Objective:To investigate the clinicopathological features, immunophenotype and molecule characteristics of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue.Methods:The clinical and pathological data of 2 cases of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue diagnosed at the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China from May 2023 to May 2024 were analyzed. Immunohistochemical study, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) were performed. Relevant literature was reviewed.Results:There were one male and one female patients, aged 35 and 29 years, respectively. The tumors developed in the somatic soft tissue, including calf and chest wall, and were 6.0 and 6.2 cm in size, respectively. The imaging studies suggested space-occupying lesions in muscle tissue. Case 1 did not involve the bone, while Case 2 showed fracture of the 8th rib. Microscopically, a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. The tumors were composed of small to medium-sized round and short spindle-shaped cells, showing nodular or sheet-like pattern. The tumor cells showed round nuclear outline, coarse chromatin with prominent nucleoli. Immunohistochemically, tumor cells showed diffuse positivity of ALK (D5F3), MUM1 and Syn, focal or patchy positivity of CKpan, EMA, S-100, NSE, WT-1 and SMA, and a high Ki-67 index (20%-30%). FISH demonstrated break-apart signals of EWSR1 gene in the 2 cases. NGS revealed EWSR1::CREM gene fusion. Case 2 showed an ATRX gene mutation. The two patients were free of recurrence or metastasis at the 10-month and 1-month follow-up, respectively.Conclusions:EWSR1::CREM fusion malignant epithelioid neoplasm is rare and lacks distinctive morphological and immunohistochemical features. FISH and NGS can help make a definitive diagnosis.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To investigate the clinicopathological features, immunophenotype and molecule characteristics of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue.Methods:The clinical and pathological data of 2 cases of EWSR1::CREM fusion malignant epithelioid neoplasm in soft tissue diagnosed at the Department of Pathology, Beijing Jishuitan Hospital, Beijing, China from May 2023 to May 2024 were analyzed. Immunohistochemical study, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) were performed. Relevant literature was reviewed.Results:There were one male and one female patients, aged 35 and 29 years, respectively. The tumors developed in the somatic soft tissue, including calf and chest wall, and were 6.0 and 6.2 cm in size, respectively. The imaging studies suggested space-occupying lesions in muscle tissue. Case 1 did not involve the bone, while Case 2 showed fracture of the 8th rib. Microscopically, a fibrous pseudocapsule surrounded by lymphocytes and plasma cells was identified. The tumors were composed of small to medium-sized round and short spindle-shaped cells, showing nodular or sheet-like pattern. The tumor cells showed round nuclear outline, coarse chromatin with prominent nucleoli. Immunohistochemically, tumor cells showed diffuse positivity of ALK (D5F3), MUM1 and Syn, focal or patchy positivity of CKpan, EMA, S-100, NSE, WT-1 and SMA, and a high Ki-67 index (20%-30%). FISH demonstrated break-apart signals of EWSR1 gene in the 2 cases. NGS revealed EWSR1::CREM gene fusion. Case 2 showed an ATRX gene mutation. The two patients were free of recurrence or metastasis at the 10-month and 1-month follow-up, respectively.Conclusions:EWSR1::CREM fusion malignant epithelioid neoplasm is rare and lacks distinctive morphological and immunohistochemical features. FISH and NGS can help make a definitive diagnosis.

Objective:To investigate the diagnostic value of detecting MDM2 gene amplification by fluorescence in situ hybridization (FISH) in low-grade osteosarcoma (LGOS).Methods:Thirty cases of parosteal osteosarcoma (POS) and 14 cases of low-grade central osteosarcoma (LGCOS) from April 2009 to August 2022 at Beijing Jishuitan Hospital, Capital Medical University were analyzed for the presence of MDM2 gene amplification by FISH. Fifty-eight additional cases were used as negative controls (including 28 cases of fibrous dysplasia, 5 cases of giant cell tumor, 4 cases of conventional osteosarcoma, 2 cases each of periosteal osteosarcoma, reparative changes after fracture, pleomorphic undifferentiated sarcoma, low grade myofibroblastic sarcoma, fibrous dysplasia with malignant transformation, one case each of leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant peripheral nerve sheath tumor, desmoplastic fibroma of bone, solitary fibrous tumor, aneurysmal bone cyst, clear cell chondrosarcoma, osteofibrous dysplasia, and 3 cases of unclassified spindle cell tumor).Results:Among the 30 patients with POS, 15 were male and 15 were female, ranging in age from 10 to 59 years (mean 35 years, median 30.5 years). Among the 14 patients with LGCOS, four were male and 10 were female, ranging in age from 15 to 56 years (mean 37 years, median 36 years). All except one case were successfully detected by FISH. MDM2 gene amplification was detected in 27 cases of POS (27/29,91.3%) and 8 cases of LGCOS (8/14). All the negative controls were negative for MDM2 gene amplification. The positive rate of MDM2 gene amplification was significantly different between the case group and the control group ( P<0.05). The sensitivity and specificity of MDM2 gene amplification in diagnosing POS and LGCOS were 91.3% and 100.0%; and 57.1% and 100.0%, respectively. The sensitivity and specificity of MDM2 gene amplification in diagnosing LGOS (including POS and LGCOS) were 81.3% and 100.0%, respectively. In cases where MDM2 gene was amplified, the MDM2 amplified signal was clustered. Nine cases showed increased CEP12 signal different from polyploidy which was displayed as small and weak signal points or cloud flocculent and cluster signals. Conclusions:Detection of MDM2 gene amplification by FISH is a highly sensitive and specific marker for LGOS. The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.

Objective:To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF).Methods:The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing.Results:The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve ( n=4), brachial plexus ( n=2) or multiple nerves ( n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of β-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions:NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.

Objective:To explore the white matter structural characteristics in patients with bipolar disorder(BD)using diffusion tensor imaging(DTI)and investigate their relationship with cognitive function.Methods:A total of 15 patients with BD type Ⅰ and 26 patients with BD type Ⅱ who met the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)diagnostic criteria and 37 normal controls were included.Cognitive function was assessed with the Trail Making Test(TMT)and Repeatable Battery for the Assessment of Neuropsy-chological Status(RBANS).The tract-based spatial statistics(TBSS)method was used to explore the differences in fractional anisotropy(FA)and mean diffusivity(MD)among the three groups and perform correlation analyses with cognitive function.Results:Patients with BD Ⅰ and BD Ⅱ had lower scores in attention(P＜0.001),delayed memory(P＜0.01),and total scores(P＜0.001)on the RBANS compared to the normal control group.They also exhibited lower FA values in the corpus callosum and right superior corona radiata compared to the normal control group(P＜0.05).In the BD Ⅰ group,there was a positive correlation between FA values in the genu of corpus cal-losum and visuospatial/constructional scores(r=0.74,P＜0.05),while in the BD Ⅱ group,a positive correlation was found between FA values in the same region and language function scores(r=0.55,P＜0.05).Conclusion:It suggests that patients with bipolar disorder may have impaired white matter integrity in the corpus callosum and right superior corona radiata,which may be associated with cognitive impairment.

Objective To observe the effects of Xinkang Granules-contained serum on the proliferation of cardiac fibroblasts(CFs)induced by angiotensin Ⅱ(Ang Ⅱ);To explore its mechanism of inhibiting the proliferation of CFs.Methods Taking out the heart of SD suckling rats,extracting the CFs from the hearts by differential attachment,and then they were used to replicate cell proliferation model induced by Ang Ⅱ.After transfection with miR-21 overexpressing lentivirus and growth arrest specific transcript 5(GAS5)silencing lentivirus,Xinkang Granules-contained serum was intervened for 24 hours,respectively.Cell viability was detected by cell CCK-8 method,cell cycle was detected by flow cytometry,α-smooth muscle actin(α-SMA)was detected by immunofluorescence,RT-qPCR was used to detect the mRNA expression of GAS5,miR-2l,phosphatase and tensin homolog(PTEN),Western blot was used to detect the expressions of PTEN,protein kinase B(Akt),Cyclin D1 and cyclin-dependent kinase 4(CDK4)protein.Results Compared with the blank group,the activity of CFs in the model group increased,the proportion of G0/G1 phase cells decreased,the proportion of S phase cells increased,the positive expression of α-SMA increased,the expressions of GAS5,PTEN mRNA and PTEN protein decreased,the expressions of miR-21 mRNA and Akt,Cyclin D1,CDK4 protein increased,with statistical significance(P<0.05).Compared with the model group,the activity of CFs in the Xinkang Granules group decreased,the proportion of G0/G1 phase cells increased,the proportion of S phase cells decreased,the positive expression of α-SMA decreased,the expressions of GAS5,PTEN mRNA and PTEN protein increased,while the expressions of miR-21 mRNA and Akt,Cyclin D1 and CDK4 protein decreased;The activity of CFs increased in the miR-21 overexpression group and the GAS5 silencing group,and the proportion of G0/G1 phase cells decreased,the proportion of S phase cells increased,and the positive expression of α-SMA increased,the expressions of GAS5,PTEN mRNA and PTEN protein decreased,while the expressions of miR-21 mRNA and Akt,Cyclin D1 and CDK4 protein increased,with statistical significance(P<0.05).Compared with the miR-21 overexpression group and the GAS5 silencing group,the miR-21 overexpression+Xinkang Granules group and the GAS5 silencing+Xinkang Granules group showed a decrease in CFs activity and an increase in the proportion of G0/G1 phase cells,the proportion of S phase cells decreased,the positive expression of α-SMA decreased,the expressions of GAS5,PTEN mRNA and PTEN protein increased,and the expressions of miR-21 mRNA and Akt,Cyclin D1,CDK4 protein decreased,with statistical significance(P<0.05).Conclusion Xinkang Granules-contained serum can inhibit the increase of miR-21 and Akt expression caused by silence GAS5,resist the decrease of GAS5 and PTEN caused by overexpress miR-21,inhibit the proliferation cycle of CFs,promote GAS5 to play the role of"molecular sponge",and improve the excessive proliferation of CFs induced by Ang Ⅱ.

Objective:To measure the overall and lobulated volume of the liver with different degrees of liver fibrosis and to further observe pathological changes such as liver microvasculature, hepatocyte apoptosis, and regeneration in order to understand the macroscopic volume changes of the liver during liver fibrosis and its relationship with liver tissue microscopic pathology in patients with chronic liver disease.Methods:53 patients with chronic hepatitis B, alcoholic fatty liver disease, autoimmune liver disease, nonalcoholic fatty liver disease, and drug-induced chronic liver disease who underwent both liver biopsy tissue and abdominal magnetic resonance imaging were collected. Patients were divided into early (F1-2), middle (F3-4), and late (F5-6) in accordance with the Ishak fibrosis stage and Masson stain. The liver and spleen volumes were measured using ITK-SNAP software. CD31 immunohistochemical staining was used to reflect intrahepatic angiogenesis. Ki67 and HNF-4α multiplex immunohistochemical staining were used to reflect hepatocyte regeneration. GS staining was used to determine parenchymal extinction lesions. TUNEL staining was used to observe hepatocyte apoptosis. Spearman correlation analysis was used to analyze the relationship between liver volume changes and liver histopathological changes.Results:As liver fibrosis progressed, the total liver volume and right lobe liver volume gradually decreased ( P<0.05), while the spleen volume gradually increased ( P<0.05). The expression of CD31 and GS gradually increased ( P<0.05), and the expression of Ki67 first increased and then decreased ( P<0.05). The positivity rate of CD31 was negatively correlated with the right lobe liver volume ( r=-0.609, P<0.001) and the total liver volume ( r=-0.363, P=0.017). The positivity rate of Ki67 was positively correlated with the right lobe liver volume ( r=0.423, P=0.018), while the positivity rate of apoptotic cells was significantly negatively correlated with the total liver volume ( r=-0.860, P<0.001). The positivity rate of GS was negatively correlated with the right lobe liver volume ( r=-0.440, P=0.002), and the number of PELs was negatively correlated with RV ( r=-0.476, P=0.013). The CD31 positive staining area was negatively correlated with the Ki67 positive staining area( r=-0.511, P=0.009). Conclusion:As liver fibrosis progresses, patients with chronic liver disease have a depletion in total liver volume and right lobe liver volume, and this is mainly in correlation with fewer liver cells and liver tissue microvasculature disorders.

Objective To investigate the application value of fractional exhaled nitric oxide (FeNO), alveolar nitric oxide (CaNO), and eosinophils (EOS) in the differential diagnosis of respiratory diseases in children aged 3 to 6 years in Lanzhou, Gansu Province. Methods A total of 360 children aged 3 to 6 years with confirmed asthma, allergic rhinitis, or lower respiratory tract infection were selected as research subjects. Spearman's rank correlation coefficient was used to evaluate the correlation between FeNO, CaNO and EOS. The diagnostic value of FeNO, CaNO, and EOS for the differential diagnosis of the three diseases was assessed through random forest models, receiver operating characteristic (ROC) curves, and multivariate Logistic regression analysis. Results The median valuesof FeNO and CaNO were higher in asthmatic children than in those with other diseases. The median value of EOS was the lowest in children with allergic rhinitis, and the median values of FeNO and CaNO were the lowest in children with lower respiratory tract infection. Correlation analysis showed a positive correlation between FeNO and CaNO (r=0.59, P < 0.05), a negative correlation between FeNO and EOS (r=-0.61, P < 0.05), and a negative correlation between CaNO and EOS (r=-0.63, P < 0.05). The random forest model indicated that FeNO had the highest importance in disease classification. ROC curve analysis revealed that FeNO, CaNO, and EOS had the highest diagnostic efficiency for lower respiratory tract infection among the three diseases (with areas under the curve of 0.86, 0.91, and 1.00, respectively). The area under the curve of the multivariate Logistic regression model for diagnosing asthma was 0.96, with a sensitivity of 0.902 and a specificity of 0.881. Conclusion FeNO, CaNO and EOS demonstrate good potential in the differential diagnosis of asthma, allergic rhinitis, and lower respiratory tract infection in children aged 3 to 6 years in Lanzhou. Furthermore, the multivariate Logistic regression model based on these three factors can effectively improve the diagnostic accuracy of asthma.