Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective:To explore the prognostic value of peripheral blood lymphocyte subsets in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The study retrospectively analyzed 133 patients with NDMM admitted to the General Hospital of Tianjin Medical University General Hospital between 2017 and 2022. The least absolute shrinkage and selection operator (LASSO) regression was used to screen the predictive subgroups from the peripheral blood lymphocyte subsets, and the optimal cutoff value was calculated through receiver operating characteristic curve analysis. A nomogram was constructed based on the results of the multiple-factor analysis, and the predictive performance of the nomogram was evaluated by the concordance index and calibration curve. Kaplan-Meier curves and log-rank tests were conducted to compare the differences in overall survival (OS) and progression-free survival between the high-risk and low-risk immune risk scores groups.Results:Using LASSO regression, the percentages and absolute counts of CD16 +CD56 + NK cells, CD3 + T lymphocytes, CD3 +CD8 + T lymphocytes, and CD3 -CD19 + B lymphocytes were selected as predictive subgroups. The immune risk score of patients with NDMM was calculated based on the coefficients of each lymphocyte subgroup. The area under the curve of the immune risk score was 0.737, and the optimal cutoff value was -1.834. Based on this, the patients were divided into high-risk and low-risk groups. Survival analysis showed a significant difference in the 3-year OS rate between the high-risk and low-risk immune risk score groups (87.4% vs 49.0%, P<0.001), and a significant difference in the 3-year OS rate between the high-risk and low-risk immune risk score groups in patients with minimal residual disease negative (100% vs 68.6%, P=0.001). Multivariate analysis showed that serum calcium ( P=0.034), high-risk cytogenetic abnormalities ( P=0.002), and immune risk score ( P<0.001) were prognostic factors for patients with NDMM, and a nomogram was constructed based on these factors. The consistency index of the nomogram was 0.793, and the calibration curve showed good predictive ability. The nomogram can accurately classify the risk of different prognostic staging systems. Conclusions:The combined analysis of lymphocyte subsets in the peripheral blood has an important value in predicting the prognosis of patients with NDMM.

Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

Objective To explore the factors influencing cognitive dysfunction in patients with vestibular migraines.Methods The clinical data of 298 patients with vestibular migraine admitted to the Second People's Hospital of Guiyang City from January 2020 to Ja-nuary 2024 were retrospectively analyzed.The patients were divided into a cognitive impairment group(n=55)and a non-cognitive impairment group(n=243).Baseline data such as sex,age,body mass index,and educational level between the two groups of patients were matched using propensity score matching in a 1∶1 ratio.Factors influencing cognitive dysfunction in patients with vestibular migraine were screened using single-factor and multiple logistic regression analyses.Results Fifty pairs of patients were successfully matched.Single-factor and multivariate logistic regression analyses showed that migraine duration≥10 years,sleep disorders,anxiety or depression,threatened migraine,and white matter lesions were risk factors for cognitive impairment in patients with vestibular migraine(P＜0.05).Conclusion Duration of migraine,sleep disorders,anxiety or depression,threatened migraine,and white matter lesions are factors influencing cognitive dysfunction in patients with vestibular migraine.Corresponding intervention strategies can be developed for risk factors to reduce the occurrence of cognitive dysfunction and improve prognosis.

Objective To investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

Objective To explore the factors influencing cognitive dysfunction in patients with vestibular migraines.Methods The clinical data of 298 patients with vestibular migraine admitted to the Second People's Hospital of Guiyang City from January 2020 to Ja-nuary 2024 were retrospectively analyzed.The patients were divided into a cognitive impairment group(n=55)and a non-cognitive impairment group(n=243).Baseline data such as sex,age,body mass index,and educational level between the two groups of patients were matched using propensity score matching in a 1∶1 ratio.Factors influencing cognitive dysfunction in patients with vestibular migraine were screened using single-factor and multiple logistic regression analyses.Results Fifty pairs of patients were successfully matched.Single-factor and multivariate logistic regression analyses showed that migraine duration≥10 years,sleep disorders,anxiety or depression,threatened migraine,and white matter lesions were risk factors for cognitive impairment in patients with vestibular migraine(P＜0.05).Conclusion Duration of migraine,sleep disorders,anxiety or depression,threatened migraine,and white matter lesions are factors influencing cognitive dysfunction in patients with vestibular migraine.Corresponding intervention strategies can be developed for risk factors to reduce the occurrence of cognitive dysfunction and improve prognosis.

Objective:To explore the prognostic value of peripheral blood lymphocyte subsets in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The study retrospectively analyzed 133 patients with NDMM admitted to the General Hospital of Tianjin Medical University General Hospital between 2017 and 2022. The least absolute shrinkage and selection operator (LASSO) regression was used to screen the predictive subgroups from the peripheral blood lymphocyte subsets, and the optimal cutoff value was calculated through receiver operating characteristic curve analysis. A nomogram was constructed based on the results of the multiple-factor analysis, and the predictive performance of the nomogram was evaluated by the concordance index and calibration curve. Kaplan-Meier curves and log-rank tests were conducted to compare the differences in overall survival (OS) and progression-free survival between the high-risk and low-risk immune risk scores groups.Results:Using LASSO regression, the percentages and absolute counts of CD16 +CD56 + NK cells, CD3 + T lymphocytes, CD3 +CD8 + T lymphocytes, and CD3 -CD19 + B lymphocytes were selected as predictive subgroups. The immune risk score of patients with NDMM was calculated based on the coefficients of each lymphocyte subgroup. The area under the curve of the immune risk score was 0.737, and the optimal cutoff value was -1.834. Based on this, the patients were divided into high-risk and low-risk groups. Survival analysis showed a significant difference in the 3-year OS rate between the high-risk and low-risk immune risk score groups (87.4% vs 49.0%, P<0.001), and a significant difference in the 3-year OS rate between the high-risk and low-risk immune risk score groups in patients with minimal residual disease negative (100% vs 68.6%, P=0.001). Multivariate analysis showed that serum calcium ( P=0.034), high-risk cytogenetic abnormalities ( P=0.002), and immune risk score ( P<0.001) were prognostic factors for patients with NDMM, and a nomogram was constructed based on these factors. The consistency index of the nomogram was 0.793, and the calibration curve showed good predictive ability. The nomogram can accurately classify the risk of different prognostic staging systems. Conclusions:The combined analysis of lymphocyte subsets in the peripheral blood has an important value in predicting the prognosis of patients with NDMM.

Objectives:To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared.Results:A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods ( P=0.008) . Conclusions:mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.

Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Objective:To investigate the role of multiparameter flow cytometry (MFC) in detecting non-neoplastic abnormal phenotypes, including monoclonal gammopathy of undetermined significance (MGUS), monoclonal B-cell lymphocytosis (MBL), Fcγ receptor Ⅲb (FcγRⅢB), and CD36 deficiencies.Methods:A retrospective and observational study was conducted on a total of 24 864 patients who underwent one-step screening for leukemia/lymphoma at Hebei Yanda Ludaopei Hospital from January 3, 2020, to March 31, 2024. Clinical data and MFC results of the patients were collected. Patients were grouped by age, group of <45 years (11 495 cases), group of 45-<60 years (5 322 cases), group of ≥60 years (7 081 cases) and disease nature, benign group (8 336 cases), malignant group (15 562), and other diseases group (966 cases). The incidence of non-neoplastic abnormal phenotypes was analyzed across groups.Results:The incidence rates of MGUS, MBL, FcγRⅢB, and CD36 deficiencies were 0.072% (18/24 864), 0.511% (127/24 864), 0.221% (55/24 864), and 0.004% (1/24 864), respectively. MBL incidence was lower in the malignant group than in the benign group ( P<0.001), while MGUS incidence was higher in the malignant group than in the benign group ( P=0.034). The incidence rate of MBL among subtypes within the benign group varied significantly ( P<0.001 ), with the highest incidence in patients with pancytopenia at 2.72% (48/1 765). In the malignant group, the incidence of MBL differed significantly across various disease types ( P<0.001), among which MDS/MPN exhibited the highest incidence at 1.95% (3/154) and 1.30% (2/154). Conclusion:Utility of multiparameter flow cytometry method for one-step screening of leukemia and lymphoma shows variety in detecting non-neoplastic abnormal phenotypes, facilitating the identification of diseases.