1.Effect of Guiqi Yiyuan Ointment on Lewis Lung Cancer Mice by Increasing Autophagic Flux and Stabilizing PD-L1 Expression Through Regulation of ERK Signaling Pathway
Nan YANG ; Qiangping MA ; Jianqing LIANG ; Kejun MIAO ; Shang LI ; Jintian LI ; Juan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):107-114
ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase (ERK) signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group, the model mice were randomly divided into the model group, Guiqi Yiyuan ointment low, medium, and high dose groups, and the extracellular ERK1/2 inhibitor group, with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75, 3.5, 7.0 g·kg-1·d-1 for the low, medium, and high dose groups, respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 (100 mg·kg-1·d-1) by gavage. The treatment was administered for 14 consecutive days, after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin (HE) staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 (p-ERK1/2) and the expression of programmed cell death ligand-1 (PD-L1) in tumor tissues. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of p-ERK1/2, PD-L1, the autophagy marker Beclin-1, the autophagic protein p62, and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group, the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment (P<0.05), and markedly reduced in the high dose and inhibitor groups (P<0.01). Tumor cells in all treatment groups became progressively irregular, with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased, and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment (P<0.05), and significantly reduced in the high dose and inhibitor groups (P<0.01). The mRNA expression of ERK1/2, PD-L1, Beclin-1, and p62 was reduced in the medium dose group (P<0.05), while LC3Ⅰ/Ⅱ mRNA expression was elevated (P<0.05). In the high dose and inhibitor groups, mRNA expression of ERK1/2, PD-L1, Beclin-1, and p62 was significantly reduced (P<0.01), while LC3Ⅰ/Ⅱ mRNA expression was significantly increased (P<0.01). Protein expression of p-ERK1/2, PD-L1, Beclin-1, and p62 was reduced in the medium dose group (P<0.05), and LC3Ⅰ/Ⅱ protein expression was elevated (P<0.05). In the high dose and inhibitor groups, protein expression of p-ERK1/2, PD-L1, Beclin-1, and p62 was significantly reduced (P<0.01), while LC3Ⅰ/Ⅱ protein expression was significantly elevated (P<0.01). ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway, downregulate the expression of p-ERK1/2, promote autophagic flux in tumor cells, and regulate the expression of PD-L1, thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.
2.Research progress of internal limiting membrane peeling in the treatment of rhegmatogenous retinal detachment
Yuchen ZHANG ; Kejun LI ; Zhiyang JIA
International Eye Science 2025;25(6):933-937
Rhegmatogenous retinal detachment(RRD)is a vision-threatening ocular emergency with the potential risk of blindness. Pars plana vitrectomy(PPV)is the treatment of choice for RRD, especially for complex retinal detachments such as posterior pole retinal tears, grade B or higher proliferative vitreoretinopathy, and concomitant choroidal detachment. Although most patients achieve good anatomical restoration after surgery, some patients may still experience postoperative symptoms such as distorted vision, abnormal color perception, and lack of improvement in corrected visual acuity. Epiretinal membranes(ERM), as one of the most common complications after RRD, occur in 4% to 13% of cases, which not only affect the recovery of patients' postoperative vision, but also are frequently associated with visual distortion. In severe cases, a second surgical intervention may be required. In recent years, internal limiting membrane peeling(ILMP)has been introduced as an adjunctive procedure in the treatment of RRD, to facilitate retinal reorientation, reduce postoperative complications, and improve patients' postoperative visual quality and quality of life. However, previous studies on the effects of combined intraoperative ILMP on retinal anatomy and visual function recovery are limited. Therefore, this article reviews the mechanism, clinical application, challenges and research progress of ILMP in RRD, providing a reference for surgical decision making, disease assessment, and prognosis evaluation.
3.Astigmatism inclusivity of regional refractive intraocular lens
Zhihua ZHAO ; Xiaoting MA ; Kejun LI ; Fuzhen LIANG ; Yinghua DU
International Eye Science 2024;24(3):356-361
AIM: To investigate the effect of residual astigmatism on visual quality after phacoemulsification combined with regional refractive intraocular lens(IOL)implantation in patients with age-related cataract, and to evaluate the astigmatism inclusivity of regional refractive IOL.METHODS: Retrospective cohort study. The clinical data of 62 cases(73 eyes)of age-related cataract patients who underwent phacoemulsification combined with regional refractive IOL(Lentis Comfort LS-313 MF15)implantation from July 2020 to March 2022 at the ophthalmology department of our hospital were collected. They were grouped according to residual astigmatism at 6 mo postoperatively, taking 35 cases(40 eyes)with residual astigmatism of 0.75 D to 1.50 D as the experimental group, and 27 cases(33 eyes)with residual astigmatism ≤0.75 D as the control group. Visual acuity, defocus curves, objective visual acuity [wavefront aberrations, Strehl ratio(SR), modulation transfer functions(MTF)], subjective visual acuity(national eye institute visual function questionnaire-25), patients' satisfaction, and spectacle independence were compared between the two groups at 6 mo postoperatively.RESULTS:There was a difference in the preoperative astigmatism and the number of postoperative 6 mo residual astigmatism between the two groups(P<0.01). At 6 mo postoperatively, there was no difference in uncorrected distance, intermediate, and near visual acuity, objective visual quality, subjective visual quality, satisfaction, and spectacle independence between the two groups(P>0.05). The defocus curves showed that there was no difference in visual acuity between the two groups at all points in the +2.00 to -4.00 D defocus range of the additional spherical equivalent(P>0.05).CONCLUSION:Lentis Comfort LS-313 MF15 IOL was able to accommodate regular astigmatism of 1.50 D.
4.Progress in the effect of blood indicators on retinopathy of prematurity
Wenwen TANG ; Qingmin MA ; Kejun LI ; Fang FAN ; Yize HAN ; Jing CHENG ; Linwei YAN ; Yafeng WANG
International Eye Science 2024;24(3):392-396
Retinopathy of prematurity(ROP), an abnormal vascular proliferative retinopathy of prematurity, is a serious condition that can lead to retinal detachment or blindness. With the development of neonatal medicine, the survival rate of low birth weight and low gestational age infants has been increasing, as well as the incidence of ROP. Therefore, studying ROP's pathogenesis and influencing factors is of great clinical importance. Numerous studies have been conducted on the risk factors for ROP, including gestational age, oxygen intake, mode of delivery, neonatal bronchopulmonary dysplasia, and the use of surfactants. At present, it is widely accepted both at home and abroad that preterm birth, low birth weight, and high oxygen concentration after birth are independent risk factors for ROP. In recent years, more and more scholars have found that abnormalities in blood indicators in preterm infants may be associated with the development of ROP. This article reviews the effects of platelets, haemoglobin, blood glucose, inflammatory cells, and lipids on ROP, providing a reference for identifying and preventing risk factors for ROP.
5.Effect of residual corneal astigmatism on visual acuity of patients undergoing regional refractive intraocular lens implantation
Xiaoting MA ; Kejun LI ; Zhihua ZHAO ; Yin ZHANG ; Yinghua DU ; Fuzhen LIANG
Recent Advances in Ophthalmology 2024;44(1):43-47
Objective To investigate the effect of residual corneal astigmatism on visual acuity after regional refrac-tive intraocular lens(IOL)implantation.Methods A retrospective cohort study was conducted.The medical records and follow-up data of 73 eyes of 57 cataract patients who underwent ultrasound emulsification cataract extraction combined with LENTIS Comfort LS-313 MF15 IOL implantation in the Ophthalmology Department of the Hebei General Hospital from June 2020 to March 2022 were collected.These patients were grouped according to postoperative residual corneal astigmatism:32 patients(40 eyes)with a residual corneal astigmatism of 0.75(exclusive)-1.50 D were taken as the experimental group,and 25 patients(33 eyes)with a residual corneal astigmatism ≤0.75 D were taken as the control group.The uncor-rected distance visual acuity(5 m),uncorrected intermediate visual acuity(80 cm),uncorrected near visual acuity(40 cm),out-of-focus curve,objective visual quality,subjective visual quality,satisfaction degree and lens removal rate of pa-tients in the two groups were recorded 6 months postoperatively.Results The postoperative uncorrected distance visual acuity(logMAR)was 0.10(0.00,0.22),the uncorrected intermediate visual acuity(logMAR)was 0.00(0.00,0.10),and the uncorrected near visual acuity(logMAR)was 0.20(0.10,0.30)and 0.20(0.10,0.20)in the experimental and control groups,with no statistically significant differences(all P>0.05).The postoperative out-of-focus curves showed that the distance visual acuity of patients with additional spherical equivalent refraction ranged from+2.00 D to-4.00 D in the two groups had no statistically significant difference(all P>0.05).There were statistically significant differences in to-tal aberration,coma aberration,modulation transfer function and Strehl ratio in the objective visual quality of patients after surgery(all P<0.05),and there was no statistically significant difference in the total higher-order aberration,spherical ab-erration and cloverleaf aberration(all P>0.05).There was no statistically significant difference in the subjective visual quality,satisfaction degree and lens removal rate in the two groups(all P>0.05).Conclusion Residual corneal astig-matism of 0.75 D to 1.50 D after LENTIS Comfort LS-313 MF15 IOL implantation has no effect on higher-order aberration,spherical aberration,and cloverleaf aberration in subjective and objective visual quality,and has an impact on total aberra-tion,coma aberration,modulation transfer function and Strehl ratio in objective visual quality.
6.Research progress on the pathological mechanism of meibomian gland dysfunction in diabetic patients
Yize HAN ; Kejun LI ; Qingmin MA ; Fang FAN ; Wenwen TANG ; Jing CHENG ; Linwei YAN ; Yafeng WANG
International Eye Science 2024;24(7):1098-1101
Meibomian gland dysfunction is a chronic and diffuse disease of the meibomian glands, characterized by obstruction and(or)abnormal secretion of the terminal ducts. Clinically, it can lead to tear film abnormalities and inflammation of the ocular surface, resulting in symptoms of ocular irritation and potential corneal damage that may impact visual function. Meibomian gland dysfunction can be classified into two types based on meibomian gland secretion: low secretion type and high secretion type. The low secretion type further includes acinar atrophy type and obstruction type. In recent years, research has revealed that patients with diabetes experience chronic damage to their meibomian gland tissue in the early stages of the disease, leading to structural and functional changes. The incidence and severity of meibomian gland dysfunction are higher in diabetic patients. However, there are numerous complex factors contributing to this condition in diabetes patients, and mechanisms remain unclear at present. This article reviews both domestic and international research progress on the pathological mechanism underlying meibomian gland dysfunction in diabetes.
7.Advances in the inclusiveness of extended depth of focus intraocular lens for astigmatism
Xiaoting MA ; Zhihua ZHAO ; Kejun LI ; Yinghua DU
International Eye Science 2024;24(8):1280-1284
Since the first intraocular lens(IOL)was implanted by Harold Ridley in 1949 and the widespread use of depth-of-focus extended intraocular lens(EDOF IOL)clinically, the IOL has been constantly updated and developed, aiming to provide patients with good postoperative visual quality. The residual astigmatism is one of the important factors affecting the postoperative visual quality of cataract patients, 35%-40% of cataract patients have astigmatism of 1.00 D, and 19%-22% have astigmatism of 1.50 D. Therefore, it is important to understand the inclusiveness of EDOF IOL for astigmatism, so that the right IOL can be selected for the patient. This article summarizes the inclusiveness of different types of EDOF IOL for astigmatism and their advantages and disadvantages, with the expectation that it will provide a reference in selecting EDOF IOL for patients with different residual astigmatism.
8.Effects of glycosylated nanoparticles on radiation-induced the polarization of macrophages in early injured lung tissue
Kejun LI ; Liqing DU ; Qiang LIU ; Huijuan SONG
Chinese Journal of Radiological Medicine and Protection 2023;43(11):858-865
Objective:To explore the effects of glycosylated nanoparticles on early radiation responses including the generation of reactive oxygen species (ROS), the polarization of pulmonary macrophages, and secretion of inflammatory cytokines in mice lung tissues.Methods:Twenty mice were randomly divided into control group, drug administration group, irradiation group and irradiation + drug administration group. The irradiation group and irradiation + drug administration group were subjected to whole lung irradiation with X-rays. The antioxidant ability of glycosylated nanoparticles was characterized using ROS indicator (CM-H 2DCFDA). The M2 polarization of pulmonary macrophages was detected by flow cytometry and PCR. The mRNA and protein expression levels of inflammatory cytokines were investigated by PCR and ELISA assay, respectively. Results:Compared with the irradiation group, the intensity of ROS fluorescence signals was significantly lower ( t=15.76, P < 0.05), the proportion of M2-type macrophages was significantly higher ( t=2.89, P < 0.05), the expression level of arginase 1 (ARG-1) gene was elevated, and the expression levels of tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) inflammatory factors were significantly reduced ( t=3.32, 2.90, 2.85, 4.55, 2.88, P < 0.05) in the lung tissues of irradiation + treatment group. Conclusions:Glycosylated nanoparticles can effectively scavenge ROS, trigger polarization of M2 macrophage, dampen inflammatory responses, and thus potentially alleviate radiation-induced lung injury.
9.Gingival mesenchymal stem cells inhibited senescence of type Ⅱ alveolar epithelial cells and prevented radiation-induced pulmonary fibrosis
Wenyue ZHAO ; Na LI ; Kejun LI ; Yan WANG ; Ningning HE ; Liqing DU ; Qiang LIU
Chinese Journal of Radiological Medicine and Protection 2022;42(11):830-838
Objective:To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods:Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results:GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% ( t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) ( t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% ( t=21.83, P<0.05), and inhibited the expressions of SASP ( t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation. Conclusions:GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF.
10.Research about clinical comprehensive evaluation methods of pediatric drugs :taking pediatric anti-allergic drugs as an example
Lu LIU ; Yue XIAO ; Chang LIU ; Suxin QU ; Rong LI ; Baodong YU ; Xiaomei MO ; Kejun LIU ; Meixing YAN
China Pharmacy 2022;33(2):142-145
OBJEC TIVE To provide reference for clinical comprehensive evaluation of pediatric drugs in China. METHODS Taking pediatric anti-allergic drugs as an example ,the clinical comprehensive evaluation methods of pediatric drugs in medical institutions were explored from the aspects of theme selection ,evaluation content and dimension ,evaluation index ,evaluation method and evaluation result report. RESULTS & CONCLUSIONS During the clinical comprehensive evaluation of pediatric drugs,under the guidance of relevant national guidelines for clinical comprehensive evaluation ,the evaluation topics could be selected according to the three principles of importance ,relevance and evaluability ,and then an appropriate evaluation index system could be developed around the six dimensions of safety , effectiveness, economy, suitability,accessibility and innovativeness;qualitative and quantitative data integration analysis of the drugs to be evaluated were performed. In the evaluation , it is necessary to focus on children ’s clinical basic drug use practice and decision-making needs ,normatively,scientifically and reasonably define the core index set and standard data set required by different dimensions of evidence ,standardize the collection and use of real-world data ,and effectively combine other types of evidence to truly play its advantageous role in the clinical comprehensive evaluation of pediatric drugs in China.

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