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 explore the role of reactive oxygen species (ROS) and lactate dehydrogenase isoenzyme X (LDH-X) in the changes of sperm mitochondrial membrane potential (MMP) in infertility patients with varicocele (VC). METHODS: This study included 38 infertility patients with VC (VCinf), 35 non-VC infertile males (NVCinf), and 30 normal fertile men as controls. We obtained the routine semen parameters using the sperm quality analysis system, examined the contents of LDH-X in the seminal plasma and sperm with the automatic biochemical analyzer, measured the level of malondialdehyde (MDA) in seminal plasma by thiobarbituric acid (TBA) colorimetry, and determined the expressions of mitochondrial membrane potential (MMP) and LDH-X mRNA in the sperm using JC-1 fluorescence probe and RT-PCR. RESULTS: No statistically significant differences were observed among the three groups of subjects in age, semen pH value, semen volume and sperm concentration (P > 0.05). Compared with the normal fertile controls, the patients in the VCinf and NVCinf groups showed significantly decreased sperm motility (［52.36 ± 12.48］% vs ［34.74 ± 15.23］% vs ［25.76 ± 13.73］%, P< 0.05), percentage of progressively motile sperm (PMS) (［42.54 ± 13.58］% vs ［29.10 ± 14.17］% vs ［20.95 ± 12.33］%, P< 0.05), sperm LDH-X (［16.46 ± 5.47］ vs ［13.63 ± 4.50］ vs ［10.18 ± 3.00］ mU/106, P< 0.05), sperm MMP (［48.04 ± 11.62］% vs ［40.86 ± 12.69］% vs ［34.41 ± 13.93］%, P< 0.05) and expression of sperm LDH-X mRNA (P< 0.05). but increased seminal plasma LDH-X (［935.36 ± 229.48］ vs ［1241.05 ± 337.07］ vs ［1425.08 ± 469.35］ U/L, P< 0.05), seminal plasma/whole sperm LDH-X (［1.06 ± 0.35］ vs ［1.40 ± 0.34］ vs ［1.63 ± 0.66］, P< 0.05), and content of seminal plasma MDA (［1.10 ± 0.19］ vs ［1.59 ± 0.27］ vs ［2.00 ± 0.22］ nmol/ml, P< 0.05). CONCLUSION Excessive ROS in the reproductive system of VCinf patients reduces the content of MMP and causes the overflow of LDH-X out of sperm cells. Therefore the decrease of sperm LDH-X may be accompanied by that of MMP.
Humans ; Male ; Infertility, Male/etiology* ; Varicocele/metabolism* ; Adult ; Reactive Oxygen Species/metabolism* ; Spermatozoa/metabolism* ; L-Lactate Dehydrogenase/metabolism* ; Membrane Potential, Mitochondrial ; Isoenzymes/metabolism* ; Case-Control Studies ; Young Adult ; Mitochondrial Membranes/metabolism*

Objective To investigate the efficacy and safety of nusinersen sodium in the treatment of children with spinal muscular atrophy(SMA).Methods A retrospective analysis was conducted on the clinical data of 50 children with 5q SMA who received nusinersen sodium treatment and multidisciplinary treatment management in Shanxi Children's Hospital from February 2022 to February 2024.Results Compared with the baseline data,67%(8/12),74%(35/47),and 74%(35/47)of the SMA children had a clinically significant improvement in the scores of Philadelphia Infant Test of Neuromuscular Disorders,Hammersmith Functional Motor Scale Expanded,and Revised Upper Limb Module,respectively,and the distance of 6-minute walking test increased from 207.00(179.00,281.50)meters to 233.00(205.25,287.50)meters(P<0.05)after nusinersen sodium treatment.Of all 50 children with SMA,24(48%)showed good tolerability after administration,with no significant or persistent abnormalities observed in 2 034 laboratory test results,and furthermore,there were no serious or immunological adverse events related to the treatment.After treatment,there was a significant change in forced vital capacity as a percentage of the predicted value in 27 children with restrictive ventilatory dysfunction,as well as a significant change in the level of 25-(OH)vitamin D in 15 children with vitamin D deficiency(P<0.05).Conclusions For children with SMA,treatment with nusinersen sodium can continuously improve the response rates of motor function scales,with good tolerability and safety.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".
Child ; Humans ; Overweight/complications* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/epidemiology* ; Hyperuricemia ; Multimorbidity ; Hypertension/epidemiology* ; Dyslipidemias ; Body Mass Index ; Risk Factors

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective:To investigate the clinical characteristics of old patients with spinal cord injury. Methods:From January 1, 2013 to December 31, 2019, totally 386 old (≥ 60 years) patients with spinal cord injury were enrolled. Their gender, age, etiology, American Spinal Injury Association Impairment Scale (AIS) and complications were analyzed. Results:In the old patients with spinal cord injury, traumatic spinal cord injury was more common in males (71.17%) and non-traumatic spinal cord injury was more common in females (56.19%). Fall on level surface was the most important cause of spinal cord injury both in old men (28.83%) and women (24.76%). Tumor (19.05%) was the most common non-traumatic cause of spinal cord injury in old female patients. Cervical segment (78.46%) was the most common site of injury in old traumatic spinal cord injury, while thoracic segment (52.14%) was the most common site of injury in non-traumatic spinal cord injury. Grade D (38.08%) was the most common AIS grade, followed by grades C (28.76%), A (21.50%), and B (11.66%). Spinal canal stenosis (23.31%) played an important role in the etiology of old spinal cord injury. Neuralgia, venous thrombosis of lower extremities and urinary tract infection were the most common complications in old patients with spinal cord injury. Conclusion:Fall on level surface is the leading cause of spinal cord injury in old patients, and the proportion of fall in the etiology of old spinal cord injury tends to increase with age. It is important to take effective measures to avoid falling in the old adults to prevent spinal cord injury.

Objective:To investigate the outcome of neurological function and the clinical characteristics of complications in children with spinal cord injury. Methods:From 2011 to 2019, children under 15 years old with spinal cord injury were selected in our hospital. Their level of injury and American Spinal Injury Association Impairment Scale (AIS) at one month, three months and one year were recorded. And the complications such as pressure ulcers/scald, urinary tract infection, hydronephrosis/vesicoureteral reflux, constipation, osteoporosis/fracture, deep vein thrombosis, neurodynia, heterotopic ossification, scoliosis and hip dysplasia were analyzed. Results:Of 159 individuals, 41 were boys and 118 were girls, the average age at injury was (6.08±2.57) years. The main cause of spinal cord injury was sports accidents (47.8%), and the main injury sites were thoracic spinal cord injury (89.3%). The cause of spinal cord injury was correlated with age at injury (r = -0.160, P = 0.044), gender (r = -0.458, P < 0.001) and injury sites (r = -0.249, P = 0.002). Complete spinal cord injury counted for 71.7%, and the AIS grade at one month was correlated with that at twelve months (r = 0.984, P < 0.001). The main complications were urinary tract infection (69.2%), constipation (67.9%), hydronephrosis/vesicoureteral reflux (37.7%), scoliosis (25.8%) and hip dysplasia (25.2%). The incidence of ulcers/scald was correlated with injury site (r = 0.179, P = 0.024). The AIS grade three months after injury was significantly correlated with urinary tract infection, constipation, scoliosis and hip dysplasia (|r| > 0.227, P < 0.01). The incidence of ulcers/scald was correlated with osteoporosis/fracture (r = 0.208, P < 0.01). The incidence of urinary tract infection was significantly correlated with hydronephrosis/vesicoureteral reflux, constipation, scoliosis and hip dysplasia (r > 0.261, P < 0.001), as well as osteoporosis/fracture (r = 0.195, P < 0.05). The incidence of hydronephrosis/vesicoureteral reflux was significantly correlated with constipation, osteoporosis/fracture, scoliosis and hip dysplasia (r > 0.146, P < 0.01). The incidence of constipation was significantly correlated with scoliosis and hip dysplasia (r > 0.313, P < 0.01), as well as osteoporosis/fracture (r = 0.160, P < 0.05). The incidence of osteoporosis/fracture was significantly correlated with scoliosis and hip dysplasia (r > 0.342, P < 0.01). The incidence of scoliosis was significantly correlated with hip dysplasia (r = 0.818, P < 0.001). Conclusion:The recovery of neurological function after spinal cord injury in children is closely correlated to AIS. The outcome of complete spinal cord injury is poor. The common complications after spinal cord injury in children demonstrate specific age characteristics, and the incidence of urinary tract infection, constipation, hydronephrosis/vesicoureteral reflux, scoliosis and hip dysplasia are common complications, which need more attention.

Objective:To explore the clinical manifestations and MRI features of pediatric spinal cord injury (SCI) after back bend. Methods:A retrospective study was performed. All the medical records and MRI images of children with SCI after back bend were identified in Beijing Bo'ai Hospital from January 1st, 2002 to August 31st, 2020. Results:A total of 120 SCI children after back bend were reviewed, out of whom 119 cases were girls, one case was boy. The age ranged from 38 to 162 months, with the median age of 76 months. More cases were discovered in July and September every year (32 cases, 26.7%), as well as in weekends (67 cases, 55.8%). The main clinical manifestations were sensory and motor dysfunction of both lower limbs (120 cases, 100%), bladder and bowl incontinence (120 cases, 100%). The common first symptoms included sudden attack of lumbar pain (39 cases, 32.5%), lower limbs paralysis (30cases, 25.0%) and leg pain (10 cases, 8.3%). The peak time of symptoms ranged from five minutes to two days, with the median time of 50 minutes. The MRI features of 104 children with SCI within one week after back bend were as follows: the abnormal signals of MRI in spinal cord involved lower cervical and all the following segments of spinal cord. The number of the segments of spinal cord with abnormal signals ranged from two to 15, with the median of seven segments. The most common segments with abnormal signals were T₉ (96 cases, 92.3%), T₁₀ (96 cases, 92.3%) and T₁₁ (90 cases, 86.5%). Among the cases followed up, 48 cases with complete injury demonstrated a vast and serous spinal cord atrophy (SCA) below the injury segments as early as 37 days after the injury, the SCA would become worse at the chronic stage and maybe involve the spinal cord above the injury segments. In 31 cases with incomplete injury, the abnormal signals of MRI in spinal cord were limited in the lumbar enlargement, with a various degree of SCA at the late stage. All the cases were diagnosed as SCI without radiologic abnormality, out of whom 89 (74.2%) cases suffered from thoracic complete SCI, 31 (25.8%) cases suffered thoracic or lumbar incomplete SCI. The common complications included scoliosis, hip joint dysplasia, urinary tract infection, hydronephrosis, osteoporosis, pathological fracture of lower limbs and valgus knee. Conclusion:The main clinical symptoms of pediatric SCI after back bend were sudden lumbar pain, sensory and motor dysfunction of both lower limbs, and bladder and bowl incontinence. Most of the cases were thoracic complete SCI, the MRI features at the early stage were multiple segments of abnormal signals of spinal cord around T₉ and T₁₀, and later an extensive severe SCA below the injury segments to the conus medullaris, accompanied by the SCA above the injury segments.

Objective:To investigate the occurrence and related factors of autonomic dysreflexia (AD) during intermittent catheterization in patients with spinal cord injury (SCI). Methods:Case control study was used in this study. Intermittent catheterization was performed on 44 SCI patients hospitalized from April, 2019 to April, 2020, The data of age, gender, time after injury, segment of injury, degree of injury, resting blood pressure, immediate blood pressure after catheterization, catheterization numbers, catheterization volume and duration of catheterization were collected. Descriptive analysis and binary Logistic regression analysis were used to analyze the occurrence and related factors of AD. Results:Totally, AD happened in 26 (59.1%) patients. Urethral catheterization was done 1738 times, out of which AD accounted for 187 times (10.8%). The risk of AD increased with the time after injury and age (P < 0.05). The probability of AD was lower in T₇ SCI and below than in T₆ SCI and above (P = 0.002). Catheterization numbers, gender, degree of injury, catheterization volume and duration of catheterization were not influencing factors of AD (P > 0.05). Conclusion:It is necessary to have a full understanding for the occurrence of AD in patients with SCI during intermittent catheterization. For patients with SCI in T₆ and above, long time after injury and elderly patients, routine monitoring of blood pressure during intermittent catheterization is recommended to detect and deal with AD in time.