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 quantitatively analyze the impact of environmental hygiene on the occurrence of health-care-associated infections(HAI).Methods Monitoring data of HAI and environmental hygiene from a tertiary first-class hospital from January 2018 to December 2022 were collected,and the impact of environmental bacterial colony forming unit(CFU)on the occurrence of HAI was analyzed by a time-series generalized additive model.Results The single-contamination model showed a significant positive correlation between HAI and staff's hand bacterial CFU(β1=0.009,P=0.012).For an increase of 1 interquartile range(IQR)in the monthly mean CFU per dish(MCFU/Dish)of staffs'hand,the incidence of HAI increased by 13.28％(95％CI:2.82％-24.81％).Subgroup and lag effect analysis showed that when the monthly MCFU/Dish(after hand disinfection)of staffs'hand in-creased by one IQR,the excess risk(ER)of HAI for the month(lag0)was 16.26％(95％CI:15.45％-17.09％).In the multi-contamination model,the correlation between surface contamination and HAI was also statistically sig-nificant.Conclusion There is a significant correlation between hospital environmental hygiene and the occurrence of HAI.

Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.

Objective:To investigate the clinical effect of jujube core-shaped tissue resection technique in the treatment of alar reduction.Methods:A retrospective analysis was performed for the clinical data of patients who underwent alar reduction from February 2019 to June 2022. A spindle-shaped incision line was designed along the outer edge of the base of the nasal lobule, with a width of 4-5 mm and a length of 8-12 mm. The incision line was 1-2 mm away from the alar groove, and the inner side of the design line was extended to the inside of the nasal vestibule. After the incision was made, the subcutaneous tissue was undermining dissected with curved sharp scissors, and the shape of the extended excision tissue was similar to that of jujube core. After reduction, the incision was closed with vertical mattress suture. The surgical effect and complications were followed up after surgery, and an independent attending plastic surgeon evaluated the outcome and scarring based on photos before and at the last postoperative follow-up using the global aesthetic improvement scale (GAIS) and the Vancouver scar scale (VSS). GAIS is graded as 1, 2, 3, 4, and 5 points, and the lower the score, the better the improvement(≤3 points as effective improvement). VSS includes four parameters: color (0-3 points), thickness (0-4 points), vascular distribution (0-3 points), and softness (0-5 points). The higher the score, the more significant the scar is.Results:A total of 20 patients were enrolled, including 6 males and 14 females, aged 20 to 33 years, with an average age of 24.9 years. Before the operation, there were different degrees of alar flare and alar hypertrophy. After surgery, 13 patients had mild swelling, ecchymosis, which resolved after 3 days. There were no major complications as infection, incision dehiscence, and delayed healing. After 3 to 16 months of postoperative follow-up, 2 patients gradually developed cartilage deformation and affected the appearance of the nostrils 6 to 9 months after surgery due to the combination of rib-based rhinoplasty, and the satisfactory results were obtained after revision surgery. The symmetry of the nostrils was significantly improved. The GAIS score of 20 patients was (1.20±0.41) points, of which, 16 patients were rated as 1 point and 4 patients were rated as 2 points, all of which met the improvement criteria, and the VSS score was (1.45±0.60) points, in which the average score for color, thickness, vasculature and compliance are 0.60, 0.05, 0.55 and 0.30 points respectively.Conclusion:The application of jujube core-shaped tissue resection technique for alar reduction can increase the amount of tissue removal with the same incision width, which can not only fully narrow the alar effectively but also correct the hypertrophy of the alar tissue.

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective: To explore the relationship between DNA methylation and occupational noise-induced hearing loss. Methods: A case-control study was conducted. People with hearing loss induced by occupational noise were recruited as the case group and those with normal hearing but still exposed to occupational noise were recruited as the control group. A total of 60 participants were included, of which 30 participants were in the case group and 30 in the control group. The methylation level was detected by 850k genome-wide DNA methylation chip technology. The significance of differential methylated position (DMP) was tested by R-packet 'Champ'. The differential methylated region (DMR) was analyzed by using Champ's Bumphunter algorithm. Cluster profiler was used to analyze the gene list for GO and KEGG pathway enrichment. Results: There was significant difference between two groups in binaural high-frequency average hearing threshold (P<0.05), but there was no significant difference in age, smoking, drinking, hypertension, physical exercise and cumulative noise exposure. The results of DMP and DMR analysis showed that 713875 sites were detected in the case group and the control group, and 439 methylation sites with significant difference, accounting for 0.06%; 650 regions were detected, and 72 methylation regions with significant differences, accounting for 11.08%. Compared with the control group, the results of GO enrichment analysis showed that the case group had statistically significant differences in four pathways: axogenesis of projection neurons in the central nervous system, neuronal development in the central nervous system, axogenesis of neurons in the central nervous system and neuronal differentiation in the central nervous system. KEGG enrichment analysis showed that there were significant differences in sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis pathway between the case group and the control group. Conclusion: The occurrence of occupational noise-induced hearing loss may be related to the regulation of gene expression related to axogenesis of projection neurons in the central nervous system, development of neurons in the central nervous system, axogenesis of neurons in the central nervous system, differentiation of neurons in the central nervous system, sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis and gene methylation related to metabolism.
Aldosterone ; Bile Acids and Salts ; Case-Control Studies ; DNA Methylation ; Hearing Loss, Noise-Induced/genetics* ; Humans ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure ; Sphingolipids

Objective:To explore the effects of Shenwei Ningyu pills （SNP）， a new Chinese medicine for depression， on the immunoinflammatory response mediated by Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88） signaling pathway in the hippocampus of rats exposed to chronic restraint stress （CRS）. Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group， a model group， an escitalopram group， and an SNP group. Except for the rats in the normal group， all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram （30 mg·kg^-1） and SNP （18 mg·kg^-1） one hour prior to CRS， respectively. The changes in body weight， sucrose preference index， horizontal movement scores， and vertical movement scores were observed by body weight assessment， sucrose preference test， and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1β （IL-1β）， IL-10， and tumor necrosis factor-α （TNF-α） was detected by enzyme-linked immunosorbent assay （ELISA）. Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However， significant differences were found among the groups following different interventions. The body weight， sugar preference index， horizontal movement score， and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group （P<0.01）. The above indicators in the SNP group and the escitalopram group were higher than those in the model group （P<0.01）， which indicated that SNP exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group， the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1β and TNF-α （P˂0.01） and dwindled serum IL-10 （P˂0.01）， while SNP and escitalopram reversed the conditions in the model group （P˂0.01） except for TNF-α. Conclusion:The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.

Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.