Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective To explore the medicinal mechanism of Actinidia Chinensis Planch Radix(ACPR)in the treatment of colorectal cancer(CRC)by network pharmacology and molecular docking technology.Methods The genes involved in the effects of the main chemical components and disease genes of ACPR were screened from the TCM database and disease database.The main genes were analyzed through protein interaction network analysis,and molecular docking was performed on the main chemical components and key targets.The effects of the drug on tumor cells were measured,and the levels of key proteins in the signaling pathway were detected.Results The primary components of ACPR for treating CRC include quercetin,β-sitosterol,aloe baicalin,and catechin.It targets 144 protein interaction sites and were involved in the protein interaction network,with key genes including AKT1,TP53,MAPK1,JUN,and TNF.The recognition network includes five modules that were involved in various biological processes and signaling pathways.The main components exhibited excellent or good activity when interacting with these targets.At a certain concentration,the drug could inhibit the proliferation,invasion,and migration of colorectal cancer cells and affect the PI3K/AKT signaling pathway.Conclusion ACPR has been used to treat colorectal cancer through multiple pathways and multiple targets,among which the PI3K/AKT signaling pathway may be the mechanism.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective To explore the medicinal mechanism of Actinidia Chinensis Planch Radix(ACPR)in the treatment of colorectal cancer(CRC)by network pharmacology and molecular docking technology.Methods The genes involved in the effects of the main chemical components and disease genes of ACPR were screened from the TCM database and disease database.The main genes were analyzed through protein interaction network analysis,and molecular docking was performed on the main chemical components and key targets.The effects of the drug on tumor cells were measured,and the levels of key proteins in the signaling pathway were detected.Results The primary components of ACPR for treating CRC include quercetin,β-sitosterol,aloe baicalin,and catechin.It targets 144 protein interaction sites and were involved in the protein interaction network,with key genes including AKT1,TP53,MAPK1,JUN,and TNF.The recognition network includes five modules that were involved in various biological processes and signaling pathways.The main components exhibited excellent or good activity when interacting with these targets.At a certain concentration,the drug could inhibit the proliferation,invasion,and migration of colorectal cancer cells and affect the PI3K/AKT signaling pathway.Conclusion ACPR has been used to treat colorectal cancer through multiple pathways and multiple targets,among which the PI3K/AKT signaling pathway may be the mechanism.

Objective:To observe the changes of small airway parameters in patients with coal workers' pneumoconiosis in different disease stages by high resolution computed tomography (HRCT) , and analyze the correlation between them and the severity of the disease.Methods:From June 2016 to June 2023, 25 healthy volunteers and 71 untreated patients with coal worker's pneumoconiosis in the Fifth People's Hospital of Ningxia were selected as the research objects. The clinical and imaging data of the patients were collected, and the disease stages were performed according to the dust exposure history and high-kilovolt chest X-ray. The patients were divided into 4 groups: control group (25 cases) , coal workers' pneumoconiosis stage Ⅰ group (17 cases) , coal workers' pneumoconiosis stage Ⅱ group (32 cases) and coal workers' pneumoconiosis stage Ⅲ group (22 cases) . Quantitative chest HRCT parameters of each group were collected, including the square root of wall area at 10 mm inner perimeter (AWT-Pi10, Pi10) , airway wall thickness, airway wall volume, airway wall area percentage of the whole lung and the 5th, 6th, 7th and 8th level airways, and low attenuation area percentage (LAA%) of the whole lung. Pulmonary function indicators were collected, including forced expiratory volume in 1 second (FEV 1) and the percentage of its projected value [FEV 1 (%pred) ], the ratio of FEV 1 to forced vital capacity (FEV 1/FVC) and the percentage of its projected value[FEV 1/FVC (%pred) ]. One-way ANOVA or Kruskal-Wallis H test and Spearman rank correlation were used to analyze the difference and correlation. Results:Compared with control group, FEV 1, FEV 1 (%pred) , FEV 1/FVC and FEV 1/FVC (%pred) in stage Ⅱ and Ⅲ coal workers' pneumoconiosis groups were lower ( P<0.05) . In addition, the FEV 1 and FEV 1 (%pred) of the stage Ⅲgroup were lower than those of the stageⅡ group ( P<0.05) , and the FEV 1/FVC and FEV 1/FVC (%pred) of the stage Ⅲgroup were lower than those of the stage Ⅰgroup ( P<0.05) . Compared with stage Ⅰ group, Pi10 in stage Ⅲ group were increased ( P < 0.05) at the 6th and 8th level airways, and airway wall thickness and airway wall volume in the 6th, 7th and 8th level airways of stage Ⅲgroup increased ( P<0.05) . Correlation analysis showed that all pulmonary function indexes were negatively correlated with Pi10 of whole lung and the 6th, 7th and 8th level airways ( P<0.05) , all pulmonary function indexes were negatively correlated with airway wall thickness of the 7th and 8th level airways ( P<0.05) , and FEV 1/FVC (%pred) was negatively correlated with airway wall volume of the 7th and 8th level airways ( P<0.05) . FEV 1, FEV 1 (%pred) , FEV 1/FVC (%pred) were negatively correlated with percentage of airway wall area of whole lung and the 6th, 7th and 8th level airways ( P<0.05) . Conclusion:The quantitative airway parameters of coal workers' pneumoconiosis based on HRCT are correlated with pulmonary function indexes, which can reflect the severity of coal workers' pneumoconiosis.

Objective:To observe the changes of small airway parameters in patients with coal workers' pneumoconiosis in different disease stages by high resolution computed tomography (HRCT) , and analyze the correlation between them and the severity of the disease.Methods:From June 2016 to June 2023, 25 healthy volunteers and 71 untreated patients with coal worker's pneumoconiosis in the Fifth People's Hospital of Ningxia were selected as the research objects. The clinical and imaging data of the patients were collected, and the disease stages were performed according to the dust exposure history and high-kilovolt chest X-ray. The patients were divided into 4 groups: control group (25 cases) , coal workers' pneumoconiosis stage Ⅰ group (17 cases) , coal workers' pneumoconiosis stage Ⅱ group (32 cases) and coal workers' pneumoconiosis stage Ⅲ group (22 cases) . Quantitative chest HRCT parameters of each group were collected, including the square root of wall area at 10 mm inner perimeter (AWT-Pi10, Pi10) , airway wall thickness, airway wall volume, airway wall area percentage of the whole lung and the 5th, 6th, 7th and 8th level airways, and low attenuation area percentage (LAA%) of the whole lung. Pulmonary function indicators were collected, including forced expiratory volume in 1 second (FEV 1) and the percentage of its projected value [FEV 1 (%pred) ], the ratio of FEV 1 to forced vital capacity (FEV 1/FVC) and the percentage of its projected value[FEV 1/FVC (%pred) ]. One-way ANOVA or Kruskal-Wallis H test and Spearman rank correlation were used to analyze the difference and correlation. Results:Compared with control group, FEV 1, FEV 1 (%pred) , FEV 1/FVC and FEV 1/FVC (%pred) in stage Ⅱ and Ⅲ coal workers' pneumoconiosis groups were lower ( P<0.05) . In addition, the FEV 1 and FEV 1 (%pred) of the stage Ⅲgroup were lower than those of the stageⅡ group ( P<0.05) , and the FEV 1/FVC and FEV 1/FVC (%pred) of the stage Ⅲgroup were lower than those of the stage Ⅰgroup ( P<0.05) . Compared with stage Ⅰ group, Pi10 in stage Ⅲ group were increased ( P < 0.05) at the 6th and 8th level airways, and airway wall thickness and airway wall volume in the 6th, 7th and 8th level airways of stage Ⅲgroup increased ( P<0.05) . Correlation analysis showed that all pulmonary function indexes were negatively correlated with Pi10 of whole lung and the 6th, 7th and 8th level airways ( P<0.05) , all pulmonary function indexes were negatively correlated with airway wall thickness of the 7th and 8th level airways ( P<0.05) , and FEV 1/FVC (%pred) was negatively correlated with airway wall volume of the 7th and 8th level airways ( P<0.05) . FEV 1, FEV 1 (%pred) , FEV 1/FVC (%pred) were negatively correlated with percentage of airway wall area of whole lung and the 6th, 7th and 8th level airways ( P<0.05) . Conclusion:The quantitative airway parameters of coal workers' pneumoconiosis based on HRCT are correlated with pulmonary function indexes, which can reflect the severity of coal workers' pneumoconiosis.

[Objective] To review the clinical information, imaging features, pathological manifestations and prognosis of low-grade oncocytic tumor (LOT), so as to improve the clinical understanding of the disease. [Methods] The imaging, clinicopathological and postoperative follow-up data of 3 LOT cases treated in Peking University Third Hospital during Feb.2020 and Sep.2022 were retrospectively collected. [Results] All patients were male, aged 51—70 years.All tumors were single, with the maximum diameter of 14—21 mm. None of the patients had any specific clinical manifestations.The mass showed a circular isodense shadow on CT.All patients underwent nephron-sparing tumor resection.Postoperative pathology showed that the incision surface of the tumors was brownish-yellow or brown, and the tumors were solid or partially cystic.HE staining showed that the cells were uniformly eosinophilic; the nucleus was round or oval, with slight local perinuclear halo.Immunohistochemistry showed positive CK7 but negative CD117.Genetic testing in case 2 showed 1 potentially clinically significant somatic mutation TSC2.During the follow-up of 12-23 months, no recurrence occurred. [Conclusion] There were no obvious clinical symptoms and imaging features of LOT, which morphologically showed heterozygous or borderline characteristics with renal eosinophilia and renal chromophobe cell carcinoma, and the biological behavior was indolent.Nephron-sparing tumor resection promised good prognosis.

Objective:To provide useful information for in-depth understanding of the epidemic and molecular evolution of Coxsackievirus A4 (CV-A4), the genetic characteristics of the complete genome and recombination events in some genome regions of CV-A4 strain isolated from a patient with severe hand, foot and mouth disease (HFMD) in Yunnan province were analyzed.Methods:The CV-A4 strain was isolated from feces using RD, KMB17 and A549 cells respectively, and the viral RNA was extracted from the supernatant with CPE. The whole VP1 and complete genome sequences of the virus were amplified by RT-PCR and sequenced through Sanger’s sequencing. Complete genome sequence and genome regions of the isolated virus were analyzed through MEGA7.0 and SimPlot 3.5.1 software.Results:The virus isolated from RD cells belonged to CV-A4 and was designated as R11-20/YN/CHN/2011 strain. This CV-A4 strain was C2 sub-genotype through phylogenetic analysis based on the VP1 sequence. CV-A4 R11-20/YN/CHN/2011 has the highest nucleotide sequence identity with 09214/SD/CHN/2009 in VP1 and CVA4/SZ/CHN/09 in the complete genome. Recombination occurred between CV-A4 R11-20/YN/CHN/2011 and EV-A71 in 3D region.Conclusions:The CV-A4 R11-20/YN/CHN/2011 strain belongs to C2 sub-genotype and recombines with EV-A71 in 3D region.

Objective:To identify the causative genes of the posterior microphthalmia-retinal pigment degeneration family.Methods:A retrospective clinical study. One child (proband) and 3 family members of a family with posterior microphthalmia-retinitis pigmentosa diagnosed by clinical and genetic examination at Henan Provincial People's Hospital in July 2019 were included in the study. Medical history and family history, and draw pedigree of the patients was collected. Visual acuity, visual field, fundus color photography, optical coherence tomography and electroretinogram (ERG) were examined. The peripheral venous blood of the proband, his parents and sister, and extract the whole genome DNA was collected. Whole-exome sequencing was used to detect genetic variations, the suspected pathogenic variations were verified by Sanger sequencing, and the pathogenicity was determined by bioinformatics analysis.Results:The parents discovered the proband was poor vision at the age of 10 months. At the age of 3, the best corrected visual acuity of the right eye and the left eye were 0.3 and 0.4, respectively. No abnormality was found in anterior segment. Extremely high hyperopia in both eyes. The axial length was 14.47 mm and 15.78 mm, respectively. The optic disc of both eyes was relatively small and flushed, retinal folds can be observed in macular area, and no obvious pigment deposition was found. ERG examination showed that the rod system response and the maximal combined response of both eyes decreased slightly to moderately, and the single-flash cone response and the 30 Hz flicker response decreased moderately to severely. Genetic analysis revealed two novel mutations in the membrane frizzled-related protein ( MFRP) gene in the proband: c.363delC/p.Thr121Thrfs*16, c.1627C>T/p.Gln543Stop,37 in exon 4 and 13, the former was a frameshift mutation, encoding 16 amino acids and then terminated, and the latter was an nonsense mutation, truncated 37 amino acids, both which were predicted to be pathogenic and segregate with disease. The mother and sister carried c.363delC, and the father carried c.1627C>T. Conclusion:MFRP gene c.363delC/p.Thr121Thrfs*16, c.1627C >T/p.Gln543Stop, 37 compound heterozygous mutation may be the pathogenic gene of this family.

Objective:To analyze the prognostic factors of primary and metastatic tumor resection for metastatic renal carcinoma.Methods:Clinical data of 12 cases of renal carcinoma with distant metastasis admitted to the Peking University Third Hospital from June 2011 to December 2019 were analyzed retrospectively, including 10 males and 2 females. Age was from 36 to 67 years old, with average of 53.7 years old. BMI was 20.9-30.8 kg/m 2, with average of 25.8 kg/m 2.There were 6 cases of right kidney tumor and 6 cases of left kidney tumor. The diameter of the primary tumor was 2.7-16.0 cm, with an average of 7.1 cm. There were 2 cases of lung metastasis, 1 case of liver metastasis and 9 cases of bone metastasis. All the 12 patients underwent primary and metastatic tumorectomy. Postoperative pathological results showed 10 cases of clear cell carcinoma, 1 case of papillary type 2 tumor and 1 case of collecting duct carcinoma. The pathological results of the metastases were the same as those of the original lesions. Results:All the 12 patients underwent primary and metastatic renal carcinoma resection, among which 3 received postoperative chemotherapy and 6 received radiotherapy .Two patients were treated with targeted drugs. The interval between primary resection and metastatic resection was 1-84 months, and the median time was 2.5 months. In this study, 12 patients were followed up for 2-96 months, with the median survival time of 34 months, and mortality rate of 25%.There was no significant correlation between age( P=0.265), gender( P=0.183), BMI( P=0.152), primary tumor size ( P=0.082), radiotherapy, chemotherapy or targeted therapy ( P=0.915) and overall survival, and the interval between primary resection and metastatic resection ( P=0.046) was significantly correlated with overall survival. Conclusion:The interval between primary and metastatic tumor resection was a risk factor for the prognosis of patients.