Seamless phase 2/3 design for trials with multiple co-primary endpoints using Bayesian predictive power.

Seamless phase 2/3 design has become increasingly popular in clinical trials with a single endpoint. Trials that define success based on the achievement of all co-primary endpoints (CPEs) encounter the challenge of inflated type 2 error rates, often leading to an overly large sample size. To tackle this challenge, we introduced a seamless phase 2/3 design strategy that employs Bayesian predictive power (BPP) for futility monitoring and sample size re-estimation at interim analysis. The correlations among multiple CPEs are incorporated using a Dirichlet-multinomial distribution. An alternative approach based on conditional power (CP) was also discussed for comparison. A seamless phase 2/3 vaccine trial employing four binary endpoints under the non-inferior hypothesis serves as an example. Our results spotlight that, in scenarios with relatively small phase 2 sample sizes (e.g., 50 or 100 subjects), the BPP approach either outperforms or matches the CP approach in terms of overall power. Particularly, with n1 = 50 and ρ = 0, BPP showcases an overall power advantage over CP by as much as 8.54%. Furthermore, when the phase 2 stage enrolled more subjects (e.g., 150 or 200), especially with a phase 2 sample size of 200 and ρ = 0, the BPP approach evidences a peak difference of 5.76% in early stop probability over the CP approach, emphasizing its better efficiency in terminating futile trials. It's noteworthy that both BPP and CP methodologies maintained type 1 error rates under 2.5%. In conclusion, the integration of the Dirichlet-Multinominal model with the BPP approach offers improvement in certain scenarios over the CP approach for seamless phase 2/3 trials with multiple CPEs.

Crystalline MnCO3@Amorphous MnOx Composite as Cathode Material for High-Performance Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries (RAZIBs) have received extensive attention because of their advantages of low cost, high safety, and nontoxicity. However, problems such as dissolution of the active cathode material, dendrites/passivation of the zinc anode, and slow reaction kinetics hindered their further applications. In this work, a crystalline/amorphous composite-type material composed of crystalline MnCO3 and amorphous MnOx was prepared and used as the cathode material for RAZIBs. The MnCO3@amorphous MnOx (MnCO3@A-MnOx) composite possesses the merits of both the pure crystalline phase of MnCO3 and the amorphous phase of MnOx, which can deliver better electrochemical performance than the corresponding single component in repeated cycles. In addition, crystalline MnCO3 undergoes a complex phase transition to the active MnO2 during the first charge process, providing the composite with a stable structure and additional electrochemical capacity. The electrochemical measurement results indicate that the MnCO3@A-MnOx electrode can display high reversible discharge capacity at 0.1 A g-1, excellent rate performance at 5.0 A g-1, and long cycling stability over 2000 cycles, showing great potential as a cathode material for high-performance RAZIBs.

Development and validation of the chemotherapy-induced peripheral neuropathy integrated assessment - oxaliplatin subscale: a prospective cohort study.

BACKGROUND: Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations. METHODS: This study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2-6 of chemotherapy. Cronbach's α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20. RESULT: A 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment - oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05). CONCLUSION: This study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN.

Legacy effects of wheat season organic fertilizer addition on microbial co-occurrence networks, soil function, and yield of the subsequent maize season in a wheat-maize rotation system.

Organic fertilizer can alleviate soil degradation. While numerous studies have explored the immediate impacts of organic fertilizer on soil properties and crop production, the legacy effects of organic fertilizer addition remain less understood. This research investigated the subsequent effects of organic fertilizer addition during the winter wheat season on soil microbial community structure, co-occurrence networks, soil function, and summer maize yield from 2018 to 2020. Six fertilization treatments were implemented as chemical nitrogen fertilizer (N) alone or combined sheep manure and nitrogen fertilizer (SMN) at low, medium, and high fertilization levels during the winter wheat season, with only N fertilizer applied during the maize season. The findings revealed significant variations in bacterial and fungal community structures between the SMN and N treatments. The SMN treatments increased the relative abundance of Proteobacteria, Actinobacteria, and Bacteroidetes and decreased the relative abundance of Rokubacteria, Acidobacteria, Gemmatimonadetes, Chloroflexi, and Nitrospirae compared to the N treatment. The SMN treatments had higher fungal network connectivity and lower mean path distance and modularity than the N treatment, resulting in heightened sensitivity of fungi to environmental changes. The legacy effects of organic fertilizer changed the functional potential of the N and C cycles, with keystone taxa such as Proteobacteria, Actinomycetes, Acidobacteria, Gemmatimonadetes, Bacteroides, and Ascomycota significantly correlating with functional genes related to the C and N cycles. Surprisingly, no significant differences in summer maize yield occurred between the SMN and N treatments. However, the random forest model revealed that the SMN treatments had significantly higher explanatory power of soil microbial community structure for maize yield (74.31%) than the N treatment (13.07%). These results were corroborated in subsequent studies and underscore the legacy effects of organic fertilizer addition on soil microbial communities. This research offers valuable insights into organic fertilizer use for enhancing soil quality and sustaining agricultural productivity.

Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study.

BACKGROUND: There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. METHODS: Totally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively. RESULTS: The gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients. CONCLUSIONS: These data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.

Synergistic Network Pharmacology for Traditional Chinese Medicine Liangxue Tongyu Formula in Acute Intracerebral Hemorrhagic Stroke.

Background: Nowadays, acute intracerebral hemorrhage stroke (AICH) still causes higher mortality. Liangxue Tongyu Formula (LXTYF), originating from a traditional Chinese medicine (TCM) prescription, is widely used as auxiliary treatment for AICH. Objective: To dig into the multicomponent, multitarget, and multipathway mechanism of LXTYF on treating AICH via network pharmacology and RNA-seq. Methods: Network pharmacology analysis was used by ingredient collection, target exploration and prediction, network construction, and Gene Ontology (GO) and KEGG analysis, with the Cytoscape software and ClusterProfiler package in R. The RNA-seq data of the AICH-rats were analyzed for differential expression and functional enrichments. Herb-Compound-Target-Pathway (H-C-T-P) network was shown to clarify the mechanism of LXTYF for AICH. Results: 76 active ingredients (quercetin, Alanine, kaempferol, etc.) of LXTYF and 376 putative targets to alleviate AICH (PTGS2, PTGS1, ESR1, etc.) were successfully identified. The protein-protein interaction (PPI) network indicated the important role of STAT3. The functional enrichment of GO and KEGG pathway showed that LXTYF is most likely to influence MAPK and PI3K-Akt signaling pathways for AICH treatment. From the RNA-seq of AICH-rats, 583 differential mRNAs were identified and 14 of them were consistent with the putative targets of LXTYF for AICH treatment. The KEGG pathway enrichment also implied that the MAPK signaling pathway was the most correlated one among all the related signaling pathways. Many important targets with expression changes of LXTYF for AICH treatment and their related pathways are great markers of antioxidation, anti-inflammatory, antiapoptosis, and lowering blood pressure, which indicated that LXTYF may play mutiroles in the mechanisms for AICH treatment. Conclusion: The LXTYF attenuates AICH partially by antioxidation, anti-inflammatory, and antiapoptosis and lowers blood pressure roles through regulating the targets involved MAPK, calcium, apoptosis, and TNF signaling pathway, which provide notable clues for further experimental validation.

Field implementation of long-distance quantum key distribution over aerial fiber with fast polarization feedback.

Quantum key distribution with polarized qubits has not yet been realized over the aerial fiber, due to rapid polarization changes. Here, we report our recent work towards quantum communication through an aerial fiber channel. We designed a fast polarization feedback module featuring high efficiency, fast speed, and good stability. With this module, we implemented long-distance quantum key distribution over different types of aerial fiber links based on polarization encoding. Our work takes a significant step towards the application of quantum communications in complex environments.

Single herbal medicine for diabetic retinopathy.

BACKGROUND: Diabetic retinopathy is one of the major causes of blindness and the number of cases has risen in recent years. Herbal medicine has been used to treat diabetes and its complications including diabetic retinopathy for thousands of years around the world. However, common practice is not always evidence-based. Evidence is needed to help people with diabetic retinopathy or doctors to make judicious judgements about using herbal medicine as treatment. OBJECTIVES: To evaluate the effectiveness and harm of single herbal medicine for diabetic retinopathy. SEARCH METHODS: We searched CENTRAL, which contains the Cochrane Eyes and Vision Trials Register, MEDLINE, Embase, OpenGrey, the ISRCTN registry, ClinicalTrials.gov and the ICTRP. The date of the search was 12 June 2018. We also searched the following Chinese databases in June 2013: Chinese BioMedical Literature Database (CBM), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), Wanfang China Dissertation Database (CDDB), Wanfang China Conference Paper Database (CCPD) and the Index to Chinese Periodical Literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that investigated the effects of any single herb (or extracts from a single herb) as a treatment for people with diabetic retinopathy. We considered the following comparators: placebo, no treatment, non-herbal (conventional) medicine or surgical treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the studies. Our prespecified outcomes were: progression of diabetic retinopathy, visual acuity, microaneurysms and haemorrhages in the retina, blood glycated haemoglobin A1c (HbA1c) (%) and adverse effects. We performed meta-analyses using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 10 studies involving 754 participants, of which nine were conducted in China and one in Poland. In all studies, participants in both groups received conventional treatment for diabetic retinopathy which included maintaining blood glucose and lipids using medicines and keeping a stable diabetic diet. In three studies, the comparator group also received an additional potentially active comparator in the form of a vasoprotective drug. The single herbs or extracts included Ruscus extract tablet, Sanqi Tongshu capsule, tetramethylpyrazine injection, Xueshuantong injection, Puerarin injection and Xuesaitong injection. The Sanqi Tongshu capsule, Xueshuantong injection and Xuesaitong injection were all made from the extract of Radix Notoginseng (San qi) and the main ingredient was sanchinoside. The risk of bias was high in all included studies mainly due to lack of masking (blinding). None of the studies reported the primary outcome of this review, progression of retinopathy.Combined analysis of herbal interventions suggested that people who took these herbs in combination with conventional treatment may have been more likely to gain 2 or more lines of visual acuity compared to people who did not take these herbs when compared to conventional intervention alone at the end of treatment (RR 1.26, 95% CI 1.08 to 1.48; 5 trials, 541 participants; low-certainty evidence). Subgroup analyses based on the different single herbs found no evidence for different effects of different herbs, but the power of this analysis was low. One study reported Sanqi Tongshu capsule might be associated with a greater reduction in microaneurysms and haemorrhages in the retina (very low-certainty evidence). The pooled analysis of two studies on tetramethylpyrazine or Xueshuantong injection showed such herbs may have had little effect on lowering HbA1c (MD 0.00, 95% CI -0.58 to 0.58; 215 participants; low-certainty evidence).There was very low-certainty evidence on adverse events. Two studies reported minor adverse events such as uncomfortable stomach, urticaria, dizziness and headache. There was no report of observation on adverse events in the other studies. AUTHORS' CONCLUSIONS: No conclusions could be drawn about the effect of any single herb or herbal extract on diabetic retinopathy from the current available evidence. It was difficult to exclude the placebo effect as a possible explanation for observed differences due to the lack of placebo control in the included studies. Further adequately designed trials are needed to establish the evidence.

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics.

BACKGROUND: The systematic mechanisms of acute intracerebral hemorrhage are still unknown and unverified, although many recent researches have indicated the secondary insults. This study was aimed to disclose the pathological mechanism and identify novel biomarker and therapeutic target candidates by plasma proteome. METHODS: Patients with AICH (n = 8) who demographically matched healthy controls (n = 4) were prospectively enrolled, and their plasma samples were obtained. The TMT-LC-MS/MS-based proteomics approach was used to quantify the differential proteome across plasma samples, and the results were analyzed by Ingenuity Pathway Analysis to explore canonical pathways and the relationship involved in the uploaded data. RESULTS: Compared with healthy controls, there were 31 differentially expressed proteins in the ICH group (P < 0.05), of which 21 proteins increased while 10 proteins decreased in abundance. These proteins are involved in 21 canonical pathways. One network with high confidence level was selected by the function network analysis, in which 23 proteins, P38MAPK and NFκB signaling pathways participated. Upstream regulator analysis found two regulators, IL6 and TNF, with an activation z-score. Seven biomarker candidates: APCS, FGB, LBP, MGMT, IGFBP2, LYZ, and APOA4 were found. Six candidate proteins were selected to assess the validity of the results by subsequent Western blotting analysis. CONCLUSION: Our analysis provided several intriguing pathways involved in ICH, like LXR/RXR activation, acute phase response signaling, and production of NO and ROS in macrophages pathways. The three upstream regulators: IL-6, TNF, LPS, and seven biomarker candidates: APCS, APOA4, FGB, IGFBP2, LBP, LYZ, and MGMT were uncovered. LPS, APOA4, IGFBP2, LBP, LYZ, and MGMT are novel potential biomarkers in ICH development. The identified proteins and pathways provide new perspectives to the potential pathological mechanism and therapeutic targets underlying ICH.

Enhanced electrochemical performance of orientated VO2(B) raft-like nanobelt arrays through direct lithiation for lithium ion batteries.

Lithiation modification of VO2(B) has been carried out by a facile hydrothermal process, and the compact and locally ordered VO2(B) raft-like nanobelt arrays have been prepared. The synthesis route provides a new approach to elaborate a VO2(B) nanostructure under a mild environment condition. It is found that the growth mechanism of VO2(B) raft-like nanobelt arrays is different from the traditional nucleation-growth process. A novel chemical lithiating-exfoliating-splitting model is proposed. Compared with the bulk counterpart, the lithiated VO2(B) raft-like nanobelt arrays as cathodes exhibit a higher discharge capacity and an enhanced high-rate performance owing to their increased structural anisotropy and decreased polarization. This work indicates that VO2(B) raft-like nanobelt arrays have great potential applications as cathode materials for lithium ion batteries.

[The Real World Study on Evaluating the Effect of Chinese Medicine Combined Western Medicine in Treating Rheumatoid Arthritis].

Objective To observe the curative effect of Chinese medicine (CM) combined West- ern medicine (WM) in treating rheumatoid arthritis (RA) patients. Methods Totally 351 RA patients were allocated into two groups by their willingness, 52 cases in the control group and 299 cases in the combination group. Treatment of WM mainly included non-steroidal anti-inflammatory drugs, glucocorti- coids, and anti-rheumatic drugs. And treatment based on syndrome differentiation of CM was adopted. Four diagnostic information of CM, joint pain, tenderness, swelling index, laboratory indices, and treat- ment expenses were observed. Disease activity score 28 (DAS28) , quality of life score [health assessment questionnaire (HAQ) ] , and efficacy of disease were assessed. Results After 2-3 months of treatment, the total effective rate was higher in the combination group than in the control group (P < 0. 05). After 6-12 months of treatment, the total effective rate, DAS28, and HAQ score were better in the combination group than in the control group (P <0. 05). There was no statistical difference in use of Western drugs, total expenses of hospitalization, total expenses of outpatient service between the two groups (P >0. 05). Patients who were treated by combined treatment, or having higher DAS obtained better effects after 2-3 months of treatment (P <0. 05). Patients who were treated by combined treatment, or having lower DAS obtained better effects after 6-12 months of treatment (P <0. 05). Conclusions Real world study (RWS) observed that combined CM and WM could get more significant effect. It also could effectively reduce disease activity, improve patients' QOL, with no economic burdens added.

[The effective parts of liangxue tongyu prescription on cooling-blood and activating-blood and analysis of chemical constituents by HPLC-MS and GC-MS].

In order to clarify material basis of effective parts of liangxue tongyu prescription, blood-heat and blood-stasis rat model induced by dry yeast was established. The changes of rectal temperature, blood viscosity and plasma viscosity were used to evaluate the cooling-blood and activating-blood effects of liangxue tongyu prescription and its parts. Compared with the model group, the extract from liangxue tongyu prescription, its volatile oil and n-butanol part could significantly reduce rectal temperature (P<0.01), and also reduce blood viscosity and plasma viscosity to various degrees (P<0.01 or P<0.05). So volatile oil and n-butanol part were primarily identified as effective parts of liangxue tongyu prescription. By using GC-MS with normalization method of area to analyze volatile oil of liangxue tongyu prescription, 70 compounds were identified, accounting for about 92.54%, mainly as ß-asarone, paeonol, α-asarone and shyobunone. 42 compounds such as peony glycosides, tannins, and iridoid glycosides were identified by HPLC-MS techniques and standard comparison. The study determined the effective parts of liangxue tongyu prescription and clarified the chemical composition providing the foundation for further studies on material basis of liangxue tongyu prescription.

Clinical improvement effect of regulating gut microbiota on metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is constantly rising globally. There are barely any effective medications or supplements for the management of MASLD. We aim to systematically evaluate the most current evidence for gut microbiota-regulating supplements in patients with MASLD. METHODS: We searched multiple electronic data for randomized controlled trials (RCTs) published from January 1, 2012, to July 15, 2023. The intervention measures included probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The control group was treated with a placebo or usual care. The intervention duration was divided into two periods (>12 weeks and ≤12 weeks). Adequate evaluation data for antibiotics and FMT have not been obtained. Therefore, the other three microbiota regulators are the primary evaluation measures in this study. RESULTS: We found that probiotics alone could not improve clinical indicators in MASLD patients. However, synbiotics exhibited an improvement in reducing liver steatosis, TNF-ɑ levels, and increasing HDL-c levels, and the inflammatory markers of liver cells (ALT and AST) were also improved. For the effective intervention duration, this systematic review suggested that around 12 weeks is an ideal intervention cycle for MASLD patients. CONCLUSIONS: This meta-analysis supported the modulation of gut microbiota with synbiotics in the management of MASLD.

Accelerate vaccine development using seamless phase 2/3 trial designs.

BACKGROUND: Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines. RESEARCH DESIGN AND METHODS: This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, the percentage of early stop, and the accuracy of dose selection. RESULTS: On average, when the experimental vaccine was assumed to be effective, the seamless design that performed interim analyses based solely on efficacy saved 555.73 subjects, shortened trials by 10.29 months, and increased power by 3.70%. When the experimental vaccine was less effective than control, it saved an average of 887.73 subjects while maintaining the type I error rate below 0.025. CONCLUSION: The seamless design proves to be a compelling strategy for vaccine development, given its versatility in early stopping, re-estimating sample sizes, and shortening trial durations.

A LC-MS-based serum pharmacochemistry approach to reveal the compatibility features of mutual promotion/assistance herb pairs in Xijiao Dihuang decoction.

Xijiao Dihuang decoction (XDT), a famous formula, was usually used to improve the prognosis of patients with blood-heat and blood-stasis syndrome-related diseases. There were some mutual promotion and mutual assistance herb pairs in XDT. However, the exact functions of these herb pairs in the compatibility of XDT were not elucidated due to the lack of appropriate methodologies. Based on the theory of serum pharmacochemistry, a systematic method was established for the qualitative and quantitative analysis of characteristic components in the extracts and drug-containing plasma samples of XDT and its relational mutual promotion/assistance herb pairs. For qualitative analysis, 85 characteristic components were identified using the liquid chromatography with triple time-of-flight mass/mass spectrometry (LC-Triple QTOF-MS/MS) based on the mass defect filtering, product ion filtering, neutral loss filtering and isotope pattern filtering techniques. For quantitative detection, a relative quantitation assay using an extract ion chromatogram (EIC) of the full scan MS experiment was validated and employed to assess the quantity of the 85 identified compounds in the test samples of single herb, herb pairs and XDT. The results of multivariate statistical analyses indicated that both the assistant and guide herbs could improve the solubilization of active compounds from the sovereign and minister herbs in XDT in vitro, might change the trans-membrane transportation, and regulate metabolism in vivo. The methods used in present study might be also valuable for the investigation of multiple components from other classic TCM formulas for the purpose of compatibility feature study.

Innovative Solutions for High-Performance Silicon Anodes in Lithium-Ion Batteries: Overcoming Challenges and Real-World Applications.

Silicon (Si) has emerged as a potent anode material for lithium-ion batteries (LIBs), but faces challenges like low electrical conductivity and significant volume changes during lithiation/delithiation, leading to material pulverization and capacity degradation. Recent research on nanostructured Si aims to mitigate volume expansion and enhance electrochemical performance, yet still grapples with issues like pulverization, unstable solid electrolyte interface (SEI) growth, and interparticle resistance. This review delves into innovative strategies for optimizing Si anodes' electrochemical performance via structural engineering, focusing on the synthesis of Si/C composites, engineering multidimensional nanostructures, and applying non-carbonaceous coatings. Forming a stable SEI is vital to prevent electrolyte decomposition and enhance Li+ transport, thereby stabilizing the Si anode interface and boosting cycling Coulombic efficiency. We also examine groundbreaking advancements such as self-healing polymers and advanced prelithiation methods to improve initial Coulombic efficiency and combat capacity loss. Our review uniquely provides a detailed examination of these strategies in real-world applications, moving beyond theoretical discussions. It offers a critical analysis of these approaches in terms of performance enhancement, scalability, and commercial feasibility. In conclusion, this review presents a comprehensive view and a forward-looking perspective on designing robust, high-performance Si-based anodes the next generation of LIBs.

Molybdenum single-atoms decorated multi-channel carbon nanofibers for advanced lithium-selenium batteries.

The cathode in lithium-selenium (Li-Se) batteries has garnered extensive attention owing to its superior specific capacity and enhanced conductivity compared to sulfur. Nonetheless, the adoption and advancement of Li-Se batteries face significant challenges due to selenium's low reactivity, substantial volume fluctuations, and the shuttle effect associated with polyselenides. Single-atom catalysts (SACs) are under the spotlight for their outstanding catalytic efficiency and optimal atomic utilization. To address the challenges of selenium's low chemical activity and volume expansion in Li-Se batteries, through electrospun, we have developed a lotus root-inspired carbon nanofiber (CNF) material, featured internal multi-channels and anchored with molybdenum (Mo) single atoms (Mo@CNFs). Mo single atoms significantly enhance the conversion kinetics of selenium (Se), facilitating rapid formation of Li2Se. The internally structured multi-channel CNF serves as an effective host matrix for Se, mitigating its volume expansion during the electrochemical process. The resulting cathode, Se/Mo@CNF composite, exhibits a high discharge specific capacity, superior rate performance, and impressive cycle stability in Li-Se batteries. After 500 cycles at a current density of 1 C, it maintains a capacity retention rate of 82% and nearly 100% coulombic efficiency (CE). This research offers a new avenue for the application of single-atom materials in enhancing advanced Li-Se battery performance.

[Experiences of Professor Zhou Zhong-ying in diagnosing and treating rheumatoid arthritis by data mining].

OBJECTIVE: To summarize Professor ZHOU Zhong-ying's academic ideas and clinical experiences in diagnosing and treating rheumatoid arthritis (RA). METHODS: Totally 153 clinical case reports were recruited. Data mining techniques like frequencies, factor analysis, and association analysis were used in order to find out laws of syndrome, pathogenesis, treatment methods, formulae and medication. RESULTS: By statistical analyses, we found 14 main symptoms, 76 commonly used clinical drugs, 8 core prescriptions for RA, and the correlation between main pathogeneses and related drugs. CONCLUSION: Results analyzed and summarized from mining his experiences in RA treatment were in line with clinical practice.

Enhancing generalizability and efficiency in clinical trials through dynamic information borrowing for both experimental and control arms: A simulation study.

AIM: Utilizing external information in clinical trials enhances validity by including a wider population and expedites the implementation of adaptive designs, ultimately improving research efficiency. However, current research focused on scenarios in which only the control group benefited from the utilization of external information, while trials involving external information in both experimental and control arms were more complex and might pose challenges when applied in real-world settings. METHODS: To address these concerns, our study pioneered the application of test-then-pool, normalized power prior, calibrated power prior, and elastic prior to a two-arm information borrowing framework and systematically compared their operating characteristics through a series of simulation studies under most and least desirable scenarios. RESULTS: In the most desirable scenarios of information borrowing, all methods managed to control the mean of type I error rates within 5%, among which the normalized power prior, calibrated power prior and elastic prior approaches increased the mean of power from 85.94% to 95%. In the least desirable scenarios, the mean type I error rates for normalized power prior, calibrated power prior and elastic prior approaches exceeded 20%, while the mean power decreased to around 80%. CONCLUSIONS: Our findings reveal that the normalized power prior, calibrated power prior and elastic prior approaches are suitable for situations with minimal heterogeneity between historical and current data, whereas the test-then-pool approach emerges as a more prudent choice when facing substantial discrepancies between historical and current information for trials consider information borrow in both arms.

CYP2D6 and ADRB1 genetic polymorphisms and the selection of antihypertensive beta-receptor blockers for hypertensive patients.

BACKGROUND: Genetic factors contribute to the variability in individual response to antihypertensive medications. We sought to investigate the frequencies of allele and genotype for CYP2D6 and ADRB1 genetic polymorphisms and explore their potential impact in influencing the selection of antihypertensive beta-receptor blockers. METHODS: The study population was selected from the Han Chinese patients in Zhongda Hospital, which contained 2419 Han Chinese hypertensive individuals and 151 normotensive controls. Each of the above participants underwent venous blood sampling. Then, the gene chip platform was adopted to evaluate the CYP2D6 and ADRB1 genetic polymorphisms. The allele as well as genotype frequencies for each gene, along with the combined genotypes, were subjected to analysis. RESULTS: The frequency of *1/*1 wild-type homozygous for CYP2D6 was 9.71%, while the frequency of *1/*10 heterozygous or *10/*10 mutant homozygous was 59.16% or 31.13%, respectively, as established by gene chip analysis. Similarly, we observed that the genotype frequencies of GG wild-type homozygous for ADRB1 was 10.29%, while that of GC heterozygous, or CC mutant homozygous was 44.98%, or 44.73%, respectively. Notably, combined genotypes *1/*10 + CC (25.88%) and *1/*10 + CG (27.78%) had the highest frequencies. Importantly, no substantial differences in the distributions of CYP2D6 and ADRB1 polymorphism were noted between hypertensive patients and normotensive controls, or among all different grades of hypertension. CONCLUSION: These findings provide insights into the CYP2D6 and ADRB1 polymorphisms in hypertensive patients from Han Chinese, which show significant differences compared to other geographic groups of Han Chinese hypertensive patients. These results offer valuable information for future prospective clinical studies on the antihypertensive effects of beta-receptor blockers in Han Chinese hypertensive patients.