AIM: To compare the control effect of spherical and toric orthokeratology on low-to-moderate myopia with astigmatism(-1.00--1.50 DC)in adolescents.METHODS: The clinical data of 119 cases(119 eyes)of low-to-moderate myopia with astigmatism(-1.00--1.50 DC)adolescents who were treated and fitted with orthokeratology in the ophthalmology department of Sichuan Provincial People's Hospital from June 2021 to January 2022 were retrospectively analyzed. They were divided into spherical group, with 65 cases(65 eyes), and toric group, with 54 cases(54 eyes)according to the type of orthokeratology. The changes of uncorrected visual acuity(UCVA), axial length and corneal astigmatism before and after wearing lenses were recorded to evaluate the therapeutic effect.RESULTS: The UCVA of both the groups significantly improved at 1 and 2 a after wearing lenses(all P<0.01); corneal astigmatism decreased, but there was no significant difference(all P>0.05); the axial length was longer than that before wearing lenses(P<0.01). There were no statistical significant differences in the UCVA and corneal astigmatism between the spherical group and the toric group(Fintergroup=0.829,Pintergroup=0.364; Fintergroup=0.997,Pintergroup=0.320); and there were no statistical significant differences in the axial length growth between the spherical group and the toric group after wearing lenses for 1 a(0.18±0.11 mm vs 0.17±0.14 mm), and 2 a(0.17±0.10 mm vs 0.16±0.10 mm; all P>0.05).CONCLUSION: Both orthokeratology lenses can improve the UCVA, reduce corneal astigmatism, and delay axial length growth of adolescents with low-to-moderate myopia with astigmatism(-1.00--1.50 DC), and there are no significant differences in the control effect of spherical design orthokeratology and the toric design orthokeratology on myopia.

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective:To analyze the drug resistance characteristics of Klebsiella pneumoniae in the nasopharynx of hospitalized patients in North China from 2022 to 2023. Methods:From November 2022 to July 2023, nasopharyngeal swabs were collected from 100 inpatients in Affiliated Hospital of North China University of Science and Technology, and Klebsiella pneumoniae was isolated and cultured. At the same time, the clinical data of the patients were collected, including gender, age, department, clinical diagnosis of disease type, etc. The minimum inhibitory concentration of strains was detected by an automatic bacterial drug sensitivity system. The drug resistance genes, ST types, capsule serotypes and population structure of the strains were analyzed by whole genome sequencing and data analysis. Results:Klebsiella pneumoniae was isolated from 55 nasopharyngeal swabs of 100 inpatients(55.00%). Among the 55 inpatients with Klebsiella pneumoniae in the nasopharynx, 70.91% (39/55) were male, with an age distribution concentrated between 61 and 80 years old (58.18%, 32/55), and 50.91% (28/55) were in intensive care units (ICU). The main underlying disease type was nervous system disease (49.09%, 27/55). The results of drug sensitivity showed that the non-susceptibility rates of 55 strains of Klebsiella pneumoniae to cephalosporins, quinolones, aztreonam and nitrofurantoin were all more than 80.00%. Twenty-eight carbapenem-resistant Klebsiella pneumoniae strains (50.91%), 47 extended-spectrum β-lactamase producing strains (85.45%), and 48 multi-drug-resistant strains (87.27%) were detected. A total of 11 antibiotic resistance genes were detected, including carbapenems (carrying rate 76.36%) and extended-spectrum β-lactamase (carrying rate 96.36%). The 55 strains could be divided into 17 ST types, and the most common type was ST11 (25.45%). The 55 strains were divided into 18 capsular serotypes, among which K102 was the most prevalent (23.64%). OXA-1_ST307_K102 (21.82%) and KPC-2_ST5492_K125 (18.18%) were the dominant clones, distributed in the Department of Neurosurgery and ICU. The result of whole genome sequence analysis showed that there were four clusters with high homology among the 55 strains. The strains from the ICU formed two independent clusters, and strains from the Neurology ICU and Neurosurgery department formed one cluster respectively. Conclusion:The carrying rate of Klebsiella pneumoniae in the nasopharynx of inpatients is high, and the drug resistance of the strains is serious. There are many types of drug-resistant genes.

Objective To construct and identify an organoid model of human placental site trophoblastic tumor(PSTT).Methods The tumor cells were obtained by digesting and separating the PSTT tissues and then embedded in Matrigel.The organoids were cultured in the specific organoid medium.The histological morphology of the organoid model was observed by HE staining and the expression levels of the PSTT specific markers[human placental prolactin(HPL),human leukocyte antigen-G(HLA-G)and placental alkaline phosphatase(PLAP)]were detected by immunohistochemistry and immunofluorescence,so as to evaluate the consistency between the organoid model and the PSTT tissue.Meanwhile,the morphology and forming efficiency of the constructed model were observed under a microscope after primary culture,passage generation and cryopreservation to evaluate its potential application as an organoid model in basic and clinical translational research of PSTT.Results The constructed organoid model could proliferate stably,growing from small microspheres into compact solid spheres or spheres with follicle-like structures,and could passage after fully grown in 7-10 days.The cell state remained stable after passage,frozen storage and recovery.HE staining showed that the morphology of the cells in the organoids was similar to that of the primary PSTT tumor cells,and immunofluorescence staining showed that the organoids highly expressed HLA-G and lowly expressed β-HCG,indicating that the constructed organoid model mainly contained intermediate trophoblast.Conclusion The adult-derived PSTT organoid(ADPO)models were successfully established.

Purpose/Significance To design a comprehensive data platform to meet the needs of collecting and sharing survey data on meteorological sensitive diseases,so as to enhance monitoring capabilities for meteorological sensitive diseases in China.Method/Process Through various methods such as data extraction,data exchange,data import and customized collection,disease data,meteoro-logical data,environmental data and diagnosis and treatment data are processed and integrated into the platform for unified management.Result/Conclusion This platform realizes the functions of data collection,aggregation,visualization display and data sharing,which can provide support for scientific researchers in various bases across the country to better manage and utilize meteorological sensitive disease survey data.

AIM:To investigate the mechanism of chronic stress-induced myocardial injury in atherosclerotic(AS)mice.METHODS:Eight-week-old SPF-grade male ApoE-/-mice and C57BL/6J mice used in this study.The mice received dietary intervention for 10 weeks followed by pathological examination to test the successful AS modeling.After AS establishment,the mice were exposed to chronic unpredictable mild stress(CUMS)for 6 weeks and then divided into five groups:control,CUMS,AS-regular diet(AS-r)+CUMS,AS-high-fat diet(AS-h),and AS-h+CUMS.During CUMS,open-field test and sucrose preference test were performed on mice in all groups.Blood lipids were characterized using an automatic biochemical analyzer.Hematoxylin-eosin(HE)and oil red O staining were performed to evaluate pathological changes in the aortic root.Cardiac function was assessed using echocardiography.The serum concentration of myocardial injury markers and ATP content was detected by ELISA.Transmission electron microscopy was employed to observe the ul-trastructure of myocardial mitochondria.Myocardial mitochondrial oxygen consumption rate was determined using the Oxy-graph-2k high-resolution respiratory energy metabolism analyzer.Western blot was conducted to quantify the expression of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3.RESULTS:compared with the Control group,the total distance traveled,the number of entries into the central area,and the sucrose preference rate were significantly decreased in all CUMS groups(P<0.05).All AS groups exhibited varying levels of lipid deposition and endo-thelial damage in the aortic root,along with a significant reduction in cardiac function(P<0.05)and varying degrees of myocardial injury(P<0.05).In the AS-h+CUMS and AS-r+CUMS groups,myocardial mitochondrial structure was signifi-cantly disrupted.ATP content was significantly reduced(P<0.05),and the rates of oxygen consumption associated with mitochondrial respiratory chain complex I,mitochondrial respiratory chain complexes I+II,and the maximum respiratory capacity of the electron transport system were all significantly decreased(P<0.05).Moreover,the protein levels of Bax and cleaved caspase-3 were significantly increased(P<0.05),while that of Bcl-2 protein was significantly decreased(P<0.05).CONCLUSION:Chronic stress triggers mitochondrial non-steady-state load by disrupting myocardial structure and energy metabolism in AS mice,promoting myocardial cell apoptosis and myocardial injury.

The complexity of coding surgical procedures related to renal replacement therapy in nephrology stems from a deficiency in clinical knowledge regarding renal replacement therapies and an incomplete understanding of the classification rules within the ICD-9-CM-3 coding system.This paper delves into the clinical aspects of renal replacement therapy and organizes the corresponding coding classification rules,clarifying the codes for various treatment modalities.For instance,the establishment of dialysis access is coded as 38.95 for hemodialysis venous intubation,39.27 for vascular fistula,and 54.93 for peritoneal dialysis intubation via a cutaneous peritoneal stoma.Maintenance hemodialysis is coded as 39.95,while peritoneal dialysis is coded as 54.98.The removal of dialysis catheter is differentiated into surgical and non-surgical;surgical removal is coded as 86.05,and non-surgical removal as 97.86 or 97.89.For instances of internal fistula stenosis or thrombosis,balloon dilation is coded as 39.50.Stent implantation for stenosis or isolation of a false aneurysm is coded as 39.90 for bare stent,and 00.55 for covered stents.The resection and reconstruction involving stenosis,thrombus segments,or false aneurysms,are coded as 39.42.This classification aims to improve the accuracy of coding for such procedures.