ObjectiveThe accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determiningY-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems. MethodsWe extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined. ResultsThe GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers. ConclusionThese findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.

ObjectiveThe accuracy of Y-chromosome haplogroup assignment is crucial for tracing paternal lineage in male samples. With the advancement of high-throughput sequencing technologies, high-density Y-SNP genotyping from whole-genome or array-based data has become a standard method for determiningY-chromosome haplogroups. This study systematically evaluated the performance of 4 commonly used high-density SNP genotyping systems—namely, the Global Screening Array (GSA), Chinese Genotyping Array (CGA), Affymetrix array, and the 1240K capture panel—for haplogroup assignment. This work provides a reference for data comparison across different systems. MethodsWe extracted genotype data for the 4 Y-SNP panels from 30× whole-genome sequencing (WGS) data of 1 590 male samples from the 1000 Genomes Project. Additionally, GSA array genotype data from 384 relative pairs (spanning 1st- to 12th-degree relationships) from 109 Chinese Han families were collected. Haplogroup assignment was performed using Y-LineageTracker v1.3.0 software. We assessed the concordance and resolution of haplogroup assignments between the four Y-SNP panels and the WGS data. The consistency and resolution of haplogroup assignments were also evaluated for both the 1000 Genomes Project samples and the 109 family samples collected in this study. Furthermore, the impact of varying numbers of Y-SNPs on haplogroup assignment was examined. ResultsThe GSA and CGA panels demonstrated superior resolution and discrimination of haplogroup subclades compared with the other two panels. The haplogroup assignments from the GSA, CGA, and 1240K panels showed high concordance with WGS data, with consistency rates exceeding 88.70%, whereas the Affymetrix platform exhibited a significantly lower consistency rate of 61.89%. Specifically, the GSA and CGA panels consistently demonstrated superior performance compared with the other two panels in the assignment of haplogroups O-M175 and H-L901, achieving complete concordance (100%) for both haplogroups. In contrast, the Affymetrix panel erroneously assigned all individuals belonging to haplogroup O-M175 to haplogroup K2-M526. Furthermore, its accuracy for haplogroup H-L901 was exceedingly low, at merely 1.41%. This poor performance was characterized by the misassignment of 98.59% of H-L901 samples—specifically, 1.41% to J-M304 and a predominant 97.18% to F-M89. For haplogroup R-M207, all four panels exhibited uniformly high levels of consistency, with concordance values exceeding 94.00%. Notably, for haplogroup E-M96, the 1240K and Affymetrix panels outperformed the GSA and CGA panels in terms of concordance, representing the first instance in which these two panels surpassed the latter. Conversely, for haplogroups J-M304, Q-M242, and I-M170, all 4 panels showed relatively elevated misclassification rates, with the Affymetrix array demonstrating the poorest overall performance. None of the four panels showed any discordant haplogroup assignments among the familial relative pairs analyzed. A positive correlation was observed between the number of Y-SNPs (ranging from 1 000 to 10 000) and classification consistency; however, classification consistency plateaued when the number of Y-SNPs exceeded 10 000. Furthermore, a random sampling analysis conducted on the GSA and CGA panels demonstrated that the haplogroup misclassification rate exhibited negligible fluctuation across the Y-SNP range of 500 to 1 000. Conversely, a marked enhancement in classification consistency was observed as the number of markers increased from 1 000 to 5 000, ultimately reaching a plateau within the interval of 5 000 to 8 000 markers. ConclusionThese findings indicate that the GSA and CGA panels provide high resolution and concordance, delivering reliable Y-haplogroup assignment for forensic investigations.

OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response.

Thyroid hormone(TH)is an iodinated derivative of the amino acid tyrosine secreted by the thyroid gland.It promotes glycolipid metabolism and is involved in various physiological and pathological processes by regulating cellular behaviors, such as cell proliferation, differentiation, and apoptosis. Recent studies have found that aberrant expression of TH in the orbit, retina, and sclera, and other ocular tissues can induce abnormal differentiation of orbital soft tissue adipocytes, alteration of retinal oxidative stress, and degradation of posterior scleral extracellular matrix(ECM), which contributes to the pathogenesis of many ophthalmic diseases, including Graves ophthalmopathy(GO), age-related macular degeneration(ARMD), diabetic retinopathy(DR), and myopia. This article reviews the role and mechanism of TH in various ophthalmic diseases, aiming to provide theoretical basis for the prevention and treatment of these ocular disorders.

OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

OBJECTIVE: To observe the efficacy and safety of eye transcutaneous electrical acupoint stimulation (Eye-TEAS) on preventing the progression of pre-myopic to myopia in children aged 6-12 years. METHODS: A total of 170 pre-myopic children aged 6-12 years were randomly divided into an Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated) and a placebo Eye-TEAS group (85 cases, 3 cases dropped out, 2 cases were eliminated). The Eye-TEAS group received Eye-TEAS intervention at bilateral Cuanzhu (BL2), Yuyao (EX-HN4), Sizhukong (TE23), Taiyang (EX-HN5), Sibai (ST2), and Jingming (BL1), with continuous wave at a frequency of 4 Hz and a current of 1-2 mA for 30 min per session. The placebo Eye-TEAS group received sham intervention with the same equipment and procedure, but no electrical stimulation. Both groups received intervention once every other day, at least 3 times a week, for a duration of 20 weeks. After intervention and during the 28-week follow-up period after the intervention completion, the changes in axial length (AL), spherical equivalent refraction (SER), and the incidence of myopia were compared between the two groups. Adherence and safety during the intervention period were also evaluated. RESULTS: Compared before intervention, both groups showed an increase in AL after the intervention and during the follow-up (P<0.01). The AL during follow-up was higher than that after the intervention in the two groups (P<0.01). The Eye-TEAS group exhibited a smaller change in AL than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01, P<0.05). Compared before intervention, both groups showed a decrease in SER after the intervention and during follow-up (P<0.01). The SER during follow-up was lower than that after the intervention in the two groups (P<0.01). The Eye-TEAS group had a higher SER than the placebo Eye-TEAS group after the intervention (P<0.05). The Eye-TEAS group exhibited a smaller change in SER than the placebo Eye-TEAS group after the intervention and during follow-up (P<0.01). The incidence of myopia in the Eye-TEAS group was lower than that in the placebo group during follow-up (20.0% [14/70] vs 34.7% [25/72], P<0.05). Both groups had good adherence, with no adverse events related to the intervention. CONCLUSION Eye-TEAS can delay the progression of pre-myopic to myopia in children, and has a high safety profile.
Humans ; Child ; Male ; Female ; Acupuncture Points ; Myopia/prevention & control* ; Transcutaneous Electric Nerve Stimulation ; Treatment Outcome ; Disease Progression

OBJECTIVE: To study the clinical effects of ibrutinib in the treatment of relapsed/refractory diffuse large B-cell lymphoma (RRDLBCL). METHODS: A total of 101 patients with RRDLBCL in Daqing People's Hospital from September 2019 to September 2022 were selected. 45 patients were received ibrutinib monotherapy, 36 patients were received a combination therapy of ibrutinib, rituximab, and lenalidomide, and 20 patients were received a combination therapy of ibrutinib and lenalidomide. The clinical effects were observed. RESULTS: The median duration of treatment for all patients was 4 (2-9) months. The disease control rates(DCR) and objective response rates(ORR) in the ibrutinib monotherapy group were 46.67% and 26.67%, respectively. In the combination therapy group of ibrutinib, rituximab, and lenalidomide, the DCR and ORR were 69.44% and 44.44%, respectively. In the combination therapy group of ibrutinib and lenalidomide, the DCR and ORR were 60.00% and 35.00%, respectively. The DCR and ORR in the combination therapy group of ibrutinib, rituximab, and lenalidomide were significantly higher than those in the ibrutinib monotherapy group (P < 0.05). There were no significant differences in DCR and ORR between the combination therapy group of ibrutinib and lenalidomide and the ibrutinib monotherapy group (P >0.05). The median follow-up time of all patients was 15 (5-35) months, with a median overall survival(OS) of 21.0 (15.8-26.2) months and a median progression-free survival(PFS) of 14.0 (12.1-15.9) months. In the ibrutinib monotherapy group, the median OS and PFS were 15.0 (12.1-17.9) months and 12.0 (11.0-13.0) months, respectively. In the combination therapy group of ibrutinib and lenalidomide, the median OS and PFS were 22.0 (13.3-30.7) months and 16.0 (14.1-19.7) months, respectively. In the combination therapy group of ibrutinib, rituximab, and lenalidomide, the median OS and PFS were 23.0 (19.7-26.3) months and 17.0 (14.8-19.1) months, respectively. The median OS and PFS in the combination therapy group of ibrutinib, rituximab, and lenalidomide were significantly higher than those in the ibrutinib monotherapy group (P < 0.05). There were no significant differences in median OS and PFS between the combination therapy group of ibrutinib and lenalidomide and the combination therapy group of ibrutinib, rituximab, and lenalidomide (P >0.05). Hematological adverse reactions included neutropenia in 14 cases (13.86%), thrombocytopenia in 16 cases (15.84%), and leukopenia in 13 cases (12.87%). Non-hematological adverse reactions mainly included nausea and vomiting in 33 cases (32.67%) and fatigue in 44 cases (43.56%). CONCLUSION Ibrutinib has certain clinical effects and good safety in the treatment of RRDLBCL.
Humans ; Piperidines/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Adenine/therapeutic use* ; Rituximab/therapeutic use* ; Lenalidomide/therapeutic use* ; Male ; Female ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adult ; Aged ; Pyrimidines/therapeutic use* ; Pyrazoles/therapeutic use* ; Treatment Outcome

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective To investigate the tongue image characteristics of patients in postoperative colorectal cancer and significant tongue image features using a multinomial Logistic regression model.Methods Totally 213 postoperative patients with colorectal cancer were included.TFDA-1 digital tongue diagnostic instrument was used to collect the tongue images of patients,and the statistical differences of tongue image characteristics of patients with qi deficiency syndrome,yin deficiency syndrome,phlegm dampness syndrome and blood stasis syndrome were analyzed.Multiple Logistic regression was used to analyze the different tongue image indexes of different syndrome types.Results In the tongue coating index,perAll had the following distribution order:yin deficiency syndromeqi deficiency syndrome>blood stasis syndrome.In the texture indexes,CON,ENT and MEAN had the following distribution order:phlegm-dampness syndrome>yin deficiency syndrome>qi deficiency syndrome>blood stasis syndrome.ASM had the following distribution order:phlegm-dampness syndromeqi deficiency syndrome>blood stasis syndrome.TB-a had the following distribution order:phlegm-dampness syndromeqi deficiency syndrome>phlegm-dampness syndrome>blood stasis syndrome.TC-L had the following distribution order:blood stasis syndromeqi deficiency syndrome>blood stasis syndrome>phlegm-dampness syndrome.TC-b had the following distribution order:yin deficiency syndrome>qi deficiency syndrome>blood stasis syndrome.In the multinomial Logistic regression model,compared with the qi deficiency syndrome,the probability of being diagnosed with the yin deficiency syndrome increased when TB-L and TC-a decreased.Additionally,the probability of being diagnosed with the phlegm-dampness syndrome increased when TB-b and TC-a decreased and TC-b increased;TB-b and TC-L decreased,principal component 1 of texture index increased,and the probability of syndrome differentiation as blood stasis syndrome was higher.Conclusion The tongue image characteristics of different TCM syndromes in postoperative colorectal cancer patients exhibit certain patterns,which can serve as an objective reference for TCM differentiation and diagnosis.