Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

Objective:To evaluate the efficacy and safety of the pegaspargase, etoposide, methotrexate, and dexamethasone (PEMD) regimen in patients with early-stage nonupper respiratory digestive tract or advanced extranodal natural killer/T-cell lymphoma (ENKTL) .Methods:This retrospective analysis included 38 patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL who received PEMD regimen for induction chemotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2016 to December 2022. Survival outcomes and prognostic factors were examined by Kaplan-Meier, and the Log-rank test was used to compare survival.Results:The study population had a median age of 48 years (range, 26-72 years) and included 30 males (78.9%) and 8 females (21.1%). 7 patients’ age >60 years (18.4%). The Eastern Cooperative Oncology Group (ECOG) performance score was >1 in 7 patients (18.4%) ; 20 patients (52.6%) had elevated lactate dehydrogenase levels; and 37 patients (97.4%) exhibited extranodal involvement. Using the Ann Arbor staging system, 37 patients (97.4%) were classified as stage Ⅲ-Ⅳ. The median number of treatment cycles was 5 (1-6), and the median follow-up duration was 60 months (24 - 101 months). Interim efficacy assessment revealed an overall response rate of 52.7%. At 2 and 4 years, the progression-free survival (PFS) rates were 34.2% (95% CI 22.0%-53.2%) and 25.5% (95% CI 14.7%-44.4%), respectively, and the overall survival rates were 50.0% (95% CI 36.4%-68.7%) and 45.5% (95% CI 31.4%-65.7%), respectively. The risk factors for worse PFS were ECOG performance score >1 [ HR=3.711 (95% CI 1.494-9.218), P=0.005]; bone marrow infiltration [ HR=2.251 (95% CI 1.026 - 4.938), P=0.043]; and Prognostic Index for Natural Killer/T-Cell Lymphoma score of 3 - 5 [ HR=2.350 (95% CI 1.009 - 5.476), P=0.048]. Multivariate analysis identified ECOG performance score >1 as an independent risk factor for PFS [ HR=7.971 (95% CI 2.222 - 28.591), P=0.001]. The main adverse effect was anemia in 31 patients (81.6%) . Conclusion:The PEMD regimen was safe and effective for patients with newly diagnosed early-stage non-upper respiratory digestive tract or advanced ENKTL.

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

Objective To investigate the clinical efficacy and safety of endoscopic ultrasonography-guided(EUS-guided)enterocolon anastomosis in treating patients with malignant bowel obstruction(MBO).Methods The clinical data of 12 patients with MBO,who underwent EUS-guided enterocolon anastomosis at the Nanjing Drum Tower Hospital of China from April 2023 to December 2023,were collected.The perioperative clinical efficacy and safety were retrospectively analyzed.Results Successful EUS-guided enterocolon anastomosis was accomplished in all the 12 patients,with a technical success rate of 100％(12/12).The clinical success rate was 83.3％(11/12),one patient developed obstruction of the stent.The clinical symptoms were relieved in 2-68 hours after treatment,and the time to resume defecation and exhaust was(18.02±15.75)hours.Within one week after the operation,4 patients took liquid diet and 8 patients took semi-fluid diet.Each dimension score of the Quality of Life Core-30 scale of The European Organization for Research and Treatment of Cancer(EORTC QLQ-C30)was remarkably improved,the patient's overall health score was increased from preoperative median 5 points to postoperative 8 points(P＜0.001).During the operation,stent displacement occurred in 2 patients,and the operation was successfully completed after promptly taking remedial measures.After operation,11 patients developed fever(37.5-39.4 ℃),and all the patients were discharged smoothly after symptomatic treatment.No complication such as bleeding,perforation,or stent displacement occurred.Conclusion EUS-guided enterocolon anastomosis is clinically safe and effective,it can effectively relieve the clinical symptoms and improve the quality of life of patients with MBO.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Objective To investigate the effect of local histopathological changes of thyroid nodules after ultrasound-guided fine needle aspiration biopsy(US-FNBA)on laparoscopic thyroid surgery.Methods The clinical data of 120 patients with thyroid malignant tumors admitted to Xiaogan Hospital of Wuhan University of Science and Technology from January 2020 to December 2022 were retrospectively analyzed,and according to whether received US-FNAB before surgery they were divided into the observation group(with US-FNAB)and the control group(without US-FNAB),with 60 cases in each group.The operation time,change of parathyroid hormone(ΔPTH)before and after surgery,change of serum Ca2+concentration(serum ΔCa2+)before and after surgery,drainage volume 24 hours after surgery and incidence of complications were compared between the two groups.According to fine needle aspiration-to-surgery(FTS),the patients in the observation group were further divided into the group A(FTS≤3 days)and the group B(FTS>3 days),and the effect of US-FNAB on laparoscopic thyroid surgery was explored combined with the pathological changes of the thyroid puncture capsule of the two groups.Results The operation time of the observation group was longer than that of the control group(P<0.05),and there was no significant difference in the drainage volume 24 hours after surgery,ΔPTH,serum ΔCa2+,or proportions of facial or limb numbness,hypoparathyroidism,recurrent laryngeal nerve integrity,and hypocalcemia between the two groups(P>0.05).There was no significant difference in the operation time,ΔPTH,serum ΔCa2+,drainage volume 24 hours after surgery,hypocalcemia,recurrent laryngeal nerve integrity or hypothyroidism between the group A and group B(P>0.05).The proportion of patients with facial or limb numbness after surgery in the group A was significantly lower than that in the group B(P<0.05).Conclusion Preoperative US-FNAB for thyroid nodules may prolong the operation time in patients undergoing laparoscopic thyroid surgery,and surgical treatment in early aspiration can help decrease this effect and reduce the incidences of postoperative hypocalcemia and hypothyroidism.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.