The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Community Structure and Water Quality Assessment of Benthic Macroinvertebrates in Hongze Lake.

This study investigated the species, density, biomass and physicochemical factors of benthic macroinvertebrates in Hongze Lake from 2016 to 2020. Redundancy analysis (RDA) was used to analyze the relationship between physicochemical parameters and the community structure of macroinvertebrates. Macroinvertebrate-based indices were used to evaluate the water quality conditions in Hongze Lake. The results showed that a total of 50 benthic species (10 annelids, 21 arthropods and 19 mollusks) were collected. The community structure of benthic macroinvertebrates varied in time and space. The dominant species were Limnodrilus hoffmeisteri (L.hoffmeisteri), Corbicula fluminea (C.fluminea), Nephtys oligobranchia (N.oligobranchia). In 2016, arthropods such as Grandidierella sp. were the dominant species of benthos in Hongze Lake while annelids and mollusks dominated from 2017 to 2020, such as L.hoffmeisteri, N.oligobranchia, C.fluminea. The benthic fauna of Chengzi Lake and Lihewa District were relatively abundant and showed slight variation, while the benthic macroinvertebrates of the Crossing the water area were few and varied greatly. RDA showed that changes in benthic macroinvertebrate structure were significantly correlated with dissolved oxygen (DO), Pondus Hydrogenii (pH) and transparency (SD). The Shannon Wiener, Pielou, and Margalef indices indicate that Hongze Lake is currently in a moderately polluted state. Future studies should focus on the combined effects of various physicochemical indicators and other environmental factors on benthic communities.

Toward the Internet of Medical Things: Architecture, trends and challenges.

In recent years, the growing pervasiveness of wearable technology has created new opportunities for medical and emergency rescue operations to protect users' health and safety, such as cost-effective medical solutions, more convenient healthcare and quick hospital treatments, which make it easier for the Internet of Medical Things (IoMT) to evolve. The study first presents an overview of the IoMT before introducing the IoMT architecture. Later, it portrays an overview of the core technologies of the IoMT, including cloud computing, big data and artificial intelligence, and it elucidates their utilization within the healthcare system. Further, several emerging challenges, such as cost-effectiveness, security, privacy, accuracy and power consumption, are discussed, and potential solutions for these challenges are also suggested.

[Application and prospect of natural active ingredients of traditional Chinese medicine in immunological adjuvant for influenza vaccine].

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.

Structural characteristics of zooplankton communities in Hongze Lake driven by water environmental factors from 2016 to 2020.

This study investigated zooplankton species, density, biomass, and water physicochemical factors in Hongze Lake between 2016 and 2020. The correlation between zooplankton community changes and physicochemical factors was explored using canonical correspondence analysis and Spearman correlation analysis. The investigation found 48 species of protozoa, 52 species of rotifers, 36 species of cladocera, and 32 species of copepoda. The yearly mean density fluctuated between 529.01 and 2234.51 individuals per liter. The yearly mean zooplankton biomass was 950.14 mg/L, ranging from 271.92 to 1365.835 mg/L. A high diversity of zooplankton was found in the Overwater Area, with a large proportion of protozoa and copepoda. Correlation analysis revealed that nitrogen content, pH, water temperature, chemical oxygen demand, biochemical oxygen demand, water transparency, and chlorophyll a were important factors influencing the distribution of zooplankton in Hongze Lake. These factors collectively contributed to the evolution of the zooplankton community structure in Hongze Lake.

Deep scRNA sequencing reveals a broadly applicable Regeneration Classifier and implicates antioxidant response in corticospinal axon regeneration.

Despite substantial progress in understanding the biology of axon regeneration in the CNS, our ability to promote regeneration of the clinically important corticospinal tract (CST) after spinal cord injury remains limited. To understand regenerative heterogeneity, we conducted patch-based single-cell RNA sequencing on rare regenerating CST neurons at high depth following PTEN and SOCS3 deletion. Supervised classification with Garnett gave rise to a Regeneration Classifier, which can be broadly applied to predict the regenerative potential of diverse neuronal types across developmental stages or after injury. Network analyses highlighted the importance of antioxidant response and mitochondrial biogenesis. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator of antioxidant response, in CST regeneration. Our data demonstrate a universal transcriptomic signature underlying the regenerative potential of vastly different neuronal populations and illustrate that deep sequencing of only hundreds of phenotypically identified neurons has the power to advance regenerative biology.

Hyphenated liquid electrode glow discharge-dielectric barrier discharge molecular emission spectrometry for determination of dithiocarbamates.

A hyphenated liquid electrode glow discharge (LEGD)-dielectric barrier discharge (DBD) molecular emission spectrometer was constructed and used as a novel liquid chromatography (LC) detector for dithiocarbamates (DTC) determination. The LEGD was used as an acidolysis reactor for the in-situ transformation of DTCs into CS2 with high efficiencies of 74.11-97.98%. The DBD was used to excite CS2 gas to generate a specific molecular emission at 257.94 nm. The linear correlation coefficient of the method was > 0.99 from 1 to 200 µg mL-1. The detection limits ranged from 0.1 to 0.3 µg mL-1 with 76-119% recovery and relative standard deviations of 0.2-8.5%. Moreover, the hyphenated microplasma spectrometer achieved low power consumption, low temperature, immediate acidolysis, and high transformational efficiency, and can detect each DTC when combined with LC.

Cellular redox homeostasis maintained by malic enzyme 2 is essential for MYC-driven T cell lymphomagenesis.

T cell lymphomas (TCLs) are a group of rare and heterogeneous tumors. Although proto-oncogene MYC has an important role in driving T cell lymphomagenesis, whether MYC carries out this function remains poorly understood. Here, we show that malic enzyme 2 (ME2), one of the NADPH-producing enzymes associated with glutamine metabolism, is essential for MYC-driven T cell lymphomagenesis. We establish a CD4-Cre; Myc flox/+transgenic mouse mode, and approximately 90% of these mice develop TCL. Interestingly, knockout of Me2 in Myc transgenic mice almost completely suppresses T cell lymphomagenesis. Mechanistically, by transcriptionally up-regulating ME2, MYC maintains redox homeostasis, thereby increasing its tumorigenicity. Reciprocally, ME2 promotes MYC translation by stimulating mTORC1 activity through adjusting glutamine metabolism. Treatment with rapamycin, an inhibitor of mTORC1, blocks the development of TCL both in vitro and in vivo. Therefore, our findings identify an important role for ME2 in MYC-driven T cell lymphomagenesis and reveal that MYC-ME2 circuit may be an effective target for TCL therapy.

Ultra-fine SnO2nanocrystals anchored on reduced graphene oxide as a high-performance anode material for sodium-ion batteries.

SnO2has attracted extensive research attentions as a promising anode material for sodium-ion batteries (SIBs) due to its high theoretical capacity. However, its application is largely hindered by sluggish sodium ion diffusion and drastic volume change during the conversion reaction and alloying process. Herein, ultra-fine SnO2nanocrystals (3-5 nm) anchored on reduced graphene oxide (rGO) is demonstrated as a promising anode material for SIBs. Ultra-fine SnO2nanocrystals are uniformly grown on rGO sheets by a facile one-step hydrothermal process. Nano-scaled SnO2grains tolerate volume expansion and provide shortened diffusion pathway for sodium ions, and meanwhile rGO acts as an excellent conductive matrix, thus endowing the composite electrode with excellent electrochemical performance. More importantly, the ratio of SnO2to rGO in the composite is optimized. The optimized sample delivers an initial charge capacity of 518 mAh g-1at a current density of 50 mA g-1, and 504 mAh g-1after 300 cycles at a current density of 100 mA g-1. Furthermore, a capacity of 287 mAh g-1can be maintained after 1000 cycles at a current density of 1000 mA g-1.

Temperature-Induced Low-Coordinate Ni Single-Atom Catalyst for Boosted CO2 Electroreduction Activity.

Single-atom catalysts (SACs) exhibit remarkable potential for electrochemical reduction of CO2 to value-added products. However, the commonly pursued methods for preparing SACs are hard to scale up, and sometimes, lack general applicability because of expensive raw materials and complex synthetic procedures. In addition, the fine tuning of coordination environment of SACs remains challenging due to their structural vulnerability. Herein, a simple and universal strategy is developed to fabricate Ni SACs with different nitrogen coordination numbers through one-step pyrolysis of melamine, Ni(NO3 )∙6H2 O, and polyvinylpyrrolidone at different temperatures. Experimental measurements and theoretical calculations reveal that the low-coordinate Ni SACs exhibit outstanding CO2 reduction performance and stability, achieving a Faradic efficiency (FECO ) of 98.5% at -0.76 V with CO current density of 24.6 mA cm-2 , and maintaining FECO of over 91.0% at all applied potential windows from -0.56 to -1.16 V, benefiting from its coordinatively unsaturated structure to afford high catalytic activity and low barrier for the formation of *COOH intermediate. No significant performance degradation is observed over 50 h of continuous operation. Additionally, several other metallic single-atom catalysts are successfully prepared by this synthetic method, demonstrating the universality of this strategy.

Emotion regulation as a mediator on the relationship between emotional awareness and depression in elementary school students.

As a cognitive skill, emotional awareness plays a fundamental role in emotional intelligence and significant effect on the development of individuals' social adaptation. However, the role of emotional awareness in children's social adaptation, especially emotional development, remains unclear, the current study sought to determine the significant influence of emotional awareness in children's emotional development. By using cross-sectional and longitudinal study designs, the current study explored the relationship between emotional awareness and children's depression, as well as the mediation effect of emotion regulation on this relationship. The sample comprised 166 Chinese elementary school students (89 girls and 77 boys) ranging from 8 to 12 years old. After adjusting for demographic variables (gender, grade, etc.), the results showed that children with high emotional awareness were less likely to adopt expressive suppression as an emotion regulation strategy and had lower depression levels currently and in the future. In contrast, children with low emotional awareness were more likely to use suppression strategies and showed higher depression levels. Thus, the results indicated that emotional awareness could predict children's current and future depression status. Meanwhile, emotional regulation strategies are an important mediating variable explaining the relationship between emotional awareness and children's depression. Implications and limitations were also discussed.

Probing regenerative heterogeneity of corticospinal neurons with scRNA-Seq.

The corticospinal tract (CST) is clinically important for the recovery of motor functions after spinal cord injury. Despite substantial progress in understanding the biology of axon regeneration in the central nervous system (CNS), our ability to promote CST regeneration remains limited. Even with molecular interventions, only a small proportion of CST axons regenerate1. Here we investigate this heterogeneity in the regenerative ability of corticospinal neurons following PTEN and SOCS3 deletion with patch-based single cell RNA sequencing (scRNA-Seq)2,3, which enables deep sequencing of rare regenerating neurons. Bioinformatic analyses highlighted the importance of antioxidant response and mitochondrial biogenesis along with protein translation. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator of antioxidant response, in CST regeneration. Applying Garnett4, a supervised classification method, to our dataset gave rise to a Regenerating Classifier (RC), which, when applied to published scRNA-Seq data, generates cell type- and developmental stage-appropriate classifications. While embryonic brain, adult dorsal root ganglion and serotonergic neurons are classified as Regenerators, most neurons from adult brain and spinal cord are classified as Non-regenerators. Adult CNS neurons partially revert to a regenerative state soon after injury, which is accelerated by molecular interventions. Our data indicate the existence of universal transcriptomic signatures underlying the regenerative abilities of vastly different neuronal populations, and further illustrate that deep sequencing of only hundreds of phenotypically identified CST neurons has the power to reveal new insights into their regenerative biology.

The therapeutic effect and targets of cellulose polysaccharide on coronary heart disease (CHD) and the construction of a prognostic signature based on network pharmacology.

Cellulose is the first rich biological polysaccharide in nature and has many excellent properties, so it is being developed as a variety of drug carriers. Moreover, applications in drug delivery, biosensors/bioanalysis, immobilization of enzymes and cells, stem cell therapy, and skin tissue repair are also highlighted by many studies. Coronary heart disease, as one of the diseases with the highest incidence, is urgent to enhance the survival outcome and life quality of patients with coronary heart disease, whereas the mechanism of cellulose's interaction with the human body remains unclear. However, the mechanism of cellulose's interaction with the human body remains unclear. We obtained 92 genes associated with cellulose and coronary heart disease through the intersection of different databases. Ten key genes were identified: HRAS, STAT3, HSP90AA1, FGF2, VEGFA, CXCR4, TERT, IL2, BCL2L1, and CDK1. Molecular docking of the 10 genes revealed their association with their respective receptors. Analysis by KEGG and GO has discovered that these related targets were more enriched in metabolic- and activation-related functions, which further confirmed that cellulose polysaccharides can also interact with cardiovascular diseases as molecules. In the end, we screened out six key genes that were more associated with the prognosis (CDK1, HSP90AA1, CXCR4, IL2, VEGFA, and TERT) and constructed a signature, which has a good predictive effect and has significant statistical significance. Our study is the first study to explore the interaction targets of cellulose and CHD and to construct a prognostic model. Our findings provide insights for future molecular design, drug development, and clinical trials.

A plasmonic AgNP decorated heterostructure substrate for synergetic surface-enhanced Raman scattering identification and quantification of pesticide residues in real samples.

Rapid and on-site Raman spectroscopic identification and quantification of pesticide residues have been restricted to the low instrumental sensitivity of a portable Raman instrument, and no ideal platforms have been reported for analyzing pesticides on real sample surfaces. An efficient method to improve the detection sensitivity is to fabricate a highly sensitive surface-enhanced Raman scattering (SERS) substrate. Here, we present a MOF-derived ZnO@TiO2 heterostructure combined with plasmonic AgNPs as a SERS sensor to achieve synergetic EM and CM enhancement, exhibiting high sensitivity, excellent signal reproducibility (RSD < 5.9%) and superior stability for analysis of model molecules. The SERS sensor achieved a low detection concentration of 10-8 M for both CV and R6G molecular solutions on a portable Raman device. As a proof of concept, we modelled a pesticide residue on real samples of dendrobium leaves. Thiram, triazophos and fonofos solutions were selected as analytes for mimicking the function of on-site analysis. The SERS analytical platform showed not only high sensitivity for single- and multi-component identification, but also quantitative detection of pesticide residues on dendrobium leaves. These preliminary investigations indicate that this SERS analytical platform will allow the development and potential applications in rapid and on-site pesticide analysis.

Identification of Critical Genes and Pathways for Influenza A Virus Infections via Bioinformatics Analysis.

Influenza A virus (IAV) requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system but also provides further targets for antiviral drug development. To uncover critical pathways and potential targets of influenza infection, we assembled a large amount of data from 8 RNA sequencing studies of IAV infection for integrative network analysis. Weighted gene co-expression network analysis (WGCNA) was performed to investigate modules and genes correlated with the time course of infection and/or multiplicity of infection (MOI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the genes in 5 significant modules. Top hub genes were identified using the cytoHubba plugin in the protein interaction network. The correlation between expression levels of 7 top hub genes and time course or MOI was displayed and validated, including BCL2L13, PLSCR1, ARID5A, LMO2, NDRG4, HAP1, and CARD10. Dysregulated expression of these genes potently impacted the development of IAV infection through modulating IAV-related biological processes and pathways. This study provides further insights into the underlying molecular mechanisms and potential targets in IAV infection.

A Preliminary Study of the Complement Component 1q Levels in Predicting the Efficacy of Combined Immunotherapy in Patients with Lung Cancer.

OBJECTIVE: To evaluate the value of serum complement component 1q (C1q) levels in predicting the efficacy of combined immunotherapy in patients with lung cancer. METHODS: A total of 42 patients with lung cancer who received combined immunotherapy in the cancer center of Renmin Hospital of Wuhan University were included in this study. The clinical data of serum C1q and lactate dehydrogenase (LDH) levels before and three weeks after immunotherapy were collected. RESULTS: Response evaluation showed that the number of patients with complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) was 0 (0%), 26 (61.9%), 14 (33.3%), and 2 (4.8%), respectively. The CR/PR group (patients with CR or PR) showed higher pC1q (C1q level before immunotherapy) and iC1q (C1q level 3 weeks after immunotherapy) than the SD/PD group (patients with SD or PD). The LDH reduction (96.2%) and C1q increment (84.6%) in the CR/PR group 3 weeks after immunotherapy were higher than those of the SD/PD group, and the differences were statistically significant. Logistic regression analysis indicated that pC1q, iC1q, and LDH level trends 3 weeks after the treatment were significantly correlated to the efficacy of combined immunotherapy with odds ratios of 8.185, 5.500, and 0.031, respectively. CONCLUSION: High C1q levels before immunotherapy and increased C1q levels and decreased LDH levels 3 weeks afterward suggest good therapeutic effects of combined immunotherapy in patients with lung cancer. Serum C1q levels have certain clinical significance in predicting the efficacy of combined immunotherapy.

Expanding the Boundary of Biorefinery: Organonitrogen Chemicals from Biomass.

Organonitrogen chemicals are essential in many aspects of modern life. Over 80% of the top 200 prescribed pharmaceutical products contain at least one nitrogen atom in the molecule, while all top 10 agrochemicals contain nitrogen, just to name a few. At present, the prevailing industrial processes for manufacturing organonitrogen chemicals start from nonrenewable fossil resources, but eventually we have to make these chemicals in a more sustainable manner. Biomass represents the largest renewable carbon resource on earth, which is inexpensive and widely available. Integrating biomass into the organonitrogen chemical supply chain will mitigate the carbon footprint, diversify the product stream, and enhance the economic competitiveness of biorefinery. Short-cut synthesis routes can be created for oxygen-containing organonitrogen compounds by exploiting the inherent oxygen functionalities in the biomass resources. Moreover, for nitrogen-containing biomass components such as chitin, a unique opportunity to make organonitrogen chemicals bypassing the energy-intensive Haber-Bosch ammonia synthesis process arises. Estimated at 100 billion tons of annual production in the world, chitin captures more nitrogen than the Haber-Bosch process in the form of amide functional groups in its polymer side chain.In this Account, we intend to summarize our efforts to establish new reaction routes to synthesize valuable organonitrogen chemicals from renewable resources. Enabled by tailor-designed catalytic systems, diverse nitrogen-containing products including amines, amino acids, nitriles, and N-heterocycles have been obtained from a range of biomass feedstock either directly or via intermediate platform compounds. Two strategies to produce organonitrogen chemicals are presented. For platform chemicals derived from cellulose, hemicellulose, lignin, and lipids, which are enriched with oxygen functionalities, in particular, hydroxyl groups, the key chemistry to be developed is the catalytic transformation of hydroxyl groups into nitrogen-containing groups using NH3 as the nitrogen source. Along this line, Ru- and Ni-based heterogeneous catalysts are developed to convert alcohols to amines and/or nitriles via a thermal catalytic pathway, while CdS nanomaterials are explored to promote -OH to -NH2 conversion under visible-light irradiation. Metal-zeolite multifunctional systems are further established to enable the synthesis of N-heterocycles from O-heterocycles. The second strategy involves the use of chitin and chitin derivatives as the starting materials. Under the concept of shell biorefinery, distinctive protocols have been established to chemically transform chitin as the sole feedstock to amino sugars, amino alcohols, furanic amides, and N-heterocycles. By combining mechanochemistry with biotransformation, an integrated process to convert shrimp shell waste to complex, high-value, chiral compounds including tyrosine and l-DOPA is also demonstrated.

[Materia medica resources benefits Lancang-Mekong River:a new approach for sub-regional cooperation on traditional medicine].

Lancang-Mekong Cooperation is a new type of subregional cooperation mechanism initiated and built by China and other five countries of the Lancang-Mekong subregion, namely Laos, Myanmar, Thailand, Cambodia, and Vietnam. Countries in the Lancang-Mekong subregion are geographically and culturally connected, and they have nurtured their unique traditional medicine. By combing the history of traditional medicine exchanges between China and other Lancang-Mekong countries and their progress of modern research, this paper summarized the challenges and opportunities of traditional medicine cooperation in the Lancang-Mekong subregion. It has been found that many regional cooperation mechanisms coexist for a long time in the Lancang-Mekong subregion and the medicinal resources are abundant. However, the degree of their development and utilization varies, and modern scientific research is insufficient. Lancang-Mekong Cooperation has provided a strong support for integrating the advantageous resources in Lancang-Mekong subregion countries and making progress together. Focusing on the development and protection of medicinal resources, this paper puts forward a new path of cooperation in the intellectual property rights and characteristic seed resource protection, the compilation of universal herbal pharmacopoeia in various countries, the research and development of public health products, and the construction of traditional herbal industry bases, thus enabling the traditional medicine to better protect the public health and building a human health community.

Effect of Tongqiao Huoxue Decoction Combined with Western Medicine on Ischemic Stroke: A Systematic Review.

OBJECTIVE: We conducted a systematic review and meta-analysis to systematically evaluate the curative effect of Tongqiao Huoxue Decoction (TQHXD) combined with Western medicine treatment (WMT) on Ischemic Stroke (IS). METHODS: Randomized controlled trials (RCTs) of TQHXD in the treatment of IS by computer retrieval of PubMed, Embase, Web of Science, Chinese Biomedical Literature Service System, CNKI, Wanfang Database, and Weipu Database. The retrieval time was taken from the establishment of the database to July 30, 2020. Two researchers, respectively, conducted a strict evaluation of the quality of the literature and extracted the data which were then entered in the RevMan5.3 software for meta-analysis. RESULTS: 40 articles were listed, which involved 3260 patients. Meta-analysis results show that TQHXD combined with WMT can significantly reduce patients' NIHSS score, serum hypersensitivity C-reactive protein (hs-CRP), plasma viscosity, serum fibrinogen, serum total cholesterol, and serum triglycerides and improve patients' ADL-Barthel scoring and treatment efficiency. However, there is no evidence that TQHXD combined with the WMT group can significantly decrease the incidence of adverse events. CONCLUSION: The therapeutic effect of TQHXD combined with the WMT group was significantly better than that of the WMT alone group. For the treatment of patients with IS, TQHXD combined with WMT is worthy of application and promotion.

Receptor-like kinase OsCR4 controls leaf morphogenesis and embryogenesis by fixing the distribution of auxin in rice.

Cell differentiation is a key event in organ development; it involves auxin gradient formation, cell signaling, and transcriptional regulation. Yet, how these processes are orchestrated during leaf morphogenesis is poorly understood. Here, we demonstrate an essential role for the receptor-like kinase OsCR4 in leaf development. oscr4 loss-of-function mutants displayed short shoots and roots, with tiny, crinkly, or even dead leaves. The delayed outgrowth of the first three leaves and seminal root in oscr4 was due to defects in plumule and radicle formation during embryogenesis. The deformed epidermal, mesophyll, and vascular tissues observed in oscr4 leaves arose at the postembryo stage; the corresponding expression pattern of proOsCR4:GUS in embryos and young leaves suggests that OsCR4 functions in these tissues. Signals from the auxin reporter DR5rev:VENUS were found to be altered in oscr4 embryos and disorganized in oscr4 leaves, in which indole-3-acetic acid accumulation was further revealed by immunofluorescence. OsWOX3A, which is auxin responsive and related to leaf development, was activated extensively and ectopically in oscr4 leaves, partially accounting for the observed lack of cell differentiation. Our data suggest that OsCR4 plays a fundamental role in leaf morphogenesis and embryogenesis by fixing the distribution of auxin.