Objective:To evaluate the relationship between preoperative concentrations of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:Six hundred and twenty-five patients of either sex, aged 50-90 yr, weighing 50-80 kg, with American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, with the preoperative Mini-Mental State Examination score > 23, who underwent elective knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital from January 2022 to December 2023, were selected. The CSF specimens 2 ml were withdrawn from the subarachnoid space after successful subarachnoid puncture for determination of the concentrations of sTREM2, Amyloid beta protein (Aβ 42), total tau protein (T-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay. POD was assessed using the Confusion Assessment Method. Patients were divided into POD group and non-POD group based on whether POD occurred. Logistic regression was used to identify the risk and protective factors for POD. The performance of CSF sTREM2 concentration combined with CSF biomarker levels in predicting POD was evaluated using the receiver operating characteristic (ROC) curve and clinical decision curve. The mediating effect of CSF biomarker concentrations in the relationship between CSF sTREM2 concentration and POD was analyzed. Results:Five hundred and nineteen patients were finally included, with 112 patients in POD group and 407 patients in non-POD group. The results of logistic regression analysis showed that the elevated preoperative sTREM2 concentration in CSF was the risk factor for POD after adjusting for multiple confounding factors such as age, sex, body mass index, years of education, Mini-Mental State Examination score, history of smoking, history of drinking, hypertension, diabetes mellitus and coronary heart disease. The area under the ROC curve of the preoperative sTREM2 concentration in CSF in predicting POD was 0.716, and the area under the ROC curve of the preoperative sTREM2 concentration in CSF combined with CSF biomarkers in predicting POD was 0.796. This model had high clinical application value and predictive efficacy. The relationship between the preoperative sTREM2 concentration in CSF and POD was partially mediated by the CSF p-tau concentration (proportion of mediated effect 24.67%) and t-tau protein concentration (proportion of mediated effect 17.33%).Conclusions:The elevated preoperative concentration of sTREM2 in CSF is a risk factor for POD in patients undergoing total knee/hip arthroplasty, and concentrations of t-tau and p-tau in CSF play a mediating role in the relationship between the preoperative CSF sTREM2 concentration and POD.

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

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 evaluate the relationship between preoperative concentrations of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) and postoperative delirium (POD) in patients undergoing total knee/hip arthroplasty.Methods:Six hundred and twenty-five patients of either sex, aged 50-90 yr, weighing 50-80 kg, with American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, with the preoperative Mini-Mental State Examination score > 23, who underwent elective knee/hip arthroplasty under combined spinal-epidural anesthesia at Qingdao Municipal Hospital from January 2022 to December 2023, were selected. The CSF specimens 2 ml were withdrawn from the subarachnoid space after successful subarachnoid puncture for determination of the concentrations of sTREM2, Amyloid beta protein (Aβ 42), total tau protein (T-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay. POD was assessed using the Confusion Assessment Method. Patients were divided into POD group and non-POD group based on whether POD occurred. Logistic regression was used to identify the risk and protective factors for POD. The performance of CSF sTREM2 concentration combined with CSF biomarker levels in predicting POD was evaluated using the receiver operating characteristic (ROC) curve and clinical decision curve. The mediating effect of CSF biomarker concentrations in the relationship between CSF sTREM2 concentration and POD was analyzed. Results:Five hundred and nineteen patients were finally included, with 112 patients in POD group and 407 patients in non-POD group. The results of logistic regression analysis showed that the elevated preoperative sTREM2 concentration in CSF was the risk factor for POD after adjusting for multiple confounding factors such as age, sex, body mass index, years of education, Mini-Mental State Examination score, history of smoking, history of drinking, hypertension, diabetes mellitus and coronary heart disease. The area under the ROC curve of the preoperative sTREM2 concentration in CSF in predicting POD was 0.716, and the area under the ROC curve of the preoperative sTREM2 concentration in CSF combined with CSF biomarkers in predicting POD was 0.796. This model had high clinical application value and predictive efficacy. The relationship between the preoperative sTREM2 concentration in CSF and POD was partially mediated by the CSF p-tau concentration (proportion of mediated effect 24.67%) and t-tau protein concentration (proportion of mediated effect 17.33%).Conclusions:The elevated preoperative concentration of sTREM2 in CSF is a risk factor for POD in patients undergoing total knee/hip arthroplasty, and concentrations of t-tau and p-tau in CSF play a mediating role in the relationship between the preoperative CSF sTREM2 concentration and POD.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Humans ; Infant ; Infant, Newborn ; Infant, Extremely Low Birth Weight ; Mesenchymal Stem Cell Transplantation ; Umbilical Cord/cytology* ; Skin/injuries*

Child ; Humans ; Infant ; Esophagus ; Electric Power Supplies ; Eating ; Foreign Bodies