AIM:To investigate the clinical efficacy of phakic implantable collamer lens(ICL)implantation in correcting low-to-moderate myopia.METHODS: Retrospective study. A total of 48 patients(85 eyes)with low to moderate myopia who underwent ICL implantation were included in the study. The changes in uncorrected visual acuity(LogMAR), corrected visual acuity(LogMAR), refractive outcomes, intraocular pressure, vault and endothelial cell were observed at 1 a postoperatively.RESULTS: At 12 mo postoperatively, uncorrected and best-corrected visual acuity were -0.10(-0.20, -0.10)and -0.10(-0.20, -0.10), respectively, with an efficacy index of 1.07±0.13 and a safe index of 1.10±0.14. The difference between the actual corrected diopter and the expected corrected diopter was 91%(77/85)in the range of ±0.50 D, and 100%(85/85)in the range of ±1.00 D. The mean vault was 501.16±210.46 μm at 12 mo postoperatively. There was no significant difference in corneal endothelial cell density between preoperative and 6 and 12 mo postoperatively(F=1.050, P=0.352). All patients had no anterior subcapsular opacification, cataract, pupillary block, or other sight threatening complications during follow-up.CONCLUSION: ICL implantation for the correction of low to moderate myopia has good efficacy, safety and predictability.

Objective To establish an indirect enzyme-linked immunosorbent assay(ELISA)method for testing the concentration of a monoclonal antibody target tumor necrosis factor-α(TNF-α)in animal serum.Methods The critical parameters of the method including coating concentration of human TNF-α,source,concentration and stability of HRP-labeled goat anti-human immunoglobulin G(IgG)were investigated.The specificity,accuracy,precision,linearity and Limited of Determination of the method were investigated.Results The critical parameters of the method were confirmed as below:TNF-α was coated at 400 ng·mL-1;HRP labeled goat anti-human IgG antibody was diluted at 1:3.0 ×105;the diluted horseradish peroxidase labeled goat anti-human IgG antibody is well stored at 4 ℃ for 3 days.Meanwhile the method was confirmed to have good specificity,the recovery rate ranged from 84.00％to 106.82％,the coefficient of variation of different antibody concentration levels were no more than 10％;the method had a good linearity and the standard curve was y=(-8.37×103-2.37 × 106)/[1+(x/29.80)106]+2.37 × 106(R2=0.999);the limit of quantification was 1 ng·mL-1,all of which met the requirements.Conclusion A accurate and robust ELISA method was developed to test the concentration of anti-TNF-α monoclonal antibody in serum.

Perimenopause is a vulnerable stage for emotional disorders such as anxiety and depression,which is the result of a combination of bio-psycho-social factors,and it seriously affect the quality of life of perimenopausal women.Therefore,finding safe and effective treatments is one of the urgent problems in modern medicine.This paper summarises the etiology and treatment of emotional disorder in perimenopause in Chinese and western medicine,and on this basis,this paper discusses the clinical diagnostic and treatment strategies and research ideas of acupuncture in treating emotional disorder in perimenopause,thus providing a new idea for the prevention and treatment of emotional disorder in perimenopause.

Objective To study the in vitro expression of three phenylalanine hydroxylase(PAH)mutants(p.R243Q,p.R241C,and p.Y356X)and determine their pathogenicity.Methods Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein.Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells.Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants,and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay.Results Bioinformatics analysis predicted that all three mutants were pathogenic.The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control(P>0.05),while the mRNA expression level of the p.Y356X mutant significantly decreased(P<0.05).The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control(P<0.05).The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control(P<0.05),while there was no significant difference between the p.R243Q mutant and the wild type control(P>0.05).Conclusions p.R243Q,p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells,with p.R241C and p.Y356X mutants also affecting the function of PAH protein.These three PAH mutants are to be pathogenic.[Chinese Journal of Contemporary Pediatrics,2024,26(2):188-193]

Objective This research was to evaluate the integrity of visual pathways in patients with Parkinson disease(PD)by visual evoked potential(VEP),especially those with visual hallucinations.Methods A total of 76 PD patients were enrolled in this study.According to the presence or absence of visual hallucinations,they were divided into two groups:24 patients with visual hallucinations and 52 patients without visual hallucinations.At the same time,22 sex-and age-matched healthy controls were selected.All subjects underwent VEP test,and Unified Parkinson's Disease Rating Scale(UPDRS),Hoehn&Yahr stage(H-Y stage)and Mini-mental State Examination(MMSE)were performed for PD patients.Results The latencies of N75,P100 and N135(88.26±10.47)ms,(118.48±8.53)ms,(144.71±9.48)ms were significantly longer in PD patients with visual hallucinations than in those without visual hallucinations[(79.00±6.96)ms,(108.60±7.01)ms,(135.95±8.21)ms](P<0.001).However,the amplitudes of N75-P100 and N135-P100[4.35(2.73,7.30)μV]、[6.40(4.15,9.90)μV]were significantly lower in PD patients with visual hallucinations than in those without visual hallucinations[7.10(5.28,9.98)μV]、[9.05(6.30,12.60)μV](P<0.001,P=0.037).Correlation analysis showed that P100 latency was positively correlated with H-Y stage,UPDRS-I,UPDRS-II,and UPDRS-III scores(r=0.537,P=0.007),(r=0.635,P=0.001),(r=0.594,P=0.004)and(r=0.558,P=0.005)in PD visual hallucinations group.Conclusion The integrity of the visual pathway is impaired in PD patients with visual hallucinations.As the progression of the disease,the impairment of visual pathway may be further deteriorated,which may extend beyond the upper pathways of visual pathway to the brain.

Objective:To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia (AML)cells and its molecular mechanism,and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.Methods:After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol.The proliferation activity of cells was detected by CCK-8 method,and the expression changes of apoptotic proteins and PI3 K/AKT signaling pathway proteins were detected by Western blot. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR ) was used to detect the expression of Caspase family mRNA.Results:Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells,promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein (P<0.05).When Curcumol interferes with HL-60 and KG-1 cells,it can also induce programmed cell death of AML by inhibiting PI3 K/AKT signaling pathway.In addition,after the intervention of Curcumol,the expression of Caspase 3,Caspase 6,Caspase 8 and Caspase 9 were up-regulated in HL-60 cells (P<0.05 ),the expression of Caspase 3,Caspase 8 and Caspase 9 were significantly up-regulated in KG-1 cells (P<0.01),while the expression of Caspase 6 was weakly affected (P<0.05 ),but low concentration of Curcumol (<60 μg/ml)had no effect on the expression of Caspase 6 in KG-1 cells (P>0.05).Conclusion:Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway,affecting the expression of Bcl-2 family proteins,and promoting the activation of core members of Caspase family,so as to play an anti-leukemia role.

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.
Female ; Animals ; Mice ; Tumor Suppressor Protein p53/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Hematoxylin ; Signal Transduction/physiology* ; TOR Serine-Threonine Kinases ; Sirolimus ; RNA, Messenger

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Antigens, CD19 ; Chemokine CCL19 ; Immunotherapy, Adoptive ; Interleukin-7 ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Programmed Cell Death 1 Receptor ; Receptors, Chimeric Antigen

Objective To investigate the effect of plateau hypoxia on the blood-brain barrier after subarachnoid hemorrhage (SAH) in rats. Methods Adult male SD rats (n = 78) were randomly divided into 4 groups: sham group (sham), SAH model group (SAH), plateau hypoxia sham group (Hp sham) and plateau hypoxia SAH model group (Hp SAH). The rat model of plateau hypoxia was established through low-pressure simulation chamber (altitude 5000 m), and the SAH model was established by endovascular perforation method. At 24 hours after SAH, neurobehavior score and SAH grade were assessed. The morphological changes of neurons and apoptosis of nerve cells in the CA1 region of hippocampal were observed by the staining of Nissl and TUNEL. The expression of phosphorylated PI3K (p-PI3K), PI3K, phosphorylated Akt (p-Akt), Akt, phosphorylated nuclear factor κB (p-NF-κB), NF-κB, matrix metalloproteinase-9 (MMP-9), occludin and claudin-5 in hippocampal were detected by the method of Western blotting. The expression of occludin and claudin-5 proteins in the CA1 region of hippocampal were observed by immunofluorescent staining. Results At 24 hours after SAH, the neurobehavior score decreased significantly and SAH grade increased significantly in the SAH and Hp SAH group (P< 0.05). Neurobehavior score decreased significantly in the Hp SAH group compared with the SAH group (P < 0.05). In the SAH group, neurons in the CA1 region of hippocampus were atrophied and deformed, the arrangement were disordered, the number of neurons decreased significantly, and the apoptosis of nerve cells increased significantly(P< 0.05). Plateau hypoxia could aggravate the morphological damage of neurons and apoptosis of nerve cells. The expression of p-PI3K/PI3K, p-Akt/Akt, occludin and claudin-5 proteins decreased significantly, while the expression of p-NF-κB/NF-κB and MMP-9 proteins increased significantly in the SAH and Hp SAH group (P< 0.05). The expression of p-PI3K/PI3K and MMP-9 proteins increased significantly in Hp SAH group compared with the SAH group. The expression of claudin-5 protein increased significantly in Hp sham group compared with the sham group (P < 0.05). Immunofluorescent staining showed that the expression of occludin and claudin-5 proteins in the CA1 region of hippocampus decreased in the SAH group. Plateau hypoxia could further decreased the expression of occludin and claudin-5 proteins. Conclusion Plateau hypoxia aggravates blood-brain barrier disruption after subarachnoid hemorrhage in rats through inhibiting PI3K/Akt/NF-κB pathway.

Objective:To analyze whether patients with myasthenia gravis (MG) have cognitive impairment and changes of brain structure, and explore the possible mechanisms of cognitive impairment in MG patients from the perspective of brain structure.Methods:Twenty-eight patients with MG admitted to Department of Neurology, First Affiliated Hospital of Soochow University from July 2019 to December 2021 were selected as MG group, and 30 family members from MG patients or healthy subjects who underwent physical examination in Physical Examination Center during the same period were selected as healthy control group. Neuropsychological test was used to evaluate the cognitive function. VBM was used to analyze the changes of brain structure on structural MRI (sMRI). Correlations of gray matter volumes of different brain regions with cognitive function between the two groups were analyzed.Results:Compared with the healthy control group, the MG group had significantly decreased scores of Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clock Painting Test (CDT), and Verbal Fluency Test (VFT), and significantly decreased Rey Auditory Verbal Learning Test (RAVLT) immediate memory and delayed memory scores, while statistically increased time consuming in Making Track Test Part A (TMT-A), and Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores ( P<0.05). Compared with healthy control group, MG group had significantly decreased gray matter volumes of the left orbital superior frontal gyrus, right orbital middle frontal gyrus, right triangular inferior frontal gyrus, left insula, left middle frontal gyrus, right superior limbic gyrus, right anterior cingulate gyrus, right lateral cingulate gyrus, left medial cingulate gyrus, left lateral cingulate gyrus, left medial superior frontal gyrus, and left dorsalateral superior frontal gyrus ( P<0.05). Correlation analysis showed that gray matter volume in the left insula was negatively correlated with time consuming in Stroop Color-Word Test-A ( r=-0.407, P=0.035). Conclusion:Patients with MG may have cognitive decline and gray matter cortical atrophy of some brain regions, and brain areas with gray matter cortical atrophy correspond to areas of cognitive impairment.