Abstract Prenatal stress is a common, systemic, nonspecific stress response that occurs during pregnancy. The gut microbiota, which is known as the “second genome” of the human body, interacts with all major systems of the body. Changes in the gut microbiota can impact the development and health of infants and young children. Advances in research technology have allowed us to uncover the relationship between prenatal stress and imbalances in offspring intestinal microbiota, as well as the development of multiple systemic diseases. However, the exact mechanisms through which prenatal stress disrupts the gut microbiota of offspring remain incompletely understood. This review summarizes the existing research on diseases caused by prenatal stress disrupting the offspring intestinal flora, and seeks future research directions to expand the understanding of the pathogenesis of infant diseases.

Abstract Asthma is a well-characterized heterogeneous disease marked by airway remodeling and chronic airway inflammation. Clinically, the treatment of asthma primarily relies on hormonal drugs. However, the long-term use of these medications can lead to significant side effects. Mitophagy is a biological process that selectively transports damaged mitochondria to lysosomes for degradation. Recent research has revealed the crosstalk between mitophagy and asthma. Accordingly, taking mitophagy as an entry point, summarizing the key molecular mechanisms and regulators of mitophagy in asthma will facilitate the development of novel intervention targets and strategies for asthmatic treatment.

Objective To compare the 12-month efficacy and safety of N-butyl cyanoacrylate (NBCA) versus radiofrequency ablation (RFA) in treating great saphenous vein (GSV) insufficiency. Methods A total of 155 patients with GSV insufficiency from five centers were randomly allocated to the NBCA group or RFA group. Postoperative efficacy and safety outcomes were evaluated. Results Immediate postoperative closure rates of the GSV trunk were 100% in both groups. The closure rates of NBCA and RFA group were 98.6% and 98.5% at 3 months, 97.1% and 98.5% at 6 months, 98.1% and 95.9% at 12 months, with no statistically significant differences (P>0.05). After treatment, CEAP classification improved significantly from baseline in both groups. In terms of safety, 1 case of phlebitis, 1 case of ablation-related thrombus extension (ARTE) and 2 cases of calf muscle venous thrombosis(CMVT) occurred in the NBCA group, while 2 cases of limb numbness, 1 case of persistent thigh pain and 2 cases of CMVT in the RFA group. All reported serious adverse events in both groups were assessed as unrelated to the medical device or the trial procedure. Conclusions NBCA demonstrates non-inferior efficacy and safety compared to RFA for treating GSV insufficiency over 12 months.

The pathogenesis of respiratory diseases such as chronic obstructive pulmonary disease(COPD),asthma,and pulmonary hypertension remains incompletely understood.However,accumulating evi-dence suggests that calcium ion channels play a critical role in these disorders.As a key second messenger,cal-cium ions regulates diverse physiological and pathological processes.Studies indicate that calcium ion homeo-stasis,including their concentration and distribution and spatial distribution is mediated primarily through ino-sitol 1,4,5-trisphosphate receptor(IP3R)channel.Disruption of this homeostasis may contribute to the devel-opment of COPD,asthma,and other respiratory diseases.Nevertheless,the role of IP3R channels in respirato-ry diseases require further investigation.

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2). METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for "delayed motor development for 1 and a half year" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097). RESULTS: The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C>T (p.Arg256Trp) and c.962G>A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C>T and c.962G>A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C>T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C>T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G>A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have included scoliosis (88.9%, 16/18), generalized hypotonia (83.3%, 15/18), and soft and lax skin (66.7%, 12/18). Some patients already showed skeletal abnormalities on prenatal ultrasound scan (22.2%, 4/18), while a few presented with cervical instability (16.7%, 3/18). One child had deceased at 18 months of age due to hypoxia caused by tracheomalacia and tracheal compression due to scoliosis. Among the 23 reported EDSSPD2 related B3GALT6 variant sites, missense variants were the most common (78.3%, 18/23), followed by nonsense variants (21.7%, 5/23). CONCLUSION Above finding has enriched the clinical and mutational spectra of EDSSPD2. Early genetic testing has important clinical value for the diagnosis, differential diagnosis, and genetic counseling of this disease.
Humans ; Male ; Ehlers-Danlos Syndrome/genetics* ; Pedigree ; N-Acetylgalactosaminyltransferases/genetics* ; Asian People/genetics* ; DNA Copy Number Variations ; Exome Sequencing ; Female ; Child ; Child, Preschool ; Phenotype ; Mutation ; China ; East Asian People ; Galactosyltransferases

AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.

Objective:To explore the clinical features and genetic basis for a child with Intellectual developmental disorder (IDD) and epilepsy.Methods:A child who was admitted to the Children′s Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The patient, a 3-month-and-27-day female infant, had developed the symptoms in the neonatal period, which included severe developmental delay, respiratory difficulties and pauses, increased muscle tone of four limbs, feeding difficulty, and seizures. Cerebral MRI revealed bilateral cerebellar hypoplasia, and video EEG showed slightly increased sharp waves emanating predominantly from the right parietal, occipital, and posterior temporal regions. WES revealed that she has harbored a missense c. 3196G>A (p.Glu1066Lys) variant of the CLTC gene, which was confirmed to be de novo by Sanger sequencing. Based on the guideline from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The c. 3196G>A (p.Glu1066Lys) missense variant of the CLTC gene probably underlay the pathogenesis in this child. Above finding has facilitated her diagnosis and treatment.

Objective:To summarize the research on oral health education for pregnant women.Methods:The literature was described and analyzed using a scoping review method. Seven databases, such as PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang Data, were electronically searched, and the search period was from database establishment to October 30, 2023.Results:A total of 43 articles were included. The implementers of health education were mainly dental professionals and prenatal healthcare personnel. The theoretical basis included the health belief model, planned behavior theory, social cognitive model and so on. The methods involved traditional teaching or lectures, family-centered, internet-based, and motivational interviews. The contents contained many aspects of oral health for pregnant women. The evaluation indicators mainly covered oral health knowledge, attitude and practice, and self-efficacy, oral health beliefs, oral health status, the incidence of oral diseases, adverse pregnancy outcomes of pregnant and postpartum women, and childhood caries incidence.Conclusions:We should establish a cooperation team of the Department of Stomatology and Obstetrics and Gynecology, incorporate oral health for pregnant women into prenatal care projects, fully utilize the platform of pregnant women's schools, explore the optimal theoretical basis for oral health education, and improve the content of oral health education for pregnant women.

Objective To investigate the effect of intestinal flora on the efficacy of polyethylene glycol losenatide(PEX168)in mice with type 2 diabetes mellitus(T2DM).Methods A total of 50 healthy male C57BL/6 mice were fed with a high-fat diet combined with STZ to establish a T2DM mouse model.Among them,40 were successfully modeled and divided into T2DM group(n=10)and PEX168 group(n=30).PEX168 group was further divided into two sub groups according to HbA1c:ideal group(IE subgroup,HbA1c≤6.5%,n=12)and unsatisfactory group(NE subgroup,HbA1c>6.5%,n=12).IE subgroup was fecal donor,NE subgroup was recipientand further divided into fecal bacteria transplantation subgroup(FMT,n=5)and Sham subgroup(Sham,n=5).Fecal bacteria transplantation(FMT)was used to transfer fecal bacteria from IE group to FMT group.Body weight,food intake and blood glucose were measured every 2 weeks in all the groups.FPG,FIns,HbA1c and insulin resistance index(HOMA-IR)were compared on the 7th day after 10 weeks of intervention in all the groups.Results FPG and body weight were lower at the 4th,6th,8th and 10th week(P<0.05),and food intake was lower in PEX168 group than in T2DM group at the 2nd,4th,6th,8th and 10th week(P<0.05).At the 4th,6th,8th and 10th week after administration,the FPG and body weight were lower in IE subgroup than in NE subgroup(P<0.05),and the food intake was lower at the 0th,4th,8th and 10th week after administration than in NE subgroup(P<0.05).The FBG,body weight and food intake were lower in FMT subgroup than in Sham subgroup at 4,6 and 8 weeks(P<0.05).The FPG,HbA1c,2 hPG,FIns and HOMA-IR were lowerin PEX168 group after treatment than in PEX168 group before treatment and T2DM group after treatment(P<0.05).FPG,HbA1c,FIns,2 hPG and HOMA-IR were lower in IE subgroup after treatment than in IE subgroup before treatment and NE subgroup after treatment(P<0.05).FPG,HbA1c,FIns,2 hPG and HOMA-IR were lower in FMT subgroup after treatment than in FMT subgroup before treatment and Sham subgroup after treatment(P<0.05).Conclusions Differences in intestinal flora between individuals affect the efficacy of PEX168.FMT treatment can improve the composition of intestinal flora and affect the efficacy of PEX168.