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 clinicopathological features and differential diagnosis of male genital system lymphoma (MGSL). METHODS: We retrospectively analyzed the clinicopathological and immunophenotypic features and prognosis of 80 cases of MGSL. RESULTS: The onset age of the MGSL patients ranged from 4 to 85 (median 62) years old. All the cases showed non-specificity of the imaging features and clinical manifestations. MGSL was located mainly in the testis (n = 66), followed by the prostate (n = 7), epididymis (n = 3), scrotum (n = 3) and penile glans (n = 1). Diffused large B cell lymphoma (DLBCL) was the most common pathological type (n = 62), next came extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) (n = 7) and other rare types (n = 12). During the 1－112-month follow-up of 10 of the 19 patients, 1 died at 1 month after diagnosed with prostatic B-lymphoblastic lymphoma (B-LBL) and another 1 died at 50 months after diagnosed with testicular DLBCL. CONCLUSION MGSL is rare clinically, mainly of the DLBCL type pathologically, lacking specificity in clinical symptoms and imaging manifestation. The definite diagnosis of the malignancy depends on histopathology combined with related molecular examination and immunohistochemical labeling, and R-CHOP chemotherapy is the first choice for its treatment.
Humans ; Male ; Middle Aged ; Aged ; Retrospective Studies ; Adult ; Aged, 80 and over ; Young Adult ; Adolescent ; Child ; Child, Preschool ; Genital Neoplasms, Male/diagnosis* ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Lymphoma/diagnosis*

ObjectiveThe detection of RNA single nucleotide polymorphism (SNP) is of great importance due to their association with protein expression related to various diseases and drug responses. At present, splintR ligase-assisted methods are important approaches for RNA direct detection, but its specificity will be limited when the fidelity of ligases is not ideal. The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection. MethodsIn this study, a dual-competitive-padlock-probe (DCPLP) assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation. To verify the method, we employed dual competitive padlock probe-mediated rolling circle amplification (DCPLP-RCA) to genotype the CYP2C9 gene. ResultsThe specificity was well improved through the competition and strand displacement of dual padlock probe, with an 83.26% reduction in nonspecific signal. By detecting synthetic RNA samples, the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L. Furthermore, clinical samples were applied to the method to evaluate its performance, and the genotyping results were consistent with those obtained using the qPCR method. ConclusionThis study has successfully established a highly specific direct RNA SNP detection method, and provided a novel avenue for accurate identification of various types of RNAs.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To understand the growth and development status and differences between small for gestational age(SGA)and appropriate for gestational age(AGA)preterm infants during corrected ages 0-24 months,and to provide a basis for early health interventions for preterm infants.Methods A retrospective study was conducted,selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022,including 144 SGA and 680 AGA infants.The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared.Results The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months(P<0.05),while there were no significant differences between the two groups at corrected age 24 months(P>0.05).At corrected age 24 months,85%(34/40)of SGA and 79%(74/94)of AGA preterm infants achieved catch-up growth.Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age<34 weeks and the AGA subgroups with gestational age<34 weeks and≥34 weeks(P<0.05).In addition,the weight and length of the SGA subgroup with gestational age≥34 weeks showed significant differences compared to the AGA subgroups with gestational age<34 weeks and≥34 weeks at corrected ages 0-18 months and corrected ages 0-12 months,respectively(P<0.05).Catch-up growth for SGA infants with gestational age<34 weeks and≥34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months,respectively.Conclusions SGA infants exhibit delayed early-life physical growth compared to AGA infants,but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants.Catch-up growth can be achieved earlier in SGA infants with a gestational age of<34 weeks compared to those with≥34 weeks.

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the effects of positive psychological intervention based on PERMA model of wellbeing on stigma,adaptation to ostomy and quality of life in patients with permanent enterostomy.Methods A total of 83 patients with permanent enterostomy were recruited from October 2022 to September 2023 in a tertiary hospital in Liaoning Province.They were randomly divided into an experimental group and a control group.While the control group received routine nursing,the experimental group received nursing intervention based on PERMA.The intervention lasted 8 weeks,and data were collected before and after the intervention.The scores of the Social Impact Scale(SIS),Ostomy Adjustment Inventory-20(OAI-20)and Stoma Quality of Life(Stoma-QOL)in the 2 groups were compared.Results Experimental group and control group were 40 cases each completed the study.After the intervention,the SIS score of the experimental group was(44.70±9.10),which was significantly lower than(62.15±12.43)of the control group,and the difference between 2 groups was statistically significant(t=-7.163,P＜0.001).The OAI-20 score of the experimental group was(52.28±5.80),which was significantly higher than(41.53±9.00)of the control group,and the difference between the 2 groups was statistically significant(t=6.349,P＜0.001).The Stoma-QOL score of the experimental group was(54.08±8.29),which was significantly higher than(42.95±9.19)of the control group,and the difference between the 2 groups was statistically significant(t=5.688,P＜0.001).Conclusion Nursing interventions based on PERMA are beneficial in reducing stigma of patients with permanent enterostomy,improving their ostomy adjustment and postoperative quality of life.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Aim To explore the mechanism of timosaponin A III increasing cisplatin sensitization of non-small cell lung cancer cisplatin-resistant A549/DDP cells. Methods The cell proliferation was detected by CCK8,the cell apoptosis was detected by Annexin V/ PI,and the cell cycle distribution was measured by PI. The effect of the combined drug on cell proliferation was detected by cell clone formation. The mRNA expression levels of C-myc, cysteinyl aspartate-specific protease-3 (caspase-3) were detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot and Flow Cytometry were performed for the mechanism study. Results The results of CCK8 and clone formation showed that the timosaponin AM group significantly increased the sensitivity of cisplatin to A549/DDP cells. Compared with the cisplatin group a-lone,the combination of timosaponin AM and cisplatin significantly elevated the apoptosis rate of A549/DDP cells (P < 0.05) , induced cell cycle arrest in G