Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a Chinese pedigree affected with Hereditary dentin dysplasia type II (DD-II) due to variant of dentin sialophosphoprotein (DSPP) gene. METHODS: A child diagnosed with DD- II at the Third Clinical Division of Peking University Hospital of Stomatology in December 2021 and her family members were selected as study subjects. Clinical data were retrospectively analyzed. Saliva samples were collected from the proband, her parents and sister for genomic DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and TOPO-TA cloning sequencing. The candidate variant was also subjected to bioinformatics analysis using Mutation Taster v2021. Secondary and tertiary structures of the wild-type and variant DSPP proteins were predicted with psipred v4.0 and PyMOL v2.3 software, respectively. The pathogenicity of the variant was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Peking University Hospital of Stomatology (Ethics No.: PKUSSIRB-202162021). RESULTS: The proband and her mother and sister had all exhibited typical clinical manifestations of hereditary DD-II. The primary dentition of the proband displayed yellowish brown discoloration, wear, and obliteration in the chamber and root canal, while the permanent teeth of the proband's sister and mother appeared nearly normal in both color and appearance, though with obliteration in the chamber and root canal. Her father showed normal dentition. WES identified a heterozygous c.1915_1918delAAGT, p.(Lys639Glnfs*674) frameshift variant in the DSPP gene. Sanger sequencing and TOPO-TA cloning sequencing confirmed the presence of this variant in the proband, the proband's sister, and the mother, while the proband's father was negative for the variant, indicating an autosomal dominant inheritance pattern. The variant was predicted to be pathogenic by Mutation Taster v2021. Prediction of the secondary structure of the DSPP protein showed that the variant has changed it from coil to helix. The tertiary structure prediction of the DSPP protein showed change of the spatial structure of the variant DSPP, with the loops in the variant region replaced by helices at multiple sites. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1+PP4). CONCLUSION Phenotypic analysis and genetic testing of this family has clarified the clinical diagnosis of hereditary DD- II. The c.1915_1918delAAGT variant probably underlay the pathogenesis of DD-II in this family. Above results have expanded the phenotypic spectrum of the disease and may contribute to further clinical and genetic research on this disease.
Humans ; Pedigree ; Female ; Extracellular Matrix Proteins/chemistry* ; Male ; Sialoglycoproteins/chemistry* ; Dentin Dysplasia/genetics* ; Asian People/genetics* ; Phosphoproteins/chemistry* ; Child ; Mutation ; China ; Exome Sequencing ; Adult ; East Asian People

Objective: To investigate the causes and characteristics of immune hemolytic transfusion reactions (HTRs) triggered by anti-E antibodies, so as to provide a scientific reference for guaranteeing clinical blood transfusion safety. Methods: Five patients who experienced HTRs in our hospital from November 2023 to October 2024 were selected as the research subjects. ABO/RhD blood grouping, antibody screening, antibody identification, and the direct antiglobulin test (DAT) were conducted using the column agglutination method. The causes of HTRs in these patients were investigated using multiple techniques such as the two-step enzyme method, polyethylene glycol (PEG), acid elution technique, and capillary centrifugation method. Results: All five patients tested negative for antibody screening prior to transfusion. However, after transfusion of E+ phenotyped blood, patients 1, 2, 3, and 5 developed delayed haemolytic transfusion reaction (DHTR), while patient 4 experienced acute haemolytic transfusion reaction (AHTR). Anti-E antibodies were detected in all blood samples from the patients after the hemolytic transfusion reaction, including the enzyme-only anti-E antibody in two cases. Conclusion: Anti-E antibody can trigger both intravascular and extravascular hemolysis. It is recommended to conduct ABO/RhD and RhE antigen-matched transfusions and establish a regional blood transfusion database to reduce immune hemolytic transfusion reactions caused by anti-E antibody.

Objective:To investigate the relationship between protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene polymorphism and the risk of gestational diabetes mellitus (GDM).Methods:In this case-control study, 4 835 pregnant women who delivered from March, 2012 to July, 2014 in the Department of Gynecology and Obstetrics at the First Hospital of Shanxi Medical University were consecutively enrolled. Among them, 789 cases were diagnosed with GDM. A simple random sampling method was used to select 334 pregnant women with GDM as the case group, and 334 healthy pregnant women matched by maternal age, gestation time and residence were set as control. The DNA genotyping was performed in the subjects, and those with genotyping deletions10% were excluded; and finally, 322 and 317 subjects were included in case and control group, respectively. Under the codominant, dominant, recessive, and allelic genetic models, the unconditional logistic regression model was used to check the relationship between 13 candidate single nucleotide polymorphism (snp) loci in PTPN1 gene and the risk of GDM. The Haploview was used to analyze the relationship between haplotypes and risk of GDM, and multiple comparisons were adjusted with the false discovery rate (FDR) method.Results:The age of the 639 pregnant women analyzed in this study was (30.28±4.32) years. The proportions of pre-pregnancy body mass index (BMI)≥24.0 kg/m 2 and having a family history of diabetes were significantly higher in the GDM group compared to those in the control group (29.19% vs 16.72% and 13.04% vs 6.31%, respectively, both P0.05). The rs6096644 locus was positively associated with increased risk of GDM in co-dominant (GG vs AA, OR=2.76, 95% CI: 1.18-6.44) and recessive (GG vs AA+AG, OR=2.78, 95% CI: 1.20-6.46) genetic models (all q0.2). The rs6096655 locus was positively associated with increased risk of GDM in codominant (AA vs GG, OR=5.90, 95% CI: 1.27-27.36) and recessive (AA vs GG+GA, OR=5.50, 95% CI: 1.19-25.38) and alleles (A vs G, OR=1.51, 95% CI: 1.09-2.08) genetic models (all q0.2). The rs6013317 locus was associated with an increased risk of GDM in the allele (A vs G, OR=1.74, 95% CI: 1.15-2.63) genetic model (all q0.2). The GAGG haplotype and GGAG haplotype in haplotype block 1 (rs4811262, rs6096646, rs6096655, rs6013317), and the GGGA haplotype in haplotype block 2 (rs6068018, rs6123105, rs6013324, rs2869621) of the PTPN1 gene were all positively associated with an increased risk of GDM (all P0.05). Conclusion:PTPN1 gene polymorphisms may associated with risk of GDM, moreover, complex haplotype structures within the gene influence the risk of GDM.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

Objective To study the clinical value of stroboscopic laryngoscope combined with narrow band imaging endoscope in the diagnosis of benign and malignant glottic lesions.Methods A total of 60 patients(84 sides of vocal cord)who visited our department from June 2022 to January 2023 with hoarseness as the main complaint and were found to have glottic lesions by electronic nasopharyngoscopy were selected.In all 60 patients with 84 sides of vocal cord degenerative lesions,stroboscopic laryngoscopy and narrow band imaging(NBI)endoscopy were com-pleted.The examination results were evaluated and graded separately.The same operative group performed the re-section biopsy of vocal cord lesions under general anesthesia and laryngoscope respectively,and the pathological re-sults were used as the diagnostic gold standard.With sensitivity,specificity,accuracy,false negative rate,and false positive rate as the main evaluation indexes,the differences in diagnostic accuracy between single test technique and combined application of the two techniques were analyzed.Results Pathological results showed squamous cell carci-noma on 18 sides,carcinoma in situ on 4 sides,severe dysplasia on 4 sides,mild and moderate dysplasia on 13 sides,and papilloma,chronic,mucosal,nflammation,hyperplasia,hypokeratosis,hyperkeratosis on 45 sides.The sensitivity of strobe laryngoscopy detection was 53.06％and specificity was 60.34％.The sensitivity of NBI endo-scopic detection was 88.46％,and the specificity was 89.66％.The sensitivity of strobe laryngoscopy combined with NBI endoscopy was 96.15％,and the specificity was 94.83％.The areas under the ROC curve of strobe laryn-goscopy,NBI endoscopy and white light imaging combined with narrowband imaging were 0.888(95％CI:0.820～0.957),0.943(95％CI:0.885～1),0.970(95％CI:0.942～0.999),respectively.The area under the curve of the combined method was higher than that of the single method,and the difference was statistically significant(P＜0.05).Conclusion Stroboscopic laryngoscope combined with NBI endoscope can improve the diagnostic accuracy of benign and malignant glottic lesions.

Objective To evaluate the impact of modified cesarean section techniques on pregnancy outcomes in cases involving placenta accreta spectrum(PAS).Methods A retrospective study was conducted to enroll 176 pregnant women with PAS who underwent cesarean delivery at the First Hospital of Shanxi Medical University between January 2016 and January 2025.Patients who received traditional cesarean delivery before January 17,2021,were assigned to the control group(n=115),while those who underwent a modified cesarean procedure after that date were included in the modified group(n=61).Clinical data,including gestational age,maternal age,gravidity,and intraoperative blood loss,were collected and compared between the two groups.Subsequently,a random forest algorithm was employed to develop a risk prediction model for adverse pregnancy outcomes in patients with PAS.Results In the modified group,only one patient required a hysterectomy(1.64%),which was signifi-cantly lower than the 19 cases observed in the control group(16.52%).The modified group also demonstrated a higher intraoperative diagnosis rate of placenta accreta,along with lower incidences of hemorrhagic shock,disseminated intravascular coagulation,and neonatal asphyxia compared to the control group.However,the proportions of patients undergoing uterine compression sutures and uterine artery ligation were higher in the modified group,with statistically significant differences(P<0.05).Patients were further classified into low-bleeding and high-bleeding subgroups for subgroup analysis.A significant difference in gravidity was observed between the two subgroups(P<0.05),whereas no significant difference was found in the proportion of patients receiving the modified procedure(P>0.05).A predictive model for refractory postpartum hemorrhage was developed with high discriminative ability(AUC=0.938,95%CI:0.917～0.958).Gini coefficient analysis identified gravidity,number of abortions,and ultrasound diagnosis of placenta accreta as key predictors of refractory postpartum hemorrhage(P<0.05).Conclusion Improved cesarean section techniques can effectively reduce intraoperative and postoperative bleeding in cases of PAS,significantly lowering the risk of hysterectomy and thereby improving pregnancy outcomes.

Objective To evaluate the impact of modified cesarean section techniques on pregnancy outcomes in cases involving placenta accreta spectrum(PAS).Methods A retrospective study was conducted to enroll 176 pregnant women with PAS who underwent cesarean delivery at the First Hospital of Shanxi Medical University between January 2016 and January 2025.Patients who received traditional cesarean delivery before January 17,2021,were assigned to the control group(n=115),while those who underwent a modified cesarean procedure after that date were included in the modified group(n=61).Clinical data,including gestational age,maternal age,gravidity,and intraoperative blood loss,were collected and compared between the two groups.Subsequently,a random forest algorithm was employed to develop a risk prediction model for adverse pregnancy outcomes in patients with PAS.Results In the modified group,only one patient required a hysterectomy(1.64%),which was signifi-cantly lower than the 19 cases observed in the control group(16.52%).The modified group also demonstrated a higher intraoperative diagnosis rate of placenta accreta,along with lower incidences of hemorrhagic shock,disseminated intravascular coagulation,and neonatal asphyxia compared to the control group.However,the proportions of patients undergoing uterine compression sutures and uterine artery ligation were higher in the modified group,with statistically significant differences(P<0.05).Patients were further classified into low-bleeding and high-bleeding subgroups for subgroup analysis.A significant difference in gravidity was observed between the two subgroups(P<0.05),whereas no significant difference was found in the proportion of patients receiving the modified procedure(P>0.05).A predictive model for refractory postpartum hemorrhage was developed with high discriminative ability(AUC=0.938,95%CI:0.917～0.958).Gini coefficient analysis identified gravidity,number of abortions,and ultrasound diagnosis of placenta accreta as key predictors of refractory postpartum hemorrhage(P<0.05).Conclusion Improved cesarean section techniques can effectively reduce intraoperative and postoperative bleeding in cases of PAS,significantly lowering the risk of hysterectomy and thereby improving pregnancy outcomes.

Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

Objective To study the clinical value of stroboscopic laryngoscope combined with narrow band imaging endoscope in the diagnosis of benign and malignant glottic lesions.Methods A total of 60 patients(84 sides of vocal cord)who visited our department from June 2022 to January 2023 with hoarseness as the main complaint and were found to have glottic lesions by electronic nasopharyngoscopy were selected.In all 60 patients with 84 sides of vocal cord degenerative lesions,stroboscopic laryngoscopy and narrow band imaging(NBI)endoscopy were com-pleted.The examination results were evaluated and graded separately.The same operative group performed the re-section biopsy of vocal cord lesions under general anesthesia and laryngoscope respectively,and the pathological re-sults were used as the diagnostic gold standard.With sensitivity,specificity,accuracy,false negative rate,and false positive rate as the main evaluation indexes,the differences in diagnostic accuracy between single test technique and combined application of the two techniques were analyzed.Results Pathological results showed squamous cell carci-noma on 18 sides,carcinoma in situ on 4 sides,severe dysplasia on 4 sides,mild and moderate dysplasia on 13 sides,and papilloma,chronic,mucosal,nflammation,hyperplasia,hypokeratosis,hyperkeratosis on 45 sides.The sensitivity of strobe laryngoscopy detection was 53.06％and specificity was 60.34％.The sensitivity of NBI endo-scopic detection was 88.46％,and the specificity was 89.66％.The sensitivity of strobe laryngoscopy combined with NBI endoscopy was 96.15％,and the specificity was 94.83％.The areas under the ROC curve of strobe laryn-goscopy,NBI endoscopy and white light imaging combined with narrowband imaging were 0.888(95％CI:0.820～0.957),0.943(95％CI:0.885～1),0.970(95％CI:0.942～0.999),respectively.The area under the curve of the combined method was higher than that of the single method,and the difference was statistically significant(P＜0.05).Conclusion Stroboscopic laryngoscope combined with NBI endoscope can improve the diagnostic accuracy of benign and malignant glottic lesions.