OBJECTIVE: To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients. METHODS: Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). RESULTS: PAH gene variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS gene variants. Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) of the variants were located in exons, with the main types being missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants have occurred in the PAH gene's catalytic center region, while 19.74% (30/152) of the variants involved non-coding sequences. The phenotypes of the 75 PAHD children were evenly distributed. The re-screened Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values (P < 0.001, P < 0.001; P = 0.004, P = 0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types have significantly affected the phenotypes (P = 0.042, P = 0.045). APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes (κ = 0.755, P < 0.001). CONCLUSION PAH gene variants were detected in most HPA children from Lianyungang area. The location and type of PAH gene variants has correlated with the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model has predicted the phenotype with high consistency with the actual phenotype.
Humans ; Phenylalanine Hydroxylase/genetics* ; Female ; Phenylketonurias/enzymology* ; Male ; Phenotype ; Genotype ; Child ; Infant ; Infant, Newborn ; Child, Preschool ; China ; Mutation ; Alleles

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.

Objective:To investigate the efficacy and safety of sleeve pulmonary resection after neoadjuvant immunotherapy combined with chemotherapy in the treatment of non-small cell lung cancer.Methods:A retrospective cohort study was conducted. The clinical data of 61 patients with non-small cell lung cancer who underwent sleeve pulmonary resection surgery at Shanxi Province Cancer Hospital from January 2018 to December 2024 were retrospectively analyzed. According to the preoperative neoadjuvant therapy, the patients were divided into the immunotherapy combined with chemotherapy group (26 cases) and the chemotherapy group (35 cases). The efficacy and incidence of adverse reactions of neoadjuvant therapy between two groups of patients were compared.Results:The open surgery was the main surgical approach in both the immunotherapy combined with chemotherapy group and the chemotherapy group, accounting for 61.5% (16/26) and 74.3% (26/35), respectively. The surgical approach of 10 cases (38.5%, 10/26) in the immunotherapy combined with chemotherapy group and 9 cases (25.7%, 9/35) in the chemotherapy group was thoracoscopy, and the difference was not statistically significant ( χ2 = 1.13, P = 0.288); the most common postoperative complications were persistent pulmonary air leakage [30.8% (8/26) in the immunotherapy combined with chemotherapy group and 22.9% (8/35) in the chemotherapy group] and lung infection [19.2% (5/26) in the immunotherapy combined with chemotherapy group and 17.1% (6/35) in the chemotherapy group], with no statistically significant differences (both P > 0.05). Two cases (5.7%) in the chemotherapy group experienced worsening pulmonary infection leading to respiratory failure and died within 90 days after surgery, but there were no cases of death within 90 days in the immunotherapy combined with chemotherapy group ( P > 0.05). One patient in each group (3.8% of the immunotherapy combined chemotherapy group and 2.9% of the chemotherapy group) underwent the second surgery due to persistent hemoptysis after surgery, and further underwent pneumonectomy. After the second surgery, the patients recovered and were discharged. There was no statistically significant difference in intraoperative bleeding, surgical time, postoperative tubing time, and hospitalization time between the two groups of patients (all P > 0.05). Postoperative pathology showed that both groups achieved R 0 resection. The main pathological remission (MPR) rate in the immunotherapy combined chemotherapy group was 65.4% (17/26), while the MPR rate in the chemotherapy group was 20.0% (7/35), with a statistically significant difference ( χ2 = 12.89, P < 0.001); the pathological complete response (PCR) rate in the immunotherapy combined chemotherapy group was 30.8% (8/26), while the PCR rate in the chemotherapy group was 8.6% (3/35), with a statistically significant difference ( χ2 = 4.97, P = 0.026). During the period of neoadjuvant therapy, the incidence of adverse reactions in the immunotherapy combined with chemotherapy group was 80.8% (21/26), while in the chemotherapy group it was 62.9% (22/35); the incidence of ≥ grade 3 adverse reactions was 19.2% (5/26) and 20.0% (7/35), respectively, with no statistically significant differences (both P > 0.05). Conclusions:Patients with non-small cell lung cancer who undergo sleeve pulmonary resection after neoadjuvant immunotherapy combined with chemotherapy have controllable adverse reactions during neoadjuvant therapy, which does not increase the difficulty of surgery or the postoperative complications, and can improve the degree of postoperative pathological remission.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective:To explore the spectrum of genetic variants and phenotypes of Phenylalanine hydroxylase deficiency (PAHD) in Lianyungang area and the correlation between genotype and phenotypes among the patients.Methods:Eighty children with Hyperphenylalaninemia (HPA) diagnosed at the Lianyungang Branch of Jiangsu Provincial Newborn Screening Center between January 2015 and December 2022 were enrolled. Peripheral blood samples were collected for genetic analysis using next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) to identify the variants of PAH gene. Clinical and phenotypic data were concurrently analyzed to investigate the correlation between the types of PAH gene variant and phenotypes. This study was approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No.: XM2022041). Results:① PAH variants were identified in 93.75% (75/80) of the children, classified as PAHD cases, while 6.25% (5/80) harbored PTS variants. ② Of the 150 PAH alleles from 75 PAHD children, a total of 152 variants (55 distinct types) were detected, with a detection rate of 100%. 80.26% (122/152) were located in exons, with the main types of variants were missense variants (67.11%, 102/152). 53.29% (81/152) of coding sequence variants occurred in the PAH gene catalytic center region of PAH protein, while 19.74% (30/152) of variants involved non-coding sequences. ③The phenotypes of the 75 PAHD children were evenly distributed. The rescreening Phe concentrations and Phe/Tyr ratios of classic-phenylketonuria (CPKU) and mild-phenylketonuria (MPKU) patients were markedly higher than initial screening values ( P<0.001, P<0.001; P=0.004, P=0.016). The genotypes of the PAHD patients mostly occurred as compound heterozygotes, and different mutation positions and variant types significantly affect the phenotype ( P=0.042, P=0.045). ④APV/GPV genotype-phenotype analysis of 61 patients showed high consistency between predicted and actual phenotypes ( κ=0.755, P<0.001). Conclusion:PAH variants were detected in the most of HPA children in Lianyungang area. The location and type of PAH variants were related to the severity of the phenotype, and the non-coding sequence variants and non-missense variants may aggravate the phenotype, and the APV/GPV model predicted the phenotype was highly consistent with the actual phenotype.

Under the Healthy China strategy, the training of preventive medicine professionals should conform to the development of the times and the needs of public health. The article analyzed the problem of "disconnection between medical care and prevention" in teaching the course of Obstetrics and Gynecology for students majoring in preventive medicine, and proposed to strengthen the strategy of "integration of medical care and prevention". Guided by the concepts of "Comprehensive Health", with the cornerstone of cultivating morality and talents, the reform focused on enhancing the post competency of preventive medicine talents. Course content was optimized by reinforcing prevention-focused elements, student-centered teaching method innovation was advocated, and simulation-based training teaching system was established. Moreover, projects integrating science and education were used to improve faculty teaching capacity with tiered and diversified approaches. Course assessment methods were revised and "ideological and political education" was incorporated to establish the education concept of "emphasis on prevention and integration of medical care and prevention". The survey showed that these reform measures effectively improved the comprehensive clinical literacy of preventive medicine students in obstetrics and gynecology, which is of great significance for building a "integration of medical care and prevention" public health talent training model. In the future, the long-term effectiveness of course reform will be ensured from the perspectives of teaching resources, personnel investment, and policy support.

Objective:To investigate the efficacy and safety of sleeve pulmonary resection after neoadjuvant immunotherapy combined with chemotherapy in the treatment of non-small cell lung cancer.Methods:A retrospective cohort study was conducted. The clinical data of 61 patients with non-small cell lung cancer who underwent sleeve pulmonary resection surgery at Shanxi Province Cancer Hospital from January 2018 to December 2024 were retrospectively analyzed. According to the preoperative neoadjuvant therapy, the patients were divided into the immunotherapy combined with chemotherapy group (26 cases) and the chemotherapy group (35 cases). The efficacy and incidence of adverse reactions of neoadjuvant therapy between two groups of patients were compared.Results:The open surgery was the main surgical approach in both the immunotherapy combined with chemotherapy group and the chemotherapy group, accounting for 61.5% (16/26) and 74.3% (26/35), respectively. The surgical approach of 10 cases (38.5%, 10/26) in the immunotherapy combined with chemotherapy group and 9 cases (25.7%, 9/35) in the chemotherapy group was thoracoscopy, and the difference was not statistically significant ( χ2 = 1.13, P = 0.288); the most common postoperative complications were persistent pulmonary air leakage [30.8% (8/26) in the immunotherapy combined with chemotherapy group and 22.9% (8/35) in the chemotherapy group] and lung infection [19.2% (5/26) in the immunotherapy combined with chemotherapy group and 17.1% (6/35) in the chemotherapy group], with no statistically significant differences (both P > 0.05). Two cases (5.7%) in the chemotherapy group experienced worsening pulmonary infection leading to respiratory failure and died within 90 days after surgery, but there were no cases of death within 90 days in the immunotherapy combined with chemotherapy group ( P > 0.05). One patient in each group (3.8% of the immunotherapy combined chemotherapy group and 2.9% of the chemotherapy group) underwent the second surgery due to persistent hemoptysis after surgery, and further underwent pneumonectomy. After the second surgery, the patients recovered and were discharged. There was no statistically significant difference in intraoperative bleeding, surgical time, postoperative tubing time, and hospitalization time between the two groups of patients (all P > 0.05). Postoperative pathology showed that both groups achieved R 0 resection. The main pathological remission (MPR) rate in the immunotherapy combined chemotherapy group was 65.4% (17/26), while the MPR rate in the chemotherapy group was 20.0% (7/35), with a statistically significant difference ( χ2 = 12.89, P < 0.001); the pathological complete response (PCR) rate in the immunotherapy combined chemotherapy group was 30.8% (8/26), while the PCR rate in the chemotherapy group was 8.6% (3/35), with a statistically significant difference ( χ2 = 4.97, P = 0.026). During the period of neoadjuvant therapy, the incidence of adverse reactions in the immunotherapy combined with chemotherapy group was 80.8% (21/26), while in the chemotherapy group it was 62.9% (22/35); the incidence of ≥ grade 3 adverse reactions was 19.2% (5/26) and 20.0% (7/35), respectively, with no statistically significant differences (both P > 0.05). Conclusions:Patients with non-small cell lung cancer who undergo sleeve pulmonary resection after neoadjuvant immunotherapy combined with chemotherapy have controllable adverse reactions during neoadjuvant therapy, which does not increase the difficulty of surgery or the postoperative complications, and can improve the degree of postoperative pathological remission.