This study employed ultrahigh-performance liquid chromatograph-hybrid quadrupole orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) to detect the chemical constituents of traditional Chinese medicine in Sizi Dingchuan granules. Network pharmacology and molecular docking techniques were then utilized to predict the effects of Sizi Dingchuan granules on bronchial asthma, along with its target molecules and signaling pathways. UHPLC analysis identified 172 compounds, including 84 flavonoids, 38 organic acids and their derivatives, 22 phenylpropanoids, 16 organic oxygen compounds, 3 phenolic compounds, 2 terpenoids, 2 sugars and glycosides, and 5 other compounds. Typical compound fragmentation patterns were documented. Using network pharmacology methods, 117 compounds were ultimately selected for target prediction, establishing a “drug-component-target-disease” network, which revealed that quercetin, schisandrin A, baicalin, gomisin H, and baicalin exhibit multiple targets related to bronchial asthma, suggesting that they may be the active components responsible for the compound’s efficacy in treating this condition. Protein-protein interaction analysis identified core targets including TNF, IL-6, JAK2, STAT3, BCL2, CASP3, and EGFR, primarily clustered within the JAK-STAT signaling pathway. This suggests that the main components of Sizi Dingchuan granules may regulate the balance between Th17 and Treg cells, as well as Th1 and Th2 cell differentiation, by modulating the JAK-STAT signaling pathway, thereby exerting a positive therapeutic effect on bronchial asthma.

Objective To investigate the status of quality control of medical electron linear accelerators and radiation protection of machine rooms housing these accelerators in Shandong Province. Methods A total of 52 medical electron linear accelerators in 40 hospitals across Shandong Province were selected as the study subjects. A series of indicators were tested according to relevant quality control testing specifications and radiation protection testing standards. Statistical analysis was performed using SPSS 25.0. Results The five performance indicators of the 52 medical electron linear accelerators, including offset of the radiation beam axis relative to the equal center point (hereinafter referred to as the equal center point offset), dose deviation, output dose repeatability, output dose linearity, and uniformity of the square X-ray radiation field (10 cm × 10 cm), all had a qualified rate of 100%. The dose deviation of accelerators in secondary hospitals was superior to that in tertiary hospitals. The output dose linearity and uniformity of the square X-ray radiation field of accelerators in tertiary hospitals were superior to those in secondary hospitals. All machine rooms housing the investigated medical electron linear accelerators were qualified in radiation protection testing. Conclusion The performance indicators of the medical electron linear accelerators investigated in this study and the radiation protection of machine rooms all complied with national standards. Relevant hospitals should continue to strictly implement radiation protection standards and strengthen the supervision of the equipment sites.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis,leading to impaired liver function.For tumors with malignant obstructive jaundice,biliary drainage is often performed before surgery in clinical practice.Currently,the commonly used drainage methods are percutaneous transhepatic biliary drainage(PTBD)and endoscopic retrograde biliary drain-age(ERBD),but there are controversies over the advantages and disadvantages of the two drainage methods.PTBD drainage can often lead to tumor implantation metastasis,but the underlying mechanism remains unclear.We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcino-ma patients,subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo.The experiments included benign gallstones group(30 cases)as a negative control,PTBD group(14 cases)and ERBD group(13 cases).Tumorsphere formation was i-dentified in 3 cases(23％)among the 13 cases of ERBD group,in 6 cases(42％)among the 14 cases of PTBD group,but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group.The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group.Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was sig-nificantly higher than that in the ERBD group.Tumor cells in PTBD bile possessed stronger tumorigenici-ty compared with the ERBD group.Mechanically,stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group.Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group,indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells.The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells,suggesting potential post-transcriptional regu-lation on Nanog mRNA.The Nanog m6A level was higher in PTBD group tumor cells compared to the ERBD group.Analysis of methyltransferases and demethylases,ALKBH5(α-ketoglutarate dependent dioxygenase alkb family homolog 5)mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m6A level of Nanog.ALKBH5 knockdown led to an increase in the m6A level of Nanog,while ALKBH5 overexpression decreased the m6A level of Nanog.Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity,whereas ALKBH5 overexpression reduced it.Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog,whereas overexpressing ALKBH5 downregulated them.ALKBH5 mediated the demethylation modification of Nanog mRNA,and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog's m6A modification.Overexpressing ALKBH5 decreased tumorsphere growth,while ALKBH5 knockdown increased it,which was subsequently reduced by the simultaneous Nanog knockdown again.In sum,tumor cells in PTBD and ERBD drainage bile from hilar cholangiocar-cinoma patients exhibited tumorigenicity.Compared to the ERBD group,tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog's m6A modification to upregulate Nanog expression levels,resulting in stronger tumorigenicity.These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.

Hilar cholangiocarcinoma is insidious in onset and often causes obstructive jaundice due to bile stasis,leading to impaired liver function.For tumors with malignant obstructive jaundice,biliary drainage is often performed before surgery in clinical practice.Currently,the commonly used drainage methods are percutaneous transhepatic biliary drainage(PTBD)and endoscopic retrograde biliary drain-age(ERBD),but there are controversies over the advantages and disadvantages of the two drainage methods.PTBD drainage can often lead to tumor implantation metastasis,but the underlying mechanism remains unclear.We detected tumor cells in PTBD and ERBD bile samples from hilar cholangiocarcino-ma patients,subsequently explored their tumorigenicity and mechanisms through tumorsphere assay in vitro and xenograft tumor models in vivo.The experiments included benign gallstones group(30 cases)as a negative control,PTBD group(14 cases)and ERBD group(13 cases).Tumorsphere formation was i-dentified in 3 cases(23％)among the 13 cases of ERBD group,in 6 cases(42％)among the 14 cases of PTBD group,but there were no tumor cells or formed tumorspheres in the 30 cases of benign gallstone group.The tumor sphere formation ability of cells in the PTBD group was significantly higher than that in ERBD group.Subcutaneous xenograft tumor assays showed that tumor growth in the PTBD group was sig-nificantly higher than that in the ERBD group.Tumor cells in PTBD bile possessed stronger tumorigenici-ty compared with the ERBD group.Mechanically,stem cell transcription factor Nanog mRNA levels were significantly higher in the PTBD group compared to the ERBD group.Both tumorsphere formation and xenograft tumor growth were reduced by Nanog knockdown in three cases of the PTBD group,indicating the important roles of Nanog in tumorigenicity of PTBD group tumor cells.The half-life of Nanog mRNA was longer in PTBD group cells than in ERBD group cells,suggesting potential post-transcriptional regu-lation on Nanog mRNA.The Nanog m6A level was higher in PTBD group tumor cells compared to the ERBD group.Analysis of methyltransferases and demethylases,ALKBH5(α-ketoglutarate dependent dioxygenase alkb family homolog 5)mRNA levels were lower in the PTBD group than in the ERBD group and significantly correlated with the m6A level of Nanog.ALKBH5 knockdown led to an increase in the m6A level of Nanog,while ALKBH5 overexpression decreased the m6A level of Nanog.Dual-luciferase activity assays demonstrated that ALKBH5 knockdown significantly enhanced luciferase activity,whereas ALKBH5 overexpression reduced it.Further studies confirmed that ALKBH5 knockdown upregulated both the mRNA and protein levels of Nanog,whereas overexpressing ALKBH5 downregulated them.ALKBH5 mediated the demethylation modification of Nanog mRNA,and the lower levels of ALKBH5 expression in the PTBD group promoted Nanog's m6A modification.Overexpressing ALKBH5 decreased tumorsphere growth,while ALKBH5 knockdown increased it,which was subsequently reduced by the simultaneous Nanog knockdown again.In sum,tumor cells in PTBD and ERBD drainage bile from hilar cholangiocar-cinoma patients exhibited tumorigenicity.Compared to the ERBD group,tumor cells in PTBD bile with lower ALKBH5 expression levels enhanced Nanog's m6A modification to upregulate Nanog expression levels,resulting in stronger tumorigenicity.These findings are significant for elucidating propensity to tumor implantation metastasis from PTBD drainage.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

Objective:To investigate the clinical efficacy and safety of venetoclax(VEN)in combination with hypomethylating agent(HMA)in the treatment of patients with high-risk myelodysplastic syndromes(MDS).Methods:A total of 30 patients with high-risk MDS who received the combination of VEN and HMA from March 2019 to November 2022 were included.The overall response rate(ORR),modified overall response rate(mORR),overall survival(OS),progression-free survival(PFS),and adverse events of all included patients were evaluated.Results:Among the 30 high-risk MDS patients treated with VEN combined with HMA regimen,24 cases achieved complete response(CR)/marrow complete response(mCR),2 cases achieved partial response(PR),the ORR was 24/30,the median OS was 28.1 months,and the median PFS was 28.1 months.In addition,patients who achieved complete remission/marrow complete remission after treatment had a significantly longer OS than those who did not.Moreover,12 patients were treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT).There were grade 3 or higher hematologic adverse events including thrombocytopenia(14 cases),neutropenia(14 cases),febrile neutropenia(10 cases)and anemia(7 cases)as well as gastrointestinal adverse events of any grade,such as vomiting(7 cases),diarrhea(5 cases),and constipation(4 cases).Conclusion:VEN in combination with HMA is an effective and safe treatment option in patients with high-risk MDS.This regimen combined with allo-HSCT can improve the prognosis of these patients.Continuous attention to the monitoring and management of adverse events is essential for the patients'safety in this combination therapy.

AIM To study endophytic fungi from Scutellaria baicalensis Georgi.and the enzyme inhibitory activities of their secondary metabolites.METHODS Six different media were used to isolate and purify endophytic fungi from S.baicalensis by tissue homogenate method.The activities of secondary metabolites were evaluated by targeting different enzymes.The highly active strains were identified by molecular biology combined with morphology,and the highly active chemical components were tracked and separated by modern chromatographic separation technology.RESULTS Sixty-four endophytic fungal strains were isolated from S.baicalensis,and one hundred and twenty-eight secondary metabolites were obtained by fermentation.The samples with certain inhibitory activities against adenosine deaminase(ADA),β-lactamase and tyrosinase(TYR)accounted for 14.06%,3.91%and 18.75%,respectively.Strain HTS-23-2 showed high TYR inhibitory activity,and 99%homology with Aspergillus flavus by molecular identification.One compound was isolated from the fermentation samples and identified as kojic acid.CONCLUSION S.baicalensis harbors a rich diversity of endophytic fungi,which serve as a valuable resource for active substances.