Objective:To explore the characteristics of bone marrow morphology and the phenotypic features involved in the flow cytometry (FCM)-based erythroid scoring system in low-risk myelodysplastic syndromes (MDS).Methods:A retrospective case series study was conducted. The clinical data of 13 low-risk MDS patients and 20 non-MDS patients (including 8 cases of iron deficiency anemia, 5 cases of thrombocytopenia, 3 cases of infectious diseases, and 4 cases of leukopenia) collected from outpatient or inpatient samples of multiple hospitals from March 2019 to December 2023 were retrospectively analyzed. The bone marrow morphology examination was performed using Wright-Giemsa staining; the immunophenotypic profiles of erythroblasts were evaluated by FCM; G-banding technique was used to analyze the chromosome karyotypes; next-generation sequencing technology was used for molecular biology detection.Results:Among the 13 low-risk MDS patients, there were 6 males and 7 females, with a median age of 61 years (IQR 15 years). Bone marrow morphological examination showed that the dysplastic hematopoietic morphology of erythroblasts was observed in the bone marrow of 13 low-risk MDS patients, with abnormal nuclear morphology such as odd nuclei, mother-daughter nuclei, petal nuclei, inter-nuclear bridges, multinucleated giants (including abnormal pentanucleated forms), and small megakaryocytes; pathological hematopoiesis in bone marrow accounted for 10%-15% of the erythroblasts system; FCM detection showed that the myeloid primitive cells occupied 0-1.2% of nuclear cells in the bone marrow of low-risk MDS group, expressing CD117, HLA-DR and CD33, partially expressing CD34 and CD38, and not expressing CD19, CD56 and CD7; the developmental pattern of granulocyte CD13/CD16/CD11b was basically normal; partial expression of CD36 and CD71 in erythroblasts was missing. The expression of CD36 and CD71 in erythroblasts of non-MDS group was normal. The expression rates of CD36 in low-risk MDS group and non-MDS group were (51.57±0.13)% and (93.50±0.03)%, respectively ( t = -6.32, P < 0.001), while the expression rates of CD71 were (22.24±0.05)% and (87.94±0.04)%, respectively ( t = -9.47, P < 0.001), with statistically significant differences. The coefficient of variation (CV) of mean fluorescence intensity of CD36 in low-risk MDS group and non-MDS group were 155±8 and 57±10, respectively ( t = 29.18, P < 0.001), and the CV of mean fluorescence intensity of CD71 was 204±33 and 56±6, respectively ( t = 19.43, P <0.001), with statistically significant differences. Among 13 low-risk MDS patients, 4 had abnormal bone marrow chromosome karyotypes, including -7, 8, del(20q), -Y, +15, etc; 5 cases had clonal gene mutations detected by next-generation sequencing, such as ASXL1, SRSF2, TET2, DNMT3A, etc; no 5q-, SF3B1 or TP53 gene mutation was detected. Patients were followed up until December 2023, among the 13 low-risk MDS patients, 7 cases achieved good clinical efficacy, 2 cases transformed into high-risk MDS with excess blasts after 1 year, 3 cases transformed into acute myeloid leukemia M 2 2 years later, and the treatment efficacy of 1 case was unknown. Conclusions:Low-risk MDS patients have pathological hematopoiesis of erythroblasts morphologically. FCM detection shows abnormal developmental patterns of erythroblasts combined with elevated CV of average fluorescence intensity, and often accompanied by genetic abnormalities.

Objective:To investigate the risk factors for detecting clinically significant prostate cancer (CSPCa) in patients with Prostate Imaging Reporting and Data System (PI-RADS) score≤3 on multi-parameter magnetic resonance imaging (mpMRI).Methods:Retrospective analysis was performed on the case data of 335 patients with suspected prostate cancer and PI-RADS score ≤3 who were admitted to Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2022. All patients underwent 24-needle prostate biopsy. Clinical data such as age, body mass index, past medical history, serological laboratory indicators, and mpMRI imaging data were collected. The patients were grouped according to whether the puncture pathology was CSPCa or not, and the differences in clinical data between the two groups were analyzed by t-test, rank sum test and Chi-test. Multivariate Logistic regression analysis was further used to determine independent risk factors for MRI invisible prostate cancer, and receiver operating characteristics (ROC) curves were drawn. At the same time, further subgroup analysis was conducted based on whether prostate-specific antigen (PSA) was positive before puncture and PI-RADS score, respectively, and the same statistical method was used to further determine the influence of different serological indicators and PI-RADS score on the analysis results of risk factors. Results:Among all patients, 81 were CSPCa patients and 254 were non-CSPCa patients. Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) and PI-RADS score of 3 were independent risk factors for MRI invisible prostate cancer. At the same time, compared with suspected lesions located only in the transitional zone, the incidence of CSPCa in patients with suspected lesions located in the peripheral zone would increase, and the incidence of CSPCa would further increase when suspected lesions were found in both the transitional zone and the peripheral zone. In PSA-negative patients, only suspected lesion location was an independent risk factor for MRI invisible prostate cancer, while in PSA-positive patients, prostate volume, PSAD, and PI-RADS scores were independent risk factors. In subgroup analysis with different PI-RADS scores, suspicious lesions in both the transitional zone and peripheral zone indicate a higher likelihood of CSPCa. For patients with PI-RADS scores of 1 to 2, suspicious lesions in the peripheral zone alone may also indicated CSPCa, while for patients with PI-RADS scores of 3, the lower free prostate-specific antigen/total prostate-specific anti-principle was more accurate in predicting CSPCa.Conclusions:For patients who are clinically suspected of prostate cancer but whose PI-RADS score is less than or equal to 3 points indicated by mpMRI, it is necessary to further focus on the results of different serological indicators according to whether their PSA is positive and PI-RADS score respectively to judge whether patients should receive systemic prostate puncture, instead of using PSA level as a single indication for puncture. At the same time, clinicians should also pay full attention to the location of suspected lesions, when they are located in the peripheral zone, or there are suspected lesions in both the peripheral zone and the transitional zone, the possibility of CSPCa should be fully considered.

Objective:To explore the independent risk factors for chemoresistance during gemcitabine plus cisplatin (GC) adjuvant chemotherapy in patients with locally advanced bladder cancer after radical cystectomy and to construct a related predictive model.Methods:The clinical data of 228 patients with locally advanced bladder cancer who received GC chemotherapy after radical cystectomy at Beijing Friendship Hospital, Capital Medical University, from January 2013 to June 2024 were retrospectively analyzed. Among them, 184 were males, and 44 were females, with an average age of (68.8±10.6)years and an average body mass index (BMI) of (24.2±3.6)kg/m 2. According to tumor progression during chemotherapy, patients were divided into a chemotherapy-resistant(CR) group ( n=59) and a non-chemotherapy-resistant(NCR) group ( n=169). Independent sample t-test, chi-square test, and non-parametric test were used to compare general clinical characteristics and relevant examination results during chemotherapy between the two groups. Multivariate linear regression analysis was used to identify independent risk factors for GC chemoresistance. Propensity score matching (PSM) was used to match the TNM stage data between the two groups, and Kaplan-Meier and log-rank tests were used to compare overall survival(OS)after matching. Results:The median number of chemotherapy cycles was 3 in the CR group and 4 in the NCR group. Compared with the NCR group, CR patients were younger [(66.3±9.4) years vs.(69.7±10.9)years], had a higher proportion of kidney transplantation history[6.8%(4/59) vs. 0.6%(1/169)], hypertension [50.8%(30/59) vs. 36.1%(61/169)], coronary heart disease[23.7%(14/59) vs.9.5% (16/169)], and hydronephrosis [13.6%(8/59) vs. 4.1%(7/169)](all P<0.05). CR patients had a higher proportion of T 4 stage [20.3% (12/59) vs. 5.9% (10/169)], N 2 stage [42.4% (25/59) vs. 8.3% (14/169)], multifocal tumors at initial diagnosis [59.3% (35/59) vs. 26.6% (45/169)], and larger maximum tumor diameter [2.5 (1.5, 3.4) cm vs. 1.6 (1.2, 2.5) cm] (all P < 0.05). The CR group showed higher proportions of long-term urinary tract infection (UTI) [90.1% (53/59) vs. 7.7% (15/169)], higher systemic immune-inflammation index (SII) [991.6 (451.0, 1577.9) vs. 462.8 (309.0, 766.7)], absolute neutrophil count [6.5(4.1, 7.8)× 10 9/L vs. 3.9 (2.9, 5.1)× 10 9/L], and platelet count [(220.0 ± 96.2)× 10 9/L vs. (191.0 ± 64.8)× 10 9/L], but lower albumin levels [(34.3 ± 4.2) g/L vs. (39.9 ± 3.8) g/L] and albumin-to-globulin ratio (A/G) [(1.2 ± 0.3) vs. (1.3 ± 0.2)] (all P < 0.05). Multivariate linear regression analysis identified only T stage and long-term UTI as independent risk factors for GC chemoresistance( P<0.05).The probability of GC chemoresistance in bladder cancer patients was calculated as: P(Chemoresistance)=[0.155×T stage+ 0.624×(long-term UTI)]×100%(long-term UTI = 1 if present during chemotherapy, otherwise=0). After PSM, survival analysis showed that the median OS was significantly higher in the NCR group (55 months) than that in the CR group (30 months) ( P=0.020). Conclusions:This study demonstrates that advanced T stage and persistent UTI are independent risk factors for GC chemotherapy resistance in locally advanced bladder cancer patients. Based on these findings, a predictive model for chemotherapy resistance probability was constructed using multivariate linear regression analysis.

Objective:To investigate the influence of genetic and environmental factors on the clinical characteristics of upper urinary tract calculi in pediatric patients.Methods:This study was a retrospective case series. The clinical data of 179 children under the age of 14 with upper urinary tract calculi treated at Beijing Friendship Hospital，Capital Medical University，from August 2014 to February 2023 were analyzed. There were 121 males（67.60%）and 58 females（32.40%），with a median age at onset of 2.10（1.14，5.17）years. Thirty-three cases（18.44%）had a family history of urinary stone disease. Stone characteristics was defined by CT，with a median stone burden（sum of the diameters of all stones）of 1.3（1.00，1.60）cm. Fifty-four（30.17%）children had staghorn calculi. Multiple stones were present in 92 cases（51.40%），and bilateral stones in 52 cases（29.05%），with hydronephrosis was present in 119 children（66.48%）. The median follow-up time was 67 months，and 36 children（20.11%）experienced stone recurrence. Dietary habits and related information were collected by electronic questionnaire，including a total of 115 children（64.25%）with an unbalanced diet，101（56.42%）with insufficient water intake，and 32 children（17.88%）with a preference for a high-protein diet. Tap water was used as the source of drinking water by 128 patients（71.51%），and 107（59.78%）took dietary supplements. Whole-exome sequencing revealed that 55 children（30.73%）carried pathogenic mutations in stone-related genes. Binary logistic regression was used for univariate analysis of above risk factors. Variables with P < 0.1 in univariate analysis and without multicollinearity were included in multivariate logistic regression to further screen for independent risk factors. Results:Multivariate analysis confirmed that carrying stone-related pathogenic gene mutations（ OR = 3.06，95% CI 1.25?7.45， P = 0.014）and insufficient water intake（ OR = 3.28，95% CI 1.14?9.47， P = 0.028）were independent risk factors for higher stone burden. A high-protein diet（ OR = 2.40，95% CI 1.03?5.63， P = 0.044），carrying stone-related pathogenic gene mutations（ OR = 4.57，95% CI 2.21?9.46， P<0.01），and a family history of stones（ OR = 3.18，95% CI 1.28 ~ 7.91， P = 0.013）were independent risk factors for staghorn calculi. Multiple stones were closely associated with a family history of stones（ OR = 2.66，95% CI 1.15-6.17， P = 0.022）and carrying stone-related pathogenic gene mutations（ OR = 3.22，95% CI 1.60-6.48， P = 0.001）. Moreover，carrying stone-related pathogenic gene mutations（ OR = 5.19，95% CI 2.52?13.82， P < 0.01）were an independent risk factor for stone recurrence，whereas dietary supplement intake was a protective factor（ OR = 0.26，95% CI 0.11?0.62， P = 0.002）. Conclusions:Genetic and environmental factors play significant roles in the occurrence and development of pediatric upper urinary tract stones. A high-protein diet as well as a positive family history of stones are independent risk factors for staghorn calculi，and insufficient water intake is a critical environmental factor for stone formation，while appropriate use of dietary supplements may help reduce the risk of stone recurrence. Genetic testing indicates that approximately 30% of children carry stone-related pathogenic gene mutations，and these patients prone to severe stone and an increased risk of recurrence.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

An imbalance between oxidative and antioxidant defense mechanisms in the body triggers oxidative stress,which causes a series of damages to the body,tissues and cells.The eye is particularly susceptible to oxidative stress due to its prolonged exposure to light and its anatomical characteristics of high metabolism and oxygen consumption.In addi-tion,inflammation,aging,genetic and environmental factors can promote the production of reactive oxygen species and weaken antioxidant defense mechanisms,which are all risk factors for oxidative stress that can lead to a variety of ocular diseases.The aim of this paper is to review the mechanisms of oxidative stress in ocular diseases such as ocular surface diseases,glaucoma,cataract,and retinopathy.At the same time,the potential therapeutic approaches to these diseases by regulating oxidative stress are discussed,so as to provide new ideas and directions for the diagnosis and treatment of ocular diseases.

N6-methyladenosine(m6A)is recognized as the most prevalent mRNA modification in mammals, intricately involved in a multitude of processes pertaining to mRNA metabolism, encompassing RNA transcription, translation, and degradation. It plays a pivotal role in various physiological functions. Under the coordinated actions of methyltransferases, demethylases, and m6A-binding proteins, m6A modifications undergo reversible changes to fulfill their diverse molecular functions.Methyltransferase-like 3(METTL3), as the core catalytic subunit of methyltransferases and the most extensively studied methyltransferase, holds a central position in m6A modification. In recent years, it has been found that METTL3-mediated m6A modification is involved in the occurrence and development of various ocular diseases, such as ocular surface diseases, glaucoma, cataract, retinal diseases, and ocular tumors, by affecting the expression of inflammatory factors and thus regulating the inflammatory response, and by regulating various pathways that affect the proliferation of cells and oxidative stress. In this paper, we comprehensively review the mechanisms under the role of METTL3 in ocular diseases, offering novel insights and perspectives for the prevention and management of these conditions.

Objective:To evaluate the efficacy of defocus incorporated multiple segments (DIMS) on spherical equivalent (SE) and axial length (AL) in myopic children.Methods:Clinical studies on the progress of DIMS lens intervention in myopia reported in CNKI, Wanfang Data, VIP, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, and Web of Science from the establishment of the database to June 2023 were searched.The experimental group and control group used DIMS lens and single vision lens (SVL) for intervention, respectively.Two researchers independently conducted the literature search, screening and data extraction based on the inclusion and exclusion criteria.Literature quality and risk of bias were evaluated in accordance with the requirements of the Cochrane Manual.Meta-analysis was performed using Revman 5.4 software.Results:A total of 7 clinical studies using DIMS lenses to intervene in the development of myopia were included .Seven studies provided complete SE data for analysis, with sample sizes of 1 164 eyes and 1 140 eyes for the DIMS group and SVL group, respectively.Five studies provided complete AL data for analysis, with sample sizes of 339 eyes and 315 eyes for the DIMS group and SVL group, respectively.There were statistically significant differences in SE and AL between DIMS group and SVL group (SE: WMD=0.40, 95% CI: 0.32-0.47, P<0.001; AL: WMD=-0.14, 95% CI: -0.17--0.11, P<0.001).DIMS lens could effectively delay SE progression and AL growth in myopic patients. Conclusions:DIMS lenses could delay the increase of SE and AL to a certain extent.

Objective:To evaluate the efficacy of defocus incorporated multiple segments (DIMS) on spherical equivalent (SE) and axial length (AL) in myopic children.Methods:Clinical studies on the progress of DIMS lens intervention in myopia reported in CNKI, Wanfang Data, VIP, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, and Web of Science from the establishment of the database to June 2023 were searched.The experimental group and control group used DIMS lens and single vision lens (SVL) for intervention, respectively.Two researchers independently conducted the literature search, screening and data extraction based on the inclusion and exclusion criteria.Literature quality and risk of bias were evaluated in accordance with the requirements of the Cochrane Manual.Meta-analysis was performed using Revman 5.4 software.Results:A total of 7 clinical studies using DIMS lenses to intervene in the development of myopia were included .Seven studies provided complete SE data for analysis, with sample sizes of 1 164 eyes and 1 140 eyes for the DIMS group and SVL group, respectively.Five studies provided complete AL data for analysis, with sample sizes of 339 eyes and 315 eyes for the DIMS group and SVL group, respectively.There were statistically significant differences in SE and AL between DIMS group and SVL group (SE: WMD=0.40, 95% CI: 0.32-0.47, P<0.001; AL: WMD=-0.14, 95% CI: -0.17--0.11, P<0.001).DIMS lens could effectively delay SE progression and AL growth in myopic patients. Conclusions:DIMS lenses could delay the increase of SE and AL to a certain extent.

An imbalance between oxidative and antioxidant defense mechanisms in the body triggers oxidative stress,which causes a series of damages to the body,tissues and cells.The eye is particularly susceptible to oxidative stress due to its prolonged exposure to light and its anatomical characteristics of high metabolism and oxygen consumption.In addi-tion,inflammation,aging,genetic and environmental factors can promote the production of reactive oxygen species and weaken antioxidant defense mechanisms,which are all risk factors for oxidative stress that can lead to a variety of ocular diseases.The aim of this paper is to review the mechanisms of oxidative stress in ocular diseases such as ocular surface diseases,glaucoma,cataract,and retinopathy.At the same time,the potential therapeutic approaches to these diseases by regulating oxidative stress are discussed,so as to provide new ideas and directions for the diagnosis and treatment of ocular diseases.