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

Pathology ; Pathologists ; Public Health

Colorectal cancer(CRC) is one of the most common malignant tumors worldwide, primarily originating from recurrent inflammatory bowel disease(IBD). Therefore, blocking the inflammation-cancer transformation in the colon has become a focus in the early prevention and treatment of CRC. The inflammation-cancer transformation in the colon involves multiple types of cells and complex pathological processes, including inflammatory responses and tumorigenesis. In this complex pathological process, immune cells(including non-specific and specific immune cells) and non-immune cells(such as tumor cells and fibroblasts) interact with each other, collectively promoting the progression of the disease. In traditional Chinese medicine(TCM), inflammation-cancer transformation in the colon belongs to the categories of dysentery and diarrhea, with the main pathogenesis being cold and heat in complexity. This paper first elaborates on the complex molecular mechanisms involved in the inflammation-cancer transformation process in the colon from the perspectives of inflammation, cancer, and their mutual influences. Subsequently, by comparing the pathogenic characteristics and clinical manifestations between inflammation-cancer transformation and the TCM pathogenesis of cold and heat in complexity, this paper explores the intrinsic connections between the two. Furthermore, based on the correlation between inflammation-cancer transformation in the colon and the TCM pathogenesis, this paper delves into the importance of the interaction between inflammation and cancer. Finally, it summarizes and discusses the clinical and basic research progress in the TCM intervention in the inflammation-cancer transformation process, providing a theoretical basis and treatment strategy for the treatment of CRC with integrated traditional Chinese and Western medicine.
Humans ; Colon/pathology* ; Integrative Medicine ; Animals ; Cold Temperature ; Cell Transformation, Neoplastic/drug effects* ; Medicine, Chinese Traditional ; Hot Temperature ; Inflammation ; Drugs, Chinese Herbal/therapeutic use* ; Colonic Neoplasms/drug therapy*

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL