The evidence framework of traditional Chinese medicine injection (Aidi injection) in controlling malignant pleural effusion: A clustered systematic review and meta-analysis.

INTRODUCTION: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE). OBJECTIVES: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety. METHODOLOGY: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality. RESULTS: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality. CONCLUSIONS: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use.

Short-term responses of nutrients and algal biomass in a eutrophic shallow lake to different scales of water transfer.

With the expansion of water transfer projects worldwide, the original hydrological and physicochemical states of the systems receiving the transferred water have experienced dynamic temporal and spatial changes, especially shallow lakes with that are more vulnerable to these changes. Understanding the short-term response of lakes to human-managed water transfer events can provide specific information on the seasonal regularity and long-term evolution pattern of lakes. The present study selected an annual water transfer event that is uniform and relatively independent. Then, field monitoring was conducted, and a hydrodynamic-eutrophication model was established to investigate the effects of the water transfer scales and regulation on TN, TP and algal biomass in Lake Nansi, a main regulating lake on the eastern route of the South-to-North Water Transfer Project (SNWDP-ER), China. The results showed that the timing of the water transfer event had an important effect on the enrichment of algal biomass. When the water transfer occurred in the spring, algal growth increased, but the reverse occurred in the summer. Under a high P concentration and the current management regulations (TP 0.05 mg/L), an algal bloom resulted in 21 % and 22 % increases in Chl-a and TP in the receiving system. When the inflow rate increased to the maximum level (100 m3/s), the algal biomass in the first mixing zone was briefly diluted, but the subsequent deterioration in water quality in the first mixing zone was more significant. Sixty days after the water transfer event began, the proportion of middle eutrophication (26 ≤ Chl-a < 160 µg/L) increased from 84 % to 92 %. The results emphasize the importance of water transfer scales on water quality in shallow lakes and provide a reference for determining the long-term stability and maintenance of specific ecosystems and optimization of water transfer practices.

H3K27 methylation regulates the fate of two cell lineages in male gametophytes.

During angiosperm male gametogenesis, microspores divide to produce a vegetative cell (VC) and a male germline (MG), each with distinct cell fates. The mechanism underlying determination of the MG cell/VC fate remains an important area of research, with many unanswered questions. Here, we report that H3K27me3 is essential for VC fate commitment in male Arabidopsis thaliana gametophytes; H3K27me3 erasure contributes to MG cell fate initiation. VC-targeted H3K27me3 erasure disturbed VC development and shifted the VC fate toward a gamete destination, which suggests that MG cells require H3K27me3 erasure to trigger gamete cell fate. Multi-omics and cytological analyses confirmed the occurrence of extensive cell identity transition due to H3K27me3 erasure. Therefore, we experimentally confirmed that MG cell/VC fate is epigenetically regulated. H3K27 methylation plays a critical role in guiding MG cell/VC fate determination for pollen fertility in Arabidopsis. Our work also provides evidence for two previous hypotheses: the germline cell fate is specified by the differential distribution of unknown determinants and VC maintains the default microspore program (i.e. the H3K27me3 setting) while MG requires reprogramming.

Epigenetic regulation and intercellular communication during male gametophyte development.

The male gametophyte of angiosperms has long been recognized as an ideal system for the study of the molecular mechanisms regulating cell fate determination. Recent findings on histone variants in two cell lineages, vegetative-cell-derived small interfering RNA and transposable element expression provide new power for relevant investigations.

Three STIGMA AND STYLE STYLISTs Pattern the Fine Architectures of Apical Gynoecium and Are Critical for Male Gametophyte-Pistil Interaction.

The gynoecium is derived from the fusion of carpels and is considered to have evolved from a simple setup followed by adaptive adjustment in cell type and tissue distribution to facilitate efficient sexual reproduction [1, 2]. As a sequence of the adjustment, the apical gynoecium differentiates into a stigma and a style. Both the structural patterning and functional specification of the apical gynoecium are critical for plant fertility [3, 4]. However, how the fine structures of the apical gynoecium are established at the interface interacting with pollen and pollen tubes remain to be elucidated. Here, we report a novel angiosperm-specific gene family, STIGMA AND STYLE STYLIST 1-3 (SSS1, SSS2, and SSS3). The SSS1 expresses predominately in the transmitting tract tissue of style, SSS2 expresses intensively in stigma, and SSS3 expresses mainly in stylar peripheral region round the transmitting tract. SSSs coregulate the patterning of the apical gynoecium via controlling cell expansion or elongation. Both the architecture and function of apical gynoecium can be affected by the alteration of SSS expression, indicating their critical roles in the establishment of a proper female interface for communication with pollen tubes. The NGATHA3 (NGA3) transcription factor [5, 6] can directly bind to SSSs promoter and control SSSs expression. Overexpression of SSSs could rescue the stylar defect of nga1nga3 double mutant, indicating their context in the same regulatory pathway. Our findings reveal a novel molecular mechanism responsible for patterning the fine architecture of apical gynoecium and establishing a proper interface for pollen tube growth, which is therefore crucial for plant sexual reproduction.

The Hepatorenal Toxicity and Tumor Response of Chemotherapy With or Without Aidi Injection in Advanced Lung Cancer: A Meta-Analysis of 80 Randomized Controlled Trials.

PURPOSE: Chemotherapy-induced hepatorenal toxicity often decreases tolerance for further therapies and results in poor quality of life and prognosis for patients with lung cancer. In this meta-analysis, all related studies were systematically re-evaluated to determine whether Aidi injection relieves hepatorenal toxicity and improves tumor response, and to determine its threshold and the optimal treatment regimen for obtaining the desired responses. METHODS: All studies regarding Aidi injection with chemotherapy were gathered from Chinese and English databases (from inception until January 2019). Their bias risk was evaluated and the data were synthesized using meta-analysis; the quality of evidence of all outcomes was rated by using the Grades of Recommendation Assessment, Development, and Evaluation approach. FINDINGS: Eighty randomized controlled trials containing 6279 patients were included in the study. Most of the trials showed unclear risk of bias. Aidi injection with chemotherapy increased the objective response rate (risk ratio [RR], 1.32; 95% CI, 1.25-1.40) and the disease control rate (RR, 1.15; 95% CI, 1.12-1.17) and resulted in a lower incidence of hepatotoxicity (RR, 0.61; 95% CI, 0.55-0.69) and nephrotoxicity (RR, 0.62; 95% CI, 0.53-0.72) than that of chemotherapy alone. Subgroup analyses showed that treatment with 50 mL per time, 10 to 14 days per cycle, and 2 to 3 cycles of Aidi injection with chemotherapy resulted in a low incidence of hepatorenal toxicity. All of the results were robust, and their quality was moderate. IMPLICATIONS: The moderate evidence indicates that Aidi injection with chemotherapy may improve tumor response and result in a low incidence of hepatorenal toxicity in patients with lung cancer. Aidi injection may relieve hepatorenal toxicity and exhibit an important protective effect against chemotherapy-induced hepatorenal toxicity. Based on the subgroup analysis results, Aidi injection seems to lower the threshold for chemotherapy. Treatment with 50 mL per time, 10 to 14 days per cycle, and 2 to 3 cycles may be the optimal usage for attaining a decrease in hepatorenal toxicity.

Clinical efficacy and safety of aidi injection combination with vinorelbine and cisplatin for advanced non-small-cell lung carcinoma: A systematic review and meta-analysis of 54 randomized controlled trials.

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m2) and cisplatin (30-35 mg/m2 or 40-50 mg/m2) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.

Clinical efficacy and safety of Aidi injection plus paclitaxel-based chemotherapy for advanced non-small cell lung cancer: A meta-analysis of 31 randomized controlled trials following the PRISMA guidelines.

ETHNOPHARMACOLOGICAL RELEVANCE: As an important Chinese herb injection, Aidi injection is composed of the extracts from Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Aidi injection plus paclitaxel-based chemotherapy is often used to in the treatment of non-small cell lung cancer (NSCLC) in China. AIM OF THE STUDY: The objective of this study is to further confirm whether Aidi injection can improve the tumor responses and survivals, and reveal its safety, optimal usage and combination with paclitaxel. MATERIALS AND METHODS: A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning the Aidi injection plus paclitaxel-based chemotherapy for NSCLC were selected. Main outcomes were objective response rate (ORR), disease control rate (DCR), survivals, quality of life (QOL) and adverse drug reactions (ADRs). All data were extracted by using a standard data extraction form and synthesized through meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. RESULTS: Thirty-one RCTs involving 2058 patients were included, and most trials had an unclear methodological bias risk. The risk ratio (RR) and 95% confidence intervals (CI) of ORR, DCR, QOL, neutropenia, thrombocytopenia, gastrointestinal toxicity and liver injury were as following: 1.32 (1.20-1.46), 1.14 (1.09-1.20), 1.89 (1.66-2.16), 0.61 (0.51-0.74), 0.62 (0.45-0.87), 0.59 (0.49-0.72) and 0.52 (0.36-0.75). Compared to chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that only with the TP, Aidi injection could increase the ORR and DCR. Treatment with 100 ml, 80 ml or 50 ml/time, and 14 days/2 cycles or 21 days/2-4 cycles, Aidi injection could increase the ORR and DCR, respectively. Sensitivity analysis showed that the results had good robustness. None of the trials reported the overall survivals (OS), progression free survival (PFS). The quality of evidences was moderate. CONCLUSIONS: Current moderate evidence revealed that Aidi injection plus paclitaxel-based chemotherapy, especially TP can significantly improve the clinical efficacy and QOL for patients with stage III/IV NSCLC. Aidi injection can relieve the risk of hematotoxicity, gastrointestinal toxicity and liver injury in patient with NSCLC receiving paclitaxel-based chemotherapy. The optimal usage may be 50 ml/time and 14 days/2 cycles.

Identification of Nutritional Components in Black Sesame Determined by Widely Targeted Metabolomics and Traditional Chinese Medicines.

Chemical composition of secondary metabolites is of great importance for quality control of agricultural products. Black sesame seeds are significantly more expensive than white sesame seeds, because it is thought that black sesame seeds are more beneficial to human health than white sesame seeds. However, the differences in nutrient composition between black sesame seeds and white sesame seeds are still unknown. The current study examined the levels of different metabolites in black and white sesame seeds via the use of a novel metabolomics strategy. Using widely targeted metabolomics data, we obtained the structure and content of 557 metabolites, out of which 217 metabolites were identified, and discovered 30 metabolic pathways activated by the secondary metabolites in both black and white sesame seeds. Our results demonstrated that the main pathways that were differentially activated included: phenylpropanoid biosynthesis, tyrosine metabolism, and riboflavin metabolism. More importantly, the biomarkers that were significantly different between black seeds and white sesame seeds are highly related to the functions recorded in traditional Chinese medicine. The results of this study may serve as a new theoretical reference for breeding experts to promote the genetic improvement of sesame seeds, and therefore the cultivation of higher quality sesame varieties.

The stereotyped positioning of the generative cell associated with vacuole dynamics is not required for male gametogenesis in rice pollen.

During male gametogenesis in cereals, the generative cell undergoes a positioning process that parallels the dynamics of the central vacuole, which is believed to be associated with generative cell movement in the male gametophyte. However, the impact of the generative cell positioning and the central vacuole dynamics on male gametogenesis has remained poorly understood. Here, we report that OsGCD1 (GAMETE CELLS DEFECTIVE1) dysfunction influenced pollen development and disrupted pollen germination. Loss of function of OsGCD1 altered the central vacuole dynamics and the generative cell was mispositioned. Nevertheless, twin sperm cells were generated normally, indicating that gametogenesis does not rely on positional information as long as a generative cell is produced. The normal vacuole dynamics seems necessary only for pollen maturation and germination. Our findings also indicate that osgcd1 mutation resulted in rice male sterility in which pollen has full cell viability and generated normal gametes, but lacks the potential to germinate.