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

The purpose of the present study was to investigate the effects of resistance combined with aerobic chrono-exercise on the common carotid artery elasticity and hemodynamics. 24 healthy young men (21.96±0.43 years old) underwent a single acute resistance combined with aerobic exercise intervention at eight time periods (6, 8, 10, 12, 14, 16, 18, and 20 o'clock). The axial flow velocity and diameter waveforms of the common carotid artery were measured, and the hemodynamics were calculated using the classical hemodynamic theory before exercise, immediately after exercise, 10 min and 20 min after exercise. The results showed that during exercise recovery, systolic and mean pressures decreased more markedly after exercise at 8 o'clock (P < 0.05); At 20 min post-exercise, arterial stiffness index and pressure-strain elastic modulus after exercise at 6 o'clock were reduced compared with the resting state, but were significantly elevated after exercise at 20 o'clock (P < 0.05). Immediately after exercise, the pressure rise was higher after exercise at 6 o'clock and the mean wall shear stress was higher after exercise at 20 o'clock (P < 0.05). These results suggest that resistance combined with aerobic chrono-exercise produces different effects on common carotid artery hemodynamics in young men. A single acute session of resistance combined with aerobic exercise at 8 o'clock is more effective in lowering blood pressure. Exercise at 6 o'clock is beneficial to improve arterial elasticity but is not recommended for young male individuals with cardiovascular disease risks because of the excessive increase in blood pressure immediately after exercise. Exercise at 20 o'clock is more effective in improving wall shear stress but is accompanied by elevated arterial stiffness indices and pressure-strain elastic modulus. These results provide a scientific basis for healthy young men in choosing the time of exercise by exploring the common carotid artery elasticity and hemodynamic-related indices.
Humans ; Male ; Young Adult ; Exercise/physiology* ; Carotid Artery, Common/physiology* ; Hemodynamics/physiology* ; Vascular Stiffness/physiology* ; Elasticity ; Resistance Training ; Adult

Ecological cultivation is an important way for the sustainable production of traditional Chinese medicine in the context of the carbon peaking and carbon neutrality goals. Facility cultivation and simulative habitat cultivation modes have been developed and applied to develop the endangered Dendrobium huoshanense on the basis of protection. However, the differences in the greenhouse gas emissions and global warming potential of these cultivation modes remain unexplored, which limits the accurate assessment of carbon-friendly ecological cultivation modes of D. huoshanense. Greenhouse gas emission flux monitoring based on the static chamber method provides an effective way to solve this problem. Therefore, this study conducted a field experiment in the facility cultivation and simulative habitat cultivation modes at a D. huoshanense cultivation base in Dabie Mountains, Anhui Province. From April 2023 to March 2024, samples of greenhouse gases were collected every month, and the concentrations of CO_2, CH_4, and N_2O of the samples were then detected by gas chromatography. The greenhouse gas emission fluxes, cumulative emissions, and global warming potential were further calculated, and the following results were obtained.(1)The two cultivation modes of D. huoshanense showed significant differences in greenhouse gas emission fluxes, especially the CO_2 emission flux, with a pattern of facility cultivation>simulative habitat cultivation [(35.60±11.70)mg·m~(-2)·h~(-1) vs(2.10±4.59)mg·m~(-2)·h~(-1)].(2) The annual cumulative CO_2 emission flux in the case of facility cultivation was significantly higher than that of simulative habitat cultivation[(3 077.00±842.00)kg·hm~(-2) vs(221.00±332.00)kg·hm~(-2)], while no significant difference was found in annual cumulative CH_4 and N_2O emission fluxes.(3) The facility cultivation mode had a significantly higher global warming potential than the simulative habitat cultivation mode [(3 053.00±847.00)kg·hm~(-2) vs(196.00±362.00)kg·hm~(-2)]. Overall, the simulative habitat cultivation of D. huoshanense has obvious carbon-friendly characteristics compared with facility cultivation, which is in line with the concept of ecological cultivation of medicinal plants. This study is of great reference significance for the implementation and promotion of the ecological cultivation mode of D. huoshanense under carbon peaking and carbon neutrality goals.
Dendrobium/chemistry* ; Greenhouse Gases/metabolism* ; Carbon/analysis* ; Ecosystem ; Carbon Dioxide/metabolism* ; China ; Global Warming

The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

Purpose To investigate the clinical feature and histopathology of pyloric gland adenoma.Methods Clinical da-ta of 16 cases of pyloric adenomas were collected.The expres-sion of Pepsinogen I,p53,MUC6,MUC5AC,CgA,Syn,CD56,Ki67,CDX-2,MUC2,β-catenin,and CD10 was detec-ted by immunohistochemistry EnVision method.The relationship with clinicopathological features and prognosis was analyzed.Results There were 7 males and 9 females,aged from 26 to 81 years with an average of 58 years.Tumor diameters ranged from 0.2 to 4 centimeter with a mean of 1.3 centimeter.The anatomi-cal sites of the 16 PGA were stomach(6 cases),including 3 ca-ses in body,3 cases in fundus and duodenum(3 cases).7 ca-ses of low-grade PGAs were composed of closely packed pyloric-type glands,lined by cuboidal/low columnar epithelia.The nu-clei(round to ovoid)were basally located,with inconspicuous nucleoli.Neoplastic cells characterized by a defined ground-glass appearance,with clear or eosinophilic cytoplasm.The cell was lack of a well-defined apical mucin cap.1 case of high-grade PGAs consistently exhibited architecture,crowded nuclei,and loss of nuclear polarity.The remaining 8 cases had both low-and high-grade components.Squamous morula was found in 5 cases.According to immunohistochemical characteristics,8 of 16 cases were mixed pattern(MUC5AC+,MUC6+).Others were pure pyloric type(MUC5AC-,MUC6+).No foveolar-dominant type(MUC5AC+,MUC6-)was found.Conclusion PGA is a rare tumor of the digestive system,with characteristic morpholog-ical characteristics and immunophenotype.Clinicians and pathol-ogists need to strengthen their understanding and better manage patients because of the risk of malignant transformation.Early detection,early diagnosis and early treatment are needed.

Objective To observe the therapeutic effect and mechanism of electroacupuncture at Jiaji(EX-B2)points for lumbar disc degeneration in rats.Methods Thirty SD rats were randomly divided into the sham-operation group,model group and electroacupuncture group,with 10 rats in each group.The rats in the model group and electroacupuncture group were constructed a lumbar disc degeneration model by annulus fibrosus puncture method,and the sham-operation group was only given separation of intervertebral discs without other treatments.After successful modeling,the electroacupuncture group was treated with electroacupuncture at the L4 and L5 bilateral Jiaji points.No treatment was given to the sham-operation group and the model group.At the end of the intervention,the paw withdrawal mechanical threshold(PMWT)was detected by electronic Von Frey filaments,the changes of the structure of lumbar disc in rats were observed by hematoxylin-eosin(HE)staining,the levels of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in the supernatant of lumbar intervertebral disc tissues were detected by enzyme-linked immunosorbent assay(ELISA),and the ratio of nucleus pulposus cell cycle was detected by flow cytometry,real-time quantitative polymerase chain reaction(RT-PCR)method was used to detect the mRNA expression levels of Fas-associated death domain protein(FADD),cysteinyl aspartate specific protease 8(Caspase-8),B-cell lymphoma/leukemia 2(Bcl-2)-associated X protein(Bax)and Bcl-2 in the nucleus pulposus of lumbar intervertebral disc,the protein expression levels of FADD,Caspase-8,Bax,and Bcl-2 in the nucleus pulposus of lumbar intervertebral disc were detected by Western Blot.Results The overall structure of the intervertebral disc in rats of the model group was abnormal and obvious degeneration was seen;the degeneration of intervertebral disc tissue in the electroacupuncture group was significantly improved compared with that of the model group.Compared with the sham-operation group,the model group showed lower PWMT,and the higher levels of IL-1β and TNF-α,the increased proportion of G0/G1 nucleus pulposus cells and decreased proportion of G2/M nucleus pulposus cells,and the increased mRNA and protein expression levels of FADD,Caspase-8 and Bax and the decreased mRNA and protein levels of Bcl-2,the differences being statistically significant(P＜0.05).Compared with the model group,the electroacupuncture group showed higher PWMT,the lower levels of IL-1β and TNF-α,the decreased proportion of G0/G1 nucleus pulposus cells and the increased proportion of G2/M nucleus pulposus cells,and the decreased mRNA and protein expression levels of FADD,Caspase-8 and Bax and the increased mRNA and protein levels of Bcl-2,the differences being statistically significant(P＜0.05).Conclusion Electroacupuncture at the Jiaji points can alleviate inflammatory reaction,regulate nucleus pulposus cell cycle to improve the structural changes of lumbar disc through regulating the FADD/Caspase-8 signaling pathway to inhibit apoptosis,thereby slowing down rat lumbar disc degeneration.

Objective:To investigate the influence of liver drainage volume on overall survival time in patients with unresectable malignant hilar bile duct obstruction.Methods:Data of 633 patients with unresectable malignant hilar bile duct obstruction (BismuthⅡ-Ⅳ) who underwent endoscopic stent drainage in 3 endoscopy centers from January 2002 to May 2019 were retrospectively analyzed. Main observation indicators included clinical success rate, stent patency, overall survival, the effective liver drainage volume, and complication incidence.Results:The clinical success rates of patients with liver drainage volume <30%, 30%-50%, and >50% were 56.8% (25/44), 77.3% (201/260) and 84.2% (277/329) respectively. The incidences of early cholangitis were 31.8% (14/44), 18.8% (49/260) and 16.1% (53/329). The median stent patency time was 4.5 (95% CI: 1.8-7.2) months, 5.6 (95% CI: 5.0-6.2) months and 6.6 (95% CI: 5.2-8.0) months. The overall survival time was 2.4 (95% CI: 1.8-3.0) months, 4.0 (95% CI: 3.4-4.6) months and 4.9 (95% CI:4.4-5.4) months, respectively. The clinical success rate ( χ 2=8.28, P=0.012), median stent patency period ( χ 2=18.87, P=0.015) and overall survival time ( χ 2=6.93, P=0.024) of 30%-50% liver drainage volume group were significantly higher than those of <30% group. Further multivariate cox regression analysis showed that the disease type (hepatocellular carcinoma VS hilar cholangiocarcinoma: HR=1.50, 95% CI:1.18-1.91, P=0.001; gallbladder carcinoma VS hilar cholangiocarcinoma: HR=1.45, 95% CI:1.14-1.85, P=0.002; metastatic cholangiocarcinoma VS hilar cholangiocarcinoma: HR=1.48, 95% CI:1.08-2.04, P=0.015), bilirubin level >200 μmol/L ( HR=1.35, 95% CI:1.14-1.60, P<0.001),metal stents ( HR=0.67, 95% CI:0.56-0.79, P<0.001), liver drainage volume (volume 30%-50% VS <30%: HR=0.64, 95% CI: 0.45-0.90, P=0.010; volume>50% VS <30%: HR=0.58, 95% CI:0.41-0.81, P=0.002) and anti-tumor therapy ( HR=0.51, 95% CI:0.42-0.61, P<0.001) were independent predictors for overall survival time of patients with unresectable malignant hilar bile duct obstruction. Conclusion:When endoscopic stent drainage is performed for patients with unresectable malignant hilar bile duct obstruction, at least 30% liver volume is required for better overall survival. In addition, the use of metal stent drainage and anti-tumor therapy may increase survival benefits.