Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

Prostate cancer (PCa) is globally the most prevalent malignancy in the male genitourinary system, with a continuously ascending incidence in China. For the treatment of localized PCa, radical prostatectomy and radiotherapy have demonstrated effective suppression of the tumor, but with obvious complications that markedly compromise the life quality of the patients. Focal therapy, by targeting the principal tumor foci, can largely reduce the incidence of complications. In this context, irreversible electroporation represents an emerging modality of focal treatment capable of ablating the tumor as thoroughly as possible while sparing such critical structures as the urethra, rectum and neurovascular bundles from thermal damage, and thus offers a promising option for the management of localized PCa. This article presents an overview of the latest advances in the studies of irreversible electroporation.
Humans ; Male ; Prostatic Neoplasms/therapy* ; Electroporation/methods*

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Patients with alcoholic cirrhosis often experience varying degrees of malnutrition， and the patients with malnutrition are more susceptible to complications such as infections and ascites， which may lead to a poor prognosis. Therefore， it is particularly important to conduct nutritional risk screening for patients in clinical practice， and appropriate nutritional assessment tools should be used to evaluate the nutritional status of patients and develop individualized nutritional supplementation regimens， thereby promoting disease recovery and improving prognosis and quality of life. This article elaborates on the specific methods for nutritional screening， assessment， and management in patients with alcoholic cirrhosis and points out that systematic nutritional screening and assessment can help to identify the patients with malnutrition in the early stage and provide timely intervention. Individualized nutritional supplementation regimens should be adjusted based on the conditions of patients， so as to meet their nutritional needs， promote the recovery of liver function， improve overall health status， and enhance long-term quality of life.

Bile acids encompass primary bile acids and secondary bile acids,the latter of which are produced from primary bile acids in the gut.In recent years,bile acids,compounds with a steroid structure found in bile,have been shown through extensive clinical investigations and fundamental studies to play a significant role in regulating intestinal and systemic immune homeostasis,inflammatory responses,and neurological disorders.In the gut,primary and secondary bile acids can disrupt the invasion of pathogenic microorganisms into the host due to their unique physical properties.Additional-ly,they regulate downstream signaling pathways by binding to effector receptors,thereby performing vital biological func-tions,including the modulation of immune responses.Consequently,bile acids function as essential small molecules in the pathophysiological processes of various intestinal diseases and extra-intestinal tissue conditions influenced by intestinal homeostasis.This article focuses on the role and regulatory mechanisms of the"microbe-bile acid"axis in intestinal inflam-mation,elucidating the synthesis and metabolism of bile acids and the significance of intestinal microbes in signal trans-duction via bile acids during the inflammatory process.It aims to provide a foundation and reference for the development of drugs and therapeutic strategies targeting diseases related to intestinal inflammation and immune dysregulation.

Bile acids encompass primary bile acids and secondary bile acids,the latter of which are produced from primary bile acids in the gut.In recent years,bile acids,compounds with a steroid structure found in bile,have been shown through extensive clinical investigations and fundamental studies to play a significant role in regulating intestinal and systemic immune homeostasis,inflammatory responses,and neurological disorders.In the gut,primary and secondary bile acids can disrupt the invasion of pathogenic microorganisms into the host due to their unique physical properties.Additional-ly,they regulate downstream signaling pathways by binding to effector receptors,thereby performing vital biological func-tions,including the modulation of immune responses.Consequently,bile acids function as essential small molecules in the pathophysiological processes of various intestinal diseases and extra-intestinal tissue conditions influenced by intestinal homeostasis.This article focuses on the role and regulatory mechanisms of the"microbe-bile acid"axis in intestinal inflam-mation,elucidating the synthesis and metabolism of bile acids and the significance of intestinal microbes in signal trans-duction via bile acids during the inflammatory process.It aims to provide a foundation and reference for the development of drugs and therapeutic strategies targeting diseases related to intestinal inflammation and immune dysregulation.

OBJECTIVE To observe the impact of Bifidobacterium quadruple viable organisms combined with inter-ferons on serum amyloid A(SAA),transforming growth factor-β(TGF-β),25-hydroxyvitamin D3[25(OH)D3]and intestinal function of the children with rotavirus-induced viral diarrhea.METHODS A total of 88 children with rotavirus-induced viral diarrhea who were treated in Affiliated Hospital of Jiangnan University from Mar.2020 to Dec.2023 were recruited as the research subjects and were randomly divided into the conventional group with 44 cases(conventional symptomatic therapy plus interferons)and the combination group with 44 cases(the conven-tional symptomatic therapy plus Bifidobacterium quadruple viable organisms),and both groups were continuously treated for 5 days.The clinical curative effect and improvement of clinical symptoms were observed and compared between the two groups.The changes of peripheral blood immune function indexes,inflammatory factors,intesti-nal function indexes,SAA,TGF-β and 25(OH)D3 were analyzed.RESULTS There was no significant difference in the effective rate of treatment between the combination group and the conventional group after the treatment for 5 days(Z=1.375,P=0.169).The duration of stool property back to normal,fever abatement,number of defeca-tion times back to normal,cessation of diarrhea,virus turning to be negative and disappearance of abdominal pain was shorter in the combination group than in the conventional group(P＜0.05).The immune function,inflamma-tory factors and intestinal function indexes were improved more remarkably in the combination group than in the conventional group after the treatment for 5 days(P＜0.05).The levels of SAA,TGF-β and 25(OH)D3 of the combination group were respectively(3.84±0.35)pg/ml,(4.87±0.28)pg/ml and(50.63±7.14)pg/ml after the treatment for 5 days,higher than those of the conventional group.CONCLUSION Bifidobacterium quadruple viable organisms combined with interferons can effectively shorten the recovery time of clinical symptoms of the children with rotavirus-induced viral diarrhea,relieve the inflammatory reactions,improve the intestinal function and immune function,and stabilize the levels of serum SAA,TGF-β and 25(OH)D3.

OBJECTIVE To observe the impact of Bifidobacterium quadruple viable organisms combined with inter-ferons on serum amyloid A(SAA),transforming growth factor-β(TGF-β),25-hydroxyvitamin D3[25(OH)D3]and intestinal function of the children with rotavirus-induced viral diarrhea.METHODS A total of 88 children with rotavirus-induced viral diarrhea who were treated in Affiliated Hospital of Jiangnan University from Mar.2020 to Dec.2023 were recruited as the research subjects and were randomly divided into the conventional group with 44 cases(conventional symptomatic therapy plus interferons)and the combination group with 44 cases(the conven-tional symptomatic therapy plus Bifidobacterium quadruple viable organisms),and both groups were continuously treated for 5 days.The clinical curative effect and improvement of clinical symptoms were observed and compared between the two groups.The changes of peripheral blood immune function indexes,inflammatory factors,intesti-nal function indexes,SAA,TGF-β and 25(OH)D3 were analyzed.RESULTS There was no significant difference in the effective rate of treatment between the combination group and the conventional group after the treatment for 5 days(Z=1.375,P=0.169).The duration of stool property back to normal,fever abatement,number of defeca-tion times back to normal,cessation of diarrhea,virus turning to be negative and disappearance of abdominal pain was shorter in the combination group than in the conventional group(P＜0.05).The immune function,inflamma-tory factors and intestinal function indexes were improved more remarkably in the combination group than in the conventional group after the treatment for 5 days(P＜0.05).The levels of SAA,TGF-β and 25(OH)D3 of the combination group were respectively(3.84±0.35)pg/ml,(4.87±0.28)pg/ml and(50.63±7.14)pg/ml after the treatment for 5 days,higher than those of the conventional group.CONCLUSION Bifidobacterium quadruple viable organisms combined with interferons can effectively shorten the recovery time of clinical symptoms of the children with rotavirus-induced viral diarrhea,relieve the inflammatory reactions,improve the intestinal function and immune function,and stabilize the levels of serum SAA,TGF-β and 25(OH)D3.

Objective:To investigate the mechanism of 6-sialyllactose (6-SL) in interfering the immune checkpoint inhibitor-induced colitis (ICIC) through the bacterial 16S rDNA sequencing.Methods:BALB/c mice were randomly divided into the normal control (NC) group ( n = 7), dextran sulfate sodium (DSS) group ( n = 6), ICIC group ( n = 6), and ICIC+6-SL group ( n = 6). The DSS group was continuously fed with 3.5% DSS drinking water for 7 days to induce colonic inflammation; the ICIC group was administered cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, 150 μg) intraperitoneally on days 0 and 4 in addition to 3.5% DSS drinking water to establish the ICIC mouse model; the ICIC+6-SL group was given 6-SL [150 mg/ (kg·d) ] by gavage simultaneously with the establishment of the ICIC model. Changes in mouse body weight and disease activity index (DAI) were statistically analyzed, and all mice were sacrificed on day 7 to observe gross and histopathological morphological changes in the colon and to tally histopathological scores; the fresh colonic feces were collected for 16S rDNA sequencing to statistically analyze the diversity and species differences in the microbiota of mice of each group. Results:The success rate of the ICIC model was 100%, with all mice surviving. At the endpoint of the study (day 7), compared with the NC and DSS groups, the ICIC group had lower mouse body weight ( P < 0.05), higher DAI ( P < 0.05), damaged integrity of colonic mucosal tissue, and typical ulcerative lesions; the ICIC+6-SL group showed significant alleviation of body weight loss, significantly lower DAI scores, and lower pathological scores compared to the ICIC group, with all differences being statistically significant (all P < 0.05). 16S rDNA sequencing of mouse intestinal feces indicated that the alpha diversity of colonic microbiota in the ICIC group was lower than that in the NC and DSS groups (both P < 0.05), while the ICIC+6-SL group had higher alpha diversity than the ICIC group ( P < 0.05). In beta diversity analysis, the ANOSIM statistical value R = 0.376, P = 0.001 for the PCoA analysis of colonic microbiota and a Stress value of 0.125, P = 0.001 for the NMDS analysis indicated differences in the composition of colonic microbiota among the groups, with the greatest difference between the NC and ICIC groups, and the ICIC+6-SL group's microbiota composition was closer to that of the NC group compared to the ICIC group. Lefse analysis and Kruskal-Wallis test-based differential microbiota analysis showed that at the phylum level, compared to the NC group, the abundance of Bacteroidetes was significantly reduced in the ICIC group, while Campilobacterota was increased, and 6-SL administration could increase the abundance of Bacteroidetes and Campilobacterota in the ICIC group. At the genus level, compared to other groups, the abundance of unclassified_f_Lachnospiraceae and norank_f_Muribaculaceae was the lowest in the ICIC group, while Helicobacter, Akkermansia, and Escherichia-Shigella were enriched. Compared to the ICIC group, the abundance of unclassified_f_Lachnospiraceae and norank_f_ Muribaculaceae was increased in the ICIC+6-SL group, while the abundance of Helicobacter and Escherichia-Shigella was significantly suppressed. Conclusions:6-SL, an oligosaccharide derived from human milk, alleviates intestinal inflammatory injury in ICIC mice, reducing disease activity. This beneficial effect may be related to its regulation of gut microbiota profiling, an increased diversity of microbiota, a restoration of Bacteroidetes, and an inhibition of the growth advantage of pathogenic bacteria such as Helicobacter and Escherichia-Shigella.

Human milk oligosaccharides (HMOs), as the third most abundant solid nutrient in breast milk, are critical for early infants growth. HMOs are not only involved in the development of the immune system, maintaining inflammation balance, regulating gut microbiota, and participating in the maturation of the digestive system, but also in the improvement of the brain's nervous system and the development of advanced cognitive functions such as learning and memory. However, the role of HMOs in regulating neural development remains unclear. Related studies have focused on the mechanism of the microbiota-gut-brain axis, indicating that there is a practical interaction between the gut and brain. The function of HMOs in children's neurocognition and the biological process of disorders via this mechanism has also been preliminary reported. This review aims to review the structural characteristics and species-specific characteristics of HMOs, and analyze the potential pathways of HMOs in infant nervous system development from the perspective of the microbiota-gut-brain axis.