OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

OBJECTIVE: To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients. METHODS: From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01). RESULTS: No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025). CONCLUSION Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans ; MicroRNAs/genetics* ; Crohn Disease/pathology* ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Asian People/genetics* ; Genetic Predisposition to Disease ; Genotype ; Young Adult ; Case-Control Studies ; Adolescent ; East Asian People

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation. METHODS: A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated 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.: 2025-12). RESULTS: A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic. CONCLUSION The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.
Humans ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Male ; Female ; Asian People/genetics* ; Adult ; Haplotypes ; Membrane Proteins/genetics* ; Exome Sequencing ; GTP-Binding Proteins/genetics* ; Mutation ; Middle Aged ; China ; Genetic Association Studies ; East Asian People

OBJECTIVE: To investigate the detection patterns, clinical phenotypic characteristics, and differences in diagnostic timeliness of Klinefelter syndrome (KS) across prenatal and postnatal stages, with an aim to provide a basis for optimizing strategies for early screening, diagnosis, and intervention. METHODS: A retrospective study was conducted to analyze data from two phases. The prenatal diagnosis group included 33,302 pregnant women who underwent amniocytic karyotyping due to advanced maternal age, abnormal ultrasound findings, or high-risk non-invasive prenatal testing (NIPT). The postnatal diagnosis group included 52,101 patients who underwent peripheral blood karyotyping due to primary infertility, abnormal external genitalia, or growth and developmental abnormalities. Additionally, medical histories of adult diagnosed patients were reviewed retrospectively to identify early occult symptoms. This study was approved by the Medical Ethics Committee of Chengdu Women's and Children's Central Hospital (Ethics No.: LCYJ-2025-030). RESULTS: In the prenatal group, 96 cases of KS were detected (detection rate 0.29%). The primary indications for referral were NIPT indicating sex chromosome abnormalities (45.83%), advanced maternal age (16.66%), and ultrasound abnormalities (17.70%). In the postnatal group, 128 cases of KS were detected (detection rate 0.25%). Clinical presentations were primarily primary infertility/azoospermia (77.34%), and the patients were predominantly adults (84.40%). Retrospective analysis revealed that adult patients presented with specific physical signs that had been overlooked during childhood. CONCLUSION As KS lacks typical early clinical manifestations, diagnosis is often delayed until adulthood when reproductive needs arise, showing a pattern of "passive detection" and resulting in missed opportunities for optimal intervention. By conducting a comparative analysis of prenatal diagnostic data and postnatal retrospective data, a risk association model linking prenatal screening indications with childhood-specific signs was developed. This study has provided empirical evidence for establishing a multidisciplinary, full life-cycle management system of "screening ~ diagnosis ~ monitoring ~ intervention" helping to shift from "passive detection in adulthood" to "proactive management across the entire life course," and laid a foundation for improving early diagnosis rate and long-term quality of life for patients.
Humans ; Klinefelter Syndrome/genetics* ; Female ; Adult ; Pregnancy ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Male ; Phenotype ; Karyotyping ; Young Adult ; Adolescent ; Middle Aged

OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

OBJECTIVES

A growing body of evidence points to a positive association between periodontitis and
various systemic diseases, including cardiovascular diseases (CVD), hypertension, and rheumatoid arthritis. However,
there is limited data on the prevalence and odds of having systemic conditions among Filipino periodontal patients.
Thus, this study aimed to determine the association of periodontal disease with systemic conditions among Filipino
patients at a university dental clinic.

METHODS

The periodontal and medical charts of all patients who underwent periodontal consult at a university
dental clinic within two academic years were reviewed. Periodontal diagnoses which had originally been assigned
using the 1999 classification of periodontal diseases were reclassified based on the 2018 European Federation
of Periodontology-American Academy of Periodontology classification. Listed medical conditions in the patients’
charts were self-reported. The prevalence of various systemic conditions in 715 periodontitis cases was compared
to that of 834 control patients without periodontitis. Fisher’s exact test was performed to evaluate the difference
in the prevalence of comorbidities between groups, while adjusted odds ratios (AOR) were computed using logistic
regression analysis, accounting for age, sex, educational attainment, and smoking status.

RESULTS

The prevalence of having at least one systemic condition was significantly higher among periodontitis patients
(44.5%) compared to non-periodontitis patients (36.3%). Compared to controls, a significantly higher number of
periodontitis cases had two systemic comorbidities (P=0.001). The prevalence of hypertension (18.6% versus 5.04%),
CVD including hypertension (20.42% versus 6.95%), arthritis (9.37% versus 3.0%), and diabetes mellitus (5.73% versus
0.84%) were all significantly higher in patients with periodontitis compared to non-periodontitis controls.
The odds of having CVD (AOR=1.81), hypertension (AOR=2.14) and diabetes (AOR=3.05) were higher in periodontitis cases. Meanwhile, the prevalence of asthma (9.23% versus 5.31%), respiratory diseases including asthma (12.95% versus 8.25%), and allergies (18.82% versus 13.71%) were significantly higher in non- periodontitis patients compared to periodontitis cases.

CONCLUSION

Periodontitis patients were more likely to present with CVD, hypertension, and diabetes mellitus. On the other hand, no association was found between periodontitis and respiratory diseases, as well as between periodontitis and asthma.

Human ; Male ; Female ; Adolescent: 13-18 Yrs Old ; Young Adult: 19-24 Yrs Old ; Adult: 25-44 Yrs Old ; Middle Aged: 45-64 Yrs Old ; Aged: 65-79 Yrs Old ; Regression (psychology) ; Respiratory Tract Diseases ; Regression Analysis ; Periodontal Diseases ; Cardiovascular Diseases

OBJECTIVES

his quantitative cross-sectional study aimed to determine the level of knowledge, attitude, and practices
regarding COVID-19 vaccination of unvaccinated adult patients admitted at Region II Trauma and Medical Center
(R2TMC). This may help determine the knowledge gap regarding COVID-19 vaccination, address it, and to achieve
the goal to vaccinate all eligible Filipinos. Furthermore, this may also be a springboard for future researches and
management regarding novel infections needing new vaccinations.

METHODS

Collected data from the sample size of 197 using the formula for finite population with 95% confidence
level, population proportion of 50%, population size of 400, allowing 5% margin of error were summarized in a
Microsoft excel database and tables, then were analyzed using Jamovi version 2.6.22 software. Frequency, mean,
and standard deviation were calculated to measure the knowledge, attitude, and practices; Pearson correlation and
Kendall’s Tau b correlation for its relationship.

RESULTS

There is moderate level of knowledge (MS: 9.80-11.8), a positive attitude (MR: 2.35-2.60), and good preventive
practices (MS: 12.00-13.00) regarding SARS-CoV-2 (COVID-19) vaccination among the unvaccinated adult in-patients
of R2TMC post-pandemic. Knowledge, attitudes, and practices statistically differed (pCONCLUSION

There is a significant correlation among the knowledge of the respondents about COVID-19 vaccination,
their attitude towards it, and their practices, implying that promoting preventive behaviors toward COVID-19 would
require promoting both knowledge and efficacy beliefs among the public.

Human ; Bacteria ; Male ; Female ; Adult: 25-44 Yrs Old ; Middle Aged: 45-64 Yrs Old ; Wounds And Injuries ; Population Density ; Cross-sectional Studies ; Forecasting ; Sars-cov-2 ; Sars Virus ; Covid-19

BACKGROUND

Penile squamous cell carcinoma (SCC) is rare in high-income regions but remains a significant oncologic burden worldwide. Nodal involvement is the most important prognostic factor, and early identification is critical.

THE CASE

A 56-year-old circumcised male presented with a six-month history of a progressively enlarging, foul-smelling fungating penile mass and bilateral inguinal lymphadenopathy. Biopsy confirmed moderately differentiated SCC. Imaging showed large bilateral inguinal nodal disease without distant metastasis. Laboratory findings revealed leukocytosis, thrombocytosis, and mildly deranged coagulation parameters. The patient underwent total penectomy with perineali urethrostomy, followed by bilateral inguinal and pelvic lymph node dissection through single-curvilinear incisions. Frozen-section analysis confirmed extensive bilateral nodal metastasis. Postoperatively, a localized left inguinal surgical site infection was treated conservatively. He was discharged on postoperative day seven with drains in situ and was recommended adjuvant chemoradiotherapy in accordance with NCCN Guidelines.

CONCLUSION

This case highlights the challenges of managing advanced penile SCC with bulky bilateral inguinal metastasis and demonstrates the utility of single-curvilinear inguinal incisions for comprehensive lymphadenectomy. Early recognition, accurate staging, and guideline-based multimodal treatment remain essential for optimizing outcomes.

Human ; Male ; Middle Aged: 45-64 Yrs Old ; Carcinoma, Squamous Cell ; Lymph Node Excision

Omental torsion is a rare cause of acute surgical abdomen from omental twisting leading to distal vascular compromise. Preoperative diagnosis has been a dilemma as clinical features, laboratory and radiographic findings are nonspecific and variable, closely mimicking acute appendicitis. Surgical excision has been suggested to offer rapid symptom relief and postoperative recovery. Presented here is a case of a 59-year-old male with omental torsion who presented with generalized abdominal tenderness and was preoperatively diagnosed as ruptured appendicitis who underwent laparotomy with uneventful post-operative course.

Human ; Male ; Middle Aged: 45-64 Yrs Old ; Abdomen, Acute ; Appendicitis

Spontaneous spinal epidural hematomas (SSEH) is a rare entity with an estimated incidence of 0.1 in 100,000, defined as a an epidural hematoma without any known inciting events such as trauma or an iatrogenic procedure. Currently, there are no local data pertaining to this disease entity. This paper presents a case of a 52 year old male, without any known comorbid coagulopathies or vasculopathies, and no preceding history of trauma or surgical procedures with sudden onset right-sided radicular pain and hemiparesis with left-sided hemianesthesia with spinal MRI findings of a spinal epidural hematoma but no vascular malformations seen on spinal angiogram. He was managed non-surgically, given short-course steroids, and sent home after 7 days in the hospital. There was no noted progression of his baseline deficits nor any recurrence of another acute spinal event. Upon follow up after 6 months, there was noted resolution of weakness and with only residual mild and patchy sensory deficit on the left. Traditionally treated surgically, this case reports highlights the role of conservative management in this rare condition with good functional outcome.

Human ; Male ; Middle Aged: 45-64 Yrs Old ; Surgical Procedures, Operative ; Hematoma, Epidural, Spinal ; Vascular Malformations ; Paresis ; Angiography ; Hematoma