Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully. FUNDING: F Hoffmann-La Roche/Genentech.

The Albumin-Bilirubin Score as a Predictor of Liver-Related Mortality in Primary Biliary Cholangitis with Compensated Cirrhosis.

BACKGROUND: Although several prognostic scores have been reported to correlate with the prognosis of primary biliary cholangitis (PBC) patients, there are limited tools to predict the prognosis of PBC with compensated cirrhosis. This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score in PBC patients with compensated cirrhosis. METHODS: We conducted a retrospective longitudinal study of 219 patients with compensated PBC cirrhosis to evaluate the prognostic performance of the ALBI using Cox regression model, receiver operating characteristic (ROC) curve, and Kaplan-Meier method. RESULTS: During follow-up, a total of 19 subjects (8.7%) met the primary endpoint of liver-related death or liver transplantation (LT). Patients who died/underwent LT have higher ALBI score (-1.06 vs. -2.06, p < 0.001) at baseline than those who survived. ALBI score (hazard ratio: 15.011, 95% confidence interval [CI]: 5.045-44.665, p < 0.001) was associated with an increase in liver-related mortality or LT. ALBI score had the best discriminative capacity to predict the 5-year liver-related mortality (area under the ROC curve: 0.871, 95% CI [0.820, 0.913]) compared with other prognostic scores. The ROC curve showed that the best cut-off value of ALBI score was -1.47, with 90.0% sensitivity and 76.6% specificity. Also, the probability of transplant-free survival decreased with increasing ALBI grade (log-rank p = 0.003). The 5-year transplant-free survival rates of patients in grade 1, grade 2, and grade 3 were 100.0%, 96.4%, and 89.4%, respectively. CONCLUSION: ALBI score is a simple and effective predictive factor estimating the clinical outcome of patients with compensated PBC cirrhosis and provides better prognostic performance compared with other prognostic scores.

Analysis of clinical features and prognostic factors in patients with hepatic hydrothorax: a single-center study from China.

BACKGROUND: The clinical features and factors affecting the prognostic survival of hepatic hydrothorax (HH) are currently unknown. METHODS: We conducted a retrospective cohort study of 131 patients with HH using the Kaplan-Meier method and Cox proportional hazards regression analysis to assess factors influencing the prognosis of HH. RESULTS: A total of 131 patients were enrolled: the male to female ratio was 80:51 (1.59:1), and the mean age was 52.76 ± 11.88 years. Hepatitis B cirrhosis was the main cause of HH, and abdominal distention and dyspnea were the most common clinical signs. Ascites was present in varying amounts in all patients and was the most common decompensated complication, with pleural effusions mostly seen on the right side (107/131; 82%), followed by the left side (16/131; 12%) and bilateral effusions (8/131; 6%). For overall survival without transplantation, the estimated median survival time was 21 (95% confidence interval [CI]:18-25) months, and survival rates at 6 months, 1 year, and 2 years were 77.2%, 62.4%, and 29.7%, respectively. After controlling for covariates that were associated with liver-related mortality in the univariate analysis, males (hazard ratio [HR]: 1.721, 95% CI: 1.114-2.658, P = 0.005) and combined hepatic encephalopathy (HR: 2.016, 95% CI: 1.101-3.693, P = 0.001) were found to be associated with an increase in liver-related mortality. CONCLUSIONS: In this cohort of HH patients without liver transplantation, male sex and hepatic encephalopathy were associated with a higher risk of liver-related death.

Organics alleviate the inhibition of sulfate on ANAMMOX sludge.

Anaerobic ammonium oxidation (Anammox) was an innovative process for nitrogen removal. In this study, the influence of sulfate in different concentrations (100, 200, 300, and 400 mg L-1) on Anammox process were investigated in nine identical sequential batch reactors, four of which were extra supplied for organics, to study the combined effect. The results indicated the obvious inhibition by sulfate which decreased the total nitrogen removal efficiency (TNRE) to 84.1%, 81.2%, 81.2%, and 72.5%, from the control results as 91.9%. Whereas, the organics addition alleviated the inhibitory effect, through consuming the oxygen in influent, promoting the secretion of protein, and inducing the denitrifying bacteria, for which the sulfate only slightly decreased the TNRE to 89.0%, 83.7%, 83.6%, and 75.7%, respectively. Candidatus Kuenenia and Denitratisoma could coexist in Anammox system and cooperatively contribute to the nitrogen removal, when treating the nitrogenous wastewater contains both sulfate and organics.

Seraprevir and sofosbuvir for treatment of chronic hepatitis C virus infection: A single-arm, open-label, phase 3 trial.

BACKGROUND AND AIM: This single-arm, open-label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. METHODS: Treatment-naive or interferon-experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). RESULTS: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post-treatment course and 3 discontinued follow-up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. CONCLUSIONS: The all-oral, ribavirin-free regimen of seraprevir and sofosbuvir is an effective and well-tolerated treatment option for Chinese patients mono-infected with HCV, including those with a history of interferon treatment.

The relationship between the posterior tibial slope and the sagittal femoral condylar shape: Two circles and ellipses.

BACKGROUND: Whether the posterior tibial slope (PTS) is associated with the femoral condylar shape has remained unclear. Classical anatomical studies considered the sagittal profiles of femoral condyles to consist of two circles. Recently, an elliptical method was described to simplify the "two circles" model. Our purpose was to analyze the relationship between the PTS and the shape of the sagittal femoral condyle, that is, two circles and two ellipses, using magnetic resonance imaging (MRI) scans. METHODS: Eighty right knees of healthy subjects were scanned by MRI at full extension. The medial and lateral PTS were measured (mPTS and lPTS). On the distal-most medial and lateral slices, the femoral condylar articular surfaces were best fitted by circles or ellipses, respectively. The radii of the medial and lateral posterior circles and inferior circles (rm and rl , Rm and Rl , respectively), the semi-major axes and the semi-minor axes of the medial and lateral ellipses (am and al , bm and bl , respectively), and the rm /Rm , bm /am , rl /Rl , bl /al ratios were measured and calculated. RESULTS: mPTS correlated significantly with the parameters of the medial condyle (all p < .05) and the ratios bm /am and rm /Rm (p = .017 and p = .027, respectively). However, the lPTS did not correlate with the parameters of the lateral condyle (all p > .05) or the ratios bl /al and rl /Rl (p = .461 and p = .241, respectively). CONCLUSION: The mPTS is associated with the sagittal shape of the medial femoral condyle but the lPTS is not. Both two circles and two ellipses are feasible ways to represent the sagittal femoral condylar shape.

Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma.

The genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen is a powerful tool used to identify therapeutic targets that can be harnessed for cancer treatment. This study aimed to assess the efficacy of genome-wide CRISPR screening to identify druggable genes associated with sorafenib-treated hepatocellular carcinoma (HCC). A genome-scale CRISPR knockout (GeCKO v2) library containing 123,411 single guide RNAs (sgRNAs) was used to identify loss-of-function mutations conferring sorafenib resistance upon HCC cells. Resistance gene screens identified SGOL1 as an indicator of prognosis of patients treated with sorafenib. Of the 19,050 genes tested, the knockout screen identified inhibition of SGOL1 expression as the most-effective genetic suppressor of sorafenib activity. Analysis of the survival of 210 patients with HCC after hepatic resection revealed that high SGOL1 expression shortened overall survival (P = 0.021). Further, matched pairs analysis of the TCGA database revealed that SGOL1 is differentially expressed. When we used a lentivirus Cas9 vector to determine the effect of targeting SGOL1 with a specific sgRNA in HCC cells, we found that SGOL1 expression was efficiently inhibited and that loss of SGOL1 was associated with sorafenib resistance. Further, loss of SGOL1 from HCC cell decreased the cytotoxicity of sorafenib in vivo. We conclude that the CRISPR screen is a powerful tool for therapeutic target analysis of sorafenib treatment and that SGOL1 serves as a druggable target for HCC treated with sorafenib and an indicator of prognosis.

Refractory sciatica caused by gluteal varicosities.

We report a case of sciatica that fulfilled the diagnostic criteria for inferior gluteal vein varicosities according to patient history and on magnetic resonance imaging. Since conservative treatment was ineffective, excision-ligation of the varicose vein was performed as recommended in the previous literature. However, pain was only slightly relieved and then aggravated. Reoperation involving wide release and resection of the piriformis outlet was performed. Pain resolved immediately thereafter. We suggest that this case of sciatica resulted from both piriformis entrapment and vein varicosities. The piriformis entrapment led to inferior gluteal vein backflow obstruction, and varicosities could have been the trigger of piriformis syndrome. Excision-ligation of the varicose vein and piriformis release were recommended.

Intraosseous Schwannoma Involving Multiple Bones of the Foot: A Case Report.

We describe a rare case of intraosseous Schwannoma in the foot involving the tarsal navicular, cuboid, all 3 cuneiforms, and the second and third metatarsal bases in a 50-year-old female. Radiographs revealed a large, well-defined osteolytic lesion with endosteal scalloping and trabeculated contours at the margins. Intralesional excision, allograft bone implantation, and Kirschner wire fixation were performed. The histologic and immunohistochemical studies confirmed the diagnosis of Schwannoma. The distinctive radiographic features might have been the result of tumor spreading within the nutrient canals of the bones and direct compression of bone as the tumor enlarged. At the 18-month follow-up point, the patient had recovered well without recurrence. Intralesional excision produced a good functional outcome; however, extensive fusion surgery is recommended.

The fate and transport of neonicotinoid insecticides and their metabolites through municipal wastewater treatment plants in South China.

Neonicotinoid insecticides (NEOs) have gained widespread usage as the most prevalent class of insecticides globally and are frequently detected in the environment, posing potential risks to biodiversity and human health. Wastewater discharged from wastewater treatment plants (WWTPs) is a substantial source of environmental NEOs. However, research tracking NEO variations in different treatment units at the WWTPs after being treated by the treatment processes remains limited. Therefore, this study aimed to comprehensively investigate the fate of nine parent NEOs (p-NEOs) and five metabolites in two municipal WWTPs using distinct treatment processes. The mean concentrations of ∑NEOs in influent (effluent) for the UNITANK, anaerobic-anoxic-oxic (A2/O), and cyclic activated sludge system (CASS) processes were 189 ng/L (195 ng/L), 173 ng/L (177 ng/L), and 123 ng/L (138 ng/L), respectively. Dinotefuran, imidacloprid, thiamethoxam, acetamiprid, and clothianidin were the most abundant p-NEOs in the WWTPs. Conventional wastewater treatment processes were ineffective in removing NEOs from wastewater (-4.91% to -12.1%), particularly major p-NEOs. Moreover, the behavior of the NEOs in various treatment units was investigated. The results showed that biodegradation and sludge adsorption were the primary mechanisms responsible for eliminating NEO. An anoxic or anaerobic treatment unit can improve the removal efficiency of NEOs during biological treatment. However, the terminal treatment unit (chlorination disinfection tank) did not facilitate the removal of most of the NEOs. The estimated total amount of NEOs released from WWTPs to receiving waters in the Pearl River of South China totaled approximately 6.90-42.6 g/d. These findings provide new insights into the efficiency of different treatment processes for removing NEOs in current wastewater treatment systems.

Establishment of anammox coupled with sulfide-depending autotrophic denitrification process and its efficient pollutants removal performance.

Nitrogen and sulfur pollutants coexist in many industrial wastewaters, which may cause serious water pollution issues. In this study, Anammox coupled with sulfide-depending autotrophic denitrification process (coupling process) was established by adding sulfide to an Anammox system in a membrane bioreactor. Variations in nitrogen and sulfur removal performance, extracellular polymeric substances (EPS), key enzyme activities, and microbial components were analyzed. The sulfide in 25.0 mg L-1 successfully induced denitrification, and then helped establish the coupling process. This process achieved 96.1% TN removal and complete sulfide removal when the sulfide was increased to 100.0 mg L-1. The protein and polysaccharide in EPS gradually increased to 2.0 and 4.9 mg g-1 SS, respectively. The hydroxylamine oxidoreductase activity, Heme-c content, nitrite reductase activity, and nitrate reductase activity slightly decreased to 19.1 EU g-1 SS, 0.001 mmol g-1 SS, 0.002 µg min-1 mg-1 protein, and 0.005 µg min-1 mg-1 protein, respectively, indicating the slight suppression of sulfide in high concentration on the coupling process. However, after acclimatization, the Anammox and denitrifying bacteria interacted and cooperatively contributed to the simultaneous nitrogen and sulfur removal, with relative abundances of Thiobacillus-denitrifying bacteria and Candidatus Kuenenia-Anammox bacteria of 31.7% and 9.0%, respectively. The establishing strategy was proposed and then verified in another Anammox system, in which the coupling process was also established, with TN removal increasing from 73.4% to 82.5%.

The intervention effect of Aitongxiao prescription on primary liver cancer rats was evaluated based on high-throughput miRNA sequencing and bioinformatics analysis.

Liver cancer is a common malignant tumor known for its difficult treatment and poor prognosis. As a traditional Chinese medicine prescription, Aitongxiao prescription (ATXP) has been used in clinical treatment of primary liver cancer (PLC) for more than ten years, and its therapeutic effect is obvious and has been verified over time. However, the mechanism of ATXP in treating PLC has not been fully elucidated. This study aimed to detect the liver-protective effect of ATXP on a PLC rat model and explore its potential mechanism from the perspective of plasma extracellular vesicle miRNAs. Fifty SPF male SD rats were randomly selected, with six rats as the control group, and the remaining rats were injected with DEN to establish a primary liver cancer model. The model rats were randomly divided into the model group and the ATXP group. After 4 weeks of intervention, the liver-protective effect of ATXP was evaluated using plasma biochemical indicators and histopathological methods. Plasma extracellular vesicles were isolated and extracted, and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Significant differentially expressed miRNAs in extracellular vesicles were screened by Illumina sequencing to explore the therapeutic targets of ATXP and conduct functional analysis. The results showed that ATXP significantly reduced plasma liver function in PLC rats and alleviated liver pathological damage. In addition, plasma extracellular vesicles were isolated and identified. According to the results of GO and KEGG analysis, they were related to multiple biological processes and covered multiple signaling pathways (PI3K-Akt and MAPK signaling pathways, etc.). The interaction between miR-199a-3p and MAP3K4 was determined by bioinformatics methods and dual-luciferase reporter gene detection, confirming that MAP3K4 is the target gene of miR-199a-3p. In conclusion, ATXP protects the liver from DEN-induced PLC, which may be related to the regulation of plasma extracellular vesicle miR-199a-3p. This study further reveals the mechanism of ATXP in treating liver cancer and provides a theoretical basis for subsequent research.

TR score: A noninvasive model to predict histological stages in patients with primary biliary cholangitis.

Introduction: The aim of this study was to develop a noninvasive prediction model for histological stages in PBC that is simple, easy to implement, and highly accurate. Methods: A total of 114 patients with PBC were included in this study. Demographic, laboratory data and histological assessments were collected. The independent predictors of histological stages were selected to establish a noninvasive serological model. The scores of 22 noninvasive models were calculated and compared with the established model. Results: This study included 99 females (86.8%) and 15 males (13.2%). The number of patients in Scheuer's stage 1, 2, 3 and 4 was 33 (29.0%), 34 (29.8%), 16 (14.0%), and 31 (27.2%), respectively. TBA and RDW are independent predictors of PBC histological stages. The above indexes were used to establish a noninvasive model-TR score. When predicting early histological change (S1) or liver fibrosis and cirrhosis (S3-S4), the AUROC of TR score were 0.887 (95% CI, 0.809-0.965) and 0.893 (95% CI, 0.816-0.969), higher than all of the other 22 models included in this study. When predicting cirrhosis (S4), its AUROC is still as high as 0.921 (95% CI, 0.837-1.000). Conclusion: TR score is an easy, cheap and stable noninvasive model, without complex calculation formulas and tools, and shows good accuracy in diagnosing the histological stages of PBC.

Efficacy evaluation of pulmonary hypertension therapy in patients with portal pulmonary hypertension: A systematic review and meta-analysis.

Objective: To determine the therapeutic effect of pulmonary arterial hypertension (PAH) agents for portal pulmonary hypertension (POPH). Design: Systematic review and meta-analysis. Background: POPH is a serious complication of end-stage liver disease with a low survival rate. Liver transplantation (LT) is an effective treatment. Due to the presence of POPH, some patients cannot undergo LT. After PAH treatment, patients with POPH can obtain good hemodynamics and cardiac function for LT, but there are no standard guidelines. Methods: Two independent researchers searched PubMed, EMBASE, Cochrane Library, and Web of Science for studies published from inception to 27 September 2022, focusing on the changes in hemodynamics and cardiac function in all patients with POPH to understand the effect of PAH treatment on the entire population of POPH patients. Among these, we specifically analyzed the changes in hemodynamics and cardiac function in moderate and severe POPH patients. After collecting the relevant data, a meta-analysis was carried out using the R program meta-package. Results: A total of 2,775 literatures were retrieved, and 24 literatures were included. The results showed that in all POPH patients (n = 1,046), the following indicators were significantly improved with PAH agents: mPAP: (MD = -9.11 mmHg, p < 0.0001); PVR: (MD = -239.33 dyn·s·cm-5, p < 0.0001); CO: (MD = 1.71 L/min, p < 0.0001); cardiac index: (MD = 0.87 L/(min·m2), p < 0.0001); 6MWD: (MD = 43.41 m, p < 0.0001). In patients with moderate to severe POPH (n = 235), the following indicators improved significantly with PAH agents: mPAP (MD = -9.63 mmHg, p < 0.0001); PVR (MD = -259.78 dyn·s·cm-5, p < 0.0001); CO (MD = 1.76 L/min, p < 0.0001); Cardiac index: (MD = 1.01 L/(min·m2), p = 0.0027); 6MWD: (MD = 61.30 m, p < 0.0001). Conclusion: The application of PAH agents can improve cardiopulmonary hemodynamics and cardiac function in patients with POPH, especially in patients with moderate to severe POPH, and the above changes are more positive. Systematic Review Registration: https://inplasy.com, identifier INPLASY202250034.

The prognostic value of antibodies to gp210 among patients with primary biliary cholangitis in Northeast China.

BACKGROUND: Whether the anti-gp210 antibody can be used as a biomarker in patients with primary biliary cholangitis (PBC) remains controversial. AIMS: We aimed to investigate the association between anti-gp210 antibodies and prognosis in ursodeoxycholic acid (UDCA)-treated PBC patients. METHODS: We conducted a retrospective cohort study of 180 UDCA-treated PBC patients to assess the prognostic value of anti-gp210 antibodies using the Kaplan-Meier method and Cox proportional hazard regression analysis. RESULTS: Of the patients included in our analysis, 50 (27.8%) were anti-gp210 positive, and 130 (72.2%) were anti-gp210 negative. The incidence of liver-related death or transplantation was more common in the anti-gp210 + group (22.0 vs. 9.2%, P=0.022). The five-year transplant-free survival rates of anti-gp210-positive patients vs. anti-gp210-negative patients were 77.0% and 90.3%, respectively. We found that the probability of transplant-free survival was significantly lower in the anti-gp210-positive patients than in the anti-gp210-negative patients (log-rank P=0.004). After adjusting for potential confounders using multivariable Cox regression model, positivity for anti-gp210 antibody (hazard ratio: 4.619, 95% confidence interval: 1.895-11.261, P=0.001) was found to be independently associated with an increase in liver-related mortality or transplantation. CONCLUSION: In this cohort of UDCA-treated PBC patients, positivity for anti-gp210 antibody was independently associated with a higher risk of liver-related death or transplantation.

Integrated Plasma Metabolomics and Gut Microbiota Analysis: The Intervention Effect of Jiawei Xiaoyao San on Liver Depression and Spleen Deficiency Liver Cancer Rats.

Primary liver cancer is the third most common malignancy, and hepatocellular carcinoma is its main subtype, with a high recurrence rate and high mortality. Intestinal microflora and metabolic disorders are present in most HCC patients. Traditional Chinese medicine (TCM) plays an important role in the composition of intestinal microorganisms and the transformation of active metabolites. Many scholars are trying to develop related drugs to assist in the treatment of liver cancer. In the preliminary study of the research group, it was found that the Jiawei Xiaoyao San has a certain therapeutic effect on liver cancer, but the specific mechanism is still unclear. Therefore, this study constructed a liver cancer rat model with liver stagnation and spleen deficiency, to explore the regulatory effect of Jiawei Xiaoyao San on plasma metabolites and intestinal microflora and to find the potential mechanism of Jiawei Xiaoyao San in the treatment of liver cancer. Plasma samples and fecal samples were collected from liver cancer rats with liver depression and spleen deficiency for microbiome 16S rDNA sequencing and metabolic ESI-QTRAP-MS/MS analysis. Various bioinformatics methods were used to analyze the dataset individually and in combination. The analysis and identification of plasma metabolomics showed that the intervention effect of Jiawei Xiaoyao San on liver cancer rats with liver depression and spleen deficiency was related to 11 differential metabolites and signal pathways such as primary bile acid biosynthesis, phenylalanine metabolism, pantothenate and COA biosynthesis, metabolic pathways, cholesterol metabolism, and bile secretion. Combined with fecal microbiological analysis, it was found that Jiawei Xiaoyao San could significantly change the composition of intestinal flora in liver cancer rates, increase beneficial bacteria, and reduce the composition of harmful bacteria. This study provides some experimental basis for the traditional Chinese medicine theory and clinical application of Jiawei Xiaoyao San in the adjuvant treatment of liver cancer. The potential mechanism may be to regulate metabolism and intestinal flora to play the role of regulating liver depression, activating blood, and detoxifying, to achieve the purpose of adjuvant treatment of liver cancer.

The impact and role of hepatic hydrothorax in the prognosis of patients with decompensated cirrhosis: A retrospective propensity score-matched study.

Background and aims: Hepatic Hydrothorax (HH) is one of the complications in patients with decompensated cirrhosis and its impact and role in the prognosis of patients with decompensated cirrhosis are not yet clear. Thus, this study aimed to determine the role of HH in patients with decompensated cirrhosis and the long-term impact on their mortality. Materials and methods: A retrospective study analyzed 624 patients with ascites without pleural effusion in decompensated cirrhosis and 113 patients with HH. Propensity scores were calculated based on eight variables, and the HH and non-HH groups were matched in a 1:1 ratio. The effect and role of HH on the prognosis of patients with decompensated cirrhosis was analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. Results: A total of 737 patients were included. Out of 113 HH patients, 106 could be matched to 106 non-HH patients. After matching, baseline characteristics were well-balanced. The multifactorial Cox proportional hazards model indicated that hepatic encephalopathy and HH were independent risk factors affecting prognostic survival in patients with decompensated cirrhosis (P < 0.01), with risk ratios and 95% confidence intervals (CI) of 2.073 (95% CI: 1.229-3.494, P < 0.01) and 4.724 (95% CI: 3.287-6.789, P < 0.01), respectively. Prognostic survival was significantly worse in the HH group compared to patients in the non-HH group, with mortality rates of 17.9, 30.1, and 59.4% at 6 months, 1 year, and 2 years in the HH group, compared to 0.9, 3.8, and 5.6% in the non-HH group, respectively. The estimated median survival time was 21 (95% CI: 18-25) months in the HH group and 49 (95% CI: 46-52) months in the non-HH group (P < 0.001). Conclusion: Hepatic hydrothorax is significantly associated with higher mortality in patients with decompensated cirrhosis and is a highly negligible independent decompensated event affecting their prognosis.

Correlation between serum cytokines and clinicopathological features in patients with drug-induced liver injury.

Objectives: Changes in serum levels of cytokines have been proposed as possible biological markers of tissue damage, including drug-induced liver injury (DILI). Here, we aimed to screen cytokine markers that have guiding significance for the degree of inflammation of DILI. Patients and methods: 54 patients with DILI were retrospectively analyzed as the experimental group, and 14 healthy subjects were randomly selected as the control group. A total of 20 cytokines were detected by using a cytokine protein antibody chip, and differentially expressed proteins were screened. Results: There were significant differences in serum cytokines between DILI patients and healthy controls. Compared with the control group, the DILI group expressed 11 differential proteins. IL-8, TNF RII, TNFα, TNF RI, MIP-1ß, MIP-1α, and IL-1ß were differentially expressed in DILI patients with different degrees of inflammation from G1 to G4. MIG, IL-12p40, and IL-10 were differentially expressed in the higher degree of inflammation groups (G2, G3, and G4 groups). Tissue inhibitor of metalloproteinases-1 (TIMP-1) was differentially expressed in the group with the highest inflammation degree (G4 group). Chemokine C-C motif ligand 1 (I-309) was only differentially expressed in the lowest inflammation group (G1 group). Conclusion: The changes and differential expression of specific cytokine levels were helpful for evaluating different degrees of inflammation of DILI.

[Pollution Characteristics and Source Apportionment of Atmospheric Volatile Organic Compounds in Summer in Yuncheng City].

Based on the online monitoring data of VOCs, O3, and NO2 in Yuncheng City from June to August 2020, the pollution characteristics of VOCs in Yuncheng City in summer were analyzed. At the same time, the main emission sources were determined using a PMF model, and the chemical reactivity of VOCs was evaluated using the maximum incremental reactivity (MIR) method and fractional aerosol coefficients (FAC). The results showed that the urban area of Yuncheng was seriously polluted by VOCs and NO2 in the early morning and evening during summer, the peak value of VOCs daily variation occurred at 08:00 and 20:00, respectively, and was mainly affected by the morning and evening peaks in traffic. The ρ(VOCs) from June to August was 50.52 µg·m-3, and the species with the highest proportion were alkanes (39.39%) and oxygenated volatile organic compounds (OVOCs, 34.63%). Five VOCs emission sources were determined by the PMF model, of which the largest contribution was from motor vehicle exhaust emission sources (33.10%), followed by industrial emission sources (29.46%), natural gas and coal combustion sources (17.31%), solvent use sources (11.94%), and plant emission sources (8.19%). Controlling motor vehicle exhaust emission sources is the key to alleviate VOCs pollution in summer in Yuncheng City. The average ozone formation potential (OFP) of VOCs was 162.88 µg·m-3, in which OVOCs had the highest contribution rate (45.37%); acetaldehyde, propionaldehyde, ethylene, isoprene, and toluene were the key active components; and industrial emission sources were the emission sources with the highest contribution rate. The average value of secondary organic aerosol formation potential (SOAp) of VOCs was 0.40 µg·m-3, in which the contribution rate of aromatic hydrocarbons was the highest (88.00%), and the solvent use source was the emission source with the highest contribution rate.

A detection and configuration method for welding completeness in the automotive body-in-white panel based on digital twin.

To address the problems of poor welding completeness and inefficient configuration for defective automotive body-in-white panels, we propose a method for detecting and configuring the welding completeness of automotive body-in-white panels based on digital twin (DT) and mixed reality (MR). The method uses DT to build an MR-oriented DT framework for the detections and configuration of body-in-white panel welding completeness. We propose a method to build a DT knowledge base for panels, a Yolov4-based welding completeness detection method, and a MR-based configuration method for the welding completeness in panels. Our team develop a panel welding completeness detection and configuration system to fully validate the effectiveness of the method.