ObjectiveTo investigate the correlation between neutrophil-to-lymphocyte ratio （NLR）， platelet-to-lymphocyte ratio （PLR）， systemic immune-inflammation index （SII） and the severity of intrauterine adhesions （IUA）. MethodsThe retrospective study included 380 patients who underwent transcervical resection of adhesions （TCRA） from December 2019 to March 2025. Based on the American Fertility Society （AFS） classification， patients were divided into mild （n=61）， moderate （n=225）， and severe （n=94） groups. NLR， PLR， and SII were calculated from preoperative blood tests. Statistical analyses included Kruskal-Wallis test and ordinal Logistic regression. ResultsNLR， PLR， and SII were significantly higher in the severe IUA group compared to the mild group （P<0.05）， with SII showing the strongest predictive ability （OR=1.004， P=0.001）. The number of intrauterine procedures was an independent risk factor （OR=1.27/level， P=0.016）. The predictive model ［Logit（P）=-0.676+0.241×operation times+0.004×SII］ effectively identified severe IUA cases. ConclusionInflammatory markers （particularly SII） are correlated with IUA severity and may serve as non-invasive tools for clinical assessment.

Objective: To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population. Methods: From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity. Results: The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05]. Conclusions Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.

Objective: To understand the current situation and related factors of screening myopia among students in special education schools, so as to provide evidence for promoting the health level of this population. Methods: From November 2021 to December 2023, a total of 281 students from 6 special education schools in 5 districts of Tianjin were selected by cluster random sampling method for computer optometry visual acuity examination for non ciliary paralysis and questionnaire survey. Multiple Logistic regression was performed to analyze the influencing factors of screening myopia among special education students. Results: The screening myopia detection rate among these special education students in Tianjin was 27.0%, and the screening myopia detection rates of students with autism, developmental delays, and intellectual disabilities were 22.4%, 12.5%, and 33.0%, respectively. The degree of myopia increased with age ( χ 2 trend =22.65, P <0.01). Multivariate Logistic regression analysis showed that age(10-13 years old: OR =5.40, 14-17 years old: OR =8.40, 18-23 years old: OR =6.02), accommodation(non resident: OR =0.29), daily mobile phone usage ≥2 hours ( OR =2.37), and daily computer/tablet usage ≥2 hours ( OR =2.70) were the risk factors for screening myopia among special education students ( P <0.05). Conclusions The detection rate and degree of screening myopia increase with age in special education students. Prolonged screen time exposure is a primary risk factor for screening myopia in special education students. Effective myopia prevention and control strategies should be designed according to the characteristics of special education students.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.

Objective:To investigate the clinicopathological characteristics, molecular features, differential diagnosis and prognosis of renal cell carcinoma (RCC) with TFEB gene amplification.Methods:A total of 113 cases of unclassified RCCs and RCCs with TFEB positive expression were collected from the Affiliated Hospital of Qingdao University and Navy 971 Hospital from January 2010 to December 2024. Eight cases of RCCs with TFEB amplification were identified using tissue microarrays, immunohistochemistry, and fluorescence in situ hybridization (FISH) techniques. The clinicopathological data and prognosis of the 8 cases were summarized, and relevant literature was reviewed.Results:Among the 8 cases, there were 5 males and 3 females. The average age was 63.4 (54, 77) year and the median age was 63.5 (59.0, 65.5) year. Seven cases were detected through physical examination, and 1 case presented with initial symptoms of metastasis to bones and lungs. The cohort included 1 biopsy specimen and 7 surgical resection specimens. The tumor diameters ranged from 2.5 to 15.0 cm. The cut surfaces of 5 cases were grayish-yellow or grayish-red, and 2 cases exhibited a colorful appearance, among which 3 cases involved renal sinus and 1 case showed invasion of the perirenal fat tissue. Microscopically, 4 cases were composed of clear cells arranged in solid sheets or acinar structures, along with varying numbers of eosinophilic cells. Two cases exhibited the morphology of high-grade eosinophilic RCC, and 1 case presented biphasic morphology with diffuse polygonal eosinophilic tumor cells and dense small cell components. The remaining 1 case exhibited the morphology of clear cell RCC. According to the WHO/ISUP nuclear grading system, 6 cases were Grade 3 and 2 cases were Grade 2. Multifocal necrosis was observed in 4 cases. In 4 surgical specimens, the tumor tissue invaded the renal parenchyma, with 2 cases showing nodular infiltration to surrounding tissues and 1 case with intravascular tumor thrombus. Immunohistochemical results showed varying degrees of TFEB nuclear positivity in 6 cases (6/8). Melanocytic markers such as Melan A (5/8) and HMB45 (3/8) were expressed at varying degrees. Cathepsin K (6/8), GPNMB (6/8), P504s (7/8) and CD10 (7/8) were positively expressed in most cases. FISH results revealed high-copy amplification of TFEB gene in 4 cases (partially showing clustered amplification) and low-copy amplification in 4 cases. During the follow-up period of 3 to 64 months of the 8 cases, 3 cases metastasized and 2 cases died of disease (both with high-copy TFEB gene amplification).Conclusions:RCC with TFEB gene amplification is rare and exhibits diverse morphological features. A common morphological characteristic of this type of tumor is a mixture of sheet-like clear cells and high nuclear grade eosinophilic cells. Combined immunohistochemical staining for TFEB, melanocytic markers, and GPNMB is helpful for the diagnosis of the tumor, and FISH detection of TFEB gene amplification is the most definitive method in diagnosing this tumor. RCC with TFEB gene amplification usually presents with strong aggressiveness and poor prognosis. Combining surgical resection with immunotherapy or VEGFR-targeted drugs might have therapeutic effects on the tumor.

Objective:To investigate the clinicopathological characteristics and diagnosis of high-grade succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC).Methods:Three cases of high-grade SDH-RCC diagnosed by immunohistochemical staining and/or molecular testing were collected from Affiliated Hospital of Qingdao University and 971 Hospital of Navy of Chinese People′s Liberation Army from January 2015 to December 2023. The clinicopathological characteristics and immunohistochemical features were summarized using light microscopy. Two cases were tested for gene mutations by next-generation sequencing.Results:Of the 3 cases, 2 were male and 1 was female. The ages were 49, 61, and 53 years, respectively. Gross examination revealed that all tumors were single nodules with diameters of 7.0, 4.5, and 5.2 cm, respectively, grayish white in color with irregular borders. Cases 1 and 2 exhibited solid cut sections, whereas case 3 had cystic and solid cut sections. Microscopically, all cases had high WHO/ISUP nuclear grade (3 or 4) and overt invasion. Case 1 exhibited a solid, sheet-like growth pattern with numerous scattered glandular ducts or acinar structures. Case 2 displayed a diffusely growth pattern reminiscent of sarcoma. Case 3 demonstrated intracystic papillary and nodular infiltrative growth patterns. Large clear cytoplasmic vacuoles could be observed in the focal areas of case 1 and case 3. Prominent peritumoral lymphocytes in stroma were noted in case 1. Case 1 was diagnosed with regional lymph node metastasis, and case 2 was diagnosed with renal vein thrombosis. Immunohistochemical staining revealed that SDHB and SDHA were deficiently expressed in 3 cases, while PAX8, FH, and INI-1 exhibited diffuse expression. CD10 (1/3), CA9 (1/3), and CK20 (1/3) were occasionally expressed. The Ki-67 proliferation index ranged from 10% to 50%. Two cases underwent next-generation sequencing and were both found to harbor pathogenic mutations in SDHA (case 2 had a frameshift mutation, and case 3 had a splice site mutation). All 3 cases were followed up for 11 to 112 months. Case 2 died 11 months post-operation, while case 1 and case 3 survived for 19 and 112 months, respectively, without any recurrence or metastasis.Conclusions:High-grade SDH-RCC is a rare subtype of SDH-RCC. The tumor exhibits various architectural patterns and is often misdiagnosed as other types of renal cell carcinoma. The presence of cytoplasmic vacuoles may be indicative for diagnosis. Compared to typical SDH-RCC, the high-grade subtype generally shows a larger tumor size, higher TNM stage, greater invasive potential, and poorer prognosis. For high-grade SDH-RCC, routine SDHB immunohistochemical staining may be necessary. The occurrence of high-grade SDH-RCC may be associated with mutations in SDHA.

Objective:To investigate the clinical characteristics of urea cycle disorder (UCD), the efficacy and safety of glyceryl phenylbutyrate (GPB) therapy in pediatric patients with UCD.Methods:This study was a retrospective, single-arm, multicenter clinical study. The clinical data of 20 pediatric patients with UCD who received GPB treatment at 9 hospitals nationwide between December 2021 and August 2024 were collected. The clinical manifestations, laboratory results, and molecular genetic characteristics were analyzed, ammonia levels and other laboratory results were evaluated pre-post GPB therapy by paired t-tests or Wilcoxon tests. Results:Among the 20 pediatric patients with UCD, there were 8 males and 12 females, and the onset age was 2.8 (1.4, 5.7) years. The ammonia levels were 174 (125, 342) μmol/L at first onset. The symptoms included vomiting in 6 cases, drowsiness in 5 cases, epilepsy in 5 cases, developmental delay in 5 cases, psychiatric and behavioral abnormalities in 3 cases, and lethargy in 1 case, and 18 cases exhibited abnormal liver function. Twenty cases included 6 UCD subtypes, with 11 cases being ornithine transcarbamylase deficiency. A total of 27 variants were identified, 11 (41%) of which were novel. The age of patients who began GPB therapy was 4.0 (1.5, 6.6) years. Ten cases stopped GPB after 4.2 (3.4, 5.3) months, with 4 patients undergoing liver transplantation and 6 discontinuing for financial reasons. The remaining ten patients continued GPB therapy for 11.6 (8.6, 14.0) months. The duration of GPB treatment was 6.0 (4.2, 12.3) months, at the final visit, the levels of ammonia, platelets and aspartate aminotransferase were lower compared to those of pre-treatment (all P<0.05). The serum albumin level was higher than that of pre-treatment ( P=0.016). Two patients suffered only one episode of acute hyperammonaemia, with ammonia levels of 232 and 141 μmol/L, respectively. Nine cases experienced adverse effects potentially related to GPB, decreased appetite in 6 cases, vomiting in 3 cases, abnormal skin oil odor in 2 cases, somnolence, fatigue and diarrhea each in 1 case, with symptoms improved within 6 (3, 10) days. Conclusions:UCD primarily manifests with neurological and gastrointestinal symptoms, and early diagnosis of UCD could be achieved through the analysis of ammonia. GPB may effectively reduce ammonia levels in UCD pediatric patients, with favorable safety and tolerability.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective To investigate the effects of Demodex infection on clinical symptoms,signs,and tear MMP-9 levels in patients with meibomian gland dysfunction(MGD).Methods A total of 680 patients with MGD were selected from our hospital,including 162 males and 518 females,with an average age of(45.05±15.41)years old.The patients were divided into two groups based on the presence of Demodex mite infestation:the Demodex positive group(340 cases)and the Demodex negative group(340 cases).All patients underwent evaluations using the OSDI questionnaire,SPEED questionnaire,eyelid margin alteration score,corneal fluorescein staining score,tear MMP-9 measurement,meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,tear film breakup time(BUT),and Schirmer I tear secretion test.The differences in these indicators between the two groups were compared.Results SPEED questionnaire score:Demodex positive group:(7.68±2.80),Demodex negative group:(6.28±1.99).There was a statistically significant difference between the two groups(t=2.582,P=0.012).Eyelid margin alteration score:Demodex positive group:(3.63±1.53),Demodex negative group:(2.85±0.77).A statistically significant difference was observed(t=2.861,P=0.006).Corneal fluorescein staining score:Demodex positive group:(2.25±1.86),Demodex negative group:(1.08±1.33).There was a statistically significant difference(t=3.247,P=0.002).Tear MMP-9 content:Demodex positive group:(30.76±43.14)ng/mL,Demodex negative group:(12.36±12.10)ng/mL.A statistically significant difference was found(t=2.598,P=0.013).No statistically significant differences were observed between the Demodex positive and negative groups in meibomian gland orifice score,meibomian gland excretion ability score,meibomian gland secretion score,meibomian gland loss score,BUT,tear secretion examination,and age comparison(P>0.05).Conclusions Demodex mite infestation in patients with MGD exhibits significant differ-ences across various clinical indicators,notably in SPEED questionnaire scores,eyelid margin alterations,corneal fluorescein staining,and tear MMP-9 levels.These changes are associated with mechanisms including inflammatory responses,cellular damage,and immune dysregulation.Demodex mite infestation may significantly influence the clinical progression of MGD by exacerbating inflammation and symptom severity,potentially playing a crucial role in disease development.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of renal solitary fibrous tumor (SFT).Methods:Five cases of renal SFT with unequivocal diagnoses at the Affiliated Hospital of Qingdao University between January 2011 and July 2025 were subject to analyses of their clinical, morphological, immunophenotypic, and molecular characteristics, accompanied by a literature review.Results:Two males and three females aged between 45 and 62 years were included, all of whom presented with the discovery of a renal mass during routine physical examinations. Gross examination showed that the five tumors were all confined in the kidney. The tumors were nodular with maximum diameters ranging from 2.5 cm to 11.0 cm (mean, 5.8 cm). Upon cross-sectioning, they exhibited gray-white or gray-yellow cut surface. Histologically, the tumor cells exhibited oval or short spindle shapes in four cases, presenting with varying densities and arranged in short bundles, woven patterns, and irregular formation. Various amounts of coarse collagen and scattered staghorn blood-vessels were found in the stroma. In one case (case 5), the tumor cells were long spindle-shaped, densely organized in bundles, and interwoven, exhibiting inconspicuous boundaries, moderate nuclear atypia, and at least 4 mitotic figures per 10 high-power fields. Irregular patchy collagen deposition was particularly prominent at the edges of the tumor tissue. In two cases (cases 3 and 5), scattered and various amounts of renal tubules were observed in the tumor. Two cases (cases 4 and 5) demonstrated focal invasion of the renal parenchyma, although no necrosis was noted. Immunohistochemical staining showed that the tumor cells were diffusely and strongly positive for vimentin and STAT6 in all 5 cases, and positive for CD34. Bcl-2 positivity was present in 4 of the 5 cases. All cases were negative for CKpan, EMA, PAX8, HMB45, Melan A, SMA, and S-100 protein. The p53 status was wild type, and the Ki-67 index ranged from 1% to 8%. Next-generation sequencing was conducted on one case (case 4), revealing the NAB2 (exon 3)::STAT6 (exon 18) gene fusion. The 5 patients were followed up for 1 to 158 months (mean, 56 months), and all were alive with no recurrence or metastasis.Conclusions:SFT of the kidney are rare and morphologically similar to extrarenal SFT. Key morphological features include short spindle-shaped tumor cells arranged in bundles, interwoven patterns or irregularly, accompanied by staghorn blood-vessels and scattered coarse hyaline collagen fibers. SFT with epithelial inclusions may represent a relatively common histological subtype in the kidney. Immunohistochemical staining that demonstrates diffuse and strong positivity for STAT6 and CD34 is instrumental in diagnosing this tumor. The pathogenesis is linked to the centromeric inversion of chromosome 12q, resulting in the fusion of the NAB2 and STAT6 genes. Most of these tumors exhibit favorable prognosis.