Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Objective:To explore and analyze the relationship between serum KLK11 and MK levels and the effect of first iodine 131 ( 131I) ablation after operation for differentiated thyroid cancer. Method:108 patients with differentiated thyroid cancer who underwent total thyroidectomy in our hospital from Jun. 2020 to Jun. 2021 were consecutively selected, and received radioactive ablation after surgery. There were 37 males and 71 females. The age was (48.32±4.25) years, ranging from 28 to 79 years. The patients were divided into successful ablation according to whether the ablation was successful after treatment. There were 64 cases in the group and 44 cases in the unsuccessful group, and 60 healthy people with no abnormality in physical examination during the same period were selected as the control group. The patients were divided into a metastasis-positive group of 20 cases and a metastasis-negative group of 88 cases according to whether lymph nodes occurred. After surgery, serum samples of all subjects were taken, and enzyme-linked immunosorbent assay was used to detect the levels of serum kallikrein-related peptidases 11 (KLK11) and midkine (MK) , and the levels of serum KLK11 and MK were analyzed. Gender, age, BMI, TNM stage, TSH, maximum diameter of lesion, and duration of nail removal were collected. Univariate analysis and logistic regression analysis were used to analyze the independent risk factors of postoperative efficacy.Result:The levels of serum KLK11 and MK in the successful and unsuccessful groups were higher than those in the control group, while the levels of KLK11 and MK in the unsuccessful group were higher than those in the successful group (KLK11: t= 2.642, P<0.05; MK: t=11.906, P<0.05) . The serum levels of KLK11 and MK in the metastasis-positive group were higher than those in the metastasis-negative group (KLK11: t= 2.908, P<0.05; MK: t=14.907, P<0.05) . Univariate analysis showed that BMI ( χ2=6.780, P=0.009) , maximum diameter of lesions ( χ2=14.819, P=0.001) , TSH ( χ2=13.627, P=0.001) , serum KLK11 ( t=2.642, P=0.01) , and serum MK ( t=11.906, P<0.001) were associated with the effect of first 131I ablation after surgery for differentiated thyroid cancer ( P<0.05) . Taking the success of ablation as the dependent variable, a multivariate logistic regression analysis was performed. The results showed that the maximum diameter of the lesions greater than 2 cm ( OR=10.740, 95%CI: 7.033-16.401) , increased level of TSH ( OR=8.559, 95%CI: 2.812-26.057) , increased serum KLK11 level ( OR=16.710, 95%CI: .548-32.666) and increased serum MK level ( OR=10.580, 95%CI: 6.294-17.786) were the factors affecting the first 131I ablation effect after DTC surgery ( P<0.05) . Conclusion:The elevated levels of serum KLK11 and MK are independent risk factors affecting the efficacy of the first 131I ablation after surgery for differentiated thyroid cancer.

Objective To investigate the expression of mitochondrial autophagy-associated protein PINK1 and Parkin in parotid pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma(CA-EX-PA). Methods The expression of PINK1 and Parkin were detected by immunohistochemistry in 24 cases of normal parotid gland tissues, 32 cases of PA tissues and 42 cases of CA-EX-PA tissues. The correlations of PINK1 and Parkin expression with the clinicopathologic characteristics of CA-EX-PA patients were analyzed. Results The positive rates of PINK1 in normal parotid gland, PA and CA-EX-PA tissues were 100%, 91% and 67% respectively; and those of Parkin were 100%, 88% and 52% respectively. The expression rates of PINK1 and Parkin in PA and CA-EX-PA tissues were significantly lower than those in normal tissues (P < 0.05). The expression of PINK1 and Parkin protein were positively correlated in CA-EX-PA tissues (r=0.877, P < 0.01). In CA-EX-PA tissues, the expression of PINK1 and Parkin were associated with tumor invasion, lymph node metastasis and TNM stage (P < 0.05). Conclusion The expression of PINK1 and Parkin are decreased in PA and CA-EX-PA tissues. The decrease of mitochondrial autophagy activity might play important roles in the development, invasion and metastasis of parotid gland tumors.

Objective To explore the expression and clinical significance of phosphoenolpyruvate carboxykinase (PCK) and plaminogen activator inhibitor-1 (PAI-1) in pleomorphic adenoma and adjacent tumor tissues of parotid gland. Methods Immunohistoehemistry was used to detect the expression of PCK and PAI-1 in10 cases of normal parotid glands, 38 cases of pleomorphic adenoma (0 cm) , adjacent tumor tissues (0.5, 1.0, 1.5, 2.0 cm from the pleomorphic adenoma). Results PCK expressed in all cases of normal parotid glands and adjacent tumor tissues, while PAI-1 expressed in 4 cases of normal parotid glands. Except 18 samples of 2.0 cm apart from pleomorphic adenoma, PAI-1 was expressed in the other adjacent tumor tissues. There was no obvious difference of PCK expression among normal, pleomorphic adenoma and adjacent tumor tissues of parotid glands (P> 0.05). The difference of PAI-1 expression was detected between pleomorphic adenoma (0 cm) and normal parotid glands and adjacent tumor tissues (2.0 cm from the tumor, P < 0.05). Conclusion During the development of pleomorphic adenoma, the expression level of PAI-1 is progressively increased while no change of PCK expression is found. It is rather remarkable that translocation of PAI-1 and PCK expression from cytoplasm and plasma membrane to nucleus occurs. The results mentioned above suggest that PCK and PAI-1 might play important roles in the progress of pleomorphic adenoma.

BACKGROUND: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy. METHODS: NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient's normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. RESULTS: Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis. CONCLUSIONS On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy.
Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; radiotherapy ; Chemoradiotherapy ; adverse effects ; DNA-(Apurinic or Apyrimidinic Site) Lyase ; blood ; Female ; Humans ; Intercellular Adhesion Molecule-1 ; blood ; Interleukin-17 ; blood ; Male ; Middle Aged ; Radiation Pneumonitis ; blood ; etiology

Objective To investigate the value of introvoxel incoherent motion(IVIM)using 3.0 T MRI to evaluate response to concurrent chemoradiotherapy(CCRT)in patients with advanced uterine cervix cancer. Methods From July 2015 to December 2016,63 patients with advanced(≥ⅡB)cervical cancer diagnosed by clinical and imaging study, who had completed CCRT plan in Henan Cancer Hospital, were prospectively enrolled.Pelvic MRI protocol including T1WI,T2WI,IVIM and dynamic contrasted enhanced scans were performed in each patient before CCRT and 3 weeks after starting therapy(total dose of 30 Gy), and at the end of therapy (total dose of 90 Gy, 8 weeks after therapy). The mean values of ADC, true molecular diffusion coefficient(D),pseudodiffusion coefficient(D*)and perfusion fraction(f)in each tumor at pre-therapy, in the middle of therapy and post-therapy were measured and recorded as ADC-pre, D-pre, D*-pre,f-pre;ADC-mid,D-mid,D*-mid,f-mid and ADC-post,D-post,D*-post,f-post,respectively;the change rates of these parameters during and after therapy (recorded as ΔADC-mid, ΔD-mid, ΔD*-mid, Δf-mid;ΔADC-post, ΔD-post, ΔD*-post, Δf-post) were also calculated. Patients were classified into response group and non-response group,according to response evaluation criteria in solid tumors after CCRT.MRI imaging study was performed in each patient within 1 month after CCRT to follow up,and tumor regression rate was calculated.The Mann-Whitney U test was used to compare differences of parameters and their change rates between response group and non-response group. Spearman correlation analysis was performed to assess relationships between parameters, parameter change rates and tumor regression rate. Logistic regression model was applied to find potential ADC values for predicting therapeutic response. ROC was used to analyze efficacy of ADC values for evaluating therapeutic response in advanced uterine cervix cancer after CCRT. Results The mean value of tumor maximum diameter before and after therapy was (47.5 ± 12.9) and(12.8 ± 10.0)mm,tumor regression rate was(66.7 ± 33.6)%.Forty-eight patients were in the response group and 15 in the non-response group.The mean value of ADC-pre,D-pre,D*-pre and f-pre was 0.74(0.43, 1.14)×10-3,0.58(0.33,0.91)×10-3,12.12(2.30,21.4)×10-3mm2/s,9.65%(4.45%,13.89%),respectively.Tumor regression rate had positive correlation with ADC-pre and D-pre (r=0.773,0.840;P<0.05). Responders had increased ADC-pre, D-pre values than non-responders, which had statistically significant difference (P<0.05). Responders had increased ADC-mid, D-mid and f-mid values than non-responders, which had statistically significant difference (P<0.05), tumor regression rate had positive correlation with ADC-mid, D-mid and f-mid (r=0.808,0.834,0.563;P<0.05). Responders had increased ADC-post, D-post and f-post values than non-responders,which had statistically significant difference(P<0.05),tumor regression rate had positive correlation with ADC-post and D-post (r=0.799, 0.829;P<0.05).Tumor regression rate had positive correlation with ΔADC-mid,ΔD-mid,Δf-mid(r=0.526,0.573,0.454;P<0.05)and with ΔADC-post,ΔD-post, Δf-post (r=0.541, 0.555, 0.388;P<0.05). Responders had increased ΔADC-mid, ΔD-mid, Δf-mid and ΔADC-post, ΔD-post, Δf-post, which had statistically significant difference (P<0.05). Logistic regression analysis revealed only ADC-pre and D-post could be independent factors to predict therapeutic response in advanced uterine cervix cancer after CCRT,values of B,Wald,odds ratio and P was 22.488,8.431,1.429, 0.004 and 16.542,8.517,1.779,0.004.ROC analysis showed the area under the curve(AUC)of ADC-pre, D-pre,ΔADC-mid,ΔD-mid,Δf-mid,ΔADC-post,ΔD-post and Δf-post for predicting therapeutic response in advanced uterine cervix cancer after CCRT were 0.890,0.926,0.942,0.851,0.803,0.929,0.951 and 0.906, respectively. Conclusion The IVIM parameters before and during CCRT process and their changes are valuable for predicting and evaluating therapeutic response in advanced uterine cervix cancer after CCRT, with high clinical practice value.

Objective To investigate the clinical and laboratory characters of infantile organic acidemia(OA) accompanied with acute metabolic crisis.Methods We analyzed retrospectively datum of infants with OA diagnosed in our unit from April 2006 to October 2014.Results Fity-three cases(37 male and 16 female,aged under 1 year old) were enrolled in this study,in which,28 cases were methylmalonic acidemia,11 cases were propionic acidemia,3 cases were biotinidase deficiency,3 cases were glutaric acidemia type Ⅱ,2 cases were glutaric acidemia type Ⅰ,2 cases were isovaleric acidemia,1 case was variety of coenzyme A carboxylase deficiency,1 case was glycerol kinase deficiency,1 case was 3-methylcrotonyl-CoA carboxylase deficiency and 1 case was holocarboxylase synthetase defect.Tweny-five of the 53 cases(47.2％)developed metabolic crisis within 7 days after onset,main manifestations included feeding difficulties,frequent seizures dyspnea,et al.The most common abnormal laboratory findings manifested severe hypoglycemia,intractable metabolic acidosis,hyperammonemia,et al.Twenty cases had family history.All patients were given symptomatic relief and supportive treatment,including colleting hypoglycemia,reducing hyperammonemia,keeping water,electrolyte and acid base balance,maintaining function of vital organs,suppling metabolic cofactor and special fomula,et al.After treatment,32 cases (60.4％) improved markedly while death occurred in 15 cases(28.3％).Conclusion OA confirmed under 1 year old is especially vulnerable to acute metabolic crisis,which characterized by sudden onset,rapid progress and is difficult to treat.Feeding difficulties,frequent seizures and dyspnea were the very common presentations.Early diagnosis and timely treatment are critical for improving the prognosis.Clinicians should be aware of it,and an early metabolic disorders screening should be intervened in patients with hypoglycemia of unknown etiology or refractory metabolic acidosis.

Objective Both decreased glomerular filtration rate (GFR) and arterial stiffness were considered as risk factors for atherosclerosis. Previous studies have suggested the association between central arterial stiffness and the degree of GFR loss. Whether decreased GFR contributes to peripheral artery stiffness remains controversial. Moreover, data analyzed from a cohort of Chinese women are rare. Our aim was to explore the relationship between GFR and regional arterial stiffness in Chinese women. Methods In this cross-sectional study, we randomly recruited 1131 adult women residents with GFR ≥ 60 mL/min per 1.73 m2 estimated by the Chinese Modification of Diet in Renal Disease equation from three large communities. Central and peripheral arterial stiffness were estimated simultaneously by measuring carotid-femoral pulse wave velocity (PWVcf) and carotid-radial PWV (PWVcr) using a validated automatic device. Augmentation Index at heart rate 75 beats/minutes (AIx-75) was measured by pulse wave analysis as a composite parameter reflecting both large and distal arterial properties. Results The mean estimated GFR (eGFR) of the study group was 100.05 ± 23.26 mL/minute per 1.73 m2. Subjects were grouped by tertiles of eGFR level. PWVcf and AIx-75 increased ongoing from the top to the bottom eGFR tertile, while the values of PWVcr were comparable. Both univariate Pearson correlations and multiple stepwise regression analyses showed that eGFR significantly correlated to PWVcf, but not to PWVcr and AIx-75. Conclusions In Chinese women with normal to mildly impaired renal function, decreased eGFR affected carotid-to-femoral rather than carotid-to-radial stiffening. This provides rational to conduct future prospective studies to investigate predictors of atherosclerosis in this population.