ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective:To determine the expression of small nucleolar RNA host gene 16(SNHG16)in fibroblast-like synovio-cytes(FLS)of patients with rheumatoid arthritis(RA)and its role in the development of RA.Methods:RT-qPCR was performed to measure SNHG16,miR-182-5p and peroxisome proliferator-activated receptor gamma(PPARG)mRNA expression;dual-luciferase assay was performed to measure the interaction between SNHG16,miR-182-5p and PPARG mRNA;EdU and Transwell were per-formed to measure cell proliferation and invasion;Western blot was performed to measure PPARG protein level.Results:SNHG16 and PPARG mRNA expression were up-regulated and miR-182-5p expression was down-regulated in RA synovial tissue and human RA-FLS line(HFLS-RA).SNHG16 negatively targeted miR-182-5p expression and positively regulated PPARG(miR-182-5p target)expression.Silencing of SNHG16 inhibited the proliferation and invasion of HFLS-RA;down-regulation of miR-182-5p partially re-versed the inhibitory effect of SNHG16 silencing on cell proliferation and invasion;overexpression of PPARG partially reversed the in-hibitory effect of up-regulation of miR-182-5p on the proliferation and invasion of HFLS-RA.Conclusion:Silencing SNHG16 target-ing miR-182-5p/PPARG axis inhibits the proliferation and invasion of HFLS-RA.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

Objective:To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism.Methods:A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed.Results:The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c. 1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+ PVS1_Supporting+ PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. Conclusion:The c. 1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

Objective:To evaluate the consistency between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) in the measurement of body composition in children aged 6-17 years in China.Methods:Fat-free mass, fat mass and fat mass percentage were measured by both BIA and DXA in 1 161 children. t-test or Wilcoxon paired test was used to evaluate the different outcome of the two methods. The correlation and consistency between the methods were evaluated by Spearman correlation coefficients ( r) and Bland-Altman analysis. Results:Body compositions measured by BIA was positively correlated with those measured by DXA (fat mass r=0.95, fat-free mass r=0.98, fat mass percentage r=0.86, all P<0.05). Comparing with DXA, BIA underestimate children's fat mass [the mean difference is -3.15 kg, and the SD is 2.35 kg, 95% limits of agreement (LoA): -7.74-1.45 kg] and fat mass percentage (the mean difference is -8.45%, and the SD is 4.63%, 95% LoA: -17.53%-0.64%). Conclusions:Body compositions measured by BIA was highly positively correlated with those measured by DXA. BIA has certain application value in the measurement of body fat mass and fat-free mass of children aged 6-17 years.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Objective To clarify and analyze the reasons for failure in screening healthy menopausal female in a bioequivalence trial.Methods To summarize and clarify the data of 185 healthy menopausal female subjects participating in a bioequivalence trial of estradiol valerate conducted,and summarize the reasons for screening failure.Results The main reasons for screening failure include laboratory tests(32.04％),gynecological transvaginal color Doppler ultrasound(16.57％),vital signs(14.36％),chest computed tomography(CT,11.60％),and medical history/medication history(7.73％).Conclusion Screening failures in healthy menopausal female subjects were characterized mainly by abnormal gynecological transvaginal color Doppler ultrasound and non-compliance with basal hormone levels compared to generally healthy subjects.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To investigate the protective effects of Huoxue Rongluo Decoction on hypoxic-ischemic brain damage (HIBD) rats; To clarify the expression of AMPK signaling pathway during HIBD injury and repair.Methods:On the basis of the hypoxia ischemia reperfusion model, an improved hypoxia bottle was used to establish a full-term HIBD rat model. Totally 60 successfully modeled mice were divided into model group and TCM group using a random number table method, with 30 mice in each group and 30 mice in a control group. Two hours before surgery, TCM group was orally administered with Huoxue Rongluo Decoction 1.17 g/100 g (equivalent dose). The control group and model group were orally administered with equal volume of physiological saline. Two hours after surgery, it was orally administered again, twice a day, for consecutive 5 d. Behavioral tests (convulsion assessment, Longa score, suspension test, water maze test) were used to evaluate the motor nerve function and long-term learning ability of young rats in different groups. HE staining and electron microscopy were used to observe the pathological changes of brain tissue and mitochondrial damage. Evans blue (EB) staining and brain water content measurement were used to detect blood-brain barrier permeability and brain edema. The expression of AMPK signaling pathway related genes in brain tissues of different groups of young rats was detected by PCR array technique.Results:Compared with the model group, the convulsions of the rats in the TCM group were improved, the Longa score was significantly reduced, the grip strength test score and suspension time were significantly improved, the escape latency was significantly shortened, and the number of crossing platforms significantly increased ( P<0.05); the degree of neuronal and mitochondrial damage in the TCM group was reduced, and cerebral vascular permeability and brain water content were significantly reduced ( P<0.01). The results of PCR array showed that compared with the control group, 2 genes were significantly up-regulated and 12 genes were significantly down-regulated in the brain tissue of the model group; compared with TCM group, 15 genes were relatively down-regulated in the model group. Conclusion:Huoxue Rongluo Decoction can significantly reduce the degree of brain injury after HIBD, improve the motor nerve function and long-term learning and cognitive ability of model rats, and its damage repair mechanism is related to the expression regulation of AMPK signaling pathway related genes.