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

BACKGROUND

Drowning is a significant cause of accidental death worldwide, and forensic investigation plays an important role in determining the circumstances and causes of these deaths. Despite its importance, research in forensic investigations related to drowning remains fragmented and insufficiently characterized.

OBJECTIVE

This study aimed to examine trends and patterns in publications on forensic examinations related to drowning deaths. Specifically, it sought to identify research gaps, highlight key contributions, and determine major thematic areas in the field.

METHODS

A total of 116 articles published between 2014 and 2023 were retrieved from the PubMed database using search terms related to forensic science and drowning deaths. Bibliometric analysis was performed using VOSviewer (version 1.6.20) to identify research clusters, patterns of author collaboration, and keyword co-occurrence. Filtered data were exported in .txt format to facilitate analysis and visualization.

RESULTS

Visualization analysis identified seven thematic clusters. China had the highest number of publications on this topic. The Academy of Forensic Science in Shanghai was the most productive institution, while Fa Yi Xue Za Zhi had the highest number of publications. Lippmann J. was the most prolific author. The most frequently cited source received 180 citations. The three most commonly discussed topics were drowning, forensic pathology, and autopsy, while the most frequent terms overall were forensic pathology, autopsy, and people.

CONCLUSION

The findings indicate substantial initial research interest in forensic investigations of drowning. However, publication output during the study period showed a downward trend, with a decrease of 16.4%. This decline suggests a notable gap in the literature and highlights the need for further research in this field.

Research ; Pathology ; Publications ; Science ; Role ; Forensic Pathology ; Forensic Sciences

BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

A unicornuate uterus with a non-communicating rudimentary horn is a rare Müllerian duct anomaly that is frequently underdiagnosed because of its variable clinical presentation and the limitations of conventional imaging modalities. Although not considered a direct cause of infertility, it may coexist with other reproductive pathologies and contribute to adverse reproductive outcomes. Presented here is a case series of three infertile women aged 30–36 years who were diagnosed with a unicornuate uterus and non-communicating rudimentary horn during fertility evaluation. Patient A presented with primary infertility, cyclic pelvic pain, endometriosis, and bilateral tubal disease; Patient B had a seven-year history of primary infertility and was initially suspected to have unilateral tubal obstruction; and Patient C was referred with a presumed diagnosis of uterine didelphys and was subsequently found to have a unicornuate uterus with a non-communicating rudimentary horn and ipsilateral renal agenesis. In all three cases, preoperative imaging failed to establish the definitive diagnosis, which was confirmed intraoperatively through laparoscopy, chromotubation, and hysteroscopy. Patients A and B underwent laparoscopic excision of the rudimentary horn with ipsilateral salpingectomy, while Patient C underwent only ipsilateral salpingectomy. Hysteroscopic transillumination was utilized in one case to facilitate safe laparoscopic dissection and delineation of the hemiuterine anatomy. All patients had uneventful postoperative recovery and were subsequently counseled regarding fertility options. This case series highlights the diagnostic challenges posed by unicornuate uterus with a non-communicating rudimentary horn, emphasizes the importance of a high index of suspicion during infertility work-up, and demonstrates the value of minimally invasive surgical management and hysteroscopic transillumination in selected cases. Early recognition and individualized treatment may help reduce reproductive complications and improve fertility counseling and management.

Human ; Female ; Adult: 25-44 Yrs Old ; Infertility, Female ; Laparoscopy ; Salpingectomy ; Hysteroscopy ; Pathology ; Endometriosis ; Fallopian Tube Diseases ; Transillumination ; Uterine Didelphys

There is a reason some melodies linger long after the performance has ended. Not because they are triumphant, but because they carry memory gently. They remind us that meaning is often found not in fanfare, but in persistence, in the patient work of returning, rebuilding, and remaining.

This issue of the Philippine Journal of Pathology comes at the end of a season of milestones for the journal, and perhaps also a season of reflection.

Pathology

Background: Histopathology has been a standard in achieving and confirming a diagnosis by offering tissue-based findings as guidance in making clinical decisions. As it is reported within a standard timeframe, ancillary testing with immunohistochemistry studies can extend turnaround time (TAT), a quality indicator in surgical pathology. This study aims to benchmark the laboratory’s current practices and quantify the impact of IHCs on reporting definitive diagnoses. Objective: To compare turnaround times of surgical pathology specimens with and without additional immunohistochemistry testing. Methodology: In-house histopathology cases processed in 2024 at the Anatomic Pathology Division of NKTI were evaluated. Specimen receipt dates, report verification dates, and IHC usage are data extracted from logbooks. Cases were categorized into one of three groups depending on the need for IHCs and whether these IHCs are done after releasing an initial histopathology report or if with IHCs altogether releasing an already definitive diagnosis. Results: A total of 5,006 specimen cases were evaluated. Each category has a distinct turnaround time with 5.27 (A), 10.03 (B), and 36.01 (C) days. The medians for each category are 5, 9, and 23 days, while the most common turnaround times were 4, 6, and 15 days, respectively. A Kruskal-Wallis test indicated significant differences among the three groups (p < 0.001), while a post hoc pairwise comparison using Dunn’s test also showed significant differences (A vs B: p < 0.001; A vs C: p < 0.001; B vs C: p < 0.001). Conclusion The use of IHCs extends the TAT of cases. The interval time between sign out of routine histopathology and request for IHCs may be eliminated with precharged reflective testing. Further studies on TATs with implemented reflective testing may be performed to determine efficiency of this service.
Immunohistochemistry ; Pathology, Surgical ; Time Factors ; Medical Records

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVES: To determine the neuroprotective effects of berberine hydrochloride (BBR) against lead-induced injuries on the hippocampus of rats. METHODS: Wistar rats were exposed orally to doses of 100 and 500 ppm lead acetate for 1 and 2 months to develop subchronic and chronic lead poisening models, respectively. For treatment, BBR (50 mg/kg daily) was injected intraperitoneally to rats poisoned with lead. At the end of the experiment, the spatial learning and memory of rats were assessed using the Morris water maze test. Hippocampal tissue changes were examined by hematoxylin and eosin staining. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels as parameters of oxidative stress and antioxidant status of the hippocampus were evaluated. RESULTS: BBR reduced cognitive impairment in rats exposed to lead (P<0.05 or P<0.01). The resulting biochemical changes included a decrease in the activity of antioxidants and an increase in lipid peroxidation of the hippocampus of lead-exposed rats (P<0.05 or P<0.01), which were significantly modified by BBR (P<0.05). BBR also increased the density of healthy cells in the hippocampus of leadexposed rats (P<0.05). Significant changes in tissue morphology and biochemical factors of the hippocampus were observed in rats that received lead for 2 months (P<0.05). Most of these changes were insignificant in rats that received lead for 1 month. CONCLUSION BBR can improve oxidative tissue changes and hippocampal dysfunction in lead-exposed rats, which may be due to the strong antioxidant potential of BBR.
Animals ; Hippocampus/pathology* ; Rats, Wistar ; Antioxidants/pharmacology* ; Berberine/therapeutic use* ; Cognition/drug effects* ; Male ; Lead Poisoning/metabolism* ; Chronic Disease ; Oxidative Stress/drug effects* ; Maze Learning/drug effects* ; Rats ; Lipid Peroxidation/drug effects* ; Malondialdehyde/metabolism*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*