Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

Background/Aims: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is an essential tool for tissue acquisition in solid pancreatic tumors. Rapid on-site evaluation (ROSE) by cytologists ensures diagnostic accuracy. However, the universal application of the ROSE is limited by its availability. Therefore, we aimed to investigate the feasibility of determining the end of the procedure based on the results of in-room cytological evaluation by trained endosonographers (IRCETE). Methods: A training course focusing on the cytological interpretation of common pancreatic tumors was provided to the three endosonographers. After training, the decision to terminate EUS-FNB was made based on IRCETE results. The diagnostic accuracy, concordance rate of diagnostic categories, and sample adequacy were compared with those determined by board-certified cytologists and macroscopic on-site evaluation (MOSE). Results: We enrolled 65 patients with solid pancreatic tumors, most of whom were malignant (86.2%). The diagnostic accuracy was 90.8% when the end of the procedure was determined based on IRCETE, compared to 87.7% and 98.5% when determined by MOSE and cytologists, respectively (p=0.060). Based on the cytologists’ results, the accuracy of IRCETE in diagnostic category interpretation was 97.3%. Conclusions In the absence of ROSE, IRCETE can serve as a supplementary alternative to MOSE in determining the end of tissue sampling with a high accuracy rate.

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

Objective To compare effectiveness between the modified and traditional pressure-overload myocardial hypertrophy(POMH) model by abdominal aorta coarctation (AAC) method. Methods Totally 45 rats were divided into three groups(n = 15 per group), sham group, traditional group, and modified group. In the traditional group, the diameter ol the abdominal aorta was narrowed to 0. 70 mm through a midline incision for 4 weeks; in the modified group, the diameter of the abdominal aorta was narrowed above the left kidney to 0. 45 mm for 1 week, and then the narrowing was lifted postoperatively. The cardiac index, heart weight (HW) /body weight (BW) and left ventricular index, left ventricular weight (LVW)/BW were measured from the heart specimens, and the cross-sectional area of cardiac myocytes, myocardial collagen area, and myocardial collagen area Iraction were measured in the pathological sections by HE staining and Masson staining. Results Compared with the sham group, the differences in end-systolic interventricular septum thickness (IVSs), left ventricular end-systolic posterior wall thickness (LVPWs), HW/BW, LVW/BW, cardiomyocyte cross-sectional area, myocardial collagen area, myocardial collagen area fraction, and brain natriuretic peptide (BNP) expression levels were statistically significant (P<0. 05) in the modilied and traditional groups of rats. The differences in these indices were not statistically significant between the modified and traditional groups (P>0. 05). Conclusion The modified abdominal aortic constriction method used in this experiment is time-saving, stable, homogeneous and easy to replicate, and is a more ideal approach to establish a rat model of POMH.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

Objective To investigate the effects of rhynchophylline on methamphetamine-dependent SH-SY5Y cells model and microRNA-375-3p(miR-375-3p)/embryonic lethal abnormal vision drosophila-like 4(Elavl4)expression.Methods A methamphetamine-dependent cell model by maximum safe dose induction was established.The cells were divided into normal group(complete culture medium),control group(complete culture medium+400 μmol·L-1 rhynchophylline incubated for 48 h),model group(complete culture medium+100 μmnol·L-1 methamphetamine incubated for 48 h)and experimental group(complete culture medium+400 μmol·L-1 rhynchophylline incubated for 15 min,then 100 μmol·L-1 methamphetamine incubated for 48 h).The cyclic adenosine monophosphate(cAMP)and 5-hydroxytryptamine(5-HT)expression were detected by enzyme-linked immunosorbent assay(ELISA),miR-375-3p expression was detected by quantitative real time polymerase chain reaction(qRT-PCR),and Elavl4 expression was detected by Western blot.Results The cAMP expression levels of normal group,control group,model group and experimental group were(6.33±0.93),(6.57±1.12),(10.89±1.03)and(7.81±1.32)pmol·mg-1;5-HT were(682.46±17.32),(690.31±15.09),(510.11±27.67)and(649.99±21.42)pg·mL-1;miR-375-3p expression were 1.00±0.13,1.13±0.24,3.48±0.18 and 1.58±0.19;Elavl4 expression were 1.00±0.05,0.89±0.10,0.50±0.09 and 0.90±0.11,respectively.The differences between above indicators in model group and normal group were statistically significant(P＜0.01,P＜0.05);the differences between above indicators in experimental group and model group were statistically significant(P＜0.01,P＜0.05).Conclusion This study preliminarily established a methamphetamine-dependent cell model,and also found that rhynchophylline may regulate miR-375-3p/Elavl4 expression to antagonize methamphetamine addiction.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.