Objective: To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells. Methods: Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1. Results: 5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01). Conclusion JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.

Objective: To explore the relationship of sleep quality and emotional regulation difficulties in middle school students, and to analyze its mediating role of daytime dysfunction, social rejection and selfcontrol ability, so as to provide a scientific reference for improving middle school students mental health. Methods: From October to November, 2023, the Pittsburgh Sleep Quality Index, Adolescent Social Rejection Questionnaire, Brief Selfcontrol Scale and Difficulties in Emotion Regulation Scaleshort Form (DERS-16) were used to assess 806 students recruited from four middle schools in Bengbu City by a convenient cluster random sampling method. And model-6 of PROCESS and 5 000 Bootstraps were used to make a chainmediating model analysis. Results: Daytime dysfunction was positively correlated with sleep quality(r=0.57), social rejection(r=0.19), selfcontrol(r=0.29, P＜0.01). Selfcontrol was positively correlated with emotional regulation difficulties(r=0.54, P<0.01).Poor sleep quality showed a significant positive association with on daytime dysfunction, and daytime dysfunction further affected social rejection, selfcontrol ability and emotional regulation difficulties (β=0.86, 0.60, 1.27, 1.56, P<0.05). Meanwhile, daytime dysfunction, social rejection and selfcontrol played a serial mediating role in the relationship between sleep quality and emotional regulation difficulties (Estimate=0.11,95%CI=0.04-0.20,P<0.05). Conclusion The study reveals the complex relationship between sleep quality and emotional regulation difficulties in middle school students and provides a new theoretical basis for adolescent sleep improvement and mental health interventions.

This article summarizes and organizes relevant publications in journals, along with a review of medical history, systematically summarizing the development process of dental alveolar surgery in China. The initial establishment phase (1935—1952) marked the starting point of Chinese Alveolar Surgery. Despite the impact of wars, it laid the foundation for subsequent research and practice. During the early development phase (1953—1966), the "Chinese Journal of Stomatology" was founded, which promoted the development of Alveolar Surgery. Research focused on tooth extraction methods and complications. Tooth Transplantation and Preprosthetic Surgery gradually began to take off. The stagnant phase (1967—1977) occurred due to the interruption of international exchanges, leading to an almost complete halt in the development of Alveolar Surgery. Entering the rapid catch-up phase (1978—1985), Alveolar Surgery scholars in China began striving to overcome the stagnation of the previous decade. While some progress was made, no significant innovative achievements emerged. In the scientific development phase (1986—2010), clinical research, basic experiments, and paper writing in modern Chinese Alveolar Surgery began to adhere to scientific standards with the rise of experimental medicine. The exploration and innovation stage (2011—2023) is the current development phase, during which Chinese Aveolar Surgery has reached its peak, making substantial progress in technology, clinical practices, and basic research, gradually reaching or even surpassing international advanced levels. Looking back at the development history in China, we can find the wisdom and hard work of the older generation of Alveolar Surgery scholars. However, contemporary challenges and issues, such as standardizing technology, promoting clinical practices, and talent cultivation, need to be addressed by present-day Alveolar Surgery professionals as they forge ahead.

Objective To investigate the clinical features in children with invasive pneumococcal disease (IPD) and early warning indicators of severe case.Methods The case data of 101 children inpatients with IPD isolated Streptococcus pneumoniae (Sp) at least once blood culture in this hospital from January 2007 to De-cember 2021 were collected retrospectively.The children patients were divided into the pediatric intensive care unit (PICU) group (35 cases) and general ward group (66 cases) according to whether or not entering PICU during hospitalization.The general clinical data,infection types and results of drug sensitivity test and bacteri-al strain serotype identification were compared between the two groups and analyzed.Results Compared with the general ward group,the male proportion,proportions of complicating nervous system disease and iron-defi-ciency anemia,winter incidence rate,disturbance of consciousness,convulsion,dyspnea,heart rate increase,oc-currence rate of vomiting and diarrhea,proportion of peripheral blood neutrophilic granulocytes,C reactive protein (CRP),lactic dehydrogenase (LDH) level,Hb<90 g/L,LDH>700 U/L,creatine kinase isoenzyme-MB (CK-MB) abnomality,proportions of bacterial meningitis,sepsis and severe pneumonia in the PICU group were higher,the proportion of 3-97 percentile of body weight,bronchopneumonia and no-focus blood stream infection were lower,WBC,Hb and albumin level were lower,and the differences were statistically significant (P<0.05).Eleven kinds of serotypes were identified in this study,ranking the top five in order were 6B,14,19F,23F and 19A.Pneumococcal 13-valent conjugate vaccine (PCV13) could cover 96.9％ of the IPD sero-types.The multivariate logistic regression analysis showed that consciousness disturbance,convulsion,per-centage of neutrophils increase,Hb<90 g/L,LDH>700 U/L and CK-MB abnormality indicated the condition of IPD children patients was critical,which was the early-warning indicator of entering PICU (P<0.05).Con-clusion Severe IPD lacks the early specific early-warning indicator,and the cover rate of PCV13 is high.

Objective To systematically evaluate the accuracy of computer navigation technique in the positioning of bone tunnel location of anterior cruciate ligament reconstruction(ACLR) and its effect on post-operative functional recovery.Methods The controlled trials of computer navigation-assisted ACLR in the da-tabases of Cochrane Library,PubMed,Embase,CNKI,Wanfang and VIP Database were retrieved.The retriev-al time limit was from the establishment of the database to August 2023.According to the inclusion and exclu-sion criteria,the NoteExpress V3.0 software was used to screen the literatures,the Cochrane risk bias assess-ment tool was used to evaluate the quality of the included literatures,and the RevMan5.4 software was used for conducting the meta analysis.Results A total of 10 trials involving 705 patients were included,including 354 cases in the navigation group and 351 cases in the conventional group.The meta analysis results showed that compared with the conventional group,the location positioning of bone tunnel in the navigation group was significantly improved[in femoral side (MD=5.59,95％CI:1.21-9.97,P=0.01) and tibial side (MD=1.32,95％CI:0.20-2.43,P=0.02).However there were no statistically significant differences in the IKDC scores (MD=1.76,95％CI:-0.17 to 3.70,P=0.07),Lysholm scores (MD=0.49,95％CI:-0.16 to 1.14,P=0.14),Tegner scores (MD=-0.08,95％CI:-0.35 to 0.20,P=0.58),KT-1000 anterior shift dis-tance (MD=0.01,95％CI:-0.49 to 0.52,P=0.96),the positive rate of Lachman test (RD=-0.01,95％CI:-0.09 to 0.07,P=0.75) and the positive rate of axial shift test (RD=-0.09,95％CI:-0.22 to 0.04,P=0.20).Conclusion The computer navigation technology is conducive to elevate the accuracy of tibial and femoral tunnel positioning in ACLR,but could not improve the postoperative functional recovery of the pa-tients.

Objective:To explore the characteristics of phenylalanine hydroxylase ( PAH) gene variants and prenatal diagnosis for 43 Chinese pedigrees affected with Phenylketonuria (PKU). Methods:Forty three PKU pedigrees diagnosed at the First Affiliated Hospital of Zhengzhou University between 2019 and 2021 were selected as the study subjects. Variants of the PAH gene of the probands were screened by high-throughput sequencing, and candidate variants were verified by Sanger sequencing. Negative cases were further analyzed by multiplex ligation-dependent probe amplification (MLPA) to detect large fragment deletions and duplications of the PAH gene. For 43 women undergoing subsequent pregnancy, Sanger sequencing, MLPA, combined with short tandem repeats (STR) sequence-based linkage analysis, were carried out for prenatal diagnosis. Results:Among the 86 alleles carried by the 43 probands, 78 nucleotide variants (90.70%) and 3 large deletions (3.49%) were found based on high-throughput sequencing and MLPA. The 81 mutant alleles had included 21 missense variants, 5 splice site variants, 4 nonsense variants, 2 microdeletions, 1 insertional variant and 2 large fragment deletions. Relatively common variants have included p. Arg243Gln (23.26%), p. Arg111Ter (8.14%), EX6-96A>G (6.98%), p. Val399Val (5.81%) and p. Arg413Pro (4.65%). Most of the variants were located in exons 7, 11, 3, 6 and 12. For the 43 families undergoing prenatal diagnosis, 9 fetuses (20.45%) were diagnosed with PKU, 20 (45.45%) were heterozygous carriers, and 15 (34.09%) did not carry the same pathogenic allele as the proband. All neonates were followed up till 6 months old, and the accuracy of prenatal diagnosis was 100%.Conclusion:The combination of high-throughput sequencing, Sanger sequencing, MLPA and linkage analysis can increase the diagnostic rate of PKU and attain accurate prenatal diagnosis.

Objective:To carry out genetic testing on a child diagnosed with Very-long-chain acyl-CoA dehydrogenase deficiency (VLADD) in order to provide a basis for genetic counseling and prenatal diagnosis for his family.Methods:Whole exome sequencing was performed for the proband. Candidate variant sites in the ACADVL gene were verified by Sanger sequencing, and their pathogenicity was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was performed on the fetus upon subsequent pregnancy. This study was approved by Medical Ethics Committe of the Luoyang Maternal and Child Health Care Hospital (Ethics No.LYFY-YCCZ-2021003). Results:The proband was found to harbor compound heterozygous variants of the ACADVL gene, namely c. 1532G>A and 1827+ 2_1827+ 12del, which were inherited from his mother and father, and classified as likely pathogenic and pathogenic, respectively. By combining the clinical manifestations of the proband and the results of blood tandem mass spectrometry and genetic testing, the child was ultimately diagnosed as cardiomyopathy type VLADD. Prenatal diagnosis showed that the fetus has carried the same compound heterozygous variants, and the couple had opted to terminate the pregnancy. Conclusion:The c. 1532G>A/1827+ 2_1827+ 12del compound heterozygous variants of the ACADVL gene probably underlay the pathogenesis of VLADD in this pedigree. The discovery of the 1827+ 2_1827+ 12del variant has enriched the mutational spectrum of the ACADVL gene.

Objective:To explore the genetic etiology of a fetus with Coffin-Siris syndrome2 (CSS2).Methods:A fetus with abnormal ultrasound findings detected at Luoyang Maternal and Child Health Care Hospital in July 2023 was selected as the study subject. Clinical data were analyzed retrospectively. Whole exome sequencing was carried out on fetal tissue and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and pathogenicity analysis. This study was approved by Medical Ethics Committee of the Luoyang Maternal and Child Health Hospital (Ethics No. LYFY-YCCZ-2023011).Results:Color Doppler ultrasound at 16 + gestational weeks revealed bilateral ventriculomegaly and cerebellar hypoplasia in the fetus. Trio-WES found that the fetus has harbored a heterozygous c. 553C>T (p.Gln185Ter) variant of the ARID1A gene, which was verified by Sanger sequencing to have a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 553C>T (p.Gln185Ter) variant of the ARID1A gene was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:The fetus was diagnosed with CSS type 2, and the heterozygous c. 553C>T (p.Gln185Ter) variant of the ARID1A gene probably underlay its brain malformations.

Objective:To summarize the clinical manifestations of Autosomal dominant complex neurodevelopmental disorders due to variants of EEF1A2 gene and explore their pathogenic mechanisms. Methods:A child who had visited Luoyang Maternal and Child Health Care Hospital in July 2021 for global developmental delay was selected as the study subject. Clinical data of the child was reviewed. The child was subjected to whole exome sequencing, and relevant literature was reviewed. This study has been approved by the Medical Ethics Committee of Luoyang Maternal and Child Health Care Hospital (No. YCCZ-KS-KY-2021-03).Results:The patient, a 2-year-and-4-month-old girl, had presented with global developmental delay, gait instability, low limb muscle strength, and absence language development. Her parents were both healthy and denied relevant family history. Genetic testing revealed that she has harbored a de novo heterozygous c. 44A>G (p.H15R) missense variant of the EEF1A2 gene (NM_001958.5), which was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was rated as pathogenic. Conclusion:The c. 44A>G (p.H15R) variant of the EEF1A2 gene probably underlay the pathogenesis in this patient. Above finding has also enriched the mutational spectrum of the EEF1A2 gene.

OBJECTIVE: To assess the influence of thyroid function on the fetal fraction (FF) during the second trimester of pregnancy. METHODS: A total of 1 861 pregnant women undergoing non-invasive prenatal testing (NIPT) and thyroxine function testing at 12 ~ 26 gestational weeks at the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital from January 2016 to December 2020 were selected as the study subjects. Univariate analysis and multivariate regression models were used to assess the correlation between free thyroxine 4 (FT4) levels and FF. RESULTS: Univariate linear regression analysis indicated that the FF is correlated to the level of FT4 (b = 0.035, P < 0.001). The median fetal FF was 10.78% (IQR: 8.2%, 13.82%), and this has increased along with the level of FT4 from 10.58% at <= 12.0 pmol/L to 11.77% at > 16.0 pmol/L. After further adjustment of gestational age and body mass index (BMI), the FF showed an increase trend along with the increase of FT4 levels, and a trend test also showed a statistical significance (Ptrend < 0.001). CONCLUSION Maternal FF can be affected by the level of free thyroxine during the second trimester of pregnancy.
Pregnancy ; Female ; Humans ; Pregnancy Trimester, Second ; Thyroid Gland ; Thyroxine ; Fetus ; Gestational Age