Objective To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-related hypophysitis. Methods A retrospective analysis was conducted on patients diagnosed with ICI-related hypophysitis and treated at the Department of Endocrinology, The First Affiliated Hospital with Nanjing Medical University, between January 2020 and March 2025. Clinical manifestations and prognosis of patients were analyzed. Results Eleven patients with ICI-related hypophysitis were included. The average age was (62.27±7.63) years, and 9 patients (81.82%) were male. The median time to onset was 9.1 months, and the median number of treatment cycles received was 5. The primary initial symptoms were fatigue and anorexia. Hyponatremia was present in 3 patients (27.27%). Evaluation of anterior pituitary function revealed adrenocorticotropic hormone deficiency as the most common manifestation (90.91%, 10/11), followed by hyperprolactinemia (81.82%, 9/11). Posterior pituitary function remained normal in all patients. Pituitary magnetic resonance imaging showed no abnormality in 4 patients (44.44%). Thyroid dysfunction was observed in 6 patients (54.55%), one of whom (9.09%) also exhibited pancreatic endocrine dysfunction. The average follow-up duration was 36.5 months. Eight patients (72.73%) were alive at the last follow-up. None of the patients recovered their pituitary hormone function. Conclusions Endocrine adverse events induced by ICIs can involve multiple glandular systems. Clinicians should be highly vigilant for the possibility of ICI-induced hypophysitis in patients receiving ICIs who present with symptoms such as fatigue, anorexia, and hyponatremia.

Objective: To analyze the disease burden and trends of oral diseases among China’s elderly population (1990-2021) and provide evidence for developing targeted intervention strategies Methods : Using data from the Global Burden of Disease (GBD) 2021 study, we extracted prevalence, incidence, and disability-adjusted life years (DALYs) for oral conditions (permanent dental caries, edentulism, periodontal diseases, and other oral disorders) in individuals aged ≥60 years in China. Due to data limitations, other oral diseases only included DALYs and prevalence. Age-standardized rates (ASR)—including age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized DALYs rate (ASDR)--were calculated. Trends were assessed via Joinpoint regression using average annual percentage change (AAPC), stratified by sex and age groups (60-64, 65-69, 70-74, 75-79, 80-84, 85-89, 90-94, 95+ years). Results: From 1990 to 2021, China’s elderly population exhibited distinct trends in oral disease burden. Overall oral diseases showed declining ASDR and ASPR, yet ASIR slightly increased. Permanent dental caries demonstrated significant rises across ASDR, ASIR, and ASPR. Edentulism showed declining ASDR and ASPR alongside stable ASIR. 95+ age group saw rising rates. Periodontal diseases remained largely stable in ASDR and ASPR but experienced a slight ASIR decline. Other oral disorders showed mild ASDR decline and stable ASPR. Notably, sex and age disparities persisted. Women consistently bore higher burdens for overall oral diseases, caries, edentulism, and other oral diseases but lower periodontal disease rates compared to men. 85-89, 90-95, 95+ age group faced rising DALYs and prevalence for overall oral diseases, while all other age groups demonstrated declining trends in both DALYs and prevalence; for permanent caries, the 60-64 age group showed the largest increases in DALY rate, incidence, and prevalence; edentulism demonstrated the most pronounced and sustained rises in DALY rate and prevalence in the 95+ group, while declining most rapidly in the 60-64 age group; for periodontal disease, both DALY rates and prevalence declined in the 90-94 and 95+ age groups, but increased across all measures (DALY rate, incidence, and prevalence) in the 70-74 and 75-79 age group; other oral conditions exhibited relatively stable burden distributions or minor changes, with no significant age-specific shifting trends observed. Conclusion From 1990 to 2021, China’s elderly oral disease burden declined overall, but caries surged, edentulism improved, periodontal diseases stabilized, and other oral diseases slightly declined. Prioritizing older women and the adults aged 85+ is critical to addressing evolving oral health needs.

Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.

Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.

Objective:To summarize the clinical phenotype and CUX2 gene variation characteristics of developmental epileptic encephalopathy type 67 confirmed by whole exome sequencing. Methods:Clinical data of 1 case diagnosed as CUX2 gene mutations related developmental epileptic encephalopathy type 67 in the Children′s Hospital Affiliated to Zhengzhou University in January 2021 were collected, the patient′s clinical characteristics, genetic testing, head imaging, electroencephalogram results and treatment were summarized, and the patient was regularly followed-up every 3 months. At the same time, the domestic and foreign literatures on epileptic encephalopathy caused by CUX2 gene mutation were reviewed. Results:The proband was a 6 years and 4 months old girl. The main clinical manifestations included focal origin progression to bilateral tonic-clonic seizures, retardation of intellectual, language, and motor development, autistic behavior, hyperactivity disorder, and involuntary hand clapping. The video electroencephalogram showed extensive spiny slow wave and multi-spiny slow wave emission in waking and sleeping stages, and spiny slow wave and spiky slow wave emission in bilateral anterior head in sleeping stage. Brain magnetic resonance imaging (MRI) plain scan and T 2-fluid attenuated inversion recovery (T 2-FLAIR) thin layer scan showed that the signal of the left hippocampus was higher than that of the right, and the left hippocampus was slightly swollen. One month later, the brain MRI and T 2-FLAIR were reexamined. The left hippocampal signal was still slightly higher and decreased, and the hippocampal volume was slightly reduced. Whole exome sequencing showed the CUX2 gene with c.1768G>A(p.Glu590Lys) heterozygous missense variant, which was a reported de novo pathogenic variant and both of her parents were wild-type. A total of 10 cases of new heterozygous missense variants in CUX2 gene [c.1768G>A (p.Gelu590Lys)] were reported in 4 literatures. No relevant cases have been reported in China. Conclusions:Developmental epileptic encephalopathy type 67 is relatively rare. The main clinical features are seizures, global developmental delay, movement disorders, athetosis, autism and hyperactivity disorder. The heterozygous missense variant c.1768G>A (Glu590Lys) of CUX2 gene maybe the genetic cause of this case.

Clinical data and genetic mutation characteristics of a patient with Coffin-Siris syndrome by 6q25.3 deletion were summarized. The child was a 7-year and 6-month old girl who had feeding difficulties, repeated infection, language and motor retardation, low intelligence, laryngeal cartilage dysplasia, thick eyebrows, sparse teeth, hairy back, hyperactivity and aggressive behavior, seizures and ataxia. There was no abnormality in chromosomal karyotype analysis by proband; genomic copy number variant sequencing (CNV-seq) indicated approximately 4.27 Mb heterozygous deletion in chromosome 6q25.3 region, with 17 genes including ARID1B gene, father maternal CNV-seq showing no abnormalities. Trio-whole-exome sequencing showed the proband missed all exons 1-20 of the ARID1B gene, with wild-type parents. The proband had severe clinical symptoms and haplodose insufficiency which was the genetic etiology.

Objective:To understand the agglutination characteristics of different subtypes of avian influenza viruses, we selected erythrocytes from different sources to find suitable erythrocytes for influenza environmental sample detection.Methods:Different subtypes of avian influenza viruses, which were isolated from environmental sample between 2009 and 2016 in China, were selected to do hemagglutination assay using 5 animal erythrocytes (chicken, turkey, guinea pig, horse, and sheep). Flow cytometry was used to detect expression level and type of sialic acid receptors of different erythrocytes, and the characteristics of the receptor binding domain (RBD) of the viral hemagglutinin protein were analyzed by amino acid sequence.Results:In this study, a total of 28 strains of avian influenza virus including 14 subtypes were detected. The result showed that all viruses could agglutinate with turkey and guinea pig erythrocytes and the rest three erythrocytes were unable to produce agglutination with some viruses; among them, one H9N2 virus (A/environment/Anhui/43762/2015) did not agglutinate with chicken erythrocytes, one H1N1 virus (A/environment/Shandong/76972/2014) and two H9N2 viruses (A/environment/Chongqing/79449/2014 and A/environment/Anhui/43762/2015) did not agglutinate with horse erythrocytes, two viruses of H9N2 (A/environment/Chongqing/79449/2014 and A/environment/Anhui/43762/2015) and two viruses of H13N8 (A/environment/Qinghai Lake/166/2012 and A/environment/Qinghai Lake/13/2012) did not agglutinate with sheep erythrocytes. The result of flow cytometry showed that two sialic acid receptors, α-2, 3 and α-2, 6, were detected on the surface of erythrocytes of turkey, chicken and guinea pig, but the expression ratios of the two receptors were different. Only the expression of α-2, 3 sialic acid receptors was detected in horse and sheep erythrocytes. Sequence analysis suggested that amino acid substitution in key regions of viral hemagglutinin protein RBD may be an important factor affecting the binding properties of different erythrocytes.Conclusions:Our result suggested that turkey and guinea pig erythrocytes are the most sensitive in the hemagglutination test. Receptor expression and type of erythrocytes from different sources can significantly affect the agglutination reaction of different subtypes of avian influenza virus, and the amino acid changes in key regions of RBD can also affect the result of agglutination reaction.

Objective To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy (FSHD) presented initially as mental retardation.Methods Wechsler Intelligence Scale for Children Revised in China (WISC-Ⅳ) was used to assess the patient's IQ.Other clinical data was also collected.With genomic DNA extracted from peripheral blood samples,the child and his parents were subjected to medical exome sequencing and copy number variation analysis by next generation sequencing (NGS).The D4Z4 repeats and their origin source were determined by molecular combing.Results By the WISC-Ⅳ test,the child was found to have a total IQ of 41,with a speech comprehension IQ of 45,and perceptual inference index IQ of 52.No pathological mutation was detected by NGS.By molecular combing method,the child was found to carry a D4Z4 spanning 5.2 kb with a copy number of 2.Analysis of his parents indicate that the mutation was de novo.Conclusion The D4Z4 copy number variation may account for the FSHD and mental retardation in the child.The molecular combing method can be used to identify the number of repeat units and facilitate the diagnosis of FSHD.

Objective To investigate the relationship between vitamin D level and thyroid peroxidase (TPO) level in Qinghai Province.Methods In 2015 and 2016,a stratified cluster sampling method was used to select 1 873 people in 9 regions of Qinghai Province,including 935 males and 938 females,the average age was (52.3 ± 10.9) years old,there were 1 040 Han people and 833 Tibetans.Fasting venous blood samples were collected,and vitamin D and TPO levels were detected by a fully automated chemiluminescence immunoassay system,vitamin D and TPO levels were compared in different gender,ethnic group,and altitude populations.Results The vitamin D level was (16.3 ± 7.5) μg/L,and abnormal rate of vitamin D was 89.2％ (1 670/1 873);the TPO level [median (quartile)] was 23.8 (16.0-35.0) U/ml,and the positive rate of TPO was 26.8％ (502/1 873).The vitamin D levels of males and females were (16.9 ± 7.6) and (15.6 ± 7.6) μg/L,respectively,the difference was statistically significant (t =3.684,P ＜ 0.01);the TPO levels were 23.8 (16.4-31.0) and 23.8 (15.9-37.6) U/ml,respectively,the difference was not statistically significant (Z =-1.084,P ＞ 0.05).The vitamin D levels of the Han people and the Tibetans were (16.2 ± 7.8) and (16.3 ± 7.3) μg/L,respectively,the difference was not statistically significant (t =-0.110,P ＞ 0.05);the TPO levels were 23.5 (15.7-34.8) and 24.0 (16.5-35.1) U/ml,respectively,the difference was not statistically significant (Z =-0.078,P ＞ 0.05).The vitamin D levels of middle-altitude (1 500-3 000 m) and high-altitude (＞ 3 000 m) populations were (16.6 ± 7.7) and (15.8 ± 7.5) μg/L,respectively,and the difference was not statistically significant (t =2.126,P ＞ 0.05);the TPO levels were 23.4 (16.0-33.0) and 24.0 (16.0-36.8) U/ml,respectively,the difference was not statistically significant (Z =-1.296,P ＞ 0.05).There was negative correlations between vitamin D level and TPO level,altitude (r =-0.150,-0.052,P＜ 0.05),and no correlation with ethnic group (r =0.003,P ＞ 0.05).Conclusions The vitamin D level is negatively correlated with TPO level in Qinghai population.The abnormal rate of vitamin D is high,and vitamin D level of males is higher than that of females.

Objective To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS+) caused by STX1B gene mutation and to review the literature.Methods Clinical data of a child with GEFS+ and his family members who visited Guangzhou Women and Children Medical Center in August 2017 were collected.DNA samples of the proband and his parents,his grandparents were analyzed by the next-generation sequencing and confirmed by Sanger sequencing.A literature search with "STX1B " as the key word was conducted at PubMed,China National Knowledge Infrastructure and Wanfang databases to include recently published studies (up to May 2018).Results The proband was a 2-year-old boy who was admitted to our hospital because of frequent epileptic seizures in a month,with focal seizures evolving into the generalized bilateral tonic-clonic epileptic attacks after febrile seizure.His seizures were well controlled by levetiracetam.His father presented febrile seizure in early childhood stage and epilepsy in adult stage,which were under control with lamotrigine.The proband's grandmother had a history of febrile seizure.Other family members had no history of convulsion.Ictal electroencephalogram showed low voltage fast activities (8-10 Hz) originating from the central region of the brain.Heterozygous mutation of STX1B gene (c.705C＞G,p.Asn235Lys) was detected in the proband,his father and grandmother.The mutation has not been reported previously.Furthermore,no other family members carried the mutation at c.705 locus of STX1B gene.No article in Chinese was found,and 4 articles in a language other than Chinese provided the complete case data of 9 mutation loci in 33 patients (4 families and 4 sporadic cases).With this research data (3 cases in 1 family) included,there were 36 cases and 10 mutation sites in STX1B gene.Of these mutations,there were 5 missense mutations,3 nonsense mutations,1 insert mutation and 1 deletion mutation;and according to the mutation distribution,there were 4 mutation sites in exon 3,2 in exon 8,2 in exon 9,and 1 in exon 1.There was incomplete penetrance in the family,so different types of epileptic attacks occurred among different family members.Conclusions In this study,a de novo mutation of STX1B gene in a family with GEFS+ was defined,which would expand the gene mutation spectrum and provide basis for family genetic counseling.Clinical heterogeneity was found in this family.Seizures caused by STX 1B gene mutation were sensitive to antiepileptic drugs.