Aim To study the difference in hepatotox-icity of psoralen on normal rats and Yin-deficiency rats from the perspective of lipid metabolism,so as to help explain the mechanism of psoralen cautiously used in patients with Yin deficiency recorded in ancient books.Methods SD rats were randomly divided into the nor-mal control group(carboxymethyl cellulose-Na,CMC-Na),normal administration group(CMC-Na+psor-alen),Yin-deficiency control group(CMC-Na+thy-roxine)and Yin-deficiency administration group(CMC-Na+thyroxine+psoralen).The model of Yin-deficiency was established by thyroxine(1 mg·kg-1)for ten days,and then psoralen(200 mg·kg-1)was given for three days.The serum indexes related to liver injury were detected by automatic biochemical analy-zer,the morphological changes of liver tissue were ob-served using HE and oil red O staining,and the relative transcription levels of lipid metabolism related enzymes and mRNA of transporter and endoplasmic reticulum stress related factors were detected using Real-time PCR.Results After intragastric administration of psoralen for three days,compared with the normal group,the levels of serum alanine aminotransferase(ALT),aspartate transaminase(AST),total bile acid(TBA)and triglyeride(TG)in Yin deficiency group increased more significantly,while TC,ALB and TP de-creased more significantly,and liver HE and oil red O staining showed more obvious lipid degeneration.TG synthesis factors adrenocortical carcinoma(ACC),fatty acid synthase(FASN)and sterolregulatory element binding protein-1(SREBP-1)were down-regulated more significantly,TG transport factors mili-total pro-tein(MTP)and lipoprotein pipase(LPL)were down-regulated more evidently,fatty acid β-oxidation related factors carnitine palmitoyltransferase 1A(CPT1A),carnitine/organic cation transporter 2(OCTN2)and peroxisome proliferators-activated receptors-alpha(PPARα)were down-regulated more apparently,TC transporter adenosine triphosphate binding cassette transporter G8(ABCG8)and bile acid receptor farne-soid X receptor(FXR)were down-regulated more ob-viously,and endoplasmic reticulum stress factor activa-ting transcription factor 4(ATF4)was up-regulated more significantly.Conclusions Psoralen can cause more severe hepatotoxicity in Yin deficiency rats than that in normal administration group,and its mechanism may be related to the disorder of hepatic lipid metabo-lism,aggravation of hepatic cholestasis and steatosis,and activation of endoplasmic reticulum stress re-sponse.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response,oxidative stress and autophagy.Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis.This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway,offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.

Aim To study the difference in hepatotox-icity of psoralen on normal rats and Yin-deficiency rats from the perspective of lipid metabolism,so as to help explain the mechanism of psoralen cautiously used in patients with Yin deficiency recorded in ancient books.Methods SD rats were randomly divided into the nor-mal control group(carboxymethyl cellulose-Na,CMC-Na),normal administration group(CMC-Na+psor-alen),Yin-deficiency control group(CMC-Na+thy-roxine)and Yin-deficiency administration group(CMC-Na+thyroxine+psoralen).The model of Yin-deficiency was established by thyroxine(1 mg·kg-1)for ten days,and then psoralen(200 mg·kg-1)was given for three days.The serum indexes related to liver injury were detected by automatic biochemical analy-zer,the morphological changes of liver tissue were ob-served using HE and oil red O staining,and the relative transcription levels of lipid metabolism related enzymes and mRNA of transporter and endoplasmic reticulum stress related factors were detected using Real-time PCR.Results After intragastric administration of psoralen for three days,compared with the normal group,the levels of serum alanine aminotransferase(ALT),aspartate transaminase(AST),total bile acid(TBA)and triglyeride(TG)in Yin deficiency group increased more significantly,while TC,ALB and TP de-creased more significantly,and liver HE and oil red O staining showed more obvious lipid degeneration.TG synthesis factors adrenocortical carcinoma(ACC),fatty acid synthase(FASN)and sterolregulatory element binding protein-1(SREBP-1)were down-regulated more significantly,TG transport factors mili-total pro-tein(MTP)and lipoprotein pipase(LPL)were down-regulated more evidently,fatty acid β-oxidation related factors carnitine palmitoyltransferase 1A(CPT1A),carnitine/organic cation transporter 2(OCTN2)and peroxisome proliferators-activated receptors-alpha(PPARα)were down-regulated more apparently,TC transporter adenosine triphosphate binding cassette transporter G8(ABCG8)and bile acid receptor farne-soid X receptor(FXR)were down-regulated more ob-viously,and endoplasmic reticulum stress factor activa-ting transcription factor 4(ATF4)was up-regulated more significantly.Conclusions Psoralen can cause more severe hepatotoxicity in Yin deficiency rats than that in normal administration group,and its mechanism may be related to the disorder of hepatic lipid metabo-lism,aggravation of hepatic cholestasis and steatosis,and activation of endoplasmic reticulum stress re-sponse.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response,oxidative stress and autophagy.Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis.This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway,offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.

AIM:To investigate the potential impact of mitoNEET[mitochondrial protein containing Asn-Glu-Glu-Thr(NEET)sequence]on mitochondrial metabolism in brown adipocytes,and to elucidate its underlying mecha-nism.METHODS:An in vitro model of primary mouse brown adipocytes was established.Western blot were utilized to detect relevant proteins,and iron ion and ATP content was measured using kits.Mitochondrial membrane potential and re-active oxygen species(ROS)were assessed by fluorescence microscopy and flow cytometry.RESULTS:The expression of the ferroptosis-related protein ACSL4 increased by 1.13 times in ferroptosis inducer erastin treatment group,whereas the expression of SLC7A11 and GPX4 decreased by 27.33%and 25.33%,respectively,compared with control group(P<0.05).The expression of Nrf1,PGC-1α,MFN2 and UCP1 proteins,related to mitochondrial energy metabolism,de-creased by 20.98%,15.17%,15.03%and 34.22%,respectively(P<0.05).Additionally,the mitoNEET protein con-tent was significantly reduced by 42.14%(P<0.05).The iron ion content in erastin group was substantially increased by 1.80 times compared with control group.However,a notable decrease in ATP content of 14.95%was seen(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated a significant decrease in the mitochon-drial membrane potential of brown adipocytes in erastin group,with reductions of 52.18%and 61.31%(P<0.05),re-spectively.A substantial increase in mitochondrial ROS content of 80.97%was seen(P<0.05).Western blot analysis of overexpressed stable strains revealed a significant elevation in mitoNEET levels in brown adipocytes following lentivirus transfection,exhibiting an increase of 11.19 times(P<0.05),thus confirming successful transfection.The LV-mitoNEET group exhibited a significant decrease of 37.95%in the expression of ferroptosis-related protein ACSL4 in brown adipose cells compared with control group.Additionally,there was a notable increase of 77.82%and 66.3%in the expression of SLC7A11 and GPX4,respectively(P<0.05).Up-regulation was observed in the expression of MFN2(79.06%),PGC-1α(72.89%),Nrf1(40.14%),and UCP1(31.68%)(P<0.05).The test results demonstrated that the LV-mitoNEET group experienced a reduction of 43.5%in iron ion content compared with control group while exhibiting an increase of 33.5%in ATP content(P<0.05).The results obtained from fluorescence microscopy and flow cytometry demonstrated that mitoNEET overexpression led to a significant increase in the mitochondrial membrane potential of erastin-induced brown adipocytes,with increments of 17.61%and 96.05%,respectively.Additionally,mitoNEET overexpression effec-tively reduced the production of mitochondrial ROS by 24.48%(P<0.05).CONCLUSION:Our findings suggest that mitoNEET overexpression can effectively inhibit the disruption of mitochondrial energy metabolism caused by ferroptosis-induced death of brown adipocytes.

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml^-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml^-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml^-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostate-Specific Antigen ; Multiparametric Magnetic Resonance Imaging ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Biopsy ; Image-Guided Biopsy/methods*

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D_(eff)) and activation energy(E_a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D_(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E_a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.
Atractylodes ; Drugs, Chinese Herbal ; Hot Temperature ; Kinetics ; Rhizome

OBJECTIVES: To compare the application effect of microwave digestion - vacuum filtration - automated scanning electron microscopy (MD-VF-Auto SEM) method and plankton gene multiplex PCR system in the diagnosis of drowning. METHODS: Lung, liver and kidney tissue of 10 non-drowning cases and 50 drowning cases were prepared for further MD-VF-Auto SEM method analysis and plankton gene multiplex PCR system analysis. The positive detection rate of the two methods in each tissue was calculated. RESULTS: The positive rate of the MD-VF-Auto SEM method detecting diatoms in drowning cases was 100%, and few diatoms were detected in the liver and kidney tissues of 6 non-drowning cases. By using the plankton gene multiplex PCR system, the diatom positive rate of drowning cases was 84%, and all the non-drowning cases were negative. There were significant differences in the positive rate of the liver, kidney tissues between MD-VF-Auto SEM method and plankton gene multiplex PCR system (P<0.05), as well as the total positive rate of cases. However, no significant differences were found in the positive rates of lung tissues (P>0.05). CONCLUSIONS MD-VF-Auto SEM method is more sensitive than plankton gene multiplex PCR system in diatom test. But the plankton gene multiplex PCR system can also detect plankton other than diatoms. Combination of the two methods can provide a more reliable basis for the diagnosis of drowning.
Diatoms/genetics* ; Drowning/diagnosis* ; Humans ; Liver ; Lung ; Microscopy, Electron, Scanning ; Multiplex Polymerase Chain Reaction ; Plankton/genetics*

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Stroke/drug therapy*