BACKGROUND: There is growing evidence that the occurrence and severity of respiratory diseases in children are related to the concentration of air pollutants. Nonetheless, evidence regarding the association between short-term exposure to air pollution and outpatient visits for respiratory diseases in children remains limited. Outpatients cover a wide range of disease severity, including both severe and mild cases, some of which may need to be transferred to inpatient treatment. This study aimed to quantitatively evaluate the impact of short-term ambient air pollution exposure on outpatient visits for respiratory conditions in children. METHODS: This study employed data of the Second People's Hospital of Yichang from January 1, 2016 to December 31, 2023, to conduct a time series analysis. The DLNM approach was integrated with a generalized additive model to examine the daily outpatient visits of pediatric patients with respiratory illnesses in hospital, alongside air pollution data obtained from monitoring stations. Adjustments were made for long-term trends, meteorological variables, and other influencing factors. RESULTS: A nonlinear association was identified between PM_2.5, PM₁₀, O₃, NO₂, SO₂, CO levels and the daily outpatient visits for respiratory diseases among children. All six pollutants exhibit a hysteresis impact, with varying durations ranging from 4 to 6 days. The risks associated with air pollutants differ across various categories of children's respiratory diseases; notably, O₃ and CO do not show statistical significance concerning the risk of chronic respiratory conditions. Furthermore, the results of infectious respiratory diseases were similar with those of respiratory diseases. CONCLUSIONS Our results indicated that short-term exposure to air pollutants may contribute to an increased incidence of outpatient visits for respiratory illnesses among children, and controlling air pollution is important to protect children's health.
Humans ; China/epidemiology* ; Air Pollutants/analysis* ; Respiratory Tract Diseases/chemically induced* ; Child ; Child, Preschool ; Environmental Exposure/adverse effects* ; Air Pollution/analysis* ; Infant ; Male ; Particulate Matter/adverse effects* ; Female ; Ambulatory Care/statistics & numerical data* ; Outpatients/statistics & numerical data* ; Adolescent ; Infant, Newborn

Osteoarthritis (OA), the most prevalent joint disease of late life, is closely linked to cellular senescence. Previously, we found that the senescence of fibroblast-like synoviocytes (FLS) played an essential role in the degradation of cartilage. In this work, single-cell sequencing data further demonstrated that cartilage acidic protein 1 (CRTAC1) is a critical secreted factor of senescent FLS, which suppresses mitophagy and induces mitochondrial dysfunction by regulating SIRT3 expression. In vivo, deletion of SIRT3 in chondrocytes accelerated cartilage degradation and aggravated the progression of OA. Oppositely, intra-articular injection of adeno-associated virus expressing SIRT3 effectively alleviated OA progression in mice. Mechanistically, we demonstrated that elevated CRTAC1 could bind with NRF2 in chondrocytes, which subsequently suppresses the transcription of SIRT3 in vitro. In addition, SIRT3 reduction could promote the acetylation of FOXO3a and result in mitochondrial dysfunction, which finally contributes to the degradation of chondrocytes. To conclude, this work revealed the critical role and underlying mechanism of senescent FLSs-derived CRTAC1 in OA progression, which provided a potential strategy for the OA therapy.

Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
Animals ; Panax/chemistry* ; Ginsenosides/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Mice ; Male ; Alkaloids/pharmacology* ; Coptis/chemistry* ; Drug Synergism ; Insulin Resistance ; Mice, Inbred C57BL ; Humans ; Transcriptome/drug effects* ; Blood Glucose/metabolism* ; Hypoglycemic Agents/administration & dosage* ; Drugs, Chinese Herbal/administration & dosage* ; Hepatocytes/metabolism*

Objective:To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor.Methods:Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed.Results:Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively.Conclusions:SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

ObjectiveTo analyze the quantity-quality transfer of standard decoction of Ginseng Radix et Rhizoma（GRR） decoction pieces produced by fresh and traditional cutting， and to provide reference for quality control and application development of the decoction pieces produced by fresh cutting. MethodTen batches of representative GRR decoction pieces produced by fresh and traditional cutting and their standard decoctions were prepared by standard process， and high performance liquid chromatography（HPLC） fingerprint of the standard decoction was established and performed on an Agilent EC-C₁₈ column（4.6 mm×150 mm， 2.7 μm） with acetonitrile（A）-0.1% phosphoric acid aqueous solution（B） as the mobile phase for gradient elution（0-23 min， 18%-21%A； 23-35 min， 21%-28%A； 35-80 min， 28%-32%A）， and the detection wavelength was 203 nm. Then similarity evaluation， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） of fingerprint of the standard decoction were performed to screen the differential components with variable importance in the projection（VIP） value>1. Quantitative analysis was carried out on the screened known differential components， and combined with the indicators of the dry extract rate and the transfer rate， to explore the differences in the quantity-quality transfer between the standard decoction of GRR decoction pieces produced by fresh and traditional cutting. ResultThe fingerprint similarity of the standard decoction of GRR decoction pieces produced by fresh and traditional cutting was more than 0.950， and 18 common peaks were identified， including 9 identified common peaks. The results of PCA and PLS-DA showed that there were some differences in the contents of index components between the two standard decoctions. The contents of ginsenoside Rg₁， Re and Ro in GRR decoction pieces produced by fresh cutting were higher than those in traditional decoction pieces， while the contents of ginsenoside Rb₁， Rc ， Rb₂ and Rd were lower than those in traditional decoction pieces. The contents of ginsenoside Rg₁， Re， Rb₁ and Ro in the standard decoction of GRR decoction pieces produced by fresh cutting were higher than those in the standard decoction of traditional decoction pieces， while the contents of ginsenoside Rc ， Rb₂ and Rd were comparable between the two standard decoctions. Compared with the standard decoction of the traditional decoction pieces， the average transfer rates of ginsenoside Rg₁， Rb₁， Rc， Rb₂ and dry extract rate of the standard decoction of GRR decoction pieces produced by fresh cutting were significantly increased（P<0.05）， and the average transfer rate of ginsenoside Re and Rd also increased， but the difference was not statistically significant. ConclusionThe dry extract rate， content and transfer rate of index components of standard decoction of GRR decoction pieces produced by fresh cutting are better than those of the standard decoction of traditional decoction pieces， which can provides data support for the subsequent clinical application of fresh cutting products.

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Objective To investigate the neuroprotective effect of Huangpu Tongqiao Capsule(HPTQ)in a rat model of Wilson disease(WD)and explore the underlying mechanisms.Methods SD rat models of WD were established by feeding of copper-supplemented chow diet and drinking water for 12 weeks,and starting from the 9th week,the rats were treated with low-,moderate-and high-dose HPTQ,penicillamine,or normal saline by gavage on a daily basis for 3 weeks.Copper levels in the liver and 24-h urine of the rats were detected,and their learning and memory abilities were evaluated using Morris water maze test.HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus,and neuronal apoptosis was detected with TUNEL staining.Hippocampal expressions of endoplasmic reticulum stress(ERS)-mediated apoptosis pathway-related proteins GRP78,CHOP,caspase-12,cleaved caspase-9,and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR,immunofluorescence assay or Western blotting.Results Compared with normal control rats,the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine,impaired learning and memory abilities,obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons(P<0.01),with also lowered mRNA and protein expressions of GRP78,CHOP,caspase-12,cleaved caspase-9,and cleaved caspase-3 in the hippocampus(all P<0.01).Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level,improved learning and memory ability,alleviated neuronal damage and apoptosis in the hippocampus,and decreased hippocampal expressions of GRP78,CHOP,caspase-12,cleaved caspase-9,and cleaved caspase-3 in the rat models(P<0.01 or 0.05).Conclusion HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.

Objective We aimed to investigate the feasibility and method of constructing a traditional Chinese medicine(TCM)curative effect prediction model based on the data of Kechuanting acupoint plastering therapy in the treatment of bronchial asthma(asthma).Methods Data from the Chronic Disease Management Research Platform of 303 patients with asthma who were treated with Kechuanting acupoint plastering therapy for 6 weeks in the Department of Acupuncture and Rehabilitation of Jiangsu Hospital of Traditional Chinese Medicine from June to August 2018 to 2021 were selected.We used Phyton 3.10 for statistical analysis.After data preprocessing,the influencing factors were used to build models by Logistic regression,support vector machine,K-means clustering algorithm,Bayes algorithm,random forest method and Light gradient boosting machine(LightGBM)respectively,with the improvement of asthma control test score(ACT),forced expiratory volume in one second(FEV1)and exhaled nitric oxide(FeNO)as the outcome indicators.Then,the models were compared and analyzed.Subsequently,the superior model was used to establish the efficacy prediction model and verify its stability to obtain the accuracy rate and eliminate the relatively important factors.Results The accuracy rate of the Kechuanting acupoint plastering therapy curative effect prediction model established by the LightGBM model was more than 70%.Five important factors were selected,including allergic history,tabacco and alcohol abuse,plastering duration,ACT before treatment,and FeNO before treatment.According to the classification analysis and the relationship between the important factors and the outcome indicators,Kechuanting acupoint plastering therapy significantly improved the ACT of patients with no history of allergy,no tabacco and alcohol abuse,and poor ACT:5-15 points(P<0.05).Furthermore,Kechuanting acupoint plastering therapy improved FeNO more significantly in patients with more than 3 years of treatment than those with no more than 3 years(P<0.05).However,Kechuanting acupoint plastering therapy only improved FeNO in a few patients with poor asthma control levels(P<0.05)and severe airway inflammation(FeNO>50×10-9)(P>0.05).Conclusion Acupoint plastering application has a significant effect on improving the control level of asthma,but its effect on improving airway inflammation is limited.It is feasible to use data from the chronic disease management research platform to construct the prediction model.After optimization and testing,the predictive model established based on the data of this study may provide an effective evaluation tool for targeted clinical treatment.

Objective:To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) .Methods:The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed.Results:①326 patients were included in the study, 190 of whom were males. The median age was 63 years, and the median followup time was 37 months. R2-ISS can effectively predict prognosis, particularly for R-ISS Ⅱ patients. The median progression-free survival (PFS) time of R2-ISS Ⅰ, R2-ISS Ⅱ, R2-ISS Ⅲ, and R2-ISS Ⅳ was 52, 29, 20, and 15 months ( P<0.001), while the median overall survival (OS) time was 91, 60, 44, and 36 months ( P<0.001). Multifactor analysis revealed that ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, LDH increased, and age >65 years old were independent negative prognostic factors for OS. ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, and LDH were independent negative prognostic factors for PFS. ②The C-index score of R2-ISS was 0.724, higher than that of R-ISS (0.678), indicating high prediction efficiency. ③The median PFS for 1q+-related double-hit in R2-ISS Ⅲ and Ⅳ were 20, 15 months ( P=0.084) and the median OS were 35, 36 months ( P=0.786), respectively. In R2-ISS Ⅲ, there were twenty-seven cases of 1q+-related double-hit, sixty-one cases of 1q+ single abnormality, and sixty-eight cases with no 1q+. The median PFS for the three groups were 20, 18, and 21 months ( P=0.974), while the median OS was 35, 47, and 56 months ( P=0.042), respectively. Adjusting the assignment of 1q+ to 1, the median PFS and OS of different R2-ISS stages differed significantly after regrouping ( P<0.001) . Conclusions:The prognostic stratification value of R2-ISS is higher than R-ISS, particularly in the highly heterogeneous R-ISS Ⅱ population. Adjusting the assignment of the 1q+-related double-hit can improve R2-ISS, which should be validated in future studies with multi-center and expanded cases.

Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.