Bile-processed Coptidis Rhizoma（B-pCR）， first documented in Shengji Zonglu， is a unique processed products of Coptidis Rhizoma（CR） characterized by "mutual enhancement processing" and "enhancing the cold property of cold-natured herbs". Pig bile can enhance the bitter and cold properties of CR， yielding potent effects in purging excess fire from the liver and gallbladder. The processing increases the dissolution of alkaloids such as berberine， coptisine， and palmatine， while introducing bile acids from pig bile， including taurine-type and glycine-type cholic acids. This enhances its pharmacological effects， such as antipyretic activity， regulation of glucose and lipid metabolism disorders， and intestinal absorption. Traditional processing techniques and quality standards for B-pCR are outlined in the Shanghai Traditional Chinese Medicine（TCM） Decoction Pieces Processing Standard and the Gansu TCM Processing Standard. However， incomplete specifications for critical process parameters and quality criteria significantly impact its production and clinical application. A review of research over the past two decades on the processing history， process optimization， quality evaluation， material basis， and changes in pharmacological effects and properties of B-pCR reveals that the pretreatment method and dosage of pig bile， and processing temperature are key factors influencing its quality. Furthermore， current quality standards lack specific indicators. Additionally， the enhancement of the cold property and medicinal efficacy direction of B-pCR is not only associated with changes in alkaloid groups but also depend on the synergistic effects of bile acids. This review can provide insights for improving the quality evaluation system of B-pCR.

Objective To investigate the mechanism of benzyl isothiocyanate(BITC)combined with sorafenib(Sor)in the treatment of anaplastic thyroid cancer(ATC).Methods Two ATC cell lines,8505C and CAL-62,were treated with Sor at concentrations of 0,20,30,40,and 50 μmol/L.The cell survival rate was assessed using CCK-8 assay.The combined dose of BITC and Sor was determined by calculating combination index(CI).CAL-62 and 8505C cells were exposed to 10 μmol/L BITC(BITC group),10 μmol/L Sor(Sor group),or a combination of 10 μmol/L BITC and 10 μmol/L Sor(BITC+Sor group)for 24 hours.The control group was not treated.The effects of Sor and BITC on ATC cell viability were evaluated using the CCK-8 method.Apoptosis was analyzed via flow cytometry.Western blot assay was employed to detect the protein expression levels of LC3B Ⅱ,Beclin-1 and nuclear factor(NF)-κB.Real-time fluorescence quantitative PCR was used to quantify the mRNA levels of LC3B.Additionally,CAL-62 cells were subcutaneously injected into mice to establish tumor xenograft model.Mice were treated with BITC(100 mg/kg,intraperitoneal injection),Sor(30 mg/kg,intragastric administration)or a combination of BITC and Sor every other day for 21 days.Finally,the expression levels of LC3B Ⅱ,Beclin-1 and NF-κB in tumor tissue were analyzed by Western blot assay.Results Sor significantly inhibited the viability of CAL-62 and 8505C cells in a concentration-dependent manner.The combination index(CI)was 0.710 at BITC 10 μmol/L and Sor 10 μmol/L,indicating a moderate synergistic effect between the two drugs.In both 8505C and CAL-62 cells,compared with the control group,treatment with BITC or Sor resulted in the decreased cell viability,as well as reduced expression levels of Beclin-1 and NF-κB proteins(P＜0.05),and the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly increased(P＜0.05).When BITC and Sor were combined,the cell viability,Beclin-1 and NF-κB protein expressions were further reduced compared to either drug alone,while the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly elevated(P＜0.05).In the mouse xenograft tumor model,the BITC+Sor group exhibited increased LC3B Ⅱ expression,along with decreased Beclin-1 and NF-κB expression levels,tumor volume and tumor mass compared to the BITC or Sor groups(P＜0.05).Conclusion The combination of BITC and Sor can inhibit ATC cells through NF-κB pathway,induce autophagy and promote apoptosis in vitro and in vivo.

Objective To investigate the mechanism of benzyl isothiocyanate(BITC)combined with sorafenib(Sor)in the treatment of anaplastic thyroid cancer(ATC).Methods Two ATC cell lines,8505C and CAL-62,were treated with Sor at concentrations of 0,20,30,40,and 50 μmol/L.The cell survival rate was assessed using CCK-8 assay.The combined dose of BITC and Sor was determined by calculating combination index(CI).CAL-62 and 8505C cells were exposed to 10 μmol/L BITC(BITC group),10 μmol/L Sor(Sor group),or a combination of 10 μmol/L BITC and 10 μmol/L Sor(BITC+Sor group)for 24 hours.The control group was not treated.The effects of Sor and BITC on ATC cell viability were evaluated using the CCK-8 method.Apoptosis was analyzed via flow cytometry.Western blot assay was employed to detect the protein expression levels of LC3B Ⅱ,Beclin-1 and nuclear factor(NF)-κB.Real-time fluorescence quantitative PCR was used to quantify the mRNA levels of LC3B.Additionally,CAL-62 cells were subcutaneously injected into mice to establish tumor xenograft model.Mice were treated with BITC(100 mg/kg,intraperitoneal injection),Sor(30 mg/kg,intragastric administration)or a combination of BITC and Sor every other day for 21 days.Finally,the expression levels of LC3B Ⅱ,Beclin-1 and NF-κB in tumor tissue were analyzed by Western blot assay.Results Sor significantly inhibited the viability of CAL-62 and 8505C cells in a concentration-dependent manner.The combination index(CI)was 0.710 at BITC 10 μmol/L and Sor 10 μmol/L,indicating a moderate synergistic effect between the two drugs.In both 8505C and CAL-62 cells,compared with the control group,treatment with BITC or Sor resulted in the decreased cell viability,as well as reduced expression levels of Beclin-1 and NF-κB proteins(P＜0.05),and the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly increased(P＜0.05).When BITC and Sor were combined,the cell viability,Beclin-1 and NF-κB protein expressions were further reduced compared to either drug alone,while the apoptosis rate,LC3B mRNA and LC3B Ⅱ protein expression levels were significantly elevated(P＜0.05).In the mouse xenograft tumor model,the BITC+Sor group exhibited increased LC3B Ⅱ expression,along with decreased Beclin-1 and NF-κB expression levels,tumor volume and tumor mass compared to the BITC or Sor groups(P＜0.05).Conclusion The combination of BITC and Sor can inhibit ATC cells through NF-κB pathway,induce autophagy and promote apoptosis in vitro and in vivo.

Objective To explore the regularity and potential mechanisms of medicinal and edible herbs(MEHs)in the treatment of myelosuppression through the retrieval,summary,sorting and visual analysis of relevant literature.Methods Literature about MEHs treatment for myelosuppression was reviewed in document databases,such as Web of Science,CNKI,Wanfang Data Knowledge Service Platform,China Science and Technology Journal Database,and China Biology Medicine Disc.Multivariate statistical analysis was performed using the SPSS and CiteSpace software to explore the frequency,efficacy and correlation of MEHs,as well as the potential mechanisms of MEHs in treating myelosuppression.Results A total of 123 recipes involving 170 traditional Chinese medicines(including 38 MEHs)were screened out.Five pairs of MEHs core combinations in the treatment of myelosuppression were obtained by cluster analysis.Their main functions included benefiting qi and nourishing blood,invigo-rating spleen and dispelling dampness,replenishing qi and solidifying kidney.The potential mechanisms were associated with many related signal pathways,such as Janus kinase 2-signal transducer and activator of transcription 5 andβ-catenini.Conclusion MEHs such as radix astragali combined with angelica sinensis,poria cocos and codonopsis pilosula are mainly used clinically to treat myelosuppression induced by chemotherapy.They play their therapeutic effects by promoting proliferation and delaying senescence of hematopoietic stem cells.

Benign anastomotic stenosis remains a common complication after bilojejunal anastomosis. Its pathogenesis includes the histology of bile duct, bile erosion, and inappropriate choice of surgical anastomosis or suture materials. Biliojejunal anastomotic stenosis can be determined preoperatively by MRCP, CT, and three-dimensional image reconstruction. Surgery remains treatment of choice for most cases, including surgical reconstruction and minimally invasive treatment, while the incidence of restenosis, residual stone, and reoperation is still high. Surgeons are still in search of optimal treatment modality to avoid anastomotic stenosis. In this article, we review the literature and summarize the latest clinical progress in the diagnosis and treatment of biliojejunal anastomotic stenosis combined with hepatic ductal stones.

Objective:To explore the role and molecular mechanism of Shikonin(SKN) in inhibiting the growth of anaplastic thyroid carcinoma(ATC) cells.Methods:The effect of SKN on ferroptosis in ATC cell lines CAL-62 was detected by flow cytometry; the expression levels of NF-κB, ferroptosis-related genes glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase 1(TXNRD1), glucose metabolism-related genes pyruvate kinase isoform 2(PKM2) and glucose transporter protein 1(GLUT1) were detected by Western blotting; real-time fluorescence quantitative(qPCR) to detect changes in the expression levels of GPX4, PKM2 and GLUT1; reactive oxygen species(ROS) fluorescent probe to detect changes in intracellular ROS positivity; glucose and lactic acid assay kit to detect the levels of glucose, the raw material of glucose metabolism(GLU), and lactate(LD), the product of glucose metabolism; and establishment of a subcutaneous tumour model in BALB/c nude mice to analyse the inhibitory effect of SKN on ATC in vivo.Results:Compared to the control group, after SKN treatment, the protein expression levels of NF-κB, GPX4, TXNRD1, GLUT1, and PKM2 in CAL-62 cells decreased( P=0.004, P=0.012, P=0.043, P=0.001, P=0.018); the mRNA expression of GPX4, GLUT1, and PKM2 also decreased( P<0.001, P=0.029, P<0.001). Additionally, ROS production increased( P=0.041). After treatment with the ferroptosis inhibitor Liproxstatin-1(L-1), the proportion of cell death was reversed to a certain extent, and there was no statistically significant difference in cell death proportion after L-1 treatment. Intracellular ferroptosis occurred( P<0.001), with reduced levels of glutamate(GLU) uptake and lipid peroxidation(LD) generation( P<0.001). SKN inhibited ATC tumor growth in vivo( P=0.016). Conclusion:SKN promotes intracellular ferroptosis in ATC cells, inhibits glycolysis and glucose uptake, and suppresses ATC cell growth.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.

Background::CD5L (CD5 molecular-like) plays an important role in lipid metabolism and immune regulation. This study aimed to investigate the roles of CD5L on liver hepatocellular carcinoma (LIHC).Methods::We analyzed the CD5L mRNA expression and its potential prognostic value based on The Cancer Genome Atlas and Gene Expression Omnibus databases. Immunohistochemical analysis was used to investigate the CD5L levels in LIHC tissues. Serum CD5L levels in LIHC were detected by enzyme-linked immunosorbent assay. Cell Counting Kit-8 (CCK-8) assay was used to investigate the effect of CD5L treatment on HepG2 and QSG-7701 cell proliferation. CD5L expression correlated genes were exhumed based on the LinkedOmics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for CD5L associated genes were performed. The correlation between CD5L and tumor immune infiltration was analyzed by using Tumor Immune Estimation Resource (TIMER) 2.0.Results::CD5L mRNA and protein levels were significantly decreased in LIHC tumor tissue compared with non-tumor control tissues. Moreover, serum CD5L levels were significantly lower in LIHC patients than that in healthy subjects. Gene Expression Profiling Interactive Analysis 2 and Kaplan-Meier plotter analysis showed that a high-CD5L expression was correlated with favorable overall survival in LIHC patients, except the LIHC patients with hepatitis virus. CCK-8 results showed that CD5L treatment significantly decreased HepG2 cell proliferation in a concentration-dependent manner, and CD5L treatment had no effect on the proliferation of non-tumor hepatocyte line QSG-7701. CD5L associated genes were enriched in the immune response biological process, and CD5L expression levels were positively correlated with the immune infiltrates of CD8 + T cell and M1 macrophage cells but negatively correlated with CD4 + T cells and M0 macrophage cell infiltration. Conclusions::Exogenous CD5L inhibits cell proliferation of hepatocellular carcinoma. CD5L may act as a role of prognostic marker.

Objective:To explore the association between body mass index (BMI) and the incidence of thyroid nodules, the clinical characteristics and efficacy evaluation of differentiated thyroid cancer (DTC), respectively.Methods:Clinical data of 1 375 healthy people (1 031 males, 344 females, age: (43.5±10.6) years) who underwent routine physical examination (PE) and 1 450 patients (490 males, 960 females, age: (44.3±12.4) years) with medium-high risk DTC in Tianjin Medical University General Hospital from April 2016 to July 2020 were analyzed retrospectively. PE and DTC patients were classified into underweight group (BMI<18.5 kg/m 2), normal weight group (18.5≤BMI<24.0 kg/m 2), overweight group (24.0≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) respectively. χ2 test was employed to analyze the relation between BMI and thyroid nodules (with/without), BMI and clinical characteristics and efficacy evaluation of DTC, respectively. Logistic regression analysis was used to analyze the independent risk factors for the occurrence of thyroid nodules and the aggressiveness of DTC. Results:Among PE, there were 779 cases with nodules, and 596 cases without nodules. Comparing with those without nodules, more overweight and obese were found in PE cases with nodules (42.1%(328/779) vs 37.2%(222/596), 24.5%(191/779) vs 20.5%(122/596); χ2=13.42, P=0.004). Higher risk of developing thyroid nodules was related with older age and lower thyroid stimulating hormone (TSH) level (odds ratio ( OR): 1.044, 0.919, 95% CI: 1.029-1.060, 0.845-0.999; P<0.001, P=0.046). People with high-risk nodules were more likely to be obese than those with intermediate and lower risk nodules (5/15 vs 24.3% (186/764); χ2=21.11, P<0.001). Among 1 450 DTC patients, comparing with patients with normal weight, patients in the overweight and obesity groups were more likely to have central regional lymph node metastasis ( OR: 1.418, 1.427, 95% CI: 1.075-1.870, 1.044-1.952; P values: 0.013, 0.026), and patients in obese group were with greater risk of lesions being bilateral ( OR=0.696, 95% CI: 0.519-0.934; P=0.016). BMI was not related with the efficacy evaluation of DTC ( χ2=9.13, P=0.425). Conclusions:The incidence of thyroid nodules in people with high BMI is higher. DTC patients with high BMI may have more aggressive incidence. But BMI has no correlation with the efficacy evaluation of DTC patients after treatment.

ObjectiveTo explore the material basis of bile-processed Coptidis Rhizoma clearing excessive fire of liver-gallbladder based on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF/MS） metabolomics and molecular docking. MethodUPLC-Q-TOF/MS metabolomics was used to analyze the chemical constituents of Coptidis Rhizoma， water-processed Coptidis Rhizoma and bile-processed Coptidis Rhizoma. Chromatographic separation was achieved with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase in gradient elution（0-2 min， 5%B； 2-20 min， 5%-65%B； 20-40 min， 65%-10%B； 40-45 min， 10%B； 45-46 min， 10%-95%B； 46-49 min， 95%B）， and electrospray ionization（ESI） was applied and operated in positive and negative ion modes， the acquisition range was m/z 80-1 200. Based on this， partial least squares-discriminant analysis（PLS-DA） and variance analysis were used to screen the differential compounds among the three products of Coptidis Rhizoma. Network pharmacology and molecular docking were used to verify the degree of association between differential compounds and excessive fire of liver-gallbladder syndrome. ResultA total of 33 chemical constituents were identified， including 2 phenolic acids， 5 binding bile acids and 26 alkaloids. And 16 differential compounds were identified by multivariate statistical analysis， including 11 alkaloids and 5 binding bile acids. Pathway enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes（KEGG） database yielded 8 pathways related to excessive fire of liver-gallbladder， and the key protein phosphatidylinositol 4，5-bisphosphate 3-kinase catalytic subunit alpha isoform（PIK3CA） was obtained according to the "component-target-pathway" network analysis. Molecular docking results showed that 11 alkaloids had good binding ability with PIK3CA. ConclusionPorcine bile is unique in the processing of bile-processed Coptidis Rhizoma， which can promote the production and dissolution of 11 alkaloids， including berberine and dihydrochelerythrine. Based on the results of molecular docking and reported pharmacological experiments， it can be concluded that 16 different compounds such as berberine， dihydrochelerythrine and taurohyodeoxycholic acid are the material basis of bile-processed Coptidis Rhizoma.