1.Development and application of regulatory T cells in corneal transplant rejection
Xin DU ; Ruijuan GUAN ; Zefeng KANG ; Ling LI ; Xin YAN ; Xiaoying ZHANG
International Eye Science 2024;24(8):1246-1249
Corneal transplantation is an effective treatment for corneal blindness, and it is the only hope for patients with corneal blindness. Cornea has no blood vessels and no lymphatic vessels, which is called immune privilege organ, so the success rate of corneal transplantation is significantly higher than that of other organ transplantation, but the rejection reaction after corneal transplantation is still the main reason for the failure of corneal transplantation. The directional movement of immune cells to lymphoid tissue and inflammatory sites is the mainly immune response after organ transplantation. And the regulatory T cells(Treg)play a key role in immune regulation, which can induce immune tolerance by regulating and inhibiting the activation of effector T cells and reduce the rejection reaction after corneal transplantation. In addition, this review also discussed the effectiveness of applying cordyceps sinensis extract FTY720 to enhance the function of Treg. Based on this, we briefly reviewed the sources, mechanism of action and treatment of Treg after corneal transplantation, so as to provide some reference for the subsequent clinical application transformation and basic research.
2.Early imaging characteristics and functional evaluation of bladder wall reconstruction neourethra after robot-assisted laparoscopic prostatectomy for prostate cancer
Zhenghui GUAN ; Jie ZHAO ; Xiaoying SHEN ; Jiangping WANG
Journal of Modern Urology 2024;29(7):607-611
Objective To evaluate the early imaging characteristics and function of bladder wall reconstruction neourethra(BWN)after robot-assisted laparoscopic prostatectomy(RALP)for prostate cancer with magnetic resonance imaging(MRI)and voiding cystourethrography(VCUG).Methods A total of 36 patients who underwent RALP using BWN technique at Taizhou People's Hospital during Mar.2021 and Jun.2023 were enrolled.Postoperative MRI was used to measure the length,wall thickness,and lumen shape of the new urethra.The morphology of the new urethra in 19 patients was observed under VCUG during the storage phase,voiding phase,and interrupted voiding phase.Results The patients'median age was 73.00 years(range:68.00 to 76.25),the prostate volume was(45.01±7.18)cm3,and the median total prostate-specific antigen(tPSA)level was 10.77 ng/mL(range:7.30 to 14.86).Two patients were classified as T1 stage,25 as T2,and 9 as T3.Gleason scores were ≤6 in 7 patients and ≥8 in 8 patients.Risk classification was low risk in 2 patients and high risk in 8 patients.Postoperatively,urinary control rates at 1,3,and 6 months were 91.67%,97.22%,and 100%,respectively.MRI revealed a median new urethra length of 15.13 mm(range:12.71 to 20.26)and a median wall thickness of 6.84 mm(range:6.18 to 8.20).The urethral lumen had a complete muscular layer and mucosal layer,which appeared petal-like.In patients with urinary incontinence,residual urine was visible in the new urethra and at the anastomosis site.Of the 19 patients who underwent VCUG,16 could close the new urethra during the storage and interrupted voiding phases,and open it during the voiding phase;3 could not close it well during the storage and interrupted voiding phases.Conclusion MRI and VCUG clearly demonstrate that the BWN technique can successfully create a new urethra with good functionality,which helps improve urinary control after RALP for prostate cancer.
3.Mechanism of GLI1 mediated macrophages polarization in hypoxic pulmonary hypertension
Xiangrui ZHU ; Jian MEI ; Zhaosi WANG ; Langlin OU ; Lixin ZHANG ; Xiaoying WANG ; Siyu HE ; Jun'e BAI ; Xiaoyu GUAN ; Hao YUAN ; Cui MA
Chinese Journal of Immunology 2024;40(5):1016-1022
Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.
4.Neoadjuvant sintilimab and apatinib combined with perioperative FLOT chemotherapy for locally advanced gastric cancer: A prospective, single-arm, phase II study.
Huinian ZHOU ; Bo LONG ; Zeyuan YU ; Junmin ZHU ; Hanteng YANG ; Changjiang LUO ; Wenjuan ZHANG ; Chi DONG ; Xiaoying GUAN ; Long LI ; Gengyuan ZHANG ; Hongtai CAO ; Shigong CHEN ; Linyan ZHOU ; Qichen HE ; Shiying GAN ; Xiangyan JIANG ; Qianlin GU ; Keshen WANG ; Wengui SHI ; Long QIN ; Zuoyi JIAO
Chinese Medical Journal 2024;137(21):2615-2617
5.Relationship between eyebrow and eye aesthetics after correction of aponeurotic ptosis
Yuan YUAN ; Waner LIN ; Xiaoying GUAN ; Dongying SU ; Yan WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(3):190-194
Objective:To evaluate the specific changes and importance of the proportions of the eyebrows and eyes after surgery by analyzing and measuring the changes of the values of the eyebrows and eyes in elderly patients with aponeurotic ptosis before.Methods:A total of 54 cases (108 eyes) of elderly patients with aponeurotic ptosis who were treated in our department from 2019.01 to 2020.12 were collected preoperatively and 6 months postoperatively, and they were set as the study group. At the same time, the data of 48 cases (96 eyes) of healthy people with good face were collected and set as the young control group, and the data of 50 cases (100 eyes) of elderly healthy people without ptosis were collected and set as the elderly control group. The corresponding objective data were analyzed, and the specific changes and proportional relationship of eyebrows and eyes after surgery were evaluated.Results:Compared with the preoperative data, the marginal reflex distance 1 (MRD1), the height of the palpebral fissure (HPF) in the study group increased at 6 months after the operation, and the distance between the eyebrow and eye at each site increased or shortened ( P<0.05). Six months after the operation, the brow height from medial canthus (MBH), the central brow and eye distance (brow height from upper eyelid margin on midpupillary level, CBH), and the lateral brow and eye distance (brow height from lateral, LBH) had been changed. The change rates of canthus compared with preoperatively were that (88.29±11.69)%, (85.04±14.96)%, and (93.61±13.56)%, respectively, among which CBH shortened most significantly, and the shortened distance was (3.76±2.43) mm. The MRD1 and HPF in the group increased significantly at 6 months after operation, which were significantly greater than those in the elderly control group ( P<0.05). CBH was significantly shortened ( P<0.05); compared with preoperative, the ratio of HPF/CBH, HPF/length of the palpebral fissure (LPF) in the study group increased at 6 months after operation, and the lateral canthus brow tail line [ratio of lateral canthus to lateral end of eyebrow (LLE)]/LPF decreased ( P<0.05); HPF/CBH in the study group was lower than that in the young control group at 6 months after operation, but greater than that in the elderly control group ( P<0.05). Monthly HPF/LPF was significantly higher than that of the elderly control group ( P<0.05), and the LLE/LPF of the study group was significantly higher than that of the young control group at 6 months after operation ( P<0.05); intraoperative levator muscle shortening (LMS) was negatively correlated with postoperative MBH, CBH and LBH ( P<0.05), among which LMS had the greatest correlation with CBH ( r=-0.587). Conclusions:After ptosis correction, the palpebral fissures are larger, the distance between the eyebrows and the eyes is shortened, and there is a certain proportional relationship. After surgery, the patient's eyebrow-eye ratio is better than that of the elderly in the same age group, and it is closer to the young people, and the intraoperative LMS has a correlation with the eyebrow-eye distance, which can be used as a factor to predict the shortened distance of the eyebrow-eye distance.
6.Advances in disease-modifying therapy of neuromyelitis optica spectrum disorders
Hongyan LI ; Kan WANG ; Haojun YU ; Rui RUI ; Xiaoying YAO ; Yangtai GUAN
Chinese Journal of Neurology 2023;56(12):1435-1446
Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune-mediated inflammatory demyelinating diseases of the central nervous system, characterized by optic nerve and spinal cord lesions, with high chance of recurrence and disability. Disease-modifying therapy, including immunosuppressants, monoclonal antibodies, stem cell transplantation etc., is the key to prevent recurrence. This article made a systematic review about the sequential treatment or prognosis of NMOSD by searching for the related articles published on PubMed from 2017 to 2022 to provide recommendations and references for disease-modifying therapy of NMOSD.
7.Risk factors of local recurrence and survival in patients with upper tract urothelial carcinoma after nephroureterectomy with lymph node dissection
Changwei YUAN ; Chunru XU ; Bao GUAN ; Cuijian ZHANG ; Xiaoying LI ; Zhisong HE ; Liqun ZHOU ; Xuesong LI
Chinese Journal of Urology 2023;44(9):641-647
Objective:To evaluate risk factors for local recurrence and prognosis in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy combined with lymph node dissection (LND).Methods:The data of 237 patients who were diagnosed with UTUC in Peking University First Hospital and received radical nephroureterectomy combined with LND during January 2010 and March 2022 were retrospectively reviewed. Clinicopathologic characteristics and oncological outcomes were compared according to lymph node metastasis. There were 122 males and 115 females. The tumors of 122 cases were located on the left, while 115 cases were on the right. The tumors of 102 cases were in the renal pelvic, 124 cases in the ureter and 11 cases in both sites. The mean age was (65.52±10.14) years old. The overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (LRFS) of all patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between two groups were analyzed by log-rank test. Univariate and multivariate Cox proportional hazards regressions were performed to identify the independent risk factors for CSS and LRFS.Results:There were 122 males and 115 females. According to the lymph node metastasis, the patients were divided into lymph node negative group ( n=180, 75.9%) and lymph node positive group ( n=57, 24.1%). Lymph node positive group had a higher percentage in renal tumor [57.9%(33/57) vs. 38.1% (69/180)], stage T 3-4 [84.2%(48/57) vs. 32.8%(59/180)], G 3 [91.2%(52/57) vs. 55.6%(100/180)], glandular differentiation [17.5%(10/57) vs. 4.4%(8/180)], sarcomatoid differentiation [22.8%(13/57) vs. 9.4%(17/180)], necrosis [47.4%(27/57) vs. 16.1%(29/180)], lymphovascular invasion [40.4%(23/57) vs. 12.2%(22/180)] and the number of lymph node dissection [ 4(1, 10) vs. 2(1, 5)]. There were significant differences between the two groups ( P<0.05). Of 237 patients, 42 lost of follow up. The median follow-up time was 46(22, 79) months. Among the 195 patients, 52 patients died, and 42 died due to the tumor. Of all patients, 58(29.7%) had local recurrence, 34 had local recurrence alone, and 24 had concurrent distant metastasis. The 5-year OS and CSS were 67.4% and 71.3%, respectively. The 5-year OS and CSS were 70.5% and 75.1% respectively in the lymph node negative group, 57.5% and 59.4% respectively in the lymph node positive group ( P < 0.05). The 3-year LRFS was 68.0% for all the patients. The 3-year LRFS was 75.6% in the lymph node negative group and 44.5% in the lymph node positive group ( P<0.05). Multivariate analysis showed that tumor stage T 3-4( HR =3.924, 95% CI 2.045-7.529, P<0.001) and G 3( HR=2.871, 95% CI 1.193-6.909, P =0.019) were independent risk factors for LRFS. Multivariate analysis showed that age ≥70 years ( HR = 3.578, 95% CI 1.917-6.678, P<0.001) and pathological stage T 3-4 ( HR =2.366, 95% CI 1.278-4.381, P =0.006) were independent risk factors for CSS. Multivariate analysis showed that age ≥70 years ( HR = 3.874, 95% CI 2.190-6.853, P<0.001) and pathological stage T 3-4 ( HR = 2.757, 95% CI 1.565-4.857, P<0.001) were independent risk factors for OS. Conclusions:Patients with high T stage, high grade, as well as glandular differentiation, sarcomatoid differentiation, necrosis, lymphovascular invasion are more likely to have positive lymph node detection. Age ≥70 years and stage T 3-4 were independent risk factors for CSS and OS. Stage T 3-4 and G 3were independent risk factors for LRFS.
8.Volatile Oils from Chinese Medicine in Prevention and Treatment of Breast Cancer: A Review
Qing DU ; Yixin LIU ; Mingfang YE ; Guangpeng WU ; Yongmei GUAN ; Huiting LI ; Xiaoying HUANG ; Ming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(17):226-234
Breast cancer is a systemic malignant tumor caused by multiple pathogenic factors, and its pathological mechanism is complex and has not been clarified so far. It has gradually become the largest killer threatening women's life. The common method for the treatment of breast cancer is lesion resection combined with radiation and chemical therapy, endocrine therapy, or targeted therapy. However, due to the limitations of western medicine therapies, there are still considerable breast cancer patients with poor disease control and high tumor recurrence rate in clinical practice. At the same time, the side effects and complications produced by these therapies affect the quality of life of patients. Therefore, it is urgent to develop new drugs or find safe and effective alternative therapies against breast cancer. Volatile oil (VO), as a unique volatile component of Chinese herbal medicines, has anti-inflammatory, antiviral, and anti-tumor activities. It has been applied in the treatment of breast cancer and has demonstrated good efficacy by exerting the unique effects of strengthening healthy Qi, eliminating pathogenic factors, moving Qi, resolving stasis, warming Yang, soothing liver, and relieving depression. The recent studies have confirmed that VO and its chemical components can prevent and treat breast cancer via multiple mechanisms, while there is a lack of systematic review. The relevant literature published in recent years has demonstrated that VO can inhibit the occurrence and development of breast cancer by regulating the level of estrogen, inhibiting the proliferation and inducing the apoptosis of cancer cells, enhancing immunity, resisting inflammation, and regulating emotions. We introduced the pathogenesis of breast cancer, as well as the mechanisms and advantages of VO in the prevention and treatment of breast cancer, aiming to provide new ideas for the research on VO in the treatment of breast cancer.
9.MFN1 ubiquitination mediates lipopolysaccharide-induced mitochondrial dysfunction and pyroptosis in Raw264.7 mouse macrophages
Jian MEI ; Xiangrui ZHU ; Langlin OU ; Zhaosi WANG ; Lixin ZHANG ; Yueshan LYU ; Xiaoying WANG ; Siyu HE ; Jun′e BAI ; Hao YUAN ; Xiaoyu GUAN ; Cui MA
Chinese Journal of Microbiology and Immunology 2022;42(9):705-713
Objective:To investigate the regulatory effects of mitofusin 1 (MFN1) on lipopolysaccharide (LPS)-induced Raw264.7 mouse macrophages pyroptosis and to provide reference for further study on the prevention of inflammation and fibrosis caused by macrophage dysfunction.Methods:Raw264.7 mouse macrophages were cultured in vitro and used to construct a model of LPS-induced pyroptosis. CCK-8 staining, PI staining, LDH release assay and Western blot were used to verify the Raw264.7 pyroptosis induced by LPS. MFN1 expression was detected by Western blot. DCFH-DA probe was used to detect the synthesis of total reactive oxygen species (ROS); Mito-SOX was used to detect mitochondrial ROS; JC-1 mitochondrial membrane potential was detected by fluorescence probe to reflect mitochondrial damage. Based on Ubibrowser database, it was predicted that MFN1 could bind to a variety of E3 ubiquitin ligases. Then, immunofluorescence and co-immunoprecipitation (CO-IP) were used to analyze MFN1 ubiquitination. An overexpression plasmid for MFN1 was constructed and transfected into Raw264.7 cells to detect the changes in pyroptosis and mitochondrial function. Results:LPS could induce the pyroptosis of Raw264.7 cells and mitochondrial dysfunction. MFN1 expression was decreased after LPS stimulation. Ubiquitinated MFN1 was detected by CO-IP. Ubiquitination inhibitor MG-132 inhibited LPS-induced expression of pyroptosis-related proteins including NLRP3, Pro-caspase-1, Caspase-1, IL-1β and IL-18 and improved mitochondrial function. MFN1 overexpression relieved the mitochondrial dysfunction and pyroptosis of Raw264.7 cells induced by LPS.Conclusions:The ubiquitination of MFN1 induced by LPS was involved in mitochondrial dysfunction and macrophage pyroptosis, suggesting that MFN1 was a potential target for the treatment of macrophage-induced inflammation and related diseases.
10.Risk factors analysis of age-related macular degeneration in Tibetan of plateau area and establishment of nomogram prediction model
Xiaoying ZHANG ; Ruijuan GUAN ; Xin YAN ; Ling LI
Chinese Journal of Experimental Ophthalmology 2022;40(3):260-265
Objective:To determine the prevalence and risk factors for age-related macular degeneration (AMD) in Tibetan of plateau area, and to establish a nomogram prediction model.Methods:A cross-sectional study was carried out.The 40-year-old and older Tibetan subjects were enrolled by cluster random sampling from Xinghai County and Tongde County with an average altitude of 3 000 meters in Qinghai Province.Questionnaire survey, routine ophthalmic examinations, direct fundus photography and health education were carried out among the subjects.The questionnaire items included age, gender, smoking, drinking, living duration in plateau region, daily sunshine duration, diabetes, hypertension and hyperlipidemia.A χ2 test was used to screen significantly factors, and risk factors for AMD were analyzed by logistic regression analysis.The nomogram plot was drawn by R software to establish a predicting model.The study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Qinghai Provincial People's Hospital (No.2017-21). Written informed consent was obtained from each subject prior to any medical examination. Results:A total of 1 223 subjects were enrolled, and AMD were detected in 190 subjects with an prevalence of 15.54%.The risk factors for AMD were old age, living duration in plateau region, sunshine duration, smoking, hypertension and hyperlipidemia.Age was the first one of risk factors for AMD ( OR: 20.183, 95% CI: 9.536-29.805, P<0.001), followed by sunshine duration ( OR: 3.785, 95% CI: 1.581-8.721, P<0.001). The nomogram prediction model showed that when the questionnaire score was >150, the probability of suffering AMD was 50%.The decision curve showed that when the threshold probability was >25%, the predicted probability of AMD was the same as the actual probability. Conclusions:Pathogesis of AMD in Tibet is associated with old age, living duration in plateau area, sunshine duration, smoking, hypertension and hyperlipidemia.

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