1.Role and research progress of gut microbiota in uveitis
Yingcheng LIN ; Qiuming HU ; Min ZHOU ; Jinqing LIU
International Eye Science 2025;25(1):64-69
Uveitis is a blinding inflammatory disease that affects multiple structures within the eye, posing significant risks to patients' vision and mental health. Current treatments mainly involve glucocorticoids and immunosuppressants, which are associated with significant side effects, high relapse rates, and substantial costs. Recent research suggests that the gut microbiota may play a role in the development of uveitis through the gut-eye axis, with related metabolites also influencing disease progression. Modulating the gut microbiota or its metabolites could offer new therapeutic avenues for uveitis. This review explores the relationship between gut microbiota and various uveitis-associated diseases, such as systemic sarcoidosis, Vogt-Koyanagi-Harada syndrome, Behcet's disease, multiple sclerosis, and birdshot chorioretinopathy. It also discusses advancements in microbiota-related therapies, including probiotics and prebiotics, antibiotics, immunomodulators, phage therapy, and fecal microbiota transplantation. The aim is to provide a reference for the development of new therapies targeting specific microbial communities and genetic markers associated with uveitis, thereby promoting the realization of precision medicine.
2.Research progress of NLRP3 inflammasome in the treatment of uveitis
International Eye Science 2024;24(4):572-576
The NLRP3 inflammasome is a cellular multimeric protein complex that plays a crucial role in inflammation and immune responses. It consists of three main components: Nod-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing(ASC)and cysteine protease 1(caspase-1). Uveitis is a broad term encompassing a range of inflammatory diseases that primarily affect the iris, ciliary body, vitreous, retina and choroid. It is considered a major cause of blindness globally. Numerous studies have demonstrated the involvement of NLRP3 inflammasome in the onset and progression of uveitis, indicating its potential as a significant therapeutic target for uveitis in the future. This article provides an overview of the structure, biological functions and activation pathways of the NLRP3 inflammasome, as well as the current research progress on its association with different types of uveitis. Additionally, it discusses the application potential of the NLRP3 inflammasome in the treatment of uveitis.
3.Clinical characteristics and treatment prognosis of ocular toxocariasis
Yongwei ZHOU ; Qiuming LI ; Jiahui WU ; Xiaoyan LU ; Ge YANG ; Zhirou HU ; Fangyuan ZHEN ; Shuqian DONG
Chinese Journal of Ocular Fundus Diseases 2023;39(6):483-488
Objective:To observe the clinical characteristics and treatment prognosis of patients with ocular toxocariasis (OT).Methods:A retrospective clinical trial. From March 2018 to September 2021, 40 eyes of 40 OT patients diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. All patients underwent best corrected visual acuity (BCVA) and scanning laser ophthalmoscope (SLO) examination. Color Doppler ultrasound flow imaging (CDFI), fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were performed in 25, 26 and 26 eyes, respectively. Among the 40 patients, there were 23 males (57.5%, 23/40) and 17 females (42.5%, 17/40). All patients were monocular. Thirty patients (75.0%, 30/40) were younger than 18 years old, with the mean age of (9.60±0.60) years. Ten patients (25.0%, 10/40) were great than or equal to 18 years old, with the mean age of (34.60±4.52) years. Thirty-three patients (82.5%, 33/40) lived in rural areas for a long time. There were 27 patients (67.5%, 27/40) with a history of contact with dogs and cats. In 40 eyes, peripheral granuloma (peripheral type), posterior pole granuloma (posterior pole type), vitreous opacity similar to endophthalmitis (turbid type) and hybrid type were 18(45.0%, 18/40), 11(27.5%, 11/40), 6(15.0%, 6/40) ang 5(12.5%,5/40), respectively. All patients were treated with drugs and/or surgery after definite diagnosis. There were 28 eyes of peripheral type, posterior pole type and hybrid type, 17 eyes were treated with surgery and 11 eyes with drug treatment, respectively. Five eyes with turbid type were only treated with drugs. In 40 patients, 33 patients participated in follow-up. The follow-up time after treatment was (18.78±9.44) months. The improvement of BCVA was observed. The number of eyes with different BCVA before and after treatment was compared by χ2 test or Fisher's test. Results:At the first visit, the BCVA ranged from light perception to 0.6, including 20 eyes with BCVA <0.1, 13 eyes with BCVA 0.1-0.3, and 7 eyes with BCVA >0.3. The posterior vitreous anterior limiting membrane was thickened in 24 eyes (60.0%, 24/40). There were 27 eyes (67.5%, 27/40) with lamellar vitreous opacity and 22 eyes (55.0%, 22/40) with peripheral/posterior pole granulomas. Among 25 eyes examined by CDFI, 14 eyes (56.0%, 14/25) showed characteristic stratified or diffuse opacity in vitreous body. Of the 26 eyes examined by FFA, 15 eyes (57.7%, 15/26) had "fern-like" leakage of retinal capillaries, and the lesion had a patchy non-perfused area. In 26 eyes examined by OCT, epiretinal membrane, cystoid macular edema and vitreoretinal traction were 8 (30.8%, 8/26), 5 (19.2%, 5/26) and 2 (7.7%, 2/26) eyes, respectively. At the last follow-up, compared with before treatment, the BCVA of 5 eyes with turbid type increased, and the difference was statistically significant ( P<0.05). In 28 eyes with peripheral type, posterior pole type and hybrid type, 17 eyes with surgical treatment improved BCVA, and the difference was statistically significant ( χ2=6.258, P<0.05). In 11 eyes only treated with drugs, BCVA remained unchanged, and the difference was not statistically significant ( χ2=0.594, P>0.05). Conclusions:OT patients are mostly children; retinal granulomas, gray-white hyperplastic membrane behind lens or vitreous stratified opacity are specific characteristics. OT is mainly treated by glucocorticoid drugs and vitrectomy.
4.Dissecting the novel abilities of aripiprazole: The generation of anti-colorectal cancer effects by targeting Gαq via HTR2B.
Haowei LIU ; Qiuming HUANG ; Yunqi FAN ; Bo LI ; Xuemei LIU ; Changhua HU
Acta Pharmaceutica Sinica B 2023;13(8):3400-3413
Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo, but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (Gαq) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of Gαq to HTR2B was decreased after Ari treatment. Knockdown of Gαq not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and Gαq was found in that the mutation at amino acid 190 of Gαq reduced the efficacy of Ari. Thus, these results confirm that Gαq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.
5.Expression of proBDNF/p75NTR in peripheral blood lymphocytes of patients with sepsis and its impact on lymphocyte differentiation
Shuang WANG ; Qiuming ZENG ; Hailiang GAO ; Shan GAO ; Ruping DAI ; Zhaolan HU
Journal of Central South University(Medical Sciences) 2023;48(11):1629-1638
Objective:Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection.Due to lack of effective treatments,it has always been the difficulty and focus of clinical treatment of sepsis.Studies have shown that pro-brain-derived neurotrophic factor(proBDNF)binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor(p75NTR),which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis.This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. Methods:From the healthy donors(control group,n=40)and sepsis patients(sepsis group,n=40)admitted to the hospital for the first time,peripheral blood samples and blood routine clinical detection indicators were obtained.By using flow cytometry,the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined.The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide(LPS).Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets.On this basis,we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. Results:White blood cell count,neutrophil count,and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group;on the contrary,lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group(all P<0.001).The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group(both P<0.05).In the peripheral blood of sepsis patients,proBDNF expression was upregulated on CD19+ B cells,whereas p75NTR expression was elevated on B cells,CD4+ T cells,and CD8+ T cells(all P<0.05).ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group(P<0.05),and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group.Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages,cytokine expression of IL-4 and IL-10,and reduced IL-1β and IL-6 production(all P<0.05). Conclusion:The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils.ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients,and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.
6.Efficacy of pars plana vitrectomy combined with segmental scleral buckling in the treatment of inferior rhegmatogenous retinal detachment
Jiajia MA ; Qiuming LI ; Xiaoyan LU ; Zhirou HU
Recent Advances in Ophthalmology 2023;43(12):979-982
Objective To investigate the clinical effect of pars plana vitrectomy combined with segmental scleral buckling(PPV-SSB)in the treatment of inferior rhegmatogenous retinal detachment(RRD).Methods Totally 87 eyes of 87 patients with inferior RRD who attended the Ophthalmology Department Ⅱ,the First Affiliated Hospital of Zhengzhou University from October 2020 to April 2022 were retrospectively included.Among them,45 patients(45 eyes)were treated with PPV-SSB(PPV-SSB group),and 42 patients(42 eyes)were treated with PPV(PPV group).The retinal reattachment rate,best corrected visual acuity(BCVA)and complications of patients who underwent single surgery in the two groups were compared.Results After a single surgery,the retinal reattachment rate was 95.56%(43/45)in the PPV-SSB group and 80.95%(34/42)in the PPV group,with a statistically significant difference(P=0.033).At 3 months and 6 months af-ter surgery,there were significant differences in BCVA between the PPV-SSB group and the PPV group(P=0.010,0.004).The incidence of postoperative phacoscotasmus in the PPV-SSB group and the PPV group was 28.89(13/45)and 54.76%(23/42),respectively,with a significant difference(P=0.018),while there were no significant differences in the inci-dence of the remaining few complications(all P>0.05).Conclusion PPV-SSB has a higher retinal reattachment rate,better visual effect and fewer complications in the treatment of inferior RRD.
7.Analysis of the complete genome sequence of the Dengue virus type 1 outbreak in Xishuangbanna in 2019
MENG Jinxin ; HU Qiuming ; LI Nan ; HE Yuwen ; WANG Jinglin
China Tropical Medicine 2023;23(12):1254-
Objective This study aims to comprehensively investigate the molecular characteristics of the predominant circulating Dengue virus type 1 (DENV-1) during the 2019 Dengue fever outbreak in Xishuangbanna, providing an essential insight to support the prevention and control of dengue fever in the local area. Methods A Dengue virus type 1 (DENV-1) strain, designated as JHS45, isolated from the blood of a febrile patient in Xishuangbanna in 2019, underwent a process of inoculation and cultivation in C6/36 cells. Second-generation sequencing was employed to capture the viral genetic sequence. Bioinformatics software, including CLC, was used for assembling the sequencing data. Sequentially, sequence alignment, construction of a phylogenetic tree, and analysis of amino acid sites were conducted using software such as Lasergene and MEGA6.1. Results Cytopathic effects of JHS45 appeared in C6/36 cells after 6 days. After sequencing and assembly, a 10 687-nucleotide (nt) long sequence of the JHS45 virus was obtained (GenBank accession number: OR593353). Genetic evolutionary analysis revealed that the JHS45 virus formed an evolutionary branch with DENV-1 genotype I viruses prevalent in Xishuangbanna, Guangzhou, Henan, and Zhejiang in China during 2019, as well as the DENV-1 genotype I virus prevalent in Thailand in 2013, with nucleotide homology of 97.6% to 99.9% and amino acid homology of 99.1% to 100%. Further analysis revealed that the JHS45 strain shared a smaller evolutionary branch with the DENV-1 genotype I viruses prevalent in Xishuangbanna (MW386863) and Guangzhou (MW261839) in 2019, showing the highest homology with nucleotide and amino acid homology of 99.9% and 100%, respectively. Amino acid differential site analysis between the JHS45 strain and the DENV-1 prevalent in Xishuangbanna since 2015 revealed 40 amino acid differential sites in the coding region of the JHS45 virus, primarily concentrated in the NS3 and NS5 regions of non-structural proteins. Conclusion The comprehensive analysis of the JHS45 strain's whole genome sequence indicates it is a DENV-1 genotype I virus. The genetic evolutionary relationship between this Xishuangbanna dengue fever outbreak is closely related to the prevalent virus strains in Xishuangbanna, Guangzhou, Henan, and Zhejiang. These findings provide a robust scientific foundation for monitoring dengue fever outbreaks, conducting virus evolution studies, and shaping effective prevention and control strategies, not only within Yunnan Province but also on a broader scale throughout China.
8.Clinical application and analysis of anatomical types of bilateral pulmonary arteries through three-dimensional reconstruction combined with three-dimensional printing
Longfei WANG ; Qiuming CHEN ; Xinjian LI ; Weijun ZHAO ; Wang LV ; Zhigang LIANG ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(07):867-877
Objective To explore the clinical applications of 3D-CT reconstruction combined with 3D printing in the analysis of anatomical types and variations of bilateral pulmonary arteries. Methods From January 2019 to February 2022, the clinical data of 547 patients who underwent anatomical lung lesion resection in our hospital were retrospectively collected. They were divided into a 3D-CT reconstruction plus printing technology group (n=298, 87 males and 211 females aged 53.84±12.94 years), a 3D-CT reconstruction group (n=148, 55 males and 93 females aged 54.21±11.39 years), and a non-3D group (n=101, 28 males and 73 females aged 53.17±10.60 years). Results In the 3D-CT reconstruction plus printing technology group, the operation time of patients (right: 125.61±20.99 min, left: 119.26±28.44 min) was shorter than that in the 3D-CT reconstruction group (right: 130.48±11.28 min, left: 125.51±10.59 min) and non-3D group (right: 134.45±10.20 min, left: 130.44±9.53 min), which was not associated with the site of surgery; intraoperative blood loss (right: 20.92±8.22 mL, left: 16.85±10.43 mL) was not statistically different compared with the 3D-CT reconstruction group (right: 21.13±8.97 mL, left: 19.09±7.01 mL), but was less than that of the non-3D group (right: 24.44±10.72 mL, left: 23.72±11.45 mL). Variation was found in the right pulmonary artery of 7 (3.91%) patients and in the left pulmonary artery of 21 (17.65%) patients. We first found four-branched lingual pulmonary artery in 2 patients. Conclusion Preoperative CT image computer-assisted 3D reconstruction combined with 3D printing technology can help surgeons to formulate accurate surgical plans, shorten operation time and reduce intraoperative blood loss.
9.Repair of defects after lumbar discectomy with autologous bone marrow mesenchymal stem cells and annular suture
Baoshan XU ; Hao ZHANG ; Qiuming YUAN ; Ying ZHANG ; Yongcheng HU ; Kaihui ZHANG ; Lilong DU ; Ning LI ; Yue LIU ; Haiwei XU
Chinese Journal of Orthopaedics 2022;42(11):685-695
Objective:To evaluate the safety and validity of enriched autologous bone marrow mesenchymal stem cells (BMSCs) and annular suture for repairing defect after lumbar discectomy.Methods:Enrichment of autologous BMSCs: autologous bone marrow blood was collected from 5 patients undergoing lumbar surgery, and nucleated cells were enriched on gelatin sponge particles by selective cell retention technique. From October 2016 to March 2019, 109 patients with lumbar disc herniation underwent discectomy with mobile microendoscopic discectomy technique, including 61 males and 48 females, aged 24-59 years. Discectomy group: 26 cases received simple discectomy. Suture group: 39 cases received annular suture after discectomy. BMSCs+suture group: 44 cases received intradisc transplantation of gelatin sponge particles enriched with autologous BMSCs and annular suture after discectomy. The perioperative conditions were recorded, with visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pfirrmann grade of disc degeneration, disc height and degree of herniationevaluated after operation.Results:In enrichment test with flow cytometry, the enrichment multiple of nucleated cells and target cells was 6.4±0.9 and 4.2±0.6 respectively, and BMSCs grew well in vitro. The operation time was 35-55 mins. 7 cases in the suture group were transferred to the discectomy group and 10 cases in the BMSCs+suture group were transferred to BMSCs group due to unsuccessful suture. There were no significant differences in VAS, ODI, Pfirrmann grade of disc degeneration, disc height and degree of herniation among the groups. There was no significant difference in intraoperative bleeding, postoperative drainage and length of hospital stay. The incision was healed without redness and swelling. 18 patients were followed up for 6 months, and 91 cases were followed up for 1-3 years (25.0±5.6 months). There was no interbody fusion, heterotopic ossification or infection during follow-up. VAS and ODI decreased significantly after operation in all patients. At final follow-up, the VAS improvement rate of BMSCs+suture group (81.7%±7.9%) was higher than discectomy group (73.0%±8.9%), suture group (74.0%±6.9%) and BMSCs group (75.3%±8.4%); the ODI improvement rate of BMSCs+suture group (91.9%±8.8%) was higher than discectomy group (86.2%±8.1%) and suture group (86.4%±5.5%). According to MRI, the Pfirrmann grade of disc increased 0.7 in discectomy group, 0.6 in suture group, while it did not increased significantly in BMSCs+suture group and BMSCs group, and the progress of Pfirrmann grade in BMSCs+suture group and BMSCs group were lighter than discectomy group and suture group.The disc height decreased in each group, the loss rate of disc height in BMSCs+suture group (17.2%±4.3%) was less than discectomy group (29.3%± 6.3%) and suture group (20.6%±5.7%); and suture group was less than discectomy group. The degree of herniation was reduced by more than 50% in all groups, while 1 case in discectomy group had herniation without clinical symptoms.Conclusion:Autologous BMSCs and annulus suture are safe and effective in repairing the defect after lumbar discectomy, which may help to slow down the degeneration of intervertebral disc.
10.Retrospective study on Jinghua Weikang capsule combined with Bifidobacterium in the treatment of spleen-somach damp-heat syndrome featured by helicobacter pylori infection with low count
Qiuming WANG ; Jing HU ; Yang DING ; Jihong LIU ; Shengsheng ZHANG
International Journal of Traditional Chinese Medicine 2022;44(7):734-738
Objective:To investigate the clinical efficacy of Jinghua Weikang capsule combined with Bifidobacterium for curing patients featured by spleen-stomach damp-heat syndrome and Helicobacter pylori (Hp) infection with low DOB values.Methods:To enroll 130 cases who were admitted to the Digestion Center of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from March 2019 to March 2020. According to the treaatment protocols, the quadruple therapy group and dual therapy group, each had 65 patients. The quadruple therapy group had two different treatment protocols, 34 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Clarithromycin, the other one had 31 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Levofloxacin tablets. The Dual therapy group was treated with Jinghua Weikang capsule combined with Bifidobacterium. As for quadruple therapy group, 14 days was a course of treatment, while28 days was a course of treatment for dual therapy group. The two groups were treated for one course, respectively. The TCM syndromes were scored before and after treatment. After 4-weeks long drug withdrawal, all cases were reexamined via 13C-UBT. The Hp eradication rate, efficacy evaluation and adverse reactions were compared between both groups.Results:The eradication rate was 90.8% (59/65) in quadruple therapy group and 78.5% (51/65) in dual therapy group. There was no statistical difference between two groups ( χ2=3.78, P=0.052). As for quadruple therapy group, the eradication rate was 91.2% (31/34) in Protocol One and 90.3% (28/31) in Protocol Two. There was no statistical difference between two protocols ( χ2=0.01, P=0.906). After treatment, the TCM syndrome score of quadruple therapy group [(7.02±0.89) vs. (6.51±0.85), Z=-3.01], was significantly higher than that of dual therapy group ( P<0.01). The total effective rate was 93.9% (61/65) in dual therapy group and 78.5% (51/65) in quadruple therapy group. There was statistically significantly difference between two groups ( χ2=6.45, P=0.011). The adverse reactions was 24.6% (16/65) in quadruple therapy group and 6.2% (4/65) in dual therapy group. There was statistically significantly difference in two groups ( χ2=8.51, P=0.004). Conclusions:The Jinghua Weikang capsule combined with Bifidobacterium had curative effects on Hp infected patients with low DOB values. It could improve TCM Syndromes with little adverse reactions.

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