Serological response and immune-related adverse events following COVID-19 vaccination in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

With the popularity of Coronavirus disease 2019 (COVID-19) vaccine and the development of vaccination strategies, the impact of COVID-19 vaccine on cancer patients receiving immune checkpoint inhibitors (ICIs) is still unclear. In the systematic review and meta-analysis of patients with ICIs, we assessed the serological response of cancer patients receiving COVID-19 vaccine, and explored the risk of immune related adverse events (irAEs). We searched PubMed, EMBASE and Cochrane Library as of 10 June 2023, and included cancer patients who received ICIs and COVID-19 vaccine. The systematic review and meta-analysis include cohort study, cross-sectional study and case report. The outcome included the serological response, Spike-specific T-cell response, irAEs and rare adverse events. When possible, the data were analysed by random effect analysis, and the statistical heterogeneity was assessed by Q-test and I2 statistics. We explored the sources of heterogeneity through L'Abbe plots, Galbraith radial plots, and sensitivity analysis. The publication bias was evaluated by Egger's, Begg's linear regression test and funnel plot, and the impact of publication bias was further analysed by trim and fill method. 27 studies were eligible (19 cohort studies, 1 cross-sectional study and 7 case reports), involving 8331 patients (with 4724 receiving ICIs). Most studies used mRNA vaccine (BNT162b2 or mRNA-1273). Compared with cancer patients receiving chemotherapy, cancer patients receiving ICIs were significantly more likely to have seroconversion (RR = 1.05, 95%CI 1.01-1.10, P = 0.02). There were no statistically significant differences in seroconversion rates when comparing cancer patients receiving ICIs with controls without cancer (RR = 0.95, 95% CI 0.89-1.01, P = 0.09) or with cancer patients receiving targeted therapy (RR = 1.05, 95% CI 0.79-1.39, P = 0.75). The incidence of irAEs in patients receiving ICIs before and after COVID-19 vaccination was (21.96%, 95%CI 16.66%-28.94%) and (14.88%, 95%CI 8.65%-25.57%), respectively. The most common irAEs were endocrine abnormalities, skin disorders, etc. The certainty of evidence was low in cancer patients with ICIs, compared with those receiving chemotherapy, and very low versus controls without cancer. Cancer patients treated with ICIs seem to be able to receive COVID-19 vaccine safely without increasing the incidence of irAEs.

Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study.

BACKGROUND: In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations. METHODS: We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13. RESULTS: By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001-1.204, P = 0.047; IL-2, OR = 1.112, 95 % CI 1.009-1.225, P = 0.032; IL-13, OR = 1.068, 95 % CI 1.007-1.132, P = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010-1.220, P = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL-13 targets in lung cancer. CONCLUSION: The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cancer prediction models and targets for anti-tumor therapy.

Pervasive soil phosphorus losses in terrestrial ecosystems in China.

Future phosphorus (P) shortages could seriously affect terrestrial productivity and food security. We investigated the changes in topsoil available P (AP) and total P (TP) in China's forests, grasslands, paddy fields, and upland croplands during the 1980s-2010s based on substantial repeated soil P measurements (63,220 samples in the 1980s, 2000s, and 2010s) and machine learning techniques. Between the 1980s and 2010s, total soil AP stock increased with a small but significant rate of 0.13 kg P ha-1 year-1 , but total soil TP stock declined substantially (4.5 kg P ha-1 year-1 ) in the four ecosystems. We quantified the P budgets of soil-plant systems by harmonizing P fluxes from various sources for this period. Matching trends of soil contents over the decades with P budgets and fluxes, we found that the P-surplus in cultivated soils (especially in upland croplands) might be overestimated due to the great soil TP pool compared to fertilization and the substantial soil P losses through plant uptake and water erosion that offset the P additions. Our findings of P-deficit in China raise the alarm on the sustainability of future biomass production (especially in forests), highlight the urgency of P recycling in croplands, and emphasize the critical role of country-level basic data in guiding sound policies to tackle the global P crises.

Synthesis, odor characteristics and biological evaluation of N-substituted pyrrolyl chalcones.

A novel approach for converting N-substituted acetylpyrroles and primary alcohols into N-substituted pyrrolyl chalcones in air with the assistance of t-BuOK is reported, and several prominent flavor and bioactive molecules were obtained. The process entails oxidizing the alcohols to the corresponding aldehydes, and t-BuOK is crucial to the effective production of CC bonds by aldol condensation. Gas chromatography-mass spectrometry-olfactometry (GC-MS-O) was used to examine the odor properties of pyrrolyl chalcones, which are usually different from those of the associated acetylpyrroles and alcohols. The biological evaluation assay showed that the products (E)-3-(3-fluorophenyl)-1-(1-methyl-1H-pyrrol-2-yl)prop-2-en-1-one (3j), (E)-1-(1-ethyl-1H-pyrrol-2-yl)-3-phenylprop-2-en-1-one (4a), (E)-3-(4-bromophenyl)-1-(1-ethyl-1H-pyrrol-2-yl)prop-2-en-1-one (4e), (E)-3-(4-chlorophenyl)-1-(1-ethyl-1H-pyrrol-2-yl)prop-2-en-1-one (4f) and (E)-1-(1-ethyl-1H-pyrrol-2-yl)-3-(4-fluorophenyl)prop-2-en-1-one (4g) exhibited excellent inhibitory activity against R. solani with EC50 values from 0.0107 to 0.0134 mg mL-1. Molecular docking of 3j with SDH (succinate dehydrogenase) was performed to reveal the binding modes in the active pocket and analyze the interactions between the molecules and the SDH protein. Meanwhile, they have good thermal stability according to the results of thermogravimetry (TG) analysis.

Economics- and policy-driven organic carbon input enhancement dominates soil organic carbon accumulation in Chinese croplands.

China's croplands have experienced drastic changes in management practices, such as fertilization, tillage, and residue treatments, since the 1980s. There is an ongoing debate about the impact of these changes on soil organic carbon (SOC) and its implications. Here we report results from an extensive study that provided direct evidence of cropland SOC sequestration in China. Based on the soil sampling locations recorded by the Second National Soil Survey of China in 1980, we collected 4,060 soil samples in 2011 from 58 counties that represent the typical cropping systems across China. Our results showed that across the country, the average SOC stock in the topsoil (0-20 cm) increased from 28.6 Mg C ha-1 in 1980 to 32.9 Mg C ha-1 in 2011, representing a net increase of 140 kg C ha-1 year-1 However, the SOC change differed among the major agricultural regions: SOC increased in all major agronomic regions except in Northeast China. The SOC sequestration was largely attributed to increased organic inputs driven by economics and policy: while higher root biomass resulting from enhanced crop productivity by chemical fertilizers predominated before 2000, higher residue inputs following the large-scale implementation of crop straw/stover return policy took over thereafter. The SOC change was negatively related to N inputs in East China, suggesting that the excessive N inputs, plus the shallowness of plow layers, may constrain the future C sequestration in Chinese croplands. Our results indicate that cropland SOC sequestration can be achieved through effectively manipulating economic and policy incentives to farmers.

Deep Nitrate Accumulation in a Highly Weathered Subtropical Critical Zone Depends on the Regolith Structure and Planting Year.

Nitrate accumulated deep (>100 cm) in the regolith (soil and saprolite) threatens groundwater quality, but most studies focus only on nitrate nearer the surface (<100 cm). Surface soil management versus regolith interactions affect deep nitrate leaching, but their combined impact remains unclear. This study measured how deep nitrate accumulation was affected by crop practices including orchard/cropland planting years, regolith structure, and soil properties in highly weathered subtropical red soils. Deep nitrate storage varied from 43.6 to 1116.3 kg ha-1. Regolith thickness was positively correlated with nitrate storage (R2 = 0.43, p < 0.05). Reticulated red clay (110-838 cm) had 81% of the accumulated nitrate and overlapped with 79% of the nitrate accumulation layer. All of the nitrate accumulation parameters (except for peak depth (PD)) generally increased with the planting years. The difference in peak nitrate concentration (9.0-20.0 mg kg-1) with planting year gradient (3-58 years) varied by 2.2 times, and the difference in nitrate storage (43.6-425.7 kg ha-1) varied by 9.8 times. Texture and pH explain 41.6% of the variation in nitrate concentration. As soil management practices interact with deeper regolith to control the spatial pattern of nitrate accumulation, vulnerable regions could be identified to avoid high accumulation.

Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

Characterization of the spatial variability of soil available zinc at various sampling densities using grouped soil type information.

The influence of anthropogenic activities and natural processes involved high uncertainties to the spatial variation modeling of soil available zinc (AZn) in plain river network regions. Four datasets with different sampling densities were split over the Qiaocheng district of Bozhou City, China. The difference of AZn concentrations regarding soil types was analyzed by the principal component analysis (PCA). Since the stationarity was not indicated and effective ranges of four datasets were larger than the sampling extent (about 400 m), two investigation tools, namely F3 test and stationarity index (SI), were employed to test the local non-stationarity. Geographically weighted regression (GWR) technique was performed to describe the spatial heterogeneity of AZn concentrations under the non-stationarity assumption. GWR based on grouped soil type information (GWRG for short) was proposed so as to benefit the local modeling of soil AZn within each soil-landscape unit. For reference, the multiple linear regression (MLR) model, a global regression technique, was also employed and incorporated the same predictors as in the GWR models. Validation results based on 100 times realization demonstrated that GWRG outperformed MLR and can produce similar or better accuracy than the GWR approach. Nevertheless, GWRG can generate better soil maps than GWR for limit soil data. Two-sample t test of produced soil maps also confirmed significantly different means. Variogram analysis of the model residuals exhibited weak spatial correlation, rejecting the use of hybrid kriging techniques. As a heuristically statistical method, the GWRG was beneficial in this study and potentially for other soil properties.

Reconstruction of Digital Skin Defects with the Free Wrist Crease Flap.

BACKGROUND: Soft-tissue digital defects frequently need to be covered by a flap rather than a skin graft. In hand surgery, functional preservation and aesthetic appearance are often as important as procedural efficacy. OBJECTIVE: We present our clinical experience with reconstruction of digital skin defects with the free wrist crease flap. METHODS: From January 2012 to September 2013, 14 digits of 14 patients (10 males, 4 females) were included for evaluation. The procedure was performed with brachial plexus block anesthesia. The superficial palmar branch of the radial artery, a subcutaneous superficial vein, and the palmar cutaneous branch of the median nerve were included in the free wrist crease flap. The flaps were used to reconstruct the skin defect of injured digits through microvascular anastomosis, and donor sites were closed primarily. RESULTS: Postoperative follow-up time ranged from 3 to 25 months. All digital deformities were corrected, all flaps survived completely without ischemia, and none were aesthetically bulky. The area of free wrist crease flaps ranged from 2.5 to 5.0 cm by 2.0 to 3.1 cm. Slight wound infections appeared in two cases. Venous crisis occurred in one case, but it was successfully addressed after vascular exploration and reanastomosis. Sensation determined by static two-point discrimination measured in these flaps 2 months postsurgery was "good" at a mean 9.7 ± 2.1 mm (range, 6-14 mm). The mean motion range of the distal interphalangeal joint and proximal interphalangeal joint was 23.4 ± 6.9 degrees (0-42 degrees) and 75.8 ± 22.1 degrees (0-98 degrees) preoperatively. The mean motion range of the distal interphalangeal joint recovered to 40.3 ± 5.7 degrees (36-42 degrees), and that of the proximal interphalangeal joint was 90.3 ± 15.3 degrees (85-98 degrees) postoperatively. Both joints reached normal motion angle and difference was statistically significant preoperatively and postoperatively (p < 0.05). The mean disabilities of arm and shoulder (DASH) score was 6.8 ± 3.4 (0-15), and there was statistically significant difference when compared with the preoperative score of 13.5 ± 4.3 (3-19) (p < 0.05). CONCLUSION: We found the free wrist crease flap to be an ideal solution for reconstruction of skin defects of digits.

T-shaped excision of the orbicularis oris muscle: an innovative technique for upper lip lift procedures.

BACKGROUND: The lips are a prominent part of the face and they age along with the face. Microsurgery for upper lip lifts is becoming popular because of its association with minimal trauma and rapid recovery. OBJECTIVES: The authors introduced an innovative method of lifting the upper lip. METHODS: From January 2009 to March 2013, a cohort of 30 women underwent an upper lip lift surgical procedure. Patients received local anesthesia for a regional block of the infraorbital nerve. A T-shaped orbicularis oris and a strip of skin were excised. The superior edge of the orbicularis oris muscle was sutured to the base of the nose, and the incision was closed with a continuous intradermal suture. Postoperative follow-up time ranged from 1 to 5 years. RESULTS: At the time of follow-up, the incisional scar was not visible on the patient. The nasolabial angle was 96.20° ± 1.86° before operation and 88.23° ± 2.58° after operation. The difference was statistically significant (P = 0.000 and P < 0.001). The upper lip angle was 65.56° ± 8.60° before operation and 51.90° ± 3.93° after operation. The difference was statistically significant (P = 0.000) and P < 0.001). After operation, the upper lip appeared to be clearly thickened. CONCLUSIONS: This innovative surgical technique is a simple and effective way to lift the upper lip.

[Study on Paddy Soil Chronosequences Based on Visiblc-Near Infrared Diffuse Reflectance Spectra].

To investigate spectral characteristics of different soil compositions, eight soil profiles from two paddy soil chronosequences developed on red clays and red sandstones respectively were collected in Jiangxi Province. A total of 37 soil samples were taken from each soil horizons of the profiles. The paddy soil chronosequences were chosen mainly because all soil profiles have the same land management and thus parent materials and rice cultivation time would be two major soil formative factors. This makes it possible to study spectral response characteristics of soil organic matter (SOM) and parent material characteristics. We measured diffuse reflectance spectra data of soil samples using the Cary 5000 spectrophotometer at 350-2500 nm spectral range. Spectral response characteristics of SOM and inorganic minerals in paddy soils were analyzed according to different soil horizons, soil forming times and parent materials. Experiment results showed that for soil samples from a single parent material, overall reflectance presented by PC_1 score can be calibrated for soil organic matter (SOM) content with high precision (R(RC)² = 0.91, R(RS)² = 0.79), even though the SOM content was low (not more than 20 g · kg⁻¹). The absorption strength (AS) at 1400, 1900 and 2200 nm was mainly affected by the minerals inherited from parent materials. And the more the sample was near to bottom of a soil profile, the higher the AS value. Samples with the same mineral components had the similar AS ratio among these three wavelength locations. The differences in parent materials can significantly affect spectral curve shape and spectral absorption strength. To make the calibration more interpretative, parent material factors should be considered.

Nitrogen loss through anaerobic ammonium oxidation coupled to iron reduction from paddy soils in a chronosequence.

Anaerobic ammonium oxidation coupled to iron(III) reduction (termed Feammox) with dinitrogen, nitrite, or nitrate as the end-product is a recently discovered process of nitrogen cycling. However, Feammox has not been described in paddy soils, which are rich in iron(III) oxides and subjected to intensive nitrogen fertilization. Here, evidence for Feammox in a paddy soil chronosequence with a gradient of microbially reducible iron(III) levels was obtained in Southern China using (15)N-labeled ammonium-based isotopic tracing and acetylene inhibition techniques. Our study demonstrated the occurrence of Feammox in the chronosequence, and direct dinitrogen production was shown to be the dominant Feammox pathway. Within the chronosequence, three paddy soils with higher microbially reducible iron(III) levels had higher Feammox rates (ranged from 0.17 to 0.59 mg N kg(-1) d(-1)) compared to an uncultivated soil (0.04 mg N kg(-1) d(-1)). It is estimated that a loss of 7.8-61 kg N ha(-1) year(-1) is associated with Feammox in the examined paddy soils. Overall, we discover that rice cultivation could enrich microbially reducible iron(III), accelerate Feammox reaction and thus fuel nitrogen loss from soils, and suggest that Feammox could be a potentially important pathway for nitrogen loss in paddy soils.

Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay.

BACKGROUND: Stellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. In our previous study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2 had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC-2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor active fraction of ESC might exist in ESC-2. Here, we further observe the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo. METHODS: In this study, we used hollow fiber tumor model to evaluate the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic rates of the cancer cells retrieved from the hollow fibers were measured with flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-α expression were determined with elisa assay and radioimmunoassay respectively. RESULTS: The results showed that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the effect strength, dose and antitumor spectrum, the order of antitumor effects of ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs. ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas-L protein, but TNF-α/TNFR1 protein expression in NCI-H460 cells changed significantly after ESC and ESC-2 treatment. CONCLUSION: ESC-2 had the similar antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be the main antitumor active fraction of ESC, which was consistent with our previous results in vitro.

Edaphic regulation of soil organic carbon fractions in the mattic layer across the Qinghai-Tibetan Plateau.

The mattic layer is a main ecological function bearer of alpine meadow soils in the Qinghai-Tibet Plateau. It has high soil organic carbon (SOC) content with a variety of SOC fractions, which are thought to have different sensitivities to climate change. The effects of soil properties and climate on the SOC fractions in the mattic layer are not well understood. To address this, we analyzed the effects of environmental factors on two SOC fractions: particulate organic carbon (POC) and mineral-associated organic carbon (MAOC). A random forest model (RFM), partial correlation analysis, and structural equation model (SEM) were used to quantify the relative effects of soil and climatic factors on SOC fractions. We found that SOC and its fractions are primarily regulated by soil properties rather than climate. Partial correlation analysis and SEM revealed that climate indirectly affects SOC by influencing soil properties. Silt+Clay and exchangeable calcium (Caex) were found to be the strongest contributing factors of MAOC and POC, respectively. A distinct shift occurs in the mechanism underlying SOC stabilization with varying soil pH. In acidic and neutral environments, amorphous Al/Fe-(hydr) oxides contribute to the stability of MAOC, whereas free Al/Fe-(hydr) oxides promote SOC mineralization. Conversely, Caex positively influences the stabilization of both POC and MAOC throughout the pH range. These results can be extrapolated to predict SOC dynamics in future soil conditions affected by environmental change, especially for use in Earth system models.

Nitrate leaching characteristics of red soils from different parent materials in subtropical China.

Globally, nitrate (NO3-) leaching from agroecosystems has been of major concern. There is evidence that NO3- leaching exhibits intense seasonal variation in subtropical regions. However, influencing factors to the seasonal dynamics remain unclear. In this study, a two-year field lysimeters experiment was conducted with three red soils derived from different parent materials (Quaternary red clay (QR), red sandstone (RS), and basalt (BA)). An N fertilizer (15N-enriched urea, 10 atom% excess) of 200 kg N ha-1 yr-1 was applied for maize. The effect of parent material on NO3- leaching characteristics was examined in surface (0-20 cm) and subsoil (20-100 cm) layers. The results showed due to the weakening of abundant drainage, there was no significant effect of parent materials on NO3- leaching characteristics in surface layers. Environmental factors (precipitation and temperature) and fertilization together led to obvious seasonal characteristics, i.e. abundant NO3- leaching during both crop growth and fallow periods. In subsoil layers, NO3- leaching characteristics were completely different among three soils. The concentrations and δ15N of NO3- in QR and RS soils showed a continuous increase after first year's fertilization, while those in BA soil remained relatively stable after reaching peak levels around harvest in first year. Meanwhile, the NO3- leaching amount in BA soil was significantly lower than in the other two soils. These might be explained by different NO3- adsorption capacities caused by the differences in mineral composition and free iron and aluminium contents. These elucidated in subsoil layers, NO3- leaching characteristics highly depended on parent materials. Meanwhile, adsorption capacity was limited and cannot slow NO3- leaching in the long run. Our results suggest that seasonal variation of NO3- leaching in surface layers and temporary retardant effect from NO3- adsorption capacity in subsoil layers should receive much attention when calculating and predicting NO3- leaching in subtropical regions.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Compound Kushen injection combined with transarterial chemoembolization for hepatocellular carcinoma: An evidence map and overview of systematic reviews.

ETHNOPHARMACOLOGICAL RELEVANCE: For the treatment of hepatocellular carcinoma (HCC), compound Kushen injection (CKi) is commonly used in combination with transarterial chemoembolization (TACE). AIMS OF THE STUDY: Our objective was to evaluate the reporting quality, methodological quality, risk of bias, and certainty of evidence for CKi combined with TACE for the treatment of patients with HCC by conducting systematic reviews (SRs). The purpose of this study was to improve the clinical application of CKis, strengthen clinical decision-making regarding CKis, and inform future research. MATERIALS AND METHODS: We used eight databases to systematically search SRs of CKi combined with TACE for HCC through February 21, 2023. The quality of reporting of SRs was evaluated using the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, methodological quality using A MeaSurement Tool to Assess systematic Reviews 2, risk of bias using the Risk of Bias in Systematic Review, and certainty of evidence using the Grading of Recommendations Assessment. Finally, the assessment results were visualized by the evidence mapping method. This overview has been registered on PROSPERO with the registration title "Compound Kushen injection for hepatocellular carcinoma: An overview of systematic reviews" and registration number CRD42022369120. RESULTS: A total of 12 SRs meeting the inclusion criteria were included. In terms of reporting quality, 42% of SRs reported relatively complete reports and 58% had certain deficiencies. The methodological quality of all SRs was " critically low". The risk of bias was evaluated as low in 33% of SRs and high in 67% of SRs. The results of the evidence synthesis showed that, in the "moderate" level of evidence, CKi combined with TACE resulted in a 12.7%-21.5% benefit for one-year survival rate, 11.7%-17.2% benefit for objective response rate (ORR), 20.5%-27.1% benefit for quality of life, 22.2% benefit for nausea and vomiting, and 24.7%-27.4% benefit for leukopenia in HCC patients. CONCLUSION: In conclusion, CKi combined with TACE improved survival, ORR and quality of life in patients with HCC, and reduced adverse events. The results should be interpreted with caution due to the low methodological quality of the included SRs. The clinical efficacy of CKis must be confirmed in a large number of randomized controlled trials.

Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.