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 investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
Humans ; Pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Gasdermins ; Chemoradiotherapy/adverse effects* ; Rectal Neoplasms/surgery* ; Caspases/metabolism* ; Diarrhea/chemically induced* ; Leukopenia/genetics* ; Genetic Variation ; Dermatitis

Antineoplastic Agents/therapeutic use* ; Bortezomib/therapeutic use* ; Humans ; Inappropriate ADH Syndrome/chemically induced* ; Multiple Myeloma/drug therapy*

Objective:To evaluate the effect of oxygen supply via the transnasal self-made pharyngeal oxygen catheter on the safe apnea time in pediatric patients undergoing tonsil surgery. Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of either sex, aged 2-6 yr, weighing 10-20 kg, scheduled for elective tonsillectomy under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: transnasal self-made pharyngeal oxygen catheter for oxygen supply group (group NO) and control group (group C). Anesthesia was induced with intravenous midazolam, propofol, fentanyl and cis-atracurium, and then ventilation was performed with a mask, and the mask was removed when the exhaled oxygen concentration (C ETO 2) reached more than 90%.In group NO, the self-made oxygen catheter was implanted into the oropharynx through the nose, and the 100% oxygen at 10 L/min was aspirated through the humidification bottle until the intubation was successful.In group C, the transnasal self-made oxygen catheter was not implanted, and the rest of the protocol was similar to those previously described in group NO.The visual laryngoscope was implanted to simulate difficult airways.When SpO 2 ≤ 95% or the safe apnoea time reached 600 s, the observation of apnea was stopped, and mechanical ventilation was started after successful rapid endotracheal intubation.The safe apnea time (from removing the mask until SpO 2 decreased to 95%), value of C ETO 2 at the end of mask ventilation, and the minimum value of SpO 2 after stopping mask ventilation were recorded.Heat rate and mean arterial pressure were observed and recorded on admission to the operating room, immediately after onset of apnea and immediately after successful endotracheal intubation.The SpO 2, P ETCO 2 and cross-sectional area of gastric antrum were also recorded immediately after onset of apnea and immediately after successful endotracheal intubation, and the rate of increase in P ETCO 2 was calculated.The nasal bleeding, nasal dryness, postoperative pharyngeal discomfort and other adverse reactions were recorded when the self-made pharyngeal oxygen catheter was placed. Results:Compared with group C, the safe apnea time was significantly prolonged, the rate of increase in P ETCO 2 was decreased, the minimum value of SpO 2 after stopping mask ventilation was increased, and the heat rate, mean arterial pressure, SpO 2 and P ETCO 2 were increased immediately after successful intubation ( P<0.05), no significant change was found in C ETO 2 after stopping mask ventilation and cross-sectional area of gastric antrum at each time point in group NO ( P>0.05). No adverse reactions such as nasal bleeding, nasal dryness and postoperative pharyngeal discomfort were found when the self-made pharyngeal oxygen catheter was inserted in group NO. Conclusions:The oxygen supply with the transnasal self-made pharyngeal oxygen catheter technique can prolong the safe apnea time in the pediatric patients undergoing tonsil surgery.

Objective - To analyze the effect of using vibration tools on the prevalence of work related musculoskeletal disorders （ ） Methods ， - WMSDs in automobile factory workers. By judgment sampling method front line workers with more than one year of working experience in an automobile factory were selected as the research subjects. Musculoskeletal Disorders Questionnaire was used for investigation. The workers were divided into the control group and the vibration tool group. The propensity score ∶ ， matching method was used to balance the confounding factors of the two groups of workers by 1 1 and 568 people were Results included in each group. The prevalence of WMSDs was compared between the two groups after matching. After ， ， ， ， ， ， matching the prevalence of WMSDs in the shoulder elbow hand/wrist upper back waist hip/buttock and knee of workers in ， （ P ） the vibration tool group was higher than that in the control group and the differences were statistically significant all <0.05 .， The prevalence of WMSDs in different body parts of workers in the vibration tool group ranking from high to low was waist ， ， ， ， ， ， ， ， ， ， neck shoulder hand/wrist upper back knee ankle/foot elbow and hip/buttock with the rate of 74.3% 61.3% 54.2% ， ， ， ， ， （P ） Conclusions 54.0% 50.9% 39.4% 35.2% 31.0% and 27.1% respectively <0.01 . The use of vibration tools can ， ， ， ， ， increase the risk of WMSDs in shoulder elbow hand/wrist upper back waist hip/buttock and knee of automobile factory workers. Corresponding measures should be taken to reduce vibration intensity and reduce contact time to protect workers'

Objective To evaluate the risk of hearing loss of assembly workers in an automobile manufacturing factory. Methods An 8-hour equivalent sound level monitoring was carried out for assembly posts in an automobile factory. The risk of noise-induced hearing loss of assembly workers was measured using the method specified in ISO 1999:2013(E). The risk of noise-induced hearing loss was assessed in a graded manner according to the Guidelines for the Management of Occupational Disease Hazards from Noise. The results were statistically analyzed using Pearson correlation analysis. Results The average 8-hour equivalent sound level of the assembly work post in this automobile manufacturing factory was 89.5 dB (A). At 4000 Hz, the hearing loss N₅₀ (dB) of assembly workers reached the maximum. The longer the exposure time, the higher the risk of high-frequency standard hearing threshold shift. The risk of high-frequency standard hearing threshold shift was at a relatively high level at 30 years of work, while the risk of noise deafness reached a higher level after 40 years of work. Conclusion The 8-hour equivalent sound level (L_EX,8h) of assembly workers in the automobile factory exceeds the occupational exposure limit. With the increase of exposure years, the risk of high-frequency standard hearing threshold shift and noise deafness increases.

The purpose of the present study was to investigate the effect and potential mechanism of knockdown of sphingosine kinase-1 (SPHK1) on the proliferation, cell cycle and apoptosis of non-small cell lung cancer (NSCLC) cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect SPHK1 mRNA expression in human healthy lung fibroblasts (MRC-5 cells) and four NSCLC cell lines. Then, A549 and H1299 cells were transfected with SPHK1-shRNA and corresponding negative control. CCK-8, Annexin V-FITC/PI dual staining and cell cycle assay were performed to evaluate cell proliferation, apoptosis and cell cycle distribution, respectively. JC-1 mitochondrial membrane potential measurement kit was adopted to measure mitochondrial membrane potential. Western blot was used to detect the protein expression levels of cell cycle and mitochondrial apoptotic pathway-related proteins, as well as MEK/ERK signaling pathway. The results showed that the mRNA expression of SPHK1 in NSCLC cells was higher than that in MRC-5 cells. SPHK1-shRNA significantly inhibited the proliferation of A549 and H1299 cells, blocked the cell cycle in G0/G1 phase, and promoted cell apoptosis through the mitochondrial pathway. Compared with the control group, the expression of p-MEK and p-ERK proteins in the SPHK1-shRNA group was significantly down-regulated. Moreover, MEK/ERK inhibitor could dramatically suppress cell proliferation and promote cell apoptosis. These results suggest that SPHK1 knockdown can inhibit the proliferation of NSCLC cells and might promote mitochondrial apoptotic pathway by inhibiting MEK/ERK signaling pathway.
Apoptosis ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Gene Knockdown Techniques ; Humans ; Lung Neoplasms/genetics* ; Phosphotransferases (Alcohol Group Acceptor)/genetics*

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*