1.Influencing factors for whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation
Yanru HE ; Wanyue LI ; Jia LIU ; Yingwei WANG ; Zifeng ZHANG
International Eye Science 2025;25(2):286-291
AIM: To explore the factors affecting the whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation.METHODS: A retrospective analysis was conducted on the medical records of 42 patients(42 eyes)with primary pterygium admitted in the ophthalmology department of Xijing Hospital from January 2023 to October 2023. They underwent pterygium excision combined with autologous limbal stem cell transplantation. The maximum invasion depth of pterygium into the cornea was measured with anterior segment optical coherence tomography(AS-OCT)before operation, the length of the pterygium invading cornea, the width of the limbus and the area of the invading cornea were measured during the operation, and three-dimensional values of corneal astigmatism of anterior segment, index of surface variance(ISV), index of vertical asymmetry(IVA), best corrected visual acuity(BCVA)and whole-eye astigmatism were collected before and at 1 mo after surgery. Patients with astigmatism ≤0.50 D or >0.50 D of the whole eye at 1 mo after surgery were assigned to group A and B, respectively. The differences of clinical data before and at 1 mo after surgery between the two groups, and the correlation between pre-operative clinical indicators and whole-eye astigmatism were analyzed. The decision tree algorithm was performed to explore the influencing factors of whole-eye astigmatism at 1 mo postoperatively.RESULTS: The maximum invasion depth of pterygium in the group A was significantly less than that in the group B [80.00(40.00, 180.00)μm vs 175.00(123.00, 190.00)μm, P=0.002]. Preoperative BCVA(LogMAR), whole-eye astigmatism, cornea astigmatism, ISV, IVA and maximum invasion depth of pterygium were positively correlated with whole-eye astigmatism at 1 mo after surgery(rs=0.317, P=0.041; rs=0.545, P<0.001; rs=0.448, P=0.003; rs=0.389, P=0.011; rs=0.382, P=0.013; rs=0.391, P=0.010). The decision tree algorithm screened out two influential factors: the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. The risk of whole-eye astigmatism >0.50 D at 1 mo after operation was higher with maximum invasion depth of pterygium into the cornea >95 μm than that with ≤95 μm. Among the patients with whole-eye astigmatism >2.63 D before operation, the probability of residual whole-eye astigmatism >0.50 D was 88.9%, and the predictive model AUC was 0.804.CONCLUSION: The whole-eye astigmatism after pterygium resection is mainly affected by the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. When the maximum invasion depth of pterygium into the corneal is >95 μm and the whole-eye stigmatism is >2.63 D before surgery, the patient should receive surgical treatment as soon as possible in order to obtain good clinical benefits.
2.Application of assisted reproductive technology in fertility pre-servation and promotion for women with malignant tumors.
Chunmei MA ; Xiaoling HU ; Shanshan ZHANG ; Lanfeng XING ; Yingwei ZHANG ; Yimin ZHU
Journal of Zhejiang University. Medical sciences 2025;():1-10
OBJECTIVES:
To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types.
METHODS:
We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up.
RESULTS:
Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence.
CONCLUSIONS
Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.
3.Efficacy and safety of PCSK9 inhibitors combined with statins in the treatment of hypercholesterolemia
Chaowei ZHANG ; Shouyu GUO ; Yingwei CHEN
Chinese Journal of Clinical Medicine 2025;32(6):1010-1016
Objective To evaluate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with high-intensity statins in the treatment of hypercholesterolemia. Methods A retrospective study was conducted on patients diagnosed with hypercholesterolemia at the First Affiliated Hospital of Zhengzhou University from June 2023 to December 2024. Patients were divided into an observation group (receiving alirocumab combined with atorvastatin) and a control group (receiving atorvastatin alone) based on their actual treatment regimens. The treatment period was 6 months. Primary outcome measures included lipid parameters such as low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and lipoprotein (a), (Lp[a]); carotid ultrasound parameters such as intima-media thickness (IMT), plaque number, plaque area; and inflammatory markers including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). Adverse reactions were also recorded. Results A total of 103 patients with hypercholesterolemia were included, with 53 in the observation group and 50 in the control group. After six months of treatment, the observation group demonstrated significantly greater reductions in LDL-C, total cholesterol (TC), triglyceride (TG), and apoB compared to the control group (P < 0.05). The reduction in plaque count and plaque area were also significantly greater in the observation group than in the control group (P=0.004). The reduction in TNF-α was also greater in the observation group (P=0.006). There was no statistically significant difference in the incidence of adverse reactions between the two groups. Conclusions PCSK9 inhibitors combined with high-intensity statins can effectively reduce LDL-C levels, improve carotid atherosclerotic plaques and systemic inflammatory status in patients with hypercholesterolemia, and demonstrate good safety in real-world clinical settings.
4.Expression and significance of heat shock protein 70,apoptosis-associated speck-like protein and vitamin D in children with febrile seizures
Meng XIE ; Yajing ZHANG ; Jing SHI ; Yingwei YANG
Journal of Clinical Medicine in Practice 2025;29(12):77-81
Objective To investigate the expression and significance of heat shock protein 70(HSP70),apoptosis-associated speck-like protein(ASC),and vitamin D in children with febrile seizures(FS).Methods A total of 200 children with FS admitted to our hospital from June 2022 to December 2023 were selected as FS group,including 158 cases of simple FS and 42 cases of complex FS.Another 200 febrile children without FS were selected as fever group,and 50 healthy children were selected as control group.The differences in HSP70,ASC mRNA,and vitamin D expression a-mong the three groups were compared.The differences in HSP70,ASC mRNA,and vitamin D ex-pression at different time points in children with different types of FS were compared.The influencing factors and predictive value of complex FS were analyzed.Results At admission,the expression lev-els of HSP70 and ASC mRNA gradually decreased,while the vitamin D levels gradually increased in the FS group,fever group,and control group,with statistically significant between-group differences(P<0.01).One hour after admission,the levels of HSP70 and ASC mRNA in both the complex FS group and the simple FS group were lower than those at admission(P<0.01).The levels of HSP70 and ASC mRNA in the complex FS group at admission and 1 hour after admission were higher than those in the simple FS group,while the vitamin D level was lower(P<0.01).Multivariate Logistic regression analysis showed that elevated HSP70 and ASC mRNA levels at admission were independ-ent risk factors for complex FS(P<0.001),while elevated vitamin D level was an independent protective factor for complex FS(P<0.001).The area under the curve(AUC)for HSP70,ASC mRNA,and vitamin D in assessing complex FS were 0.785(95%CI,0.721 to 0.840),0.766(95%CI,0.701 to 0.823),and0.760(95%CI,0.695 to 0.817),respectively.The combined AUC of HSP70,ASC mRNA,and vitamin D for assessing complex FS was 0.915,with a sensitivity of 90.48%and a specificity of 81.65%.The AUC of combined assessment of complex FS by vari-ous factors was greater than that of HSP70,ASC mRNA,and vitamin D alone(Z=2.743,2.749,3.086,P=0.006,0.006,0.002).Conclusion The levels of HSP70 and ASC mRNA are elevat-ed,while the vitamin D level is reduced in children with complex and simple FS.The combined as-sessment of HSP70,ASC mRNA,and vitamin D at admission has high value in assessing complex FS.
5.Ubiquitinome profiling of cysteinyl aspartate-specific proteinase-2 deficient cells under heat shock
Yi CHEN ; Yingwei GE ; Lijie ZHOU ; Siying WANG ; Lingqiang ZHANG
Military Medical Sciences 2025;49(8):561-568
Objective To profile ubiquitination in cysteinyl aspartate-specific proteinase-2(CASP2)deficient cells under heat shock and investigate the role of CASP2 in stress response.Methods Ubiquitination levels in subcellular fractions of control and C ASP2 knockout(KO)cells were detected via Western blotting.After 2 hours of heat shock treatment,Soluble Ⅱ and Pellet fractions were collected from both control and CASP2 KO cells for ubiquitinome analysis.Anti-di-glycine remnant(K-ε-GG)antibody-based proteomic analysis was performed to identify differentially ubiquitinated proteins and associated key signaling pathways.Proteins that displayed significantly upregulated ubiquitination in CASP2 KO cells under heat shock were subjected to His-tag pull-down assays to find out whether CASP2 regulated the ubiquitination of these proteins.Results Under heat shock,CASP2 KO cells displayed significantly higher accumulation of overloaded ubiquitinated conjugates in the Pellet fraction compared to controls.Ubiquitinomics analysis revealed substantial alterations in protein ubiquitination patterns following CASP2 KO.One hundred proteins exhibited significantly elevated ubiquitination levels while 36 proteins had their ubiquitination reduced relative to controls.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis indicated that hyper-ubiquitinated proteins were primarily associated with Huntington disease,Alzheimer disease,bile secretion,carbon metabolism and autophagy.His-tag pull-down assays combined with Western blotting revealed increased ubiquitination of nicotinamide adenine dinucleotide reduced-ubiquinone oxidoreductase 1 beta subcomplex subunit 3(NDUFB3)and autophagy-related protein 9A(ATG9A)in CASP2 KO cells under heat shock.Conclusion Overloaded ubiquitinated conjugates are accumulated due to CASP2 deficiency during heat shock.CASP2 modulates ubiquitination levels through multiple signaling pathways.
6.Feasible analysis of DR long board detector in clinical application
Wenhai WANG ; Shaotian JIA ; Guangning YIN ; Junfeng SONG ; Lixin ZHANG ; Yingwei ZHAO
China Medical Equipment 2024;21(3):24-28
Objective:To explore the feasibility of long board detector of digital radiography(DR)in clinical application.Methods:The long board detector(detector)was erected and placed upright.The scale long ruler with marked metal lead wire was placed at 20 cm in front of the center of long axis of the board of detector,which paralleled medial axis.Three test cards of spatial resolution were respectively placed at three positions(upper,middle and lower)of detector,and they were stuck on the board of detector as 30cm intervals between each other and 45° position.The exposures were conducted at 100,150,and 200 cm of source image distance(SID).The incident doses were tested,which obtained from different SID spots of upper,middle and lower positions of detector.The spatial resolutions of 3 positions were determined through observed the images of cards.The ratio of the marked scale length with metal lead wire to actual length of lead wire was measured through the projection of the scale length,so as to obtain the amplification rate of different spot positions.The spatial distribution of effective focal plane on the direction of long axis of detector,and the morphological change of that were observed.Results:When SID spots were respectively 100,150 and 200cm,the amplification rates of images decreased with increasing SID.The difference of amplification rates among three SID spots was significant(F=223.80,P<0.001).There was significant difference in the corresponding radiation doses among different SID spots(F=7.57,P<0.05).The spatial resolution was constantly 1.8 LP/mm.There was heel effect along with the direction of short axis of detector.The effective focal spot on the direction of long axis of detector appeared up-down symmetrical display.Conclusion:The long board detector of DR equipment has realized the capture for the images of the overall length of spine or the overall length of lower limbs in one exposure,which can meet the clinical requirement,and improve the detection efficiency of X-ray.
7.Mechanisms for phase separation between TDP-43 and ubiquitin in vitro
Lijuan HE ; Lijie ZHOU ; Yingwei GE ; Lingqiang ZHANG
Military Medical Sciences 2024;48(2):81-87
Objective To explore the characteristics and mechanism of phase separation between TAR DNA binding protein-43(TDP-43)and ubiquitin.Methods The TARDBP gene and its truncated genes were inserted into vectors to construct recombinant plasmids for expression and protein purification.The phase separation system of ubiquitin and TDP-43 was constructed in vitro.The characteristics of the droplets formed via liquid-liquid phase separation were observed by fluorescence microscopy.The plasmids of ubiquitin and TDP-43 were co-transfected into HEK293T cells to observe aggregates containing TDP-43 and ubiquitin and find out whether TDP-43 could be ubiquitinated.Results The GFP-8Ub,TDP-43 full-length(FL)and truncated proteins were purified.TDP-43 FL and C-terminal domain(CTD)proteins were able to form droplets via phase separation with ubiquitin.The droplets changed into solid-like aggregates after prolonged incubation.Insolvable aggregates containing TDP-43 and ubiquitin were formed.TDP-43 was ubiquitinated under stress conditions in HEK293T cells after being co-transfected with ubiquitin and TDP-43 recombinant plasmids.Conclusion TDP-43 undergoes co-phase separation with ubiquitin,mainly driven by the multivalent interaction between TDP-43′s CTD structural domain and ubiquitin.The droplets finally form aggregates with solid-like properties.Under stress conditions,especially when the protein homeostasis is disrupted,TDP-43 and ubiquitin form aggregates while TDP-43 is ubiquitinated.This study reveals the basic mechanism of TDP-43 co-phase separation with ubiquitin and liquid-solid transformation.
8.Clinical features and therapeutic effects of patients with demodex blepharitis
Yanru HE ; Wanyue LI ; Yingwei WANG ; Zifeng ZHANG
International Eye Science 2024;24(12):1964-1969
AIM:To investigate the differences in clinical features and therapeutic effects of the tea tree oil wipes combined with deep massages of the meibomian glands for different age groups of patients with demodex blepharitis.METHODS:The clinical data of 146 patients(292 eyes)diagnosed with demodex blepharitis, hospitalized in Department of Ophthalmology, Xijing Hospital from January 2023 to October 2023, was collected in this retrospective study, and the patients were divided into group A(64 cases with 128 eyes)aged ≤45 years old and group B(82 cases with 164 eyes)aged >45 years old according to different ages. The differences in total numbers of binocular mites, Schirmer I tests, symptom and sign scores before, and at 1 and 3 mo after the treatment of the tea tree oil wipes combined with deep massages of the meibomian glands were analyzed between the two groups.RESULTS: Before the treatments, the total number of the mites in the group A [7(6, 8)] was lower than that in the group B [8(7, 9.25); P<0.05]. The dry eye score in the group A [6(6, 7)] was lower than that in the group B [11(10, 12); P<0.001], and the ocular surface irritation symptom score in the group A [10(9, 11)] was higher than that in the group B [6(6, 7); P<0.001]. Both groups experienced a decrease in mite counts and improvement in symptoms and signs scores at 1 mo after treatment, and there was still a degree of improvement in all clinical indicators, with patients in the group B showing a further reduction in mite counts [-1(-3, 0)] even after the treatment was continued for 3 mo.CONCLUSION:The total numbers of mites in patients of older than 45 years old were higher than those in patients of ages younger than 45, and older patients have more serious dry eyes, with less serious symptoms of ocular surface irritation. The treatment can effectively reduce the number of mites in patients of different ages with demodex blepharitis, but the outcomes of Schirmer I tests do not change after the treatment. Longer treatment duration provide sustained clinical benefits.
9.Effects of EPO on NK cell activation receptor and HMGB1/Beclin-1 signaling pathway in diabetic nephropathy rats
Limin ZHAO ; Yajing LI ; Yonggang ZHANG ; Yingwei ZHANG
Chinese Journal of Immunology 2024;40(7):1392-1398
Objective:To explore the mechanism of EPO on activating receptors of NK cells in rats with diabetic nephropathy based on HMGB1/Beclin-1 signaling pathway.Methods:Forty SPF male SD rats were randomly divided into normal group(A),model group(B),metformin group(C)and EPO group(D),with 10 rats in each group.Diabetic nephropathy modeling was performed on groups B,C and D using high-fat diet and streptozotocin.After successful modeling,group C was given metformin 100 mg/kg by intra-gastric administration,and group D was intraperitoneal injection of EPO 100 U/kg.Group A and B were given normal saline at the same volume by intragastric administration simultaneously.After successful modeling,the remaining 20 rats were randomly divided into group E and group F.Group E was given 30 mg/kg HMGB1 inhibitor by intragastric administration,group F was given 30 mg/kg HMGB1 inhibitor by intragastric administration and 100 U/kg EPO by intraperitoneal injection.HK-2 cells were taken and divided into high glucose+HK-2 cells(HH)group,EPO+high glucose+HK-2 cells(EH)group,glycyrrhizin L+high glucose+HK-2 cells(LH)group,and cultured with glucose for cell experiment.Blood glucose was detected by glucose analyzer,biochemical indexes were de-tected by automatic biochemical analyzer,and renal pathological morphology of rats was detected by PAS staining.Expression of HMGB1/Beclin-1 protein was detected by Western blot,and expressions of NK cell activated receptors were detected by RT-PCR and immunohistochemistry.Results:Compared with group A,blood glucose,24 h urine volume,blood glucose curve,BUN,Scr,UAlb contents in blood and urine,mRNA and protein expressions of NKp30,NKp44,NKp46 in group B were significantly increased(P<0.05),while body weight was significantly decreased(P<0.05).Compared with group B,blood glucose,24 h urine volume,blood glucose curve,BUN,Scr,UAlb contents in blood and urine,mRNA and protein expression of NKp30,NKp44 and NKp46 in group C and group D were significantly decreased(P<0.05),while body weight was significantly increased(P<0.05),renal pathology was also significantly improved,the changes of group D was significantly higher than that of group C(P<0.05).Compared with group A,expression of HMGB1/Beclin-1 protein in renal tissues of rats in group B was significantly increased(P<0.05),and expression of HMGB1/Beclin-1 protein in renal tissues of rats in groups C,D,E and F was significantly decreased(P<0.05),expression of HMGB1/Beclin-1 protein in group D was significantly decreased compared with group C(P<0.05),there was no significant difference between group E and group D,and expression of HMGB1/Beclin-1 protein in group F was significantly decreased compared with group E.HMGB1/Beclin-1 protein expression was positively correlated with NKp30,NKp44 and NKp46 mRNA(P<0.05).Compared with HH group,proliferation rates of EH and LH groups were significantly increased(P<0.05),while apoptosis rate and HMGB1/Beclin-1 protein expression were significantly decreased(P<0.05),there was no significant difference between LH group and EH group(P>0.05).Conclusion:EPO can effectively reduce expressions of NK cell activated receptors and inhibit HMGB1/Beclin-1 signaling path-way in diabetic nephropathy rats,suggesting that EPO may exert its effect by regulating NK cell activated receptors and HMGB1/Beclin-1 signaling pathway.NK cell activation receptors expressions are positively correlated with HMGB1/Beclin-1 signaling pathway.
10.Effect of diquafosol sodium combined with sodium hyaluronate on dry eye after pterygium surgery
Yingwei WANG ; Yanru HE ; Jing BAI ; Xiaoyan LIU ; Yan ZHANG ; Jian ZHOU
International Eye Science 2024;24(8):1303-1307
AIM:To observe the clinical efficacy of 3% diquafosol sodium eye drops combined with sodium hyaluronate eye drops in the treatment of dry eyes after pterygium surgery with lacrimal insufficiency.METHODS: A total of 64 cases(64 eyes)of pterygium patients with lacrimal insufficiency were treated with pterygium resection combined with limbal stem cell transplantation, and they were given routine anti-inflammatory and infection prevention treatment postoperatively. In terms of postoperative dry eye treatment, all patients were randomly divided into two groups. The observation group was treated with 3% diquafosol sodium eye drops combined with sodium hyaluronate eye drops, and the control group was treated with sodium hyaluronate eye drops. The break-up time of tear film(BUT), fluorescein(FL), Schirmer's Ⅰ test(SⅠt), ocular surface disease index(OSDI)score, central corneal thickness(CCT)changes, adverse reactions and complications were observed and compared between the two groups at different times postoperatively.RESULTS: Both groups of pterygium patients were accompanied with mild to moderate dry eyes with insufficient tear secretion preoperatively. At 2 wk after operation, both groups showed shorter BUT and higher FL score compared with those preoperatively(P<0.05). There was no significant difference between the two groups(P>0.05). At 4 wk after operation, BUT in the observation group was prolonged, OSDI score was decreased(both P<0.05), and FL score in both groups was decreased compared with those at with 2 wk after operation(P<0.05). The observation group was better than the control group(P<0.05). At the first day after operation, the CCT of the two groups was thicker than that preoperatively(P<0.05), and there was no significant difference in SⅠt between the two groups before and after operation(P>0.05).CONCLUSION: In the treatment of dry eye after pterygium surgery with lacrimal insufficiency, 3% diquafosol sodium eye drops combined with sodium hyaluronate eye drops can effectively reduce the postoperative dry eye symptoms, and its clinical effect is better than that of sodium hyaluronate eye drops alone.

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