Transcription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog-mediated epithelial-mesenchymal transition.

As a POU homeodomain transcription factor, POU4F2 has been implicated in regulating tumorigenic processes in various cancers. However, the role of POU4F2 in colorectal cancer (CRC) remains unclear. Here, we revealed that POU4F2 functions as a tumor promotor in CRC. Bioinformatics analysis in specimens from CRC patients and expression analysis in CRC cell lines showed that POU4F2 was upregulated at the mRNA and protein levels in CRC. Depletion of POU4F2 suppressed the metastatic phenotypes of CRC cells, including cell migration, invasion, and the expression of epithelial-mesenchymal transition (EMT) markers. Moreover, depletion of POU4F2 decreased the number of lung metastatic nodes in nude mice. Mechanistically, POU4F2 positively regulated the Hedgehog signaling pathway, as inferred from the downregulation of the expression of sonic Hedgehog homolog, patched 1, Smoothened, and GLI family zinc finger 1 in vitro and vivo following silencing of POU4F2. Furthermore, the SMO agonist SAG reversed the effects of POU4F2 knockdown in CRC. Functionally, POU4F2 contributed to the Hedgehog signaling-regulated activation of the EMT process and promotion of CRC cell migration and invasion. Collectively, these findings elucidated the role of POU4F2 as a tumor promotor in CRC through the regulation of Hedgehog signaling-mediated EMT and suggested that POU4F2 suppression might be a promising therapeutic target in inhibiting CRC metastasis.

Transitions in the cell-fate induction induced by colored noise associated with the inductive stimulus.

The cell-fate induction based on the saddle-node bifurcation is undoubtedly a very important concept in developmental biology, which provides a possible mechanism to explain the intrinsic irreversibility in the developmental process. In this paper, the effect of a colored noise, which is associated with the inductive stimulus, on the saddle-node landscape of cell-fate induction is investigated, especially, the effect of the change of correlation time of colored noise on cell-fate induction. The main results show clearly that the change of correlation time of colored noise could induce the transitions of the system. This implies that the colored noise associated with inductive stimulus may have a profound effect on the saddle-node bifurcation landscape of cell-fate induction. This will also help us to understand more deeply the role of cell-fate induction in developmental biology.

Imitation dynamics with time delay.

Based on the classic imitation dynamics (Hofbauer and Sigmund, 1998, Evolutionary Games and Population Dynamics, Cambridge University Press), the imitation dynamics with time delay is investigated, where the probability that an individual will imitate its opponent's own strategy is assumed to depend on the comparison between the past expected payoff of this individual's own strategy and the past expected payoff of its opponent's own strategy, i.e. there is a time delay effect. For the two-phenotype model, we show that if the system has an interior equilibrium and this interior equilibrium is stable when there is no time delay, then there must be a critical value of time delay such that the system tends to a stable periodic solution when the time delay is larger than the critical value. On the other hand, for three-phenotype (rock-scissors-paper) model, the numerical analysis shows that for the stable periodic solution induced by the time delay, the amplitude and the period will increase with the increase of the time delay. These results should help to understand the evolution of behavior based on the imitation dynamics with time delay.

A simple rule of direct reciprocity leads to the stable coexistence of cooperation and defection in the Prisoner's Dilemma game.

The long-term coexistence of cooperation and defection is a common phenomenon in nature and human society. However, none of the theoretical models based on the Prisoner's Dilemma (PD) game can provide a concise theoretical model to explain what leads to the stable coexistence of cooperation and defection in the long-term even though some rules for promoting cooperation have been summarized (Nowak, 2006, Science 314, 1560-1563). Here, based on the concept of direct reciprocity, we develop an elementary model to show why stable coexistence of cooperation and defection in the PD game is possible. The basic idea behind our theoretical model is that all players in a PD game prefer a cooperator as an opponent, and our results show that considering strategies allowing opting out against defection provide a general and concise way of understanding the fundamental importance of direct reciprocity in driving the evolution of cooperation.

Antibody-drug conjugates and immune checkpoint inhibitors in cancer treatment: a systematic review and meta-analysis.

Although antibody-drug conjugate (ADC) or immune checkpoint inhibitors (ICIs) alone fosters hope for the treatment of cancer, the effect of single drug treatment is limited and the safety profile of ADC and ICI therapy remains unclear. This meta-analysis aimed to examine the efficacy and safety of the combination of ADC and ICI therapy. This study type is a systematic review and meta-analysis. Literature retrieval was carried out through PubMed, Embase, Cochrane from inception to Jun. 5, 2024. Then, after data extraction, overall response rate (ORR) and adverse effects (AEs) were used to study its efficiency and safety. Publication bias was also calculated through Funnel plot, Begg's Test and Egger's test. Heterogeneity was investigated through subgroup and sensitivity analysis. The research protocol was registered with the PROSPERO (CRD42023375601). A total of 12 eligible clinical studies with 584 patients were included. The pooled ORR was 58% (95%CI 46%, 70%). Subgroup analysis showed an ORR of 77% (95%CI 63%, 91%) in classical Hodgkin lymphoma (cHL) and an ORR of 73% (95%CI 56%, 90%) in non-Hodgkin lymphoma (NHL). The most common AEs was peripheral neuropathy (38.0%). Meanwhile, AEs on skin (13.1-20.0%) and digestive system (9.0-36.0%) was hard be overlooked. ADC + ICI therapy may be recommended in cancer treatment, especially in cHL and NHL. However, strategies to manage toxicities warranted further exploration.

Intervention of epithelial mesenchymal transition against colon cancer cell growth and metastasis based on SOX21/POU4F2/Hedgehog signaling axis.

AIMS: Colon cancer poses a major threat to human health and a heavy burden on the national economy. As a member of the SOX transcription factor family, SRY-box transcription factor 21 (SOX21) is associated with various cancers, but its mechanism of action in colon cancer remains unclear. This study focused on the molecular mechanisms of transcription factor SOX21 in proliferation and metastasis of colon cancer cells. MAIN METHODS: We analyzed SOX21 expression level and its impact on survival in colon cancer patients by bioinformatics analysis. We used public databases for gene correlation, GSEA enrichment analysis. Cell function experiments (colony formation assay, wound healing assay, Transwell migration and invasion assay) were utilized to determine the impact of SOX21 silencing and over-expression on cell proliferation and metastasis. The luciferase reporter assay, CUT&RUN-qPCR assay and Methylation Specific PCR were used to explore SOX21-POU class 4 homeobox 2 (POU4F2) molecular interactions. The molecular mechanisms were verified by Quantitative real-time PCR and Western blot analysis. KEY FINDINGS: SOX21 is highly expressed and affects the overall survival of colon cancer patients. SOX21 can attenuates POU4F2 methylation state by binding with it. In addition, this interaction facilitate its transcriptional activation of Hedgehog pathway, mediates epithelial-mesenchymal transition (EMT), consequently promoting the proliferation and metastasis of colon cancer cells. SIGNIFICANCE: Our study reveals that SOX21 is an oncogenic molecule and suggests its regulatory role in colon carcinogenesis and progression, providing new insights into the treatment of this disease.

Diterpenoid tanshinones inhibit gastric cancer angiogenesis through the PI3K/Akt/mTOR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a kind of Chinese herbal medicine known for activating blood circulation and removing blood stasis, with the effect of cooling blood and eliminating carbuncles, and has been proven to have the effect of treating tumors. However, the inhibitory effect of Salvia miltiorrhiza Bunge extracts (Diterpenoid tanshinones) on tumors by inhibiting angiogenesis has not been studied in detail. AIM OF THE STUDY: This study aimed to investigate the anti-gastric cancer effect of diterpenoid tanshinones (DT) on angiogenesis, including the therapeutic effects and pathways. MATERIALS AND METHODS: This experiment utilized network pharmacology was used to identify relevant targets and pathways of Salvia miltiorrhiza Bunge-related components in the treatment of gastric cancer. The effects of DT on the proliferation and migration of human gastric cancer cell line SGC-7901 and human umbilical vein endothelial cell line HUVECs were evaluated, and changes in the expression of angiogenesis-related factors were measured. In vivo, experiments were conducted on nude mice to determine tumor activity, size, immunohistochemistry, and related proteins. RESULTS: The findings showed that DT could inhibit the development of gastric cancer by suppressing the proliferation of gastric cancer cells, inducing apoptosis, and inhibiting invasion and metastasis. In addition, the content of angiogenesis-related factors and proteins was significantly altered in DT-affected cells and animals. CONCLUSIONS: Results suggest that DT has potential as a therapeutic agent for the treatment of gastric cancer, as it can inhibit tumor growth and angiogenesis. It was also found that DT may affect the expression of the angiogenic factor VEGF through the PI3K/Akt/mTOR pathway, leading to the regulation of tumor angiogenesis. This study provides a new approach to the development of anti-tumor agents and has significant theoretical and clinical implications for the treatment of gastric cancer.

Jeans and language: kin networks and reproductive success are associated with the adoption of outgroup norms.

Traditional norms of human societies in rural China may have changed owing to population expansion, rapid development of the tourism economy and globalization since the 1990s; people from different ethnic groups might adopt cultural traits from outside their group or lose their own culture at different rates. Human behavioural ecology can help to explain adoption of outgroup cultural values. We compared the adoption of four cultural values, specifically speaking outgroup languages/mother tongue and wearing jeans, in two co-residing ethnic groups, the Mosuo and Han. Both groups are learning outgroup traits, including each other's languages through contact in economic activities, education and kin networks, but only the Mosuo are starting to lose their own language. Males are more likely to adopt outgroup values than females in both groups. Females of the two groups are no different in speaking Mandarin and wearing jeans, whereas males do differ, with Mosuo males being keener to adopt them than Han males. The reason might be that Mosuo men experience more reproductive competition over mates, as Mosuo men have larger reproductive skew than others. Moreover, Mosuo men but not others gain fitness benefits from the adoption of Mandarin (they start reproducing earlier than non-speakers). This article is part of the theme issue 'Social norm change: drivers and consequences'.

Survival analysis of age-related oral squamous cell carcinoma: a population study based on SEER.

BACKGROUND: This research aimed to investigate the prognostic factors of oral squamous cell carcinoma (OSCC), especially the role of age. METHODS: A total of 33,619 cases of OSCC were received from the Surveillance, Epidemiology, and End Results (SEER) database during 2005-2015. Kaplan-Meier curves of 5-year overall survival rates and 5-year cancer-specific survival rates were performed, and univariate and multivariate Cox regression analyses as well as competing risk model were used to help understand the relationship between various factors and mortality of OSCC. RESULTS: Compared to 18-39-year-old group, the older age was an important predictor of worse prognosis. The multivariate analysis of overall survival (OS) was 50-59 years (HR, 1.32; 95% CI 1.17-1.48; p ≤ .001), 60-69 years (HR, 1.66; 95% CI 1.42-1.87; p ≤ .001) and 70 + years (HR, 3.21; 95% CI 2.86-3.62; p ≤ .001), respectively, while the specific value of competing risk model was 60-69 years (HR, 1.21; 95% CI 1.07-1.38; p = .002) and 70 + years (HR, 1.85; 95% CI 1.63-2.10; p ≤ .001). In addition, female gender, unmarried, Blacks, tumor in floor of mouth, size and higher Tumor Node Metastasis (TNM) classification were also other predictors that signify significant clinically deterioration of OS/cancer-specific survival (CSS). CONCLUSIONS: Our research revealed that age was an important factor in explaining the difference of survival in the whole process of OSCC. It is suggested that we should pay attention to the influence of age on diagnosis, treatment and prognosis in the clinical process.

The difference of human gut microbiome in colorectal cancer with and without metastases.

Metastasis of colorectal cancer is deemed to be closely related to the changes in the human gut microbiome. The purpose of our study is to distinguish the differences in gut microbiota between colorectal cancer with and without metastases. Firstly, this study recruited colorectal cancer patients who met the established inclusion and exclusion criteria in the Oncology Department of Zhejiang Hospital of Traditional Chinese Medicine from February 2019 to June 2019. Fresh stool samples from healthy volunteers, non-metastatic patients, and metastatic patients were collected for 16S rRNA gene sequencing, to analyze the diversity and abundance of intestinal microorganisms in each group. The results showed that the microbial composition of the control group was more aplenty than the experimental group, while the difference also happened in the Tumor and the metastases group. At the phylum level, the abundance of Bacteroidetes significantly declined in the Tumor and the metastases group, compared with the control group. At the class level, Bacilli increased in experimental groups, while its abundance in the Tumor group was significantly higher than that in the metastases group. At the order level, the Tumor group had the highest abundance of Lactobacillales, followed by the metastases group and the control group had the lowest abundance. Overall, our study showed that the composition of the flora changed with the occurrence of metastasis in colorectal cancer. Therefore, the analysis of gut microbiota can serve as a supplement biological basis for the diagnosis and treatment of metastatic colorectal cancer which may offer the potential to develop non-invasive diagnostic tests.

Exploring the Pharmacological Mechanism of the Effective Chinese Medicines Against Gynecological Cancer Based on Meta-Analysis Combined With Network Pharmacology Analysis.

This meta-analysis plus network pharmacology aimed to investigate whether traditional Chinese medicine (TCM) combined with chemotherapy is associated with more beneficial efficacy data in the treatment of gynecological cancer (GC). A total of 11 randomized controlled trials (RCTs) consisting of 863 GC patients were included. Results showed a better ORR (RR: 1.42, 95% CI: 1.18-1.71; I 2 = 21.4%; p = 0.282), DCR (RR: 1.13, 95% CI: 1.03-1.25; I 2 = 0.0%; p = 0.492), PD (RR: 0.27, 95% CI: 0.11-0.65, p = 0.003; I 2 = 0.0%, p = 0.930), and QOL (SMD: 0.85, 95% CI: 0.38-1.33, p = 0.005) and higher proportions of CD3+ T (WMD: 5.65, 95% CI: 4.23-7.08, p = 0.000; I 2 = 68.3%, p = 0.004), CD4+ T (WMD: 6.97, 95% CI: 5.35-8.59, p = 0.000; I 2 = 83.4%, p = 0.000), and the CD4+/CD8+ T ratio (WMD: 0.32, 95% CI: 0.23-0.42, p = 0.000; I 2 = 78.0%, p = 0.000). The number of adverse events (AEs) was significantly lower in the TCM + chemotherapy group. The active components and targets of 19 high-frequency Chinese medicines obtained from the meta-analysis were screened and explored in network pharmacology analysis. Also, a regulatory network of active components and targets, a core network and key genes, a diagram of protein interaction, network topology analysis, and gene body GO function and KEGG pathway enrichment analysis were performed. A total of 120 active components were identified. NPM1 and HSPA8 are the most critical target proteins in the core network of protein interaction. HSP90AA1 is the most important target protein in the TCM group. KEGG enrichment analysis showed that it was highly significant in the lipid and atherosclerotic pathways. Therefore, moderate evidence revealed that TCM plus chemotherapy has obvious advantages over chemotherapy alone in terms of tumor responses, QOL, peripheral blood lymphocyte levels, and fewer AEs in the treatment of GC. The potential important targets and core genes were displayed. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021252500.

Is antibody-drug conjugate a rising star for clinical treatment of solid tumors? A systematic review and meta-analysis.

Antibody-drug conjugates (ADCs) show significant advantages in cancer treatment due to their high selectivity and anti-tumor activity, but the efficacy and safety of the treatment of solid tumors are unknown. We searched research databases, major conference proceedings and trial registries for randomized controlled trials (RCTs). Then, we selected qualified studies and extracted dates. Studies were assessed for quality, and a meta-analysis was conducted to quantify effects of ADCs on overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events (AEs). The within-study heterogeneity was evaluated by subgroup and sensitivity analysis. Eleven RCTs with 4353 participants were included. ADCs had better PFS (HR: 0.69, 95 % CI: 0.56-0.82) and OS (HR: 0.76, 95 % CI: 0.61-0.92). ADCs resulted in lower risk of febrile neutropenia in blood system. Conversely, ADC therapy had not a prepotent on ORR (RR: 1.36, 95 % CI: 0.71-2.60).

Hesitate between confocal laser endomicroscopy and narrow-band imaging: how to choose a better method in the detection of focal precancerous state of gastric cancer.

BACKGROUND: With a high incidence globally, deaths form gastric cancer (GC) are not rare. Early diagnosis is crucial to ameliorate its prognosis. Confocal laser endomicroscopy (CLE) and narrow band imaging (NBI) have been extensively applied in gastroscopy, particularly when it comes to the detection and management of premalignant gastric lesion. Our meta-analysis intends to appraise the diagnostic capability and compare the efficacy of NBI and CLE for focal precancerous state of gastric cancer. METHODS: We performed a literature search up to November 5, 2020 in online databases and major conferences. Two investigators assessed the methodological bias by QUADAS-2, followed by sophisticated study selection and data exaction to make a comparison between sensitivity, specificity, positive and negative likelihood values, and diagnostic odds ratio. A symmetric summary receiver-operating curve (sROC) and its area under the curve (AUC) were used to estimate threshold effect. Additionally, we evaluated the publication bias by Deeks' asymmetry test. RESULTS AND CONCLUSIONS: Four studies involved 248 patients and 526 lesions. In analysis drawn from every lesion, the NBI's pooled sensitivity and specificity were 87% (95% CI: 0.80-0.92) and 85% (95% CI: 0.75-0.91), and those of CLE were 90% (95% CI: 0.85-0.91) and 87% (95% CI: 0.83-0.91). CLE illustrated that the pooled two were slightly higher than NBI when compared at the level of every lesion. The AUC for NBI and CLE was 0.92 (0.90-0.94) and 0.95 (0.92-0.96), and there might be a threshold effect, according to the shoulder-like distribution of scatter points in the sROC. We did not find obvious publication bias in our meta-analysis.

Variation of soil microbial carbon use efficiency (CUE) and its Influence mechanism in the context of global environmental change: a review.

Soil microbial carbon utilization efficiency (CUE) is the efficiency with which microorganisms convert absorbed carbon (C) into their own biomass C, also referred to as microorganism growth efficiency. Soil microbial CUE is a critical physiological and ecological parameter in the ecosystem's C cycle, influencing the processes of C retention, turnover, soil mineralization, and greenhouse gas emission. Understanding the variation of soil microbial CUE and its influence mechanism in the context of global environmental change is critical for a better understanding of the ecosystem's C cycle process and its response to global changes. In this review, the definition of CUE and its measurement methods are reviewed, and the research progress of soil microbial CUE variation and influencing factors is primarily reviewed and analyzed. Soil microbial CUE is usually expressed as the ratio of microbial growth and absorption, which is divided into methods based on the microbial growth rate, microbial biomass, substrate absorption rate, and substrate concentration change, and varies from 0.2 to 0.8. Thermodynamics, ecological environmental factors, substrate nutrient quality and availability, stoichiometric balance, and microbial community composition all influence this variation. In the future, soil microbial CUE research should focus on quantitative analysis of trace metabolic components, analysis of the regulation mechanism of biological-environmental interactions, and optimization of the carbon cycle model of microorganisms' dynamic physiological response process.

Land-use change influence soil quality parameters at an ecologically fragile area of YongDeng County of Gansu Province, China.

Dry ecosystems, despite their relative levels of aridity, are very diverse, and play a vital role in the livelihoods of many dryland inhabitants. It is therefore critical to investigate the relationship between land-use change and soil quality parameters to offer a scientific basis for optimizing land-use planning and improving soil quality status in dry ecosystems and ecologically vulnerable areas. This study, therefore, analyzed the physicochemical properties of soils in five different land-use types namely farmland, abandoned farmland, natural grassland, artificial lemon forest, and poplar woodland at YongDeng County. The soil quality status of the aforementioned land-use types was also evaluated through Principal component analysis. The results revealed that abandoned farmland and natural grassland recorded the highest average values of soil coarse particles of 24.0% and 23.4% respectively compared to the other land-use types. The highest average value (46.1%) of fine soil particles was recorded in poplar woodland followed by natural grassland (36.6%) and the average value of very fine soil particles was higher in farmland (40.8%) and artificial lemon woodland (38.3%) than in the other land-use types. The average value of clayey particles was highest in farmland (11.1%), followed by artificial lemon woodland (9.3%), and abandoned farmland (6.5%), then poplar woodland which recorded an average value of (4.2%). The average values of Soil water content, soil pH, soil electrical conductivity, and soil total nitrogen content were significantly higher in farmland compared to the other land-use types. Soil organic carbon content was significantly higher in abandoned farmland at (P < 0.03) and lemon woodland at (P < 0.01) than in farmlands, natural grasslands, and poplar stands. The soil quality indicators of the different land-use types were significantly correlated with each other. Among them, the correlation coefficient of each evaluation index was highest in poplar woodland, followed by natural grassland, lower in farmland and artificial lemon woodland, and lowest in abandoned farmland. The overall soil quality scores were in the following order: farmland > abandoned farmland > 0 > grassland > lemon woodland > poplar woodland. In the study area, the soil quality of farmland that has been finely managed and naturally restored to grassland following abandonment is superior, whereas the soil quality of natural grassland, artificial lemon woodland, and poplar forest land is substandard. The comprehensive analysis of soil quality demonstrates that conservation tillage and fine management of water-irrigated farmland, as well as the natural conversion of abandoned farmland to grassland, can significantly improve the soil quality of sandy soils, reduce water and soil loss, increase fertility, and gradually improve regional ecological environmental conditions.

Network Pharmacology Analysis to Explore the Pharmacological Mechanism of Effective Chinese Medicines in Treating Metastatic Colorectal Cancer using Meta-Analysis Approach.

The role of traditional Chinese medicine (TCM) on treatment of metastatic colorectal cancer (mCRC) remains controversial, and its active components and potential targets are still unclear. This study mainly aimed to assess the efficacy and safety of TCM in mCRC treatment through meta-analysis and explore the effective components and potential targets based on the network pharmacology method. We systematically searched PubMed, EMBASE, Cochrane, CBM, WanFang, and CNKI database for randomized controlled trials (RCTs) comparing the treatment of mCRC patients with and without TCM. A meta-analysis using RevMan 5.4 was conducted. In total, 25 clinical trials were analyzed, and the result demonstrated that TCM was closely correlated with the improved OS (HR: 0.63; 95% CI: 0.52-0.76; [Formula: see text] < 0.00001) and PFS (HR: 0.73; 95% CI: 0.61-0.88; [Formula: see text] = 0.0010). Then, high-frequency Chinese herbs from the prescriptions extracted from the trails included in the OS meta-analysis were counted to construct a core-effective prescription. The TCMSP database was used to retrieve the active chemical components and predict herb targets. The Genecards, OMIM, Disgenet, DrugBank, and TTD database were searched for colorectal cancer targets. R-package was used to construct the Component-Target (C-T) network based on the intersection genes. Further, we extracted hub genes from C-T network and performed functional enrichment and pathway analysis. Finally, the C-T network showed 120 herb and disease co-target genes, and the most important top 10 active components were: Quercetin, Luteolin, Wogonin, Kaempferol, Nobiletin, Baicalein, Licochalcone A, Naringenin, Isorhamnetin, and Acacetin. The first 20 hub genes were extracted: CDKN1A, CDK1, CDK2, E2F1, CDK4, PCNA, RB1, CCNA2, MAPK3, CCND1, CCNB1, JUN, MAPK1, RELA, FOS, MAPK8, STAT3, MAPK14, NR3C1, and MYC. Thus, effective Chinese herb components may inhibit the mCRC by targeting multiple biological processes of the above hub genes.

Efficacy and Safety of PARP Inhibitor Combination Therapy in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Though it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy. MATERIALS AND METHODS: We searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis. RESULTS AND CONCLUSION: A total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).

Association of Survival and Immune-Related Adverse Events With Anti-PD-1/PD-L1 and Anti-CTLA-4 Inhibitors, Alone or Their Combination for the Treatment of Cancer: A Systematic Review and Meta-Analysis of 13 Clinical Trials.

BACKGROUND: Cancer, with sustained high mortality, is a worldwide threat to public health. Despite the survival benefit over conventional therapies shown in immune checkpoint inhibitor (ICI), only a minority of patients benefit from single ICI. But combination therapy holds the promise of achieving better efficacy over monotherapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of ICI-based combination therapy for cancer. METHODS: A search was conducted to retrieve relevant studies in electronic databases and major conferences. Two investigators independently performed data extraction, making a systematic data extraction, assembly, analysis and interpretation to compare the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), all and high grade immune related adverse events (IRAEs) between combination therapy and monotherapy. Therefore, only the studies satisfying the criteria were included. Finally, we performed subgroup, sensitivity, and publication bias analysis to examine the heterogeneity and bias of resources. RESULTS: A total of 2,532 patients from thirteen studies were enrolled. Compared to ICI alone, combination therapy, with a high risk and high grade IRAEs for the majority of all, offers a better survival benefit (OS: HR: 0.86, 95% CI: 0.76 to 0.98; PFS: HR: 0.79, 95% CI: 0.69 to 0.90) and objective response (ORR: RR: 1.91, 95% CI: 1.40 to 2.60). CONCLUSIONS: ICI-based combination therapy was confirmed as the optimum treatment for cancer, especially when using specific dosage and regimen to treat certain tumor types with no absolute demand for the detection of PD-L1 expression. Meanwhile, attention should also be paid on potential toxicity, especially the IRAEs.

Multimode participation of traditional Chinese medicine in the treatment of COVID-19.

BACKGROUND: The outbreak of COVID-19 has swiftly spread across China and all over the world, resulting in severe contagious pneumonia. However, no specific anti-COVID-19 drugs or methods are available for the treatment of this acute and fatal disease. In recent years, as the efficacy and safety of traditional Chinese medicine (TCM) have been universally acknowledged, it has been brought to a crucial status domestically and overseas for the treatment of COVID-19. METHODS: We searched relevant literature, electronic databases, and official statements, diagnoses and protocols to retrieve studies and applications related to traditional Chinese medicine for COVID-19 in terms of regulations and policies, clinical evidence, preclinical rationale and big data analysis and then summarized the discovery and development of potential drugs and their targets. RESULTS: Clinicians, researchers, governments, the public, colleges, institutes and companies collected and classified associated policies, regulations and actual contributions, searched clinical trials and preclinical experimental outcomes from databases, studied potential TCM drugs with possible mechanisms, retrieved numerous big data analysis method and gathered pooled results of compounds along with their effective targets to make traditional Chinese medicine vital to cover all stages of patients in the treatment and control of COVID-19. CONCLUSION: Traditional Chinese medicine provides new evidence to support the clinical value of TCM for COVID-19.

Becoming a Faithful Defender: Traditional Chinese Medicine against Coronavirus Disease 2019 (COVID-19).

The outbreak caused by COVID-19 is causing a major challenge to clinical management and a worldwide threat to public health. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. Recently, as the efficacy and safety of traditional Chinese medicine (TCM) is widely acknowledged, it has been brought to a crucial status by the public, governments, and World Health Organization (WHO). For a better popularization of TCM, governments have made several advances in regulations and policies for treatment and measures of novel coronavirus pneumonia (NCP). Therefore, on the basis of epidemiology and virology information, we reviewed relevant meta-analysis and clinical studies of anti-coronavirus therapeutics by TCM, in the aspect of mortality, symptom improvement, duration and dosage of corticosteroid, incidence of complications and the like. In addition, we also summarized preclinical rationale for anti-coronavirus activity by TCM in terms of virion assembly and release, as well as viral entry and replication, which could be a useful contribution for figuring out effective Chinese herbal medicine (CHM) for coronavirus, including ingredients from single monomeric compounds, Chinese herbs, Chinese herb extracts and Chinese herb formulas, or potential targets for medicine. We would like to see these relevant studies, ranging from basic researches to clinical application, could provide some idea on effects of CHM to combat COVID-19 or other coronaviruses, and also offer new thinking for the exploration of therapeutic strategies under the guidance of TCM.