The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Objective:To investigate the clinicopathological characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity.Methods:The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review.Results:All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization.Conclusions:CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.

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 and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Objective:To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

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 characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity.Methods:The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review.Results:All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization.Conclusions:CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.

ObjectiveTo investigate the protective effect of salidroside against nonalcoholic fatty liver disease （NAFLD） and its mechanism of action. MethodsA total of 24 male KM mice were randomly divided into normal group， HFD group， HFD+blank control group， and HFD+salidroside group， with 6 mice in each group. The mice in the normal group were given normal diet， and those in the other groups were given high-fat diet. After 14 weeks of modeling， the mice were given salidroside 100 mg/kg/day by gavage， and related samples were collected at the end of week 22. Enzyme-linked immunosorbent assay was used to measure the serum levels of related biochemical parameters including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）； HE staining and NAFLD activity score （NAS） were used to observe the liver histopathology of mice； Western blot was used to measure the changes in the expression of NAMPT， Sirt1， AMPKα， and SREBP1 in liver tissue. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the HFD group had obvious steatosis and extensive large lipid droplets in liver tissue， with significant increases in NAS score （P<0.01） and the content of AST， ALT， TG， TC， and LDL-C in peripheral blood （all P<0.05） and a significant reduction in the content of HDL-C （P<0.05）， as well as significant reductions in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant increase in the expression level of SERBP1 （P<0.01）. Compared with the HFD group and the HFD+blank control group， the HFD+salidroside group had reductions in the distribution of vacuolar lipid droplets and intralobular inflammation in liver tissue， alleviation of the ballooning degeneration of hepatocytes， significant reductions in NAS score （P<0.01） and the content of AST， ALT， TG， and LDL-C in peripheral blood （all P<0.05）， and a significant increase in the content of HDL-C （P<0.05）， as well as significant increases in the expression levels of NAMPT， AMPKα， and Sirt1 in liver tissue （all P<0.05） and a significant reduction in the expression level of SERBP1 （P<0.01）. ConclusionSalidroside can significantly improve the pathological state of mice with NAFLD induced by high-fat diet and exert a protective effect against NAFLD by increasing the expression of NAMPT， Sirt1， and AMPKα and reducing the expression of SERBP1.

Objective To study the clinicopathological features of ovarian clear cell carcinoma to pro-vide a basis for the differential diagnosis of whether it originates from endometrioid cyst.Methods A total of 30 patients with ovarian clear cell carcinoma receiving treatment in Jinjiang Municipal Hospital from January 2009 to December 2022 were collected as the research subjects.The patients not originating from endometrioid cysts were included in the control group(n=15)and the patients originating from endometrioid cysts were in-cluded in the observation group(n=15).Macroexamination,microscopic examination,hematoxylin-eosin stai-ning and immunohistochemical staining were used to analyze the clinicopathological characteristics.The gener-al data and pathological examination results of the two groups were statistically analyzed.Results Among the two groups,there were 22 cases(73.33％)of clear cells,3 cases(10.00％)of shoe-tack like cells,2 cases(6.67％)with about half of each cell type,and 3 cases(10.00％)of hyaline bodies or eosinophils.There were 27 cases(90.00％)of aspartic acid peptidase A(Napsin-A)positive and 29 cases(96.67％)of hepatocyte nu-clear factor-1β(HNF-1β)positive.Staging,ascites,lymph node metastasis,abdominal/pelvic metastasis,CA125,complicating endometrioid cyst,coffee-colored fluid in the sac,uneven thickness of the cyst wall,men-strual disorders and infertility all were the influencing factors of ovarian clear cell carcinoma originating from endometrioid cyst(P＜0.05).Conclusion The relevant pathological features could provide an important ref-erence base for the clinical differential diagnosis of whether ovarian clear cell carcinoma originates from endo-metrioid cysts,and it is of great significance to improve the detection rate of ovarian clear cell carcinoma.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.