. Levels of serum specific IgG and its subtypes IgG1 and IgG2 antibodies against rSjHsc20, and the serum titers of anti-rSjHsc20 antibody were detected in mice using indirect enzyme-linked immunosorbent assay (ELISA). All mice were sacrifice 42 days post-infection, and S. japonicum worms were collected from the hepatic portal vein and counted. The eggs per gram (EPG), worm burden reductions and egg burden reductions were estimated to evaluate the protective efficacy of the rSjHsc20 protein. Results The SjHsc20 gene had an open reading frame (ORF) with 756 bp in length and encoded 252 amino acids, and the rSjHsc20 protein had a relative molecular mass of approximately 29 kDa. The rSjHsc20 protein was recognized by the serum of mice infected with S. japonicum and the serum of mice immunized with the rSjHsc20 protein, indicating that rSjHsc20 had a good immunogenicity. There was a significant difference in the transcriptional levels of the SjHsc20 gene among the 7-day (1.001 4 ± 0.065 7), 12-day (2.268 3 ± 0.129 2), 21-day (1.378 5 ± 0.160 4), 28-day (1.196 4 ± 0.244 0), 35-day (1.646 3 ± 0.226 1), 42-day worms of S. japonicum (1.758 0 ± 0.611 1) (F = 38.45, P < 0.000 1), and the transcriptional level of the SjHsc20 gene was higher in the 12-day worms than in worms at other developmental stages (all P values < 0.000 1). The serum levels of anti-rSjHsc20 IgG antibody were 0.106 6 ± 0.010 7, 0.108 3 ± 0.010 4, and 0.553 2 ± 0.069 1 in the PBS control group, ISA 206 adjuvant group, and rSjHsc20 immunization group following the last immunization, respectively, and the serum levels of IgG1 antibody were 0.137 3 ± 0.054 0, 0.181 1 ± 0.096 8, and 1.765 8 ± 0.221 1, while the levels of IgG2a antibody were 0.280 3 ± 0.197 6, 0.274 0 ± 0.146 3, and 1.560 4 ± 0.106 0, respectively. There were significant differences in the serum levels of anti-rSjHsc20 IgG (F = 397.70, P < 0.000 1), IgG1 (F = 401.00, P < 0.000 1) and IgG2a antibodies (F = 229.70, P < 0.000 1) among the three groups, and the serum levels of anti-rSjHsc20 IgG, IgG1 and IgG2a antibodies were higher in the rSjHsc20 immunization group than in the PBS control group and the ISA 206 adjuvant group (all P values < 0.000 1). There was a significant difference in the IgG1/IgG2a ratio among the rSjHsc20 immunization group (1.177 2 ± 0.143 6), the PBS control group (0.428 4 ± 0.199 8) and the ISA 206 adjuvant group (0.559 9 ± 0.181 1) (F = 43.97, P < 0.000 1), and the IgG1/IgG2a ratio was > 1 in the rSjHsc20 immunization group, which was higher than in the PBS control group and the ISA 206 adjuvant group (both P values < 0.000 1). The titers of serum anti-rSjHsc20 antibody were all above 1∶16 384 in the rSjHsc20 immunization group following immunizations on days 1, 15 and 31, indicating that the rSjHsc20 protein had a strong immunogenicity. The mean worm burdens were (16.60±5.75), (15.80±5.58) worms per mouse and (14.40±5.75) worms per mouse in the PBS control group, the ISA 206 adjuvant group and the rSjHsc20 immunization group 42 days post-infection with S. japonicum cercariae (F = 0.50, P > 0.05), and the EPG were 68 370 ± 22 690, 67 972 ± 19 502, and 41 075 ± 13 251 in the PBS control group, the ISA 206 adjuvant group and the rSjHsc20 immunization group (F = 4.55, P < 0.05), with lower EPG in the PBS control group and the ISA 206 adjuvant group than in the rSjHsc20 immunization group (both P values < 0.05). Immunization with the rSjHsc20 protein resulted in a worm burden reduction of 13.25% and an egg burden reduction of 39.92% relative to the PBS control group. Conclusions SjHsc20 is successfully cloned and expressed, and the rSjHsc20 protein induces partial immunoprotective effects in mice, which provides a basis for deciphering the biological functions of SjHsc20 and assessing the potential of SjH-sc20 as a vaccine candidate.
3.Effect of Curcumin on Promoting Skin Wound Healing in Diabetes Mice
Jin ZHANG ; Xingang CUI ; Yanzhao ZHU ; Meng SU ; Ying BEI ; Yu HUANG ; Meiyun LI ; Yan WU
Herald of Medicine 2024;43(2):167-174
Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P<0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P<0.01)and significantly reduced expression of CD86(P<0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P<0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.
4.Development and preliminary application of a multiplex PCR assay for simultaneous detection of four intestinal parasites in goats
Yilong LI ; Xuanru MU ; Hui XU ; Xiaoping LUO ; Runzi YU ; Xinyi XU ; Linlin YANG ; Xingang YU ; Yang HONG
Chinese Journal of Schistosomiasis Control 2024;36(4):376-383
Objective To develop a multiplex PCR assay for simultaneous detection of four intestinal parasites, including Giardia duodenalis, Cryptosporidium parvum, Enterocytozoon bieneusi and Moniezia, and to preliminarily evaluate its detection efficiency. Methods Four pairs of specific primers were designed based on the conserved sequences of the corresponding genes of G. duodenalis (GenBank accession number: XM_001710026.2), C. parvum (GenBank accession number: XM_626998.1), E. bieneusi (GenBank accession number: KJ719492.1) and Moniezia (GenBank accession number: OM296991.1) retrieved from the GenBank database, and a multiplex PCR assay for simultaneous detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia was developed and optimized. A total of 116 fresh goat stool samples were collected from four goat farms in Zhanjiang City, Guangdong Province during the period from October to December 2022, including 96 samples used for evaluating the detection efficacy of the multiplex PCR assay, and 20 samples as baseline controls for sample testing. Genomic DNA extracted from 96 goat stool samples was tested using the single-target PCR assay and the developed multiplex PCR assay, and the sensitivity, specificity, positive predictive value, and negative predictive value of the multiplex PCR assay were evaluated for detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia DNA in goat stool samples with the single-target PCR assay as the gold standard. Results The multiplex PCR assay developed in this study allowed simultaneous amplification of specific gene fragments of G. duodenalis, C. parvum, E. bieneusi and Moniezia, with 1 400, 755, 314 bp and 585 bp in sizes, respectively, and the detection limit was 102 and higher copies of parasite DNA clones, while the multiplex PCR assay was negative for gene amplification of Schistosoma japonicum, Fasciola hepatica, Echinococcus granulosus, Blastocystis hominis and Homalogaster paloniae. Single-target PCR assay and the developed multiplex PCR assay were employed to test DNA samples extracted from 96 goat stool samples, and single-target PCR assay tested positive in 40 goat stool samples (41.67%), including 39 positive samples tested with the multiplex PCR assay, with a mean coincidence rate of 97.50% (39/40). The multiplex PCR assay tested positive for G. duodenalis DNA in 26 goat stool samples (27.10%), C. parvum DNA in 22 samples (22.90%), E. bieneusi DNA in 24 samples (25.00%), and Moniezia in 9 samples (9.40%), which was consistent with the detection using the single-target PCR assay. The sensitivity, negative predictive value, and positive predictive value of the multiplex PCR assay were 96.15%, 95.83%, 100.00% and 100.00%, 98.90%, 98.92%, 100.00% and 100.00%, 100.00%, 100.00%, 100.00% and 100.00% for detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia DNA in goat stool samples, respectively, if the single-target PCR assay served as the gold standard. Conclusion A highly sensitive and specific multiplex PCR assay has been developed for simultaneous detection of G. duodenalis, C. parvum, E. bieneusi and Moniezia in goats, which is suitable for rapid, large-scale screening of intestinal parasites in sheep stool samples.
5.Exploring the relationship between red blood cell levels and emotional regulation through the miR191-Riok3-Mxi1 pathway
Da Zhang ; Xiaoqing Zhang ; Li Yang ; Yan Zhao ; Xingang Hu
Journal of Traditional Chinese Medical Sciences 2024;11(1):101-110
Objective:
To assess emotional fluctuations, physical and mental health status, and indicators closely related to red blood cells, such as RIO kinase 3 (Riok3), MAX interactor 1 (Mxi1), and microRNA 191 (miR191), in participants with different levels of red blood cells.
Methods:
Participants who underwent physical examinations at Dongfang Hospital between April and October 2019 were divided into healthy, blood deficiency, and anemia groups (30 individuals in the healthy and blood deficiency group respectively, and 13 in the anemia group). The physical and mental conditions of the participants were evaluated through questionnaires, and emotional fluctuations were assessed through an emotion-inducing experiment, in which participants watched video segments designed to induce specific emotions. Relative expression levels of miR191, Riok3, and Mxi1 from venous blood samples were also determined.
Results:
The main psychological factors identified in the anemia and blood deficiency groups were obsessive-compulsive symptoms, depression, anxiety, and other negative emotions. Relative gene expression levels indicated that miR191 was upregulated and Riok3 and Mxi1 were downregulated in both the blood deficiency and anemia groups. Regarding the emotional score of disgust on video stage, the main effect was significant (F = 335.58, P < .001), which showed that watching the three videos caused participants to have a dominant emotion, and there is a difference on group (F = 5.35, P = .01), with higher disgust scores in the anemia and blood deficiency groups. The symptoms of blood deficiency and anemia, such as weakness in limbs were significantly negatively correlated with Riok3 and Mxi1 expression (r = −0.38 and −0.31 respectively), but was significantly positively correlated with miR191 expression (r = 0.29).
Conclusion
We determined that a close relationship exists between red blood cell levels and emotional status. Our findings suggest that individuals with anemia and blood deficiency are more likely to experience psychological problems and negative emotions, particularly disgust. We also demonstrate that emotional regulation is related to mir191-Riok3-Mxi1 pathway activity, identifying these pathway components are potential targets for genetic therapies in combination with psychological therapy.
6.Overview of traditional Chinese medicine's role in regulating the mechanism of regulatory cell death in vascular dementia
Hui LI ; Xingang DONG ; Weifeng LI
Chinese Journal of Comparative Medicine 2024;34(9):146-156
Vascular dementia(VD)is a neurodegenerative disease caused by brain injury.Research on the processes leading to its occurrence is lacking depth.In recent years,it has been proposed that regulatory cell death(RCD)mechanisms,including apoptosis,pyroptosis,autophagy,ferroptosis,and cuproptosis,are related to the pathological mechanisms of VD.Therefore,studies aiming to explain the links between the mechanisms of regulatory death and the pathology of VD would be beneficial to our understanding of VD.This article provides a review of the roles of five mechanisms of RCD in VD and summarizes the recent progress made in researching the treatment of VD with traditional Chinese medicine,providing a resource for the development of new traditional Chinese medicine drugs.
7.Epidemiological investigation of caprine enterovirus infection in Jiangsu Province
Xuhang CAI ; Wenliang LI ; Jizong LI ; Siyuan LI ; Li MAO ; Xingang XU ; Bin LI
Chinese Journal of Veterinary Science 2024;44(6):1140-1147
Caprine enterovirus(CEV)is one of the most important infectious diarrheal diseases for goats.In order to understand the prevalence of CEV in different areas of Jiangsu province,410 goat fecal samples(212 diarrhea and 198 non-diarrhea samples)were collected from goat farms in 8 re-gions.127 CEV positive samples were detected by RT-PCR,and the positive rates varied greatly from 12.50%to 62.50%among different areas,with a total positive rate as 30.98%.Through the significance analysis of the positive rate of diarrhea and non-diarrhea samples,CEV was found to be one of the important pathogens causing diarrhea in goats.The results of homology and genetic evolution analysis for the 5'-UTR sequences showed that the EV-G5、G7、G21、G22 and G23 were epidemic types in Jiangsu province,and G21-G23 are new found CEV types.The homologies of 5'-UTR,VP1 and 2AB genes with the classical CEV strains in China were 78.6%-95.8%,56.9%-95.0%and 77.9%-98.4%,respectively.Of these sequences,the 5'-UTR and 2AB gene of HaiMen-SJH strain was significantly different from other sequences,and belonged to an independent branch in the genetic evolution trees.According to the results of epidemiological survey,the infection of CEV was widespread in most areas of Jiangsu province,and the epidemic types and situation varied in different areas.This study will enrich the epidemiological data of CEV in China,and provide the-oretical basis for the targeted prevention and control of new enterovirus infections in sheep.
8.Clinicopathological study of 24 cases of monkeypox virus infection-related rashes
Yanhua PANG ; Xingang ZHOU ; Man LI ; Xiangmei CHEN ; Liang ZHANG ; Kun YANG ; Ting LIU ; Jiamin CHEN ; Simeng LIU ; Weimin TONG ; Jiangyang LU ; Peng WANG
Chinese Journal of Pathology 2024;53(10):1011-1017
Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.
9.Progress in the treatment of femoral head fracture combined with posterior hip dislocation
Xingang JIANG ; Zhaopeng GAO ; Bo CHANG ; Li LIU ; Haibin WANG
Chinese Journal of Orthopaedics 2024;44(22):1489-1495
Femoral head fracture combined with posterior hip dislocation is a serious traumatic condition. Conservative treatment has a long time of bed rest, and may cause muscle apraxia atrophy, hypostatic pneumonia, deep vein thrombosis of the lower limbs, or pulmonary embolism, which has poor clinical efficacy. Therefore, surgical treatment is the first choice for femoral head fracture combined with posterior hip dislocation. The direct anterior approach of the hip can better expose Pipkin type I and type II femoral head fractures without the need to dislocate the hip completely. However, the disadvantage is that it destroys the structural integrity of the anterior hip joint, which increases the risk of femoral head necrosis and heterotopic ossification to a certain extent. The medial approach can also be chosen for Pipkin type I and II fractures, but it is important to avoid damaging the integrity of the fascial layer, some small vascular branches can be ligated, and injury to the medial rotary femoral artery should be avoided. The lateral approach is considered to be an effective treatment for Pipkin type III fractures, but there is limited exposure of the posterior acetabular injury and a risk of injury to the superior gluteal vessels and nerves, which may be secondary to adductor weakness postoperatively. The posterior approach is the main surgical approach for type IV Pipkin fracture. The classic posterior lateral approaches mainly include the Kocher - Langenbeck approach and the Ganz surgical dislocation approach. The Kocher - Langenbeck approach does not destroy the abductors and is particularly suitable for patients with posterior hip dislocation and difficult to reposition. Ganz surgical approach protects the blood supply of the medial femoral circumcator artery, so the incidence of femoral head necrosis is low. It can achieve all-round visualization of the femoral head and acetabulum, comprehensively evaluate the lesions of the femoral head and acetabulum, and find the occult injuries missed in imaging examinations..
10.A case report of urethral reconstruction for necrotizing fasciitis and urethral defects in the scrotal region
Liujian DUAN ; Jianwei CAO ; Lin ZHANG ; Xingang CUI ; Chao LI
Chinese Journal of Urology 2024;45(7):554-556
Clinical cases of necrotizing fasciitis and complete urethral defects in the scrotal region are rare. The diagnosis and treatment are very challenging. This article reports one case. The patient was admitted to the hospital after 1 week of poor urination and 2 days of scrotal swelling, and then underwent bladder diversion, surgical debridement, vacuum-sealing drainage, and wound closure. After four weeks, the wound healed and the patient was discharged. Six months later after surgery, scrotal urethral reconstruction was performed using a circular phimosis pedicled skin flap graft to repair the 12 cm urethral defect. The urethral catheter was removed after three weeks. The bladder fistula tube was removed after 5 weeks. During the follow-up of one year, there was no occurrence of urinary fistula and urinary obstruction.


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