Objective:To investigate the effects of dexmedetomidine combined with esketamine on postoperative analgesia, immune function and inflammatory response in patients undergoing radical mastectomy.Methods:108 patients with breast cancer who received radical mastectomy in Breast Surgery Department, Shanxi Cancer Hospital from Apr. 2022 to Apr. 2024 were divided into the control group (n=54, esketamine) and the observation group (n=54, esketamine + dexmedetomidine) by random number table method. The postoperative recovery, analgesic effect, immune function indexes and inflammatory factors were compared between the two groups, and the occurrence of adverse reactions were recorded.Results:The number of postoperative analgesic pump compression in the observation group was less than that in the control group ( t = 6.60, P<0.05); There was no significant difference between the two groups in the proportion of patients with additional analgesic drugs, postoperative wakefulness-eye opening time or 15-item quality of recovery (QoR-15) scale ( χ2=0.32, t=1.32, 1.15, P>0.05); The observation group had lower VAS scores at 30min (T1), 4 h (T2), 8 h (T3) and 12 h (T4) after surgery ( t=4.82, 6.53, 14.01, 12.87, P<0.05); At T1, T2, T3 and T4, peripheral helper T cells (Th) 1 and Th1/Th2 in observation group were higher, while Th2 was lower ( t=3.98, 4.62, 4.12, 8.52, 3.81, 9.47, 13.98, 9.53, 4.44, 4.50, 4.31, 5.45, all P<0.05); The observation group had lower tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6) at T1, T2, T3 and T4, while higher IL-2 ( t=2.46, 2.99, 2.29, 3.05, 2.85, 3.64, 4.70, 2.51, 3.17, 3.74, 3.24, 2.79, all P<0.05); The incidence of adverse reactions between the two groups showed no significant difference ( χ2=2.31, P>0.05) . Conclusion:Dexmedetomidine combined with esketamine analgesia regimen can significantly improve the analgesic effect after radical mastectomy, reduce postoperative inflammatory response, and effectively protect postoperative immune function of patients, with certain safety.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective To explore the expression of urinary exosomal microRNA-145-5p(miR-145-5p)and the targeted relationship with SLIT-ROBO guanosine triphosphatase activating protein 2(Srgap2)in diabetic kidney disease(DKD)mice.Methods A total of 11 db/db mice with random blood glucose≥16.7 mmol/L were selected to construct DKD model,and 10 C57BL/6J wild-type mice were assigned to the normal control(NC)group.The urine exosomes were isolated from each group.The expression of miR-145-5p in urinary exosomes and renal tissue were detected using RT-qPCR.Pearson correlation analysis was used to analyze the correlation between urinary exosomal miR-145-5p and UACR as well as the glycolipid metabolism indicators.Luciferase activity was performed to verify the targeting relationship between miR-145-5p and Srgap2.The expression Srgap2 and the ROCK activity in the renal tissues were detected using Western blot.Results Compared with NC group,the body weight,fasting plasma glucose(FPG),FIns,HbA1c,TC,UACR,urinary exosomal miR-145-5p and the expression of miR-145-5p in renal tissue and p-MYPT1 protein expression were significantly higher(P<0.05),while the expression of Srgap2 protein was significantly lower in DKD group(P<0.05).Pearson correlation analysis revealed that the exosomal miR-145-5p was positively correlated with UACR,FPG,HbA1c and TC(r=0.836,0.888,0.843,0.882,P<0.05).MiR-145-5p could directly target the Srgap2 protein and activate the ROCK pathway.Conclusions The expression of urinary exosomal miR-145-5p was significantly increased and the miR-145-5p/Srgap2/ROCK axis may be closely related to renal damage in DKD mice,and it is a promising diagnostic biomarker and future therapeutic target for DKD.

Objective:To investigate the effects of dexmedetomidine combined with esketamine on postoperative analgesia, immune function and inflammatory response in patients undergoing radical mastectomy.Methods:108 patients with breast cancer who received radical mastectomy in Breast Surgery Department, Shanxi Cancer Hospital from Apr. 2022 to Apr. 2024 were divided into the control group (n=54, esketamine) and the observation group (n=54, esketamine + dexmedetomidine) by random number table method. The postoperative recovery, analgesic effect, immune function indexes and inflammatory factors were compared between the two groups, and the occurrence of adverse reactions were recorded.Results:The number of postoperative analgesic pump compression in the observation group was less than that in the control group ( t = 6.60, P<0.05); There was no significant difference between the two groups in the proportion of patients with additional analgesic drugs, postoperative wakefulness-eye opening time or 15-item quality of recovery (QoR-15) scale ( χ2=0.32, t=1.32, 1.15, P>0.05); The observation group had lower VAS scores at 30min (T1), 4 h (T2), 8 h (T3) and 12 h (T4) after surgery ( t=4.82, 6.53, 14.01, 12.87, P<0.05); At T1, T2, T3 and T4, peripheral helper T cells (Th) 1 and Th1/Th2 in observation group were higher, while Th2 was lower ( t=3.98, 4.62, 4.12, 8.52, 3.81, 9.47, 13.98, 9.53, 4.44, 4.50, 4.31, 5.45, all P<0.05); The observation group had lower tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6) at T1, T2, T3 and T4, while higher IL-2 ( t=2.46, 2.99, 2.29, 3.05, 2.85, 3.64, 4.70, 2.51, 3.17, 3.74, 3.24, 2.79, all P<0.05); The incidence of adverse reactions between the two groups showed no significant difference ( χ2=2.31, P>0.05) . Conclusion:Dexmedetomidine combined with esketamine analgesia regimen can significantly improve the analgesic effect after radical mastectomy, reduce postoperative inflammatory response, and effectively protect postoperative immune function of patients, with certain safety.

Objective To explore the expression of urinary exosomal microRNA-145-5p(miR-145-5p)and the targeted relationship with SLIT-ROBO guanosine triphosphatase activating protein 2(Srgap2)in diabetic kidney disease(DKD)mice.Methods A total of 11 db/db mice with random blood glucose≥16.7 mmol/L were selected to construct DKD model,and 10 C57BL/6J wild-type mice were assigned to the normal control(NC)group.The urine exosomes were isolated from each group.The expression of miR-145-5p in urinary exosomes and renal tissue were detected using RT-qPCR.Pearson correlation analysis was used to analyze the correlation between urinary exosomal miR-145-5p and UACR as well as the glycolipid metabolism indicators.Luciferase activity was performed to verify the targeting relationship between miR-145-5p and Srgap2.The expression Srgap2 and the ROCK activity in the renal tissues were detected using Western blot.Results Compared with NC group,the body weight,fasting plasma glucose(FPG),FIns,HbA1c,TC,UACR,urinary exosomal miR-145-5p and the expression of miR-145-5p in renal tissue and p-MYPT1 protein expression were significantly higher(P<0.05),while the expression of Srgap2 protein was significantly lower in DKD group(P<0.05).Pearson correlation analysis revealed that the exosomal miR-145-5p was positively correlated with UACR,FPG,HbA1c and TC(r=0.836,0.888,0.843,0.882,P<0.05).MiR-145-5p could directly target the Srgap2 protein and activate the ROCK pathway.Conclusions The expression of urinary exosomal miR-145-5p was significantly increased and the miR-145-5p/Srgap2/ROCK axis may be closely related to renal damage in DKD mice,and it is a promising diagnostic biomarker and future therapeutic target for DKD.

OBJECTIVE: To explore the clinical characteristics and gene variant of a fetus with Farber lipogranulomatosis caused by ASAH1 gene variant. METHODS: A fetus with Farber lipogranulomatosis caused by ASAH1 gene variant diagnosed at Women and Children's Hospital of Ningbo University in August 2024 was selected as the subject. Clinical data and abortion tissue samples of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Sanger sequencing validation and bioinformatics analysis were performed on candidate variants. This study was approved by Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: Generalized skin oedema, pericardial effusion, right pleural effusion and increased bowel echogenicity of the fetus were founded by prenatal ultrasound. WES revealed that the fetus has harbored a homozygous c.101C>A (p.Ser34Ter) variation in exon 2 of the ASAH1 gene. Sanger sequencing confirmed that both parents carry the heterozygous nonsense variation c.101C>A (p.Ser34Ter) in ASAH1 gene, which has not been included in databases such as HGMD, ClinVar, 1000 Genomes, ExAC, dbSNP, and gnomAD. Based on the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PM2_Supporting+PVS1+PM3_Supporting). The AlphaFold3 model protein structure prediction reveals that the c.101C>A variant caused the premature appearance of a termination codon, resulting in only a small partial α-helix structure in the N-terminal of the encoded ASAH1 protein, with the complete loss of the α-helix structure in the core domain, which might lead to the loss of function of this protein. CONCLUSION The c.101C>A (p.Ser34Ter) variant of the ASAH1 gene probably underlay the Farber lipogranulomatosis with hydrops fetalis in this fetus. The newly discovered c.101C>A (p.Ser34Ter) variant has enriched the mutational spectrum of Farber lipogranulomatosis.
Humans ; Female ; Pregnancy ; Acid Ceramidase/chemistry* ; Farber Lipogranulomatosis/diagnostic imaging* ; Fetus ; Exome Sequencing ; Adult

OBJECTIVE: To explore the genetic characteristics of a fetus affected with Structural heart defects and renal anomalies syndrome (SHDRA). METHODS: A pedigree with SHDRA (fetus and the parents) who had visited the Affiliated Women and Children's Hospital of Ningbo University in April 2023 was selected as the study subject. Clinical data of the family were collected. A total of 10 mL of amniotic fluid cells from the fetus and 5 mL of peripheral blood samples from the parents were collected for genomic DNA extraction. Trio whole-exome sequencing (Trio-WES) was performed, and Sanger sequencing was used to validate candidate variants in the family. The identified variants were classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines). Relevant research literature on SHDRA in domestic and international databases were searched for literature review. This study was approved by the Affiliated Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: In this family, prenatal ultrasound at 18 weeks of gestation revealed left renal multicystic dysplasia in the fetus. After birth, the infant exhibited an ostium secundum atrial septal defect, patent ductus arteriosus, and left renal multicystic dysplasia. Trio-WES revealed that the fetus had carried c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) compound heterozygous variants in the TMEM260 gene, which were respectively inherited from its father and mother. According to the ACMG guidelines, the c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) variants were classified as pathogenic (PM2_Supporting+PVS1+PP4) and likely pathogenic (PM2_Supporting+PM4+PM3+PP4), respectively. According to the literature search strategy set for this study, a total of 6 literature was retrieved, involving 25 SHDRA patients from 20 families. Together with the patients in this study, there were 14 TMEM260 gene variants, most of which were frameshift variants (7 types) and had located in exons 3, 11 and 13. The main clinical features of SHDRA were congenital heart malformation, renal abnormality and neurodevelopmental abnormality, and there was a lack of genotype-phenotype correlation. CONCLUSION The c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) variants of the TMEM260 gene probably underlay the SHDRA in this family. Above finding has provided a basis for clinical diagnosis and genetic counseling for the family.
Humans ; Female ; Pedigree ; Membrane Proteins/genetics* ; Male ; Heart Defects, Congenital/genetics* ; Kidney/abnormalities* ; Pregnancy ; Adult ; Kidney Diseases/congenital* ; Exome Sequencing ; Mutation ; Genetic Testing

OBJECTIVE: To explore the genetic etiology of a child with Brain small vessel disease 1 with ocular anomalies. METHODS: A child who was admitted to Ningbo Women and Children's Hospital on May 28, 2022 was selected for the study. Clinical data were collected, and peripheral blood samples from the child and her parents were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed to screen for pathogenic variants. Candidate variants were validated via Sanger sequencing and subjected to bioinformatic analysis. This study was approved by the Medical Ethics Committee of Ningbo Women and Children's Hospital (Ethics No. EC2020-014). RESULTS: The child was a 7-year-old female with a diagnosis of epilepsy. WES revealed that she has carried a heterozygous missense variant in the COL4A1 gene: c.1792G>A (p.Gly598Ser). Sanger sequencing confirmed that her parents both had the wild-type genotype for this variant. Based on American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, the variant were predicted to be a likely pathogenic (PS2+PM1+PM2_Supporting+PP3). Bioinformatics predicted that amino acid 598 was highly conserved in different species, formed hydrogen bond with Asp599 after becoming Ser598. CONCLUSION The heterozygous missense variant of the COL4A1 gene c.1792T>C (p.G598S) could be the pathogenic cause of this child with Brain small vessel disease 1 with ocular anomalies.
Humans ; Female ; Child ; Collagen Type IV/genetics* ; Eye Abnormalities/genetics* ; Exome Sequencing ; Mutation, Missense ; Cerebral Small Vessel Diseases/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with Fliedner-Zweier syndrome (FZS). METHODS: A pregnant woman who was diagnosed with FZS at the Affiliated Women and Children's Hospital of Ningbo University in November 2023 for "intellectual disability, epilepsy, delayed language development and facial abnormalities" was selected as the study subject. Peripheral blood samples were collected from the woman and her husband, whilst amniotic fluid sample was obtained from the fetus. Following extraction of genomic DNA, whole-exome sequencing (WES) and chromosomal karyotyping analysis were performed. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: The proband, a 23-year-old woman, was at 19⁺² weeks of gestation and had a history of epilepsy, mild intellectual disability, delayed language development, and subtle facial dysmorphism. Chromosomal analysis showed the she has a normal karyotype. WES revealed that the woman and her fetus both harbored a heterozygous c.1489C>T (p.Gln497Ter) nonsense variant of the SCAF4 gene, which was verified by Sanger sequencing as de novo. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_supporting+PS2_supporting). According to pre-set search strategy, five articles were retrieved. Together with the patient in this study, a total of 69 FZS patients were involved (including 7 from China). The main clinical features have included intellectual disability, epilepsy, behavioral abnormalities, and facial dysmorphism. CONCLUSION The heterozygous c.1489C>T (p.Gln497Ter) variant of the SCAF4 gene probably underlyay the FZS in this patient. Above finding has expanded the mutational spectrum of the SCAF4 gene.
Humans ; Female ; Intellectual Disability/genetics* ; Pregnancy ; Young Adult ; Exome Sequencing ; Epilepsy/genetics* ; Abnormalities, Multiple/genetics* ; Mutation ; Karyotyping

OBJECTIVE: To explore the clinical characteristics and genetic etiology of STISS syndrome (an autosomal dominant disorder characterized by ubiquitin-proteasome system dysfunction) in a child. METHODS: A child with STISS syndrome diagnosed at the Affiliated Women and Children's Hospital of Ningbo University in September 2024 due to "abnormal development of external genitalia" was selected as the study subject. Clinical data were retrospectively collected. Peripheral blood samples were obtained from the child and his family members. Following genomic DNA extraction, whole-exome sequencing (WES) and Sanger sequencing validation were carried out. Pathogenicity of the candidate variants was assessed based on the guidelines from American College of Medical Genetics and Genomics (ACMG). The study was approved by the Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: The proband, a 16-year-old boy, presented with micropenis, testicular hypoplasia, delayed sexual development, insulin resistance, diabetes mellitus, and obesity. WES revealed that he has harbored a c.934del; p.Met312TrpfsTer3 frameshifting variant of the PSMD12 gene, which was unreported previously. Sanger sequencing confirmed that the variant to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_supporting+PM6_supporting). The variant was predicted to result in a premature termination codon. Bioinformatics analysis suggested that the amino acid at position 312 is highly conserved, and the variant may therefore affect the protein structure. CONCLUSION Patients with STISS syndrome exhibit clinical features including psychomotor retardation, intellectual disability, distinctive facial features, and urogenital abnormalities. The c.934del (p.Met312TrpfsTer3) frameshift variant of the PSMD12 gene probably underlay the pathogenesis in the proband. Above finding has enriched the mutational spectrum of the PSMD12 gene.
Adolescent ; Humans ; Male ; Exome Sequencing ; Mutation ; Proteasome Endopeptidase Complex/genetics* ; Syndrome