Effect of liver metastasis on the efficacy of immune checkpoint inhibitors in cancer patients: a systemic review and meta-analysis.

Liver metastasis is a frequent phenomenon in advanced tumor disease. Immune checkpoint inhibitors (ICIs) are a new class of therapeutics that can improve the prognosis of cancer patients. The purpose of this study is to elucidate the relationship between liver metastasis and survival outcomes of patients receiving ICIs treatment. We searched four main databases, including PubMed, EMBASE, Cochrane Library, and Web of Science. Overall survival (OS) and progression-free survival (PFS) were the survival outcomes of our concern. Hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the relationship between liver metastasis and OS/ PFS. Finally, 163 articles were included in the study. The pooled results showed that patients with liver metastasis receiving ICIs treatment had worse OS (HR=1.82, 95%CI:1.59-2.08) and PFS (HR=1.68, 95%CI:1.49-1.89) than patients without liver metastasis. The effect of liver metastasis on ICIs efficacy differed in different tumor types, and patients with urinary system tumors (renal cell carcinoma OS: HR=2.47, 95%CI:1.76-3.45; urothelial carcinoma OS: HR=2.37, 95%CI:2.03-2.76) had the worst prognosis, followed by patients with melanoma (OS: HR=2.04, 95%CI:1.68-2.49) or non-small cell lung cancer (OS: HR=1.81, 95%CI:1.72-1.91). ICIs efficacy in digestive system tumors (colorectal cancer OS: HR=1.35, 95%CI:1.07-1.71; gastric cancer/ esophagogastric cancer OS: HR=1.17, 95%CI:0.90-1.52) was less affected, and peritoneal metastasis and the number of metastases have a greater clinical significance than liver metastasis based on univariate data. For cancer patients receiving ICIs treatment, the occurrence of liver metastasis is associated with poor prognosis. Different cancer types and metastatic sites may hold a different prognostic effect on the efficacy of ICIs treatment in cancer patients.

Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Tenofovir (TDF) and entecavir (ETV) are first-line treatments for patients with chronic hepatitis B virus (HBV) infection. However, the effect of TDF versus ETV on the prognosis of HBV-related hepatocellular carcinoma (HCC) has not been fully clarified yet. RESEARCH DESIGN AND METHODS: PubMed, Embase and Web of science were searched up to March, 2021. Meta-analyses were performed for overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) to assess the effect of TDF versus ETV on the prognosis of HBV-related HCC. RESULTS: A total of 10 studies comprising 4706 Asian patients were included. The pooled results revealed that TDF was associated with better OS (adjusted HR = 0.50, 95% CI: 0.40-0.62; I2 = 36.0%, p = 0.167) and better RFS/DFS (adjusted HR = 0.70, 95% CI: 0.55-0.89, I2 = 71.9%, p = 0.002) than ETV in treatment of HBV-related HCC. Subgroup analysis revealed that OS benefit from TDF was generally consistent, except for patients who underwent non-surgical treatment for HCC. Subgroup analysis also indicated that TDF reduces the risk of late recurrence (HR = 0.41, 95% CI: 0.18-0.0.93; I2 = 63.0%, p = 0.067) rather than early recurrence (HR = 0.99, 95% CI: 0.64-1.52; I2 = 61.3%, p = 0.076). CONCLUSIONS: Compared with ETV, TDF has the advantage of improving OS and reducing late recurrence of patients with HBV-related HCC patients who underwent resection.

Identification of the most effective subgroup of advanced hepatocellular carcinoma from immune checkpoint blocker treatment: a meta-analysis.

Aims: This work was designed to identify the subgroup of advanced hepatocellular carcinoma (HCC) patients for whom treatments containing immune checkpoint blockers (ICBs) were most effective. Materials & methods: A meta-analysis was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs. Results: A total of 2228 patients from four randomized control trials were included. Treatments containing ICBs had better overall survival, progression-free survival and higher objective response rate over treatment without ICBs. Subgroup analysis revealed that treatments containing ICBs were highly effective in improving the overall survival of males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients. Conclusion: Treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.

Immune checkpoint blockers (ICBs) have significantly improved the prognosis of advanced cancers. However, some patients still cannot benefit from ICBs. The use of ICBs in the treatment of advanced hepatocellular carcinoma (HCC) started late. The subgroup of advanced HCC patients that will benefit most from treatments containing ICBs is still largely unknown. Therefore, a meta-analysis (meta-analysis is a statistical method used to compare or synthesize research results on the same scientific problem) was performed to explore the subgroup population with the greatest benefit of treatments containing ICBs (ICBs alone or in combination with anti-VEGF agents). The results show that treatments containing ICBs are more effective for males, patients with macrovascular invasion and/or extrahepatic spread and viral-related HCC patients.

A novel prognostic scoring model based on copper homeostasis and cuproptosis which indicates changes in tumor microenvironment and affects treatment response.

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive. Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells' pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes' expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation. Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines. Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time.

Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.

BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.

Systemic therapy with or without locoregional therapy for advanced hepatocellular carcinoma: A systematic review and network meta-analysis.

We aim to identify the optimal treatment option of systemic therapy with or without locoregional therapy for advanced hepatocellular carcinoma (HCC). Outcomes of interest include overall survival (OS), progression-free survival (PFS), objective response rate (ORR), grade 3-4 treatment-related adverse events (TRAEs), and incidence of treatment discontinuation due to AEs. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the interventions. 23 randomized-controlled trials including 14,303 patients with advanced HCC were included. Lenvatinib plus transcatheter arterial chemoembolization (TACE) ranked best regarding OS benefit (SUCRA: 0.99). Immuno-oncology (IO)-multikinase inhibitor (MKI)/vascular endothelial growth factor (VEGF) inhibitor combinations had a higher probability of providing better OS than IO-IO combinations. IO monotherapies demonstrated superior safety profile while combination therapies caused more toxicity in general. We conclude that combination therapies achieve remarkable efficacy in patients with advanced HCC and clinical decision making requires a careful balance of efficacy versus risk.

Hepatitis B virus reactivation in patients undergoing immune checkpoint inhibition: systematic review with meta-analysis.

PURPOSE: Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy. METHODS: A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0-3%) and 0% (95% CI 0-0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0-2%) and 10.0% (95% CI 4-18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16-34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02-0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01-0.28)] in patients with chronic HBV infection. CONCLUSIONS: Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy.

Evaluating liver function and the impact of immune checkpoint inhibitors in the prognosis of hepatocellular carcinoma patients: A systemic review and meta-analysis.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) have underlying cirrhosis and a compromised liver function. Immune checkpoint inhibitors (ICIs) have emerged as an important approach for HCC treatment. The purpose of our study was to explore the prognostic significance of liver function in HCC patients receiving ICIs. METHODS: Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the relationship between liver function and overall survival (OS)/progression-free survival (PFS). RESULTS: 41 articles with 4483 patients with HCC were included. The pooled results revealed that either Child-Pugh score (OS:HR = 2.01,95 %CI:1.69-2.38; PFS:HR = 1.39,95 %CI:1.15-1.68) or albumin-bilirubin (ALBI) score (OS:HR = 2.04,95 %CI:1.55-2.69; PFS:HR = 1.42,95 %CI:1.21-1.67) can predict the patient prognosis. The Child-Pugh score has some degree of subjectivity, and the ALBI score can better stratify patients. Therefore, the ALBI score was used to evaluate patients' liver function and determine treatment options. Further subgroup analysis found that the results of prospective studies were statistically significant only for the ALBI score with regards to OS (HR = 1.69,95 %CI:1.26-2.26). Meanwhile, the effect of liver function on the efficacy of ICIs in the large-sample studies was not as obvious as that in small-sample studies. Moreover, the incidence of adverse events did not significantly increase in patients with impaired liver function. CONCLUSION: Poor liver function is associated with a poor prognosis in patients with HCC receiving ICIs. The ALBI score is simpler and reliable for patient stratification than the Child-Pugh score. Although the survival time of patients with impaired liver function may be relatively short, ICIs still have great potential for therapeutic applications.

Early alpha-fetoprotein response predicts prognosis of immune checkpoint inhibitor and targeted therapy for hepatocellular carcinoma: a systematic review with meta-analysis.

BACKGROUND: The prognostic value of alpha-fetoprotein (AFP) response for efficacy of targeted therapy or immune checkpoint inhibitors (ICIs) has not been established. The purpose of this meta-analysis is to elucidate the relationship between AFP response and survival outcomes in hepatocellular carcinoma (HCC) patients who received targeted therapy or ICIs. METHODS: The hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the relationship between AFP response and overall survival (OS)/progression-free survival (PFS). RESULTS: Twenty-six articles containing 3056 HCC patients were finally included in the study. The pooled results showed that after targeted therapy or ICIs, patients with decrease in AFP had better prognosis (OS:HR = 0.48, 95%CI:0.40-0.56; PFS:HR = 0.39, 95%CI:0.33-0.46), while patients with increase in AFP had worse prognosis (OS:HR = 2.30, 95%CI:1.82-2.89; PFS:HR = 2.34, 95%CI = 1.69-3.24). Subgroup analysis revealed that compared to AFP decrease >50%, AFP decrease >20% can better predict the prognosis of patients who received targeted therapy (OS:HR = 0.51, 95%CI:0.41-0.62; PFS:HR = 0.39, 95%CI:0.30-0.51) or ICIs treatment (OS:HR = 0.34, 95%CI:0.16-0.71; PFS:HR = 0.22, 95%CI:0.10-0.47), and 8 weeks after targeted therapy may be the appropriate time point for AFP assessment. CONCLUSION: AFP decrease >20% within 8 weeks may be the appropriate definition for early AFP response which probably works best in predicting the efficacy of therapy. REGISTRATION: The review was not registered.

Adverse events of immune checkpoint inhibitors in hepatocellular carcinoma: a systemic review and meta-analysis.

The introduction of immune checkpoint inhibitors (ICIs) has reshaped the therapy of hepatocellular carcinoma (HCC). ICIs are a novel therapy with frequent adverse events (AEs), including treatment-related adverse events (trAEs) and immune-related adverse events (irAEs). However, no comprehensive overview of the toxicity spectrum of ICIs in HCC patients has been provided. Electronic databases were searched to identify eligible studies. A meta-analysis of the incidence rate of AEs in HCC patients treated with ICIs was performed. Lastly, the prognostic value of irAEs in HCC patients treated with ICIs was verified. Forty-seven studies with 6472 participations met the inclusion criteria. The pooled all-grade trAEs incidence rate was 83.4% (95% confidence interval [95% CI] 77.0-89.1%), ≥ grade 3 trAEs incidence rate was 33.0% (95% CI 26.9-39.5%), all-grade irAEs incidence rate was 34% (95% CI 22-47%), and ≥ grade 3 irAEs incidence rate was 9% (95% CI 5-14%). Aspartate aminotransferase (AST) increase (38%, 95% CI 35-40%) is the most common trAEs. Fatigue (14%, 95% CI 7-23%) is the most common irAEs. The pooled results also showed that 18.8% (95% CI 13.2-25.2%) of patients required systemic steroid therapy due to AEs, while 6.6% (95% CI 4.6-9.0%) of patients withdrew from treatment due to AEs. Additionally, patients experiencing irAEs may have a better progression-free survival (PFS) (multivariate analysis: hazard ratio [HR] = 0.41, 95% CI 0.27-0.61, I2 = 36.3%) but not overall survival (OS) (multivariate analysis: HR = 0.54, 95% CI 0.22-1.36, I2 = 83.2%) than those with no irAEs. Our study presents a systemic assessment of the AEs profile in HCC patients receiving ICIs, providing important reference for clinicians on toxicity profile. Besides, patients with irAEs may have a better PFS. More large-scale and prospective studies are needed to confirm our conclusions.

Systemic immune-inflammation index predicts prognosis of cancer immunotherapy: systemic review and meta-analysis.

Objective: This meta-analysis was designed to explore the association between the systemic immune-inflammation index (SII) and the therapeutic effect of immune checkpoint inhibitors. Materials & methods: The authors retrieved relevant studies published before May 25, 2022. Hazard ratio (HR) with 95% CI was used to evaluate the relationship between SII and overall survival (OS) and progression-free survival (PFS). Results: 14 articles comprising 2721 patients were included in this study. The pooled results proved that high SII levels were closely related to poor prognosis in cancer patients receiving immune checkpoint inhibitors (OS HR = 2.40; 95% CI: 2.04-2.82; PFS HR = 1.57; 95% CI: 1.33-1.86) and that an SII value of 750 was appropriate as a cut-off value (OS HR = 2.20; 95% CI: 1.83-2.63; PFS HR = 1.54; 95% CI: 1.33-1.80). Conclusion: High SII levels (>750) may be an indicator of worse OS and PFS in cancer patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of many patients with advanced cancer. However, some patients still do not benefit from ICIs. Therefore, determining indicators that can identify patients who may benefit from ICIs is essential. As a noninvasive, convenient and inexpensive clinical indicator, the systemic immune­inflammation index is expected to solve the aforementioned issue. Through this meta-analysis, the authors demonstrated that patients with cancers with high systemic immune­inflammation index levels had shorter survival and a smaller degree of clinical benefit after ICI treatment. Moreover, a systemic immune­inflammation index value of 750 is recommended to be the cut-off value for stratifying patients.

Clinical efficacy of recombinant human thrombopoietin combined with glucocorticoids in the treatment of immune thrombocytopenia.

OBJECTIVE: Herein, we aimed to determine the clinical efficacy of recombinant human thrombopoietin (rhTPO) combined with glucocorticoids for treating immune thrombocytopenia (ITP). METHODS: Clinical data of 87 patients with ITP admitted to our hospital were retrospectively analyzed, and patients were divided into two groups according to the treatment employed: 42 patients in the control group (CG) were prescribed glucocorticoids, and 45 patients in the study group (SG) received rhTPO combined with glucocorticoids. RESULTS: The total effective treatment rate in the SG (95.56%) was higher than that in the CG (76.19%) (P < 0.05). The SG achieved a platelet (PLT) count > 50 × 109/L faster and required fewer PLT transfusions than the CG (P < 0.05). At 1, 7, and 14 days after treatment, the PLT count increased in both groups and was higher in the SG than in the CG (P < 0.05). After treatment, CD3+, CD4+, and CD4+/CD8+ T cells increased, whereas CD8 + decreased in both groups, with the SG exhibiting a superior improvement to the CG (P < 0.05). Considering prothrombin time, activated partial thromboplastin time, and fibrinogen, differences between the two groups were not statistically significant, both before and after treatment (P > 0.05). CONCLUSION: rhTPO combined with glucocorticoids for treating ITP can effectively enhance the therapeutic effect, regulate the T lymphocyte subpopulation, rapidly increase the PLT level, and induce no significant effect on the coagulation function of patients, with good safety and high clinical promotion value.

The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Natural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear. Methods: Several electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI). Results: 26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57-0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear. Conclusion: NK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.

Structural, magnetic, and electronic properties of EuSi2 thin films on the Si(111) surface.

Searching for magnetic silicide thin films has long been a hot topic in condensed matter physics and materials science based on their fundamental physics and promising device applications. Here we report a systematic study on the structural, magnetic, and electronic properties of EuSi2 thin films on the Si(111) surface by ab initio calculations. Total energy calculations show that the EuSi2 thin film in AA stacking is more favorable than that in AB or ABC stacking. The Eu2 + ions are coupled ferromagnetically within each layer and antiferromagnetically across the adjacent silicene layers with a large local spin moment of 6.96-7.00µB derived from the Eu-4f orbital electrons. Electronic band structure calculations indicate that the monolayer EuSi2 thin film is a semiconductor with an indirect surface band gap of 0.45 eV, while the multilayer EuSi2 thin films exhibit metallic behavior. These findings provide a systematic understanding of rare-earth metal silicides on the Si surface and will provide guidance for Si-based nanoelectronics and spintronics.

The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis.

Background: The relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy. Methods: All associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias. Results: Thirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41-1.56; HR = 1.46, 95% CI = 1.34-1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15-1.45; HR = 1.20, 95% CI = 1.02-1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24-1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23-2.03, P = 0.521). Conclusions: High baseline CRP level (>1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.

Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. METHODS: We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74-3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47-3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55-2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36-2.49, P = 0.906). CONCLUSION: sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.

Research on Rapid Detection Technology for Quality Control of Emergency Ventilator / 中国医疗器械杂志

OBJECTIVE@#In order to grasp the quality status of the first-aid ventilator in pre-hospital and field environment in time, the quality control and detection items of invasive ventilator were optimized to form a rapid detection operation process of first-aid ventilator and ensure the safety of patient treatment.@*METHODS@#Based on the quality control detection data of invasive ventilator in hospital in recent years, methods such as narrowing the range of qualified criteria and analyzing confidence interval were adopted to extract indicators prone to deviation and verify their correlation with similar indicators, so as to form an optimized rapid detection portfolio.@*RESULTS@#Compared with the original quality control detection procedures, the detection indicators of the rapid detection procedures were reduced from 5 categories of 24 indicators to 3 categories of 7 indicators. The detection time was shortened by 56.1% and the coincidence rate of the detection results was 100% after the actual measurement and verification.@*CONCLUSIONS@#Under the premise of ensuring the testing quality, the operating procedure for rapid detection of emergency ventilator can greatly reduce the detection time, and realize the rapid and high frequency quality control detection, so as to ensure the quality and safety of the equipment.

La induced Si3 trimer bilayer on the Si(111) surface.

Using first-principles calculations, we identify a robust R30° reconstruction of a Si3 trimer bilayer on the Si(111) surface with a La coverage of 2/3 monolayer. Each surface unit cell contains two Si3 trimers and two La atoms, where the upper Si3 trimer is located just above the lower one with a rotation of about 60°, while two La atoms with different heights are distributed between the Si3 trimers and located on the T4 top site of the Si(111) surface, forming a honeycomb-like network structure. We find that the two La atoms have different valence states, La2+ and La3+, respectively. The high structural stability is attributed to the lower La atom saturating all the three dangling bonds of the upper Si3 trimer, while the higher La atom compensates two electrons to the lower Si3 trimer. The electronic band structure and band-decomposed charge density distribution show a semiconducting characteristic with a small surface band gap of 42 meV. Moreover, simulated STM images show a good structural match with the recent experimental observations.

Effect of replacing inorganic trace minerals at lower organic levels on growth performance, blood parameters, antioxidant status, immune indexes, and fecal mineral excretion in weaned piglets.

Organic trace minerals (OTMs) have the potential to replace inorganic trace minerals (ITMs), but the degree to which the dietary levels can be reduced is not well defined. This study aimed to investigate the effect of replacing of ITMs with lower levels of OTMs on growth performance, blood parameters, antioxidant status, and immune indexes in weaned piglets. The experiment was conducted in a subtropical city in Guangdong Province in South China (subtropical climate) from July to September 2018. A total of 600 pigs with an average initial BW of 8.90 kg were allotted by gender and weight to 5 treatments with 6 replicate pens per treatment. Experimental treatments: (A) Control group (a basal diet with iron, copper, manganese, and zinc from sulfates and sodium selenite providing commercially utilized levels in China of 150, 25, 40, 150, and 0.5 mg/kg, respectively). (B) 1/2 ITM group (inorganic trace minerals providing 1/2 control group levels). (C) 1/2 OTM group (1/2 control group trace mineral levels with manganese, iron, zinc, and selenium from Sel-Plex® and Cu from Bioplex®). (D) 1/3 ITM group (1/3 control group trace mineral levels from inorganic forms). (E) 1/3 OTM group (1/3 control group trace mineral levels from organic forms). The results suggest no significant effects of trace mineral sources or levels, on average daily gain (ADG) and average daily feed intake (ADFI) among different treatments during the entire experiment. The level of zinc in serum was significantly decreased in the 1/3 ITM group. The 1/3 OTM group had a significantly higher (P < 0.05) immunoglobulin G (IgG) level in serum. Fecal mineral excretion decreased significantly (P < 0.05) when decreased dietary levels of trace minerals were included at 1/2 and 1/3 levels regardless of sources. Fecal concentrations of zinc excretion were lower (P < 0.05) with 1/2 OTM supplementation than 1/2 ITMs. The present study shows that replacing high doses of ITMs with low concentrations (1/3) of OTMs does not adversely affect the growth performance of piglets. At low levels, total replacement of ITMs with OTMs improved IgG and reduced fecal excretion of copper, zinc, iron, and manganese, thereby mitigating environmental pollution.

Impact of trigger timing of gonadotropin-releasing hormone antagonist regimen for infertility patients of various ages / 中华妇产科杂志

Objective:To investigate the impact of trigger timing of gonadotropin- releasing hormone (GnRH) antagonist regimen for infertility patients of various ages.Methods:This was a retrospective study, 1 529 infertility patients who receiving GnRH antagonist regimen in Chongqing Health Center for Women and Children from January 2017 to December 2018 were divided into the advance trigger group and the standard trigger group, and further divided into three subgroups according to age:<35 years, 35-40 years,>40 years. The number of retrieved oocytes and transplantable embryos, the clinical pregnancy rate and the live birth rate among patients in the advance trigger group and standard trigger group in various age subgroups were compared.Results:(1) The gonadotropin (Gn) days among the three age subgroups were significantly shorter in the advance trigger group compared to the same-aged standard trigger group (all P<0.01), but only in the 35－40 years and >40 years subgroups, the Gn doses in the advance trigger group [(2 702±551) and (2 780±561) U] were significantly less than those in the standard trigger group (all P<0.01). In the <35 years subgroup, the number of oocytes retrieved and transplantable embryos of the advance trigger group (6.6±4.8 and 2.6±2.7) were significantly less than those of the standard trigger group (all P<0.01), but there was no difference in the number of top-quality embryos ( P=0.580); however, in the 35－40 years and >40 years subgroups, there were no significant differences between advance and standard trigger groups in terms of the afore mentioned 3 indicators (all P>0.05), only the numbers of top-quality embryos in the advance trigger group (0.6±1.0 and 0.6±0.9) were significantly higher than those in the standard trigger group (all P<0.01). (2) In the <35 years and 35－40 years subgroups, no significant differences were noted between the advance trigger group and standard trigger group with regard to the clinical pregnancy rate and live birth rate (all P>0.05); but in the >40 years subgroup, the clinical pregnancy rate of the advance trigger group was significantly higher than that of the standard trigger group [33.0% (30/91) vs 19.2% (25/130), P=0.020], and there was no statistical difference in the live birth rate ( P=0.064). (3) Multivariate logistic regression analysis showed that trigger timing was an independent predictor of clinical pregnancy rate in the >40 years subgroup ( OR=0.334, 95% CI: 0.119-0.937, P=0.037), but not an independent predictor of live birth rate ( P>0.05). Conclusions:Advance trigger in the GnRH antagonist protocol for infertility patients >40 years old could effectively reduce Gn times and Gn dosage, increase the number of top-quality embryos, and improve the clinical pregnancy rate. Therefore, compared with patients ≤40 years of age, patients >40 years might benefit more from advance trigger.