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The combination of lenvatinib, toripalimab and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) suggested encouraging antitumour activity in our retrospective study. We hereby prospectively establish the efficacy, safety and predictive biomarkers of the combination therapy as a first-line treatment in patients with high-risk advanced hepatocellular carcinoma (HCC). This phase II, single-centre, single-arm trial enrolled advanced HCC participants with high-risk. Of 51 screened participants, 36 received lenvatinib, toripalimab plus FOLFOX-HAIC. Participants received 21-day treatment cycles of lenvatinib, toripalimab, and FOLFOX-HAIC. The primary end-point was the progression-free survival (PFS) rate per RECIST at six months. Thirty-six participants (86.1% with high-risk features) were enrolled in our study. The primary end-point was met with a PFS rate of 80.6% (95% CI, 64.0%–91.8%) at six months. The median PFS was 10.4 months (95% CI, 5.8–15.0), and the median OS was not reached at the prespecified final analysis and was 17.9 months (95% CI, 14.5–21.3) after follow-up was extended. The ORR per RECIST was 63.9%, and per mRECIST was 66.7%. The median duration of response was 14.4 months (95% CI, 8.9–19.9). The most common adverse events were thrombocytopenia, elevated aspartate aminotransferase, and hypertension, and no treatment-related death was reported. Participants with low levels of both CCL28 and BTC had unsatisfactory prognosis. Lenvatinib, toripalimab and FOLFOX-HAIC showed safe and encouraging antitumour activity for advanced HCC with high-risk features. The levels of CCL28 and BTC might be the predictive biomarkers for the triple combination therapy. • High-risk advanced HCC is associated with poor outcomes of systemic therapy. • Combination FOLFOX-HAIC with lenvatinib and toripalimab was tolerable and effective. • CCL28 and BTC levels before therapy might be the predictive biomarkers of efficacy. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Quality Uniformity Evaluation strategy was adopted to evaluate the consistencies of Babao Dan capsule (BBDC). • An optimized UHPLC–QQQ–MS/MS method was developed to simultaneously determine the 14 main compounds of BBDC. • The 10 batches were divided into three categories based on the inter–batches consistency. • The anti-inflammatory activities of BBDC were studied and clearly distinguished in vitro by RAW264.7 and NF-ĸB-RE-luc HEK293 cells. • The correlation analysis confirmed that the main chemical compounds related to anti-inflammatory activity in BBDC. Babao Dan capsule (BBDC) is a state secrecy traditional Chinese medicine patent prescription (TCMPP) that is widely used for hepatobiliary and urinary diseases. However, its quality uniformity evaluation (QUE) is lacking. It is necessary to develop a novel and multi–dimensional QUE strategy for BBDC based on chemical properties and bioactivities. An ultrahigh performance liquid chromatography–triple quadrupole–mass spectrometry (UHPLC–QQQ–MS/MS) was developed to quantify 14 compounds, and a QUE strategy was to assess intra–batch and inter–batches consistency. Furthermore, the anti-inflammatory activities were measured in vitro by RAW264.7 cell and NF-κB-RE-luc HEK293 cell. The results indicated that 14 compounds from 16 samples (10 batches) were accurately quantified. And the intra–batch consistency values were less than or equal to 20.1%, whereas the largest inter–batches consistency value was 167.5% of glycocholic acid. 10 batches were divided into three categories to distinction inter–batches differences. BBDC had anti-inflammatory activities including inhibition of LPS–induced NO production and TNF α–activated luciferase counts. The NO inhibition difference of 10 batches was 10.87 μM and accounted for 49.8%. Briefly, the anti-inflammatory activities of 10 batches were different, but the dynamic trends within the same batch were similar, which was supported by luciferase counts. And the correlation was confirmed that the main compounds related to anti-inflammatory in BBDC were bile acids and saponins. Hence, a QUE strategy for BBDC was proposed to improve quality and ensure efficacy. This strategy can be utilized as a reference for consistency evaluations of TCMPPs. [ABSTRACT FROM AUTHOR]

Electro-dewatering of sewage sludge with pulsating direct current (PDC-dewatering) was conducted to investigate the effects of pulsating frequency (0.01–60 Hz) and duty cycle (DTC) (20–100%) on sludge dewatering. The results indicated that both the frequency and DTC showed marked influences on electro-dewatering. Compared with the condition under the stable direct current (SDC-dewatering) of 30 V, the filtrate discharged from PDC-dewatering (at DTC of 40–60% and frequency of 30 Hz) was about 8% higher than that from SDC-dewatering. At DTC of 40%, the sludge electro-dewatering performance was promoted when the frequency increased from 0.01 Hz to 30 Hz. Compared with SDC-dewatering, PDC-dewatering can effectively mitigate ohmic heating. Layered tests were also conducted to investigate the differences of SDC- and PDC-dewatering in the distributions of water, pH, organic matters, zeta potential and conductivity in the upper, middle and lower layer of sludge cake. The results indicated that the variation tendencies of these parameters were similar between SDC- and PDC-dewatering, but the water, organic matters and charged ions in sludge cake were more homogeneously distributed during PDC-dewatering than SDC-dewatering. In addition, the anodic pH of PDC-dewatering was higher than that of SDC-dewatering, suggesting the potential of mitigating anodic corrosion during PDC-dewatering. Finally, energy consumptions of PDC- and SDC-dewatering were calculated and compared. The effects of frequency and DTC on energy consumption were investigated. PDC-dewatering was found to be more energy efficient than that of SDC-dewatering, making PDC-dewatering a promising electro-dewatering technology in future. Image 102110 • PDC-dewatering can promote dewatering and mitigate ohmic heating simultaneously. • PDC-dewatering showed the optimum performance in the DTC range of 40–60% (30 Hz). • PDC-dewatering showed the potential of mitigating anodic corrosion. • The charged species in sludge cake were more homogeneously distributed during PDC-dewatering than SDC-dewatering. • PDC-dewatering was found to be more energy efficient than that of SDC-dewatering. [ABSTRACT FROM AUTHOR]

Hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX-HAIC) has shown a strong anti-tumor effect in hepatocellular carcinoma in China. Different from hepatocellular carcinoma in China, hepatocellular carcinoma in Western countries is caused by hepatitis C and alcoholic liver disease, and is often diagnosed at an early stage, when the tumor is small or the thrombus is not serious. Although there are no reports of FOLFOX-HAIC efficacy for hepatocellular carcinoma in Western countries, FOLFOX-HAIC can be used in patients with large tumors (> 5 cm) (or T3 by TNM stage), and rich blood supply. [ABSTRACT FROM AUTHOR]

Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC). To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC. We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro. In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8+ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway. BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM. BBD alone or in combination with low-dose CLM inhibits the proliferation and metastasis of HCC cells by inhibiting the PI3K/AKT/mTOR signalling pathway, and BBD in combination with high-dose CLM slows down the side effects of CLM via the TGF-β/pSmad3 signaling pathway. [Display omitted] • BBD modulates macrophage polarization and increases CD8+ T cell abundance in the tumor immune microenvironment to achieve anti-HCC effects. • BBD inhibits the proliferation and metastasis of HCC cells by remodeling tumor-associated macrophages in the tumor microenvironment. • BBD increases the anti-HCC effect of Camrelizumab by regulating the immune microenvironment and reduces the organ toxicity of Camrelizumab. [ABSTRACT FROM AUTHOR]

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae , Aerococcus , Blautia , Jeotgalicoccus , Odoribacter , Roseburia , Rikenella , Intestinimonas , unidentified_Lachnospiraceae , Enterorhabdus , Ruminiclostridium , and downregulated the abundance of Bacteroides , Parabacteroides , Parasutterella , Erysipelatoclostridium , which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury. [Display omitted] • 5-FU-induced intestinal injury containing gut immune and microbiota disorder. • 5-FU induced abnormal activation of TLR4/MyD88/NF-кB pathway in intestine. • Babao Dan attenuated 5-FU-induced intestinal injury, immune and microbiota disorders. • Babao Dan inhibited the activation of TLR4/MyD88/NF-кB pathway. • Established a network of 5-FU, BBD, intestinal injury, immune, microbiota and pathways. [ABSTRACT FROM AUTHOR]