OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

Objective:To explore the influencing factors of the therapeutic effect of fiberoptic bronchoscopic alveolar lavage (BAL) in children with severe pneumonia (SP), and the relationship between pulmonary ultrasound parameters and the clearance rates of procalcitonin (PCT) and C-reactive protein (CRP) after treatment.Methods:A total of 284 children with SP admitted to the Yan ′an People′s Hospital from February 2019 to October 2023 were selected as the research subjects; According to the prognosis after 30 days of treatment, they were divided into the good prognosis group ( n=213) and the poor prognosis group ( n=71). The changes of PCT clearance rate, CRP clearance rate and Lung Ultrasound Score (LUS) before and after treatment were compared between the two groups. The correlation between indexes was analyzed using the multiple linear regression (MLR) model. The odds ratio ( OR) of risk factors was calculated using the multivariate logistic regression model. The dose-response relationship was evaluated using the restricted cubic spline (RCS) model. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of each index for poor prognosis after 30 days of treatment. Results:Compared with the good prognosis group, the CRP clearance rate and PCT clearance rate of children in the poor prognosis group were lower 7-14 days after treatment (all P<0.05), and the LUS was higher (all P<0.05). The MLR analysis results showed that LUS was negatively correlated with both CRP clearance rate and PCT clearance rate (all P<0.05), and there was still a significant correlation after adjusting for confounding factors (all P<0.05). The results of logistic regression analysis showed that after excluding confounding factors (Model 4), LUS, PCT clearance rate, and CRP clearance rate were independent risk factors for poor prognosis in children with SP after 30 days of treatment (all P<0.05). The results of RCS analysis showed that there was a nonlinear relationship between the continuous changes of LUS, PCT clearance rate and CRP clearance rate and the risk of poor prognosis in children with SP after 30 days of treatment (nonlinear tests all P<0.001). The combined accuracy of LUS, PCT clearance rate and CRP clearance rate in predicting the poor prognosis of children with SP after 30 days of treatment was relatively high ( P<0.05, AUC>0.75). Conclusions:The clearance rates of LUS and CRP, as well as PCT, are all associated with poor prognosis in children with SP, and the decreased clearance rates of CRP and PCT are independent factors for predicting the increase of LUS. The combined clearance rates of LUS and CRP, as well as PCT, can accurately predict the risk of poor prognosis in children.

Objective:To explore the influencing factors of the therapeutic effect of fiberoptic bronchoscopic alveolar lavage (BAL) in children with severe pneumonia (SP), and the relationship between pulmonary ultrasound parameters and the clearance rates of procalcitonin (PCT) and C-reactive protein (CRP) after treatment.Methods:A total of 284 children with SP admitted to the Yan ′an People′s Hospital from February 2019 to October 2023 were selected as the research subjects; According to the prognosis after 30 days of treatment, they were divided into the good prognosis group ( n=213) and the poor prognosis group ( n=71). The changes of PCT clearance rate, CRP clearance rate and Lung Ultrasound Score (LUS) before and after treatment were compared between the two groups. The correlation between indexes was analyzed using the multiple linear regression (MLR) model. The odds ratio ( OR) of risk factors was calculated using the multivariate logistic regression model. The dose-response relationship was evaluated using the restricted cubic spline (RCS) model. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of each index for poor prognosis after 30 days of treatment. Results:Compared with the good prognosis group, the CRP clearance rate and PCT clearance rate of children in the poor prognosis group were lower 7-14 days after treatment (all P<0.05), and the LUS was higher (all P<0.05). The MLR analysis results showed that LUS was negatively correlated with both CRP clearance rate and PCT clearance rate (all P<0.05), and there was still a significant correlation after adjusting for confounding factors (all P<0.05). The results of logistic regression analysis showed that after excluding confounding factors (Model 4), LUS, PCT clearance rate, and CRP clearance rate were independent risk factors for poor prognosis in children with SP after 30 days of treatment (all P<0.05). The results of RCS analysis showed that there was a nonlinear relationship between the continuous changes of LUS, PCT clearance rate and CRP clearance rate and the risk of poor prognosis in children with SP after 30 days of treatment (nonlinear tests all P<0.001). The combined accuracy of LUS, PCT clearance rate and CRP clearance rate in predicting the poor prognosis of children with SP after 30 days of treatment was relatively high ( P<0.05, AUC>0.75). Conclusions:The clearance rates of LUS and CRP, as well as PCT, are all associated with poor prognosis in children with SP, and the decreased clearance rates of CRP and PCT are independent factors for predicting the increase of LUS. The combined clearance rates of LUS and CRP, as well as PCT, can accurately predict the risk of poor prognosis in children.

Based on the previous transcriptomic experimental data of Trichinella spiralis(T.spira-lis)in this study,the larval stage specific gene TP12446 was screened and its identity in the ubiq-uitin ligase RNF family was predicted.In the study,bioinformatics methods were used to analyze its physicochemical properties and its activity to lay the foundation for further exploring the func-tion of TP12446 gene.The physicochemical properties and protein structure of TP12446 protein were predicted by bioinformatics.Its ubiquitin ligase activity was also verified by ubiquitination re-actions in vitro.The expression characteristics of TP12446 protein in different stage of T.spiralis infection were analyzed by qPCR and Western blot.Bioinformatics analysis showed that TP12446 protein was composed of 453 amino acids and its molecular weight was 51.48 kDa.The protein had a transmembrane structure and contained signal peptides.The results indicated that it was a secre-tory protein and mainly located in the cytoplasmic membrane.The protein structure analysis re-vealed that the protein contained RING and PA domain,its secondary structure was mainly com-posed of α-helix and irregular crimp and there were 10 B cell epitopes on TP12446 protein.The prediction of glycosylation and phosphorylation sites indicated that TP12446 protein contained 38 potential phosphorylation sites.Results of PPI interaction protein prediction showed that TP12446 protein had strong interaction with Usp8,Tmem37,Otub1,Otub2,Ubox5 and CD151.The results of qPCR and Western blot showed that TP12446 gene expression was the highest in the larva stage of T.spiralis,the activity of ubiquitin ligase was verified by ubiquitination reaction in vitro.TP12446 protein was a secretory hydrophobic protein with E3 ubiquitin ligase activity,which was involved in regulating cell cycle and apoptosis.

Objective:To investigate role of miR-4738-3p in targeting tryptophan 2,3-dioxygenase 2(TDO2)to regulate energy metabolism and inhibit immune escape in thyroid cancer cells.Methods:A total of 68 cases of thyroid cancer tissues and their corresponding adjacent non-cancerous tissues were collected,expressions of miR-4738-3p and TDO2 in tissues and cell lines were de-tected by qRT-PCR,relationship between miR-4738-3p expression and clinicopathological characteristics was analyzed.Effects of miR-4738-3p and TDO2 on proliferation,migration,invasion,energy metabolism and immune escape of TPC-1 and BCPAP cells were examined through CCK-8,clone formation,wound healing,Transwell experiments,biochemical analyses,ELISA and NK cell co-culture experiments,targeting relationship between miR-4738-3p and TDO2 was validated by dual luciferase reporter gene assay.In vivo xenograft experiments and immunohistochemical detections were conducted to observe effects of miR-4738-3p on tumorigenesis and expression of immune escape-related proteins in TPC-1 and BCPAP cells.Results:miR-4738-3p was lowly expressed(P<0.05),while TDO2 was highly expressed in thyroid cancer(P<0.05).Tumor size,lymph node metastasis and TNM staging were correlated with expression of miR-4738-3p(P<0.05).Compared with miR-NC group,miR-4738-3p mimics group exhibited decreased prolifera-tion,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions,tumor volume,mass,Ki-67,TDO2 and PD-L1 expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).miR-4738-3p inhibitor group showed increased proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Binding sites were identified between miR-4738-3p and TDO2,and their expression were negatively correlated(r=-0.485 3,P<0.001).Compared with sh-NC group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were decreased in sh-TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).Compared with Scrambled group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were increased in TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Conclusion:miR-4738-3p targets TDO2 to regulate energy metabolism,inhibiting thyroid cancer cell proliferation,metastasis and immune escape.

Objective:To investigate role of miR-4738-3p in targeting tryptophan 2,3-dioxygenase 2(TDO2)to regulate energy metabolism and inhibit immune escape in thyroid cancer cells.Methods:A total of 68 cases of thyroid cancer tissues and their corresponding adjacent non-cancerous tissues were collected,expressions of miR-4738-3p and TDO2 in tissues and cell lines were de-tected by qRT-PCR,relationship between miR-4738-3p expression and clinicopathological characteristics was analyzed.Effects of miR-4738-3p and TDO2 on proliferation,migration,invasion,energy metabolism and immune escape of TPC-1 and BCPAP cells were examined through CCK-8,clone formation,wound healing,Transwell experiments,biochemical analyses,ELISA and NK cell co-culture experiments,targeting relationship between miR-4738-3p and TDO2 was validated by dual luciferase reporter gene assay.In vivo xenograft experiments and immunohistochemical detections were conducted to observe effects of miR-4738-3p on tumorigenesis and expression of immune escape-related proteins in TPC-1 and BCPAP cells.Results:miR-4738-3p was lowly expressed(P<0.05),while TDO2 was highly expressed in thyroid cancer(P<0.05).Tumor size,lymph node metastasis and TNM staging were correlated with expression of miR-4738-3p(P<0.05).Compared with miR-NC group,miR-4738-3p mimics group exhibited decreased prolifera-tion,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions,tumor volume,mass,Ki-67,TDO2 and PD-L1 expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).miR-4738-3p inhibitor group showed increased proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production,ATP/ADP ratio,TDO2 mRNA and protein expressions(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Binding sites were identified between miR-4738-3p and TDO2,and their expression were negatively correlated(r=-0.485 3,P<0.001).Compared with sh-NC group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were decreased in sh-TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were increased(P<0.05).Compared with Scrambled group,proliferation,clone formation,migration,invasion ability,glucose uptake,lactate production and ATP/ADP ratio were increased in TDO2 group(P<0.05),NAD+/NADH ratio,IFN-γ,TNF-α levels and NK cell killing rate were decreased(P<0.05).Conclusion:miR-4738-3p targets TDO2 to regulate energy metabolism,inhibiting thyroid cancer cell proliferation,metastasis and immune escape.

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Based on the previous transcriptomic experimental data of Trichinella spiralis(T.spira-lis)in this study,the larval stage specific gene TP12446 was screened and its identity in the ubiq-uitin ligase RNF family was predicted.In the study,bioinformatics methods were used to analyze its physicochemical properties and its activity to lay the foundation for further exploring the func-tion of TP12446 gene.The physicochemical properties and protein structure of TP12446 protein were predicted by bioinformatics.Its ubiquitin ligase activity was also verified by ubiquitination re-actions in vitro.The expression characteristics of TP12446 protein in different stage of T.spiralis infection were analyzed by qPCR and Western blot.Bioinformatics analysis showed that TP12446 protein was composed of 453 amino acids and its molecular weight was 51.48 kDa.The protein had a transmembrane structure and contained signal peptides.The results indicated that it was a secre-tory protein and mainly located in the cytoplasmic membrane.The protein structure analysis re-vealed that the protein contained RING and PA domain,its secondary structure was mainly com-posed of α-helix and irregular crimp and there were 10 B cell epitopes on TP12446 protein.The prediction of glycosylation and phosphorylation sites indicated that TP12446 protein contained 38 potential phosphorylation sites.Results of PPI interaction protein prediction showed that TP12446 protein had strong interaction with Usp8,Tmem37,Otub1,Otub2,Ubox5 and CD151.The results of qPCR and Western blot showed that TP12446 gene expression was the highest in the larva stage of T.spiralis,the activity of ubiquitin ligase was verified by ubiquitination reaction in vitro.TP12446 protein was a secretory hydrophobic protein with E3 ubiquitin ligase activity,which was involved in regulating cell cycle and apoptosis.

Objective:The aim of this study was to analyze the registration status of osteoporosis drug clinical trials in China, providing a reference for the research and development of therapeutic drugs for osteoporosis.Methods:Using the Drug Clinical Trial Registration and Information Publication Platform on the website of the State Drug Administration as the search platform, we retrieved the information on the public announcement of drug clinical trials with osteoporosis as an indication, and the search period was limited from 2013 to February 2025.Researchers extracted the key information and performed statistics.Results:A total of 182 registered osteoporosis drug clinical trial projects were collected.The main target indications were predominantly osteoporosis in postmenopausal women, and there were relatively few trials targeting the elderly subjects.56.0%(102/182)of the registered trials were bioequivalence studies, and 21.4%(39/182)were phase I clinical studies.Conclusions:The number of registered trials and the research and development process of domestic osteoporosis drug clinical trials in China have shown a stable trend in general, and the types of trials are mainly concentrated in bioequivalence studies and early clinical studies.In order to further meet the medication needs of domestic patients, China still needs to increase the research and development efforts of innovative osteoporosis drugs.

Objective:To investigate the role of the Brock, Mayo, and PKUPH combined model in risk stratification of solitary pulmonary nodules (SPNs) in health check-up population.Methods:An ambispective cohort study was conducted on 668 eligible SPNs cases from the health management center in Chongqing General Hospital from June 2018 to June 2019. The exposure condition was prospectively followed or historically retrospected, and the clinical outcomes were prospectively followed. SPNs were classified into benign and malignant groups. Descriptive statistics and univariate analysis were performed to assess the differences in risk characteristics between two groups. Receiver operating characteristic (ROC) curve, clinical decision curve, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate and compare the predictive performance, clinical utility, and calibration of the combined model versus individual Brock, Mayo, and PKUPH models.Results:Among the 668 SPNs cases, 82 (12.28%) were diagnosed as malignant. Age, sex, smoking history, extrapulmonary tumor history, diameter, upper lobe, clear border and spicule sign in the malignant group were significantly different from those in the benign group (all P<0.05). The combined model demonstrated superior predictive performance, clinical utility, and calibration compared to the best-performing individual Brock model [Area under the curve (AUC): 0.88 (95% CI: 0.84-0.92) vs 0.86 (95% CI: 0.82-0.91)]. Besides, multi-grade risk stratification enabled by the combined model was better than binary classification, with the malignant rate of the four risk levels were 0.60%, 4.62%, 14.58% and 56.07%, respectively. Conclusion:The combined model addresses the limitations of individual models in SPNs risk stratification for health examination populations, improving predictive performance, clinical utility, and calibration, while proposing a superior multi-grade risk stratification system.