Isoastragaloside I attenuates cholestatic liver diseases by ameliorating liver injury, regulating bile acid metabolism and restoring intestinal barrier.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver diseases (CLD) are liver disorders resulting from abnormal bile formation, secretion, and excretion from various causes. Due to the lack of suitable and safe medications, liver transplantation is the ultimate treatment for CLD patients. Isoastragaloside I (IAS I) is one of the main saponin found in Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge, which has been demonstrated to obviously alleviate CLD. Nevertheless, the IAS I's specific anti-CLD mechanism remains undecipherable. AIM OF THE STUDY: This study's purpose was to elucidate the protective consequence of IAS I on 0.1% 3, 5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) diet-induced CLD mice, and to reveal its potential mechanism. MATERIALS AND METHODS: In this study, mice with CLD that had been fed a 0.1% DDC diet were distributed two doses of IAS I (20 mg/kg, 50 mg/kg). The effects of IAS I on CLD models were investigated by assessing blood biochemistry, liver histology, and Hyp concentrations. We investigated markers of liver fibrosis and ductular reaction using immunohistochemistry, Western blot, and qRT-PCR. Liver inflammation indicators, arachidonic acid (ARA), and ω-3 fatty acid (FA) metabolites were also analyzed. Quantitative determination of 39 bile acids (BAs) in different organs employing UHPLC-Q-Exactive Orbitrap HRMS technology. Additionally, the H&E and Western blot analysis were used to evaluate differences in intestinal barrier function in DDC-induced mice before and after administering IAS I. RESULTS: After treatment with IAS I, serum biochemical indicators and liver hydroxyproline (Hyp) increased in a dose-dependent manner in CLD mice. The IAS I group showed significant improvement in indicators of liver fibrosis and ductular response, including as α-smooth muscle actin (α-SMA) and cytokeratin 19 (CK19), and transforming growth factor-ß (TGF-ß)/Smads signaling pathway. And inflammatory factors: F4/80, tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), ARA and ω-3 FA metabolites showed significant improvement following IAS I treatment. Moreover, IAS I significantly ameliorated liver tau-BAs levels, particularly TCA, THCA, THDCA, TCDCA, and TDCA contents, which were associated with enhanced expression of hepatic farnesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (Cyp7a1), and bile-salt export pump (BSEP). Furthermore, IAS I significantly improved pathological changes and protein expression related to intestinal barrier function, including zonula occludens protein 1 (ZO-1), Muc2, and Occludin. CONCLUSIONS: IAS I alleviated cholestatic liver injury, relieved inflammation, improved the altered tau-BAs metabolism and restored intestinal barrier function to protect against DDC-induced cholestatic liver diseases.

Independent and joint associations of multiple metals exposure with vital capacity index: a cross-sectional study in Chinese children and adolescents.

OBJECTIVE: The current study aimed to explore the relationships between urinary metals and vital capacity index (VCI) in 380 children and adolescents in Northeast China using a variety of statistical methods. METHODS: A cross-sectional survey was conducted among 380 children and adolescents in Liaoning Province, China. To assess the relationships between urinary metals and VCI, Elastic-net (ENET) regression, multivariate linear regression, weighted quantile sum (WQS), bayesian kernel machine regression (BKMR) and quantile-based g computation (qgcomp) were adopted. RESULTS: The ENET model selected magnesium (Mg), vanadium (V), manganese (Mn), arsenic (As), tin (Sn) and lead (Pb) as crucial elements. In multiple linear regression, we observed urinary Pb, Mn was negatively correlated with VCI individually in both total study population and adolescents (all p values < 0.05) in the adjustment model. The WQS indices were negatively related with VCI in total study population (ß=-3.19, 95%CI: -6.07, -0.30) and adolescents (ß=-3.46, 95%CI: -6.58, -0.35). The highest weight in total study population was Pb (38.80%), in adolescents was Mn (35.10%). In the qgcomp, Pb (31.90%), Mn (27.20%) were the major negative contributors to the association in the total population (ß=-3.51, 95%CI: -6.29, -0.74). As (42.50%), Mn (39.90%) were the main negative contributors (ß=-3.95, 95% CI: -6.68, -1.22) among adolescents. The results of BKMR were basically consistent with WQS and qgcomp analyses. CONCLUSIONS: Our results indicated that Pb and Mn were priority toxic materials on VCI. The cumulative effect of metals was negatively related to VCI, and this relationship was more pronounced in adolescents.

Total astragalus saponins attenuate primary sclerosing cholangitis in mice by upregulation of TGR5.

Total astragalus saponins (TAS) are the main active components of astragali radix, and have potent anti-hepatic fibrosis effect. However, the therapeutic efficacy of TAS and their potential mechanisms in the treatment of primary sclerosing cholangitis (PSC) remain unclear. In this study, two mouse models of PSC, including 3,5-Diethoxycarbonyl-1,4-Dihydro-2,4,6-Collidine (DDC)-induced PSC and Mdr2-/- spontaneous PSC, and the Tgr5-/- mice were used to investigate the therapeutic effect and mechanisms of TAS. Treatment with TAS, particularly with a dose of 56 mg/kg, significantly ameliorated the PSC-related liver injury, cholestasis, collagen deposition, ductular reaction (DR), and fibrosis in the DDC-induced and Mdr2-/-spontaneous PSC mice. Furthermore, treatment with TAS significantly mitigated the PSC-related inflammatory responses in vivo and HIBEpiC cells by inhibiting the expression of TNF-α, IL-6, and IL-1ß. Mechanistically, treatment with TAS rescued the PSC-decreased hepatic TGR5 expression to attenuate the NF-κB p65 phosphorylation. Notably, the therapeutic efficacy of TAS on PSC in DDC-induced mice was abrogated in Tgr5-/- mice, suggesting the anti-PSC effect of TAS may depend on enhancing TGR5 expression. In conclusion, TAS ameliorated DR, inflammation and liver fibrosis in both models of PSC mice by rescuing TGR5 expression. Our findings may aid in the design of new therapeutic strategies for the treatment of PSC.

Compare Clinical Characteristics of Psittacosis Pneumonia in 35 Patients and of Non Psittacosis Bacterial Pneumonia in 46 Patients.

Background: We aimed to describe the difference between Chlamydia psittaci pneumonia group and non C. psittaci bacterial pneumonia group in community acquired pneumonia in this single-center clinical study. Methods: We collected the data of 35 patients with C. psittaci pneumonia cases and 46 patients with non C. psittaci bacterial pneumonia cases diagnosed with metagenomic next-generation sequencing assays from February 2019 to December 2021 in Huaihua First People's Hospital in China. Results: In the C. psittaci pneumonia group, 35 patients (100%) had a chance of exposure to poultry or birds, and their body temperature was greater than or equal to 39.0°C. The other common symptoms were a slow pulse (68.6%), cough (65.7%), expectoration (54.3%), chills (51.4%) and a shortness of breath (37.1%). Laboratory tests showed that >90% of the cases had markedly elevated infection indicators, and 97.1% of the cases had markedly declined calcium. The most common imaging finding was patchy shadows (94.3%), pleural effusion (68.6%), bilateral in 54.3% (n = 19) and unilateral in 45.7% (n = 16) participants, and 51.4% (n = 18) of cases met the criteria for severe pneumonia. In the non C. psittaci bacterial pneumonia group, 18 patients (39.1%) had a chance of exposure to poultry or birds, and 11 patients (23.9%) body temperature was greater than or equal to 39.0°C. Laboratory tests showed that >67% of cases had a mildly elevated infection indicators, and mildly declined serum albumin. Conclusion: The following characteristics are more likely to help distinguish C. psittaci pneumonia from non C. psittaci bacterial pneumonia. Including had a chance of exposure to poultry or birds, high fever, exhibit chills, expectoration, relatively slow pulse, and progress into severe pneumonia. Percentage of neutrophils, C-reactive protein, procalcitonin, lactate dehydrogenase, and myoglobin levels are higher. Blood calcium and corrected calcium are lower. Chest CT showed pleural effusion, pericardial effusion, and mediastinal lymphadenopathy.

Global, regional, and national burden of cancers attributable to particulate matter pollution from 1990 to 2019 and projection to 2050: Worsening or improving?

Particulate matter pollution (PMP) has been identified as a substantial contributor to cancer. However, accurately delineating the evolving trends in cancer burden attributable to PMP remains an ongoing challenge. The 1990-2019 disability-adjusted life years (DALYs) were used for cancers attributable to PMP from the Global Burden and Disease Study (GBD) 2019, including ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP). The joinpoint regression and the Bayesian age-period-cohort (BAPC) model were employed to assess the corresponding trends over the periods 1990-2019 and 2020-2050, respectively. Additionally, statistical models such as frontier analysis and health inequality analysis were also utilized. During the 30-year period, cancer DALYs attributable to APMP increased globally, while those attributable to HAP and PMP decreased. Cancer DALYs attributable to APMP were positively correlated with socio-demographic index (SDI), while those attributable to PMP and HAP were negatively correlated with SDI. Frontier analysis identified the countries and regions requiring urgent action to mitigate PMP-attributable cancer. Finally, it was anticipated that the cancer burden attributable to APMP would increase during 2020 to 2050, while the burden attributable to HAP and PMP would decrease. This study conducted an epidemiological investigation of the burden of cancer attributable to APMP, HAP and PMP in various regions and populations worldwide, providing epidemiological insights into the global burden of cancer attributable to PMP and guiding policy and research directions.

Interactions between plants and bacterial communities for phytoremediation of petroleum-contaminated soil.

Plants can stimulate the microbes to degrade ubiquitous petroleum hydrocarbons (PHCs), which has prompted a novel view on rhizoremediation. In the present study, the degradation rate of PHCs was investigated and 16S rRNA gene analysis was performed to investigate the PHC-degrading bacteria in petroleum-contaminated soil with different plants. Mirabilis jalapa (M. jalapa) has a higher PHC degradation rate than Lolium perenne (L. perenne) under petroleum contamination. The bacterial diversity in rhizospheric soil was decreased but the relative abundance of Actinobacteriota, Proteobacteria, and Candidatus Saccharibacteria were significant increased on 45 days petroleum-contaminated rhizospheric soil. In addition, the relative expression of PHC degradation-related genes, the content of malic acid and citric acid of the root exudates in the two plants was significantly increased in response to petroleum stress. The content of citric acid increased 11.9 times in M. jalapa and 3.4 times in L. perenne, respectively, in response to petroleum stress. These results indicate that M. jalapa changes the hydrocarbon-degrading microbial community to enhance the degradation of PHCs by root exudates and phytostimulation.

Salt-Assisted, In Situ Current Nanowelding of an Interfacial Au Nanoparticle Film for a High-Performance Electrocatalyst.

Interfacial self-assembly is a well-established method for the preparation of a two-dimensional (2D) metal nanofilm from nanoscale building blocks. However, the as-prepared nanofilm exhibits limited conductivity because of the large contact resistance at the junctions among its building blocks. Here, we report a salt-assisted, in situ current nanowelding strategy to weld an interfacial Au nanoparticle (NP) film for downstream applications, such as high-performance electrocatalysts. Particularly, we found that salt-assisted interfacial assembly can reduce the size of the nanogaps among neighboring Au NPs and, in turn, greatly improve the conductivity of the resultant Au NP film. Consequently, the Au NP film can be readily welded using current, and the welding extent can be monitored in real-time by looking at the passing current. The welding finally produces a nanoporous Au film (NPGF) with a network nanostructure, high conductivity, and abundant active sites so that it delivers a large current density of 86.96 µA·cm-2 (1.81 times higher than that from the pristine Au NP film) and shows improved cycling stability for methanol electrooxidation. Thus, these results offer a low-cost, solution-processable approach for the fabrication of a large-area, interconnected nanofilm from nanoscale building blocks beyond Au NPs, which may find diverse downstream applications.

The role of hsa_circ_0042260/miR-4782-3p/LAPTM4A axis in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic condition during pregnancy, posing risks to both mother and fetus. CircRNAs have emerged as important players in various diseases, including GDM. We aimed to investigate the role of newly discovered circRNA, hsa_circ_0042260, in GDM pathogenesis. Using GSE194119 dataset, hsa_circ_0042260 was identified and its expression in plasma, placenta, and HG-stimulated HK-2 cells was examined. Silencing hsa_circ_0042260 in HK-2 cells assessed its impact on cell viability, apoptosis, and inflammation. Bioinformatics analysis revealed downstream targets of hsa_circ_0042260, namely miR-4782-3p and LAPTM4A. The interaction between hsa_circ_0042260, miR-4782-3p, and LAPTM4A was validated through various assays. hsa_circ_0042260 was upregulated in plasma from GDM patients and HG-stimulated HK-2 cells. Silencing hsa_circ_0042260 improved cell viability, suppressed apoptosis and inflammation. Hsa_circ_0042260 interacted with miR-4782-3p, which exhibited low expression in GDM patient plasma and HG-stimulated cells. MiR-4782-3p targeted LAPTM4A, confirmed by additional assays. LAPTM4A expression increased in GDM patient plasma and HG-induced HK-2 cells following hsa_circ_0042260 knockdown or miR-4782-3p overexpression. In rescue assays, inhibition of miR-4782-3p or overexpression of LAPTM4A counteracted the effects of hsa_circ_0042260 downregulation on cell viability, apoptosis, and inflammation. In conclusion, the hsa_circ_0042260/miR-4782-3p/LAPTM4A axis plays a role in regulating GDM progression in HG-stimulated HK-2 cells.

Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.

Progress in clinical and basic research of fuzheng Huayu formula for the treatment of liver fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine has great potential and advantages in the treatment of liver fibrosis, with Fuzheng Huayu formula (FZHY) serving as a prime example due to its remarkable efficacy in delaying and reversing liver fibrosis while simultaneously improving clinical symptoms for patients. AIM OF THE REVIEW: In this paper, we present a comprehensive review of recent studies on the therapeutic potential of FZHY and its components/ingredients in the treatment of liver fibrosis and cirrhosis, with the aim of providing insights for future research endeavors. MATERIALS AND METHODS: A comprehensive literature search was conducted on FZHY, TCM319, traditional Chinese medicine 319, liver fibrosis and cirrhosis using multiple internationally recognized databases including PubMed, Embase, Springer, Web of science, SciVerse ScienceDirect, Clinical Trails. Gov, CNKI, Wanfang, and VIP. RESULTS: FZHY is widely used clinically for liver fibrosis and cirrhosis caused by various chronic liver diseases, with the effects of improving serum liver function, liver pathological histology, serological indices related to liver fibrosis, decreasing liver stiffness values and portal hypertension, as well as reducing the incidence of hepatocellular carcinoma and morbidity/mortality in patients with cirrhosis. Numerous in vivo and in vitro experiments have demonstrated that FZHY possesses anti-fibrotic effects by inhibiting hepatic stellate cell activation, reducing inflammation, protecting hepatocytes, inhibiting hepatic sinusoidal capillarization and angiogenesis, promoting extracellular matrix degradation, and facilitating liver regeneration. In recent years, there has been a growing focus on investigating the primary active components/ingredients of FZHY, and significant strides have been made in comprehending their synergistic mechanisms that enhance efficacy. CONCLUSION: FZHY is a safe and effective drug for treating liver fibrosis. Future research on FZHY should focus on its active components/ingredients and their synergistic effects, as well as the development of modern cocktail drugs based on its components/ingredients. This will facilitate a more comprehensive understanding of the molecular mechanisms and targets of FZHY in treating liver fibrosis, thereby further guide clinical applications and drug development.

Colorectal cancer histopathology image analysis: A comparative study of prognostic values of automatically extracted morphometric nuclear features in multispectral and red-blue-green imagery.

OBJECTIVES: Multispectral imaging (MSI) has been utilized to predict the prognosis of colorectal cancer (CRC) patients, however, our understanding of the prognostic value of nuclear morphological parameters of bright-field MSI in CRC is still limited. This study was designed to compare the efficiency of MSI and standard red-green-blue (RGB) images in predicting the prognosis of CRC. METHODS: We compared the efficiency of MS and conventional RGB images on the quantitative assessment of hematoxylin-eosin (HE) stained histopathology images. A pipeline was developed using a pixel-wise support vector machine (SVM) classifier for gland-stroma segmentation, and a marker-controlled watershed algorithm was used for nuclei segmentation. The correlation between extracted morphological parameters and the five-year disease-free survival (5-DFS) was analyzed. RESULTS: Forty-seven nuclear morphological parameters were extracted in total. Based on Kaplan-Meier analysis, eight features derived from MS images and seven featured derived from RGB images were significantly associated with 5-DFS, respectively. Compared with RGB images, MSI showed higher accuracy, precision, and Dice index in nuclei segmentation. Multivariate analysis indicated that both integrated parameters 1 (factors negatively correlated with CRC prognosis including nuclear number, circularity, eccentricity, major axis length) and 2 (factors positively correlated with CRC prognosis including nuclear average area, area perimeter, total area/total perimeter ratio, average area/perimeter ratio) in MS images were independent prognostic factors of 5-DFS, in contrast with only integrated parameter 1 (P<0.001) in RGB images. More importantly, the quantification of HE-stained MS images displayed higher accuracy in predicting 5-DFS compared with RGB images (76.9% vs 70.9%). CONCLUSIONS: Quantitative evaluation of HE-stained MS images could yield more information and better predictive performance for CRC prognosis than conventional RGB images, thereby contributing to precision oncology.

Structural characterization of an inulin neoseries-type fructan from Ophiopogonis Radix and the therapeutic effect on liver fibrosis in vivo.

Ophiopogonis Radix is a well-known Traditional Chinese Medicine and functional food that is rich in polysaccharides and has fructan as a characteristic component. In this study, an inulin neoseries-type fructan designated as OJP-W2 was obtained and characterized from Ophiopogonis Radix, and its potential therapeutic effect on liver fibrosis in vivo were investigated. Structural studies revealed that OJP-W2 had a molecular weight of 5.76 kDa and was composed of glucose and fructose with a molar ratio of 1.00:30.87. Further analysis revealed OJP-W2 has a predominantly lineal (1-2)-linked ß-D-fructosyl units linked to the glucose moiety of the sucrose molecule with (2-6)-linked ß-D-fructosyl side chains. Pharmacological studies revealed that OJP-W2 exerted a marked hepatoprotective effect against liver fibrosis, the mechanism of action was involved in regulating collagen deposition (α-SMA, COL1A1 and liver Hyp contents) and TGF-ß/Smads signaling pathway, alleviating liver inflammation (IL-1ß, IL-6, CCL5 and F4/80) and MAPK signaling pathway, and inhibiting hepatic apoptosis (Bax, Bcl-2, ATF4 and Caspase 3). These data provide evidence for expanding Ophiopogonis Radix-acquired fructan types and advancing our understanding of the specific role of inulin neoseries-type fructan in liver fibrosis therapy.

Salvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis.

Hepatocyte ferroptosis promotes the pathogenesis and progression of liver fibrosis. Salvianolic acid B (Sal B) exerts antifibrotic effects. However, the pharmacological mechanism and target has not yet been fully elucidated. In this study, liver fibrosis was induced by CCl4 in wild-type mice and hepatocyte-specific extracellular matrix protein 1 (Ecm1)-deficient mice, which were separately treated with Sal B, ferrostatin-1, sorafenib or cilengitide. Erastin- or CCl4-induced hepatocyte ferroptosis models with or without Ecm1 gene knockdown were evaluated in vitro. Subsequently, the interaction between Ecm1 and xCT and the binding kinetics of Sal B and Ecm1 were determined. We found that Sal B significantly attenuated liver fibrosis in CCl4-induced mice. Ecm1 deletion in hepatocytes abolished the antifibrotic effect of Sal B. Mechanistically, Sal B protected against hepatocyte ferroptosis by upregulating Ecm1. Further research revealed that Ecm1 as a direct target for treating liver fibrosis with Sal B. Interestingly, Ecm1 interacted with xCT to regulate hepatocyte ferroptosis. Hepatocyte ferroptosis in vitro was significantly attenuated by Sal B treatment, which was abrogated after knockdown of Ecm1 in LO2 cells. Therefore, Sal B alleviates liver fibrosis in mice by targeting up-regulation of Ecm1 and inhibiting hepatocyte ferroptosis. The interaction between Ecm1 and xCT regulates hepatocyte ferroptosis.

Schisantherin A protects hepatocyte via upregulating DDAH1 to ameliorate liver fibrosis in mice.

BACKGROUND: Hepatic fibrosis is the pivotal determinant in the progression of chronic liver diseases towards cirrhosis or advanced stages. Studies have shown that Schisantherin A (Sin A), the primary active compound from Schizandra chinensis (Turcz.) Baill., exhibits anti-hepatic fibrosis effects. However, the mechanism of Sin A in liver fibrosis remain unclear. PURPOSE: To examine the effects and underlying mechanism of Sin A on hepatic fibrosis. STUDY DESIGN AND METHODS: The effects and mechanism of Sin A were investigated using liver fibrosis mouse models induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN), as well as H2O2-induced hepatocyte injury in vitro. RESULTS: Sin A treatment ameliorated hepatocyte injury, inflammation, hepatic sinusoidal capillarization, and hepatic fibrosis in both CCl4-induced and DMN-induced mice. Sin A effectively reversed the reduction of DDAH1 expression, the p-eNOS/eNOS ratio and NO generation and attenuated the elevation of hepatic ADMA level induced by CCl4 and DMN. Knockdown of DDAH1 in hepatocytes not only triggered hepatocyte damage, but it also counteracted the effect of Sin A on protecting hepatocytes in vitro. CONCLUSION: Our findings indicate that Sin A ameliorates liver fibrosis by upregulating DDAH1 to protect against hepatocyte injury. These results provide compelling evidence for Sin A treatment in liver fibrosis.

Recent progress on the application of compound formulas of traditional Chinese medicine in clinical trials and basic research in vivo for chronic liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic liver diseases mainly include chronic viral liver disease, metabolic liver disease, cholestatic liver disease (CLD), autoimmune liver disease, and liver fibrosis or cirrhosis. Notably, the compound formulas of traditional Chinese medicine (TCM) is effective for chronic liver diseases in clinical trials and basic research in vivo, which provide evidence of chronic liver disease treatment with integrated TCM and traditional Western medicine. AIM OF THE REVIEW: This paper aims to provide a comprehensive review of the compound formulas of TCM for treating different chronic liver diseases to elucidate the composition, main curative effects, and mechanisms of these formulas and research methods. MATERIALS AND METHODS: Different keywords related to chronic liver diseases and keywords related to the compound formulas of TCM were used to search the literature. PubMed, Scopus, Web of Science, and CNKI were searched to screen out original articles about the compound formulas of TCM related to the treatment of chronic liver diseases, mainly including clinical trials and basic in vivo research related to Chinese patent drugs, classic prescriptions, proven prescriptions, and hospital preparations. We excluded review articles, meta-analysis articles, in vitro experiments, articles about TCM monomers, articles about single-medicine extracts, and articles with incomplete or uncertain description of prescription composition. Plant names were checked with MPNS (http://mpns.kew.org). RESULTS: In this review, the clinical efficacy and mechanism of compound formulas of TCM were summarized for the treatment of chronic viral hepatitis, nonalcoholic fatty liver disease, CLD, and liver fibrosis or cirrhosis developed from these diseases and other chronic liver diseases. For each clinical trial and basic research in vivo, this review provides a detailed record of the specific composition of the compound formulas of TCM, type of clinical research, modeling method of animal experiments, grouping methods, medication administration, main efficacy, and mechanisms. CONCLUSION: The general development process of chronic liver disease can be summarized as chronic hepatitis, liver fibrosis or cirrhosis, and hepatocellular carcinoma. The compound formulas of TCM have some applications in these stages of chronic liver diseases. Owing to the continuous progress of medical technology, the benefits of the compound formulas of TCM in the treatment of chronic liver diseases are constantly changing and developing.

A Comparison of Clinicopathologic Outcomes and Patterns of Lymphatic Spread Across Neoadjuvant Chemotherapy, Neoadjuvant Chemoradiotherapy, and Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) is recommended as the treatment standard for locally advanced esophageal squamous cell carcinoma (ESCC). The use of immunotherapy in the neoadjuvant setting has gained attention. Multiple, clinical trials have explored the efficacy and safety of neoadjuvant immunochemotherapy (NICT). We evaluated the differences in clinicopathologic outcomes and the patterns of lymphatic spread among patients receiving neoadjuvant chemotherapy (NCT), NCRT, and NICT before esophagectomy for locally advanced ESCC. METHODS: A total of 702 patients with ESCC who completed transthoracic esophagectomy followed neoadjuvant therapy were included. Pathological characteristics, including pathologic complete response (pCR), tumor regression grade (TRG) score and patterns of lymphatic spread, were evaluated. RESULTS: Compared with the NCT group, the NCRT group and NICT group had an advantage in pathological response (P < 0.05). The pCR rate was 8.1% in the NCT group, 29.9% in the NCRT group, and 23.6% in the NICT group. The TRG score (P < 0.05) and pathologic T stage (P < 0.05) in the NCT group were significantly higher. Compared with NICT, NCRT can significantly reduce the rate of lymph node metastasis rate in station 1R (0 vs. 3.4%, P < 0.05) and 2R (1.1% vs. 6.8%, P < 0.05). Subgroup analysis according to the tumor location distribution showed that NICT group had higher lymph node metastasis rate in station 2R (9.1%) in middle thoracic cases (P < 0.05) and in station 18 (7.5%) (P < 0.05) in lower thoracic cases. CONCLUSIONS: NCRT or NICT followed by surgery may result in a promising pCR rate and show a better performance in therapeutic response of primary lesion. For patients with lymph node metastasis in station 1R and 2R, NCRT should be the optimal preoperative treatment strategy.

Effects of Ambient O3 on Respiratory Mortality, Especially the Combined Effects of PM2.5 and O3.

BACKGROUND: In China, the increasing concentration of ozone (O3) has emerged as a significant air pollution issue, leading to adverse effects on public health, particularly the respiratory system. Despite the progress made in managing air pollution in China, it is crucial to address the problem of environmental O3 pollution at present. METHODS: The connection between O3 exposure and respiratory mortality in Shenyang, China, from 2014 to 2018 was analyzed by a time-series generalized additive regression model (GAM) with quasi-Poisson regression. Additionally, the potential combined effects of fine particulate matter (PM2.5) and O3 were investigated using the synergy index (SI). RESULTS: Our findings indicate that each 10 µg/m3 increase in O3 at lag 2 days was associated with a maximum relative risk (RR) of 1.0150 (95% CI: 1.0098-1.0202) for respiratory mortality in the total population. For individuals aged ≥55 years, unmarried individuals, those engaged in indoor occupations, and those with low educational attainment, each 10 µg/m3 increase in O3 at lag 07 days was linked to RR values of 1.0301 (95% CI: 1.0187-1.0417), 1.0437 (95% CI: 1.0266-1.0610), 1.0317 (95% CI: 1.0186-1.0450), and 1.0346 (95% CI: 1.0222-1.0471), respectively. Importantly, we discovered a synergistic effect of PM2.5 and O3, resulting in an SI of 2.372 on the occurrence of respiratory mortality. CONCLUSIONS: This study confirmed a positive association between O3 exposure and respiratory mortality. Furthermore, it highlighted the interaction between O3 and PM2.5 in exacerbating respiratory deaths.

Improving the physicochemical and pharmacokinetic properties of olaparib through cocrystallization strategy.

Olaparib (OLA) is the first PARP inhibitor worldwide used for the treatment of ovarian cancer. However, the oral absorption of OLA is extremely limited by its poor solubility. Herein, pharmaceutical cocrystallization strategy was employed to optimize the physicochemical and pharmacokinetic properties. Four cocrystals of OLA with oxalic acid (OLA-OA), malonic acid (OLA-MA), fumaric acid (OLA-FA) and maleic acid (OLA-MLA) were successfully discovered and characterized. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the formation of cocrystals rather than salts, and the possible hydrogen bonding patterns were analyzed through molecular surface electrostatic potential calculations. The in vitro and in vivo evaluations indicate that all of the cocrystals demonstrate significantly improved dissolution performance, oral absorption and tabletability compared to pure OLA. Among them, OLA-FA exhibit sufficient stability and the most increased Cmax and AUC0-24h values that were 11.6 and 6.1 times of free OLA, respectively, which has great potential to be developed into the improved solid preparations of OLA.

[Q-marker prediction of resin ethanol extract of Gegen Qinlian Decoction based on characteristic spectrum and network pharmacology].

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.