Washed microbiota transplantation improves renal function in patients with renal dysfunction: a retrospective cohort study.

BACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction. METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed. RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05). CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.

Comparison of presepsin and Mid-regional pro-adrenomedullin in the diagnosis of sepsis or septic shock: a systematic review and meta-analysis.

BACKGROUND: The early diagnosis of sepsis is hampered by the lack of reliable laboratory measures. There is growing evidence that presepsin and Mid-regional pro-adrenomedullin (MR-proADM) are promising biomarkers in the diagnosis of sepsis. This study was conducted to evaluate and compare the diagnostic value of MR-proADM and presepsin in sepsis patients. METHODS: We searched Web of Science, PubMed, Embase, China national knowledge infrastructure, and Wanfang up to 22th July, 2022, for studies evaluating the diagnosis performance of presepsin and MR-proADM in adult sepsis patients. Risk of bias was assessed using quadas-2. Pooled sensitivity and specificity were calculated using bivariate meta-analysis. Meta-regression and subgroup analysis were used to find source of heterogeneity. RESULTS: A total of 40 studies were eventually selected for inclusion in this meta-analysis, including 33 for presepsin and seven for MR-proADM. Presepsin had a sensitivity of 0.86 (0.82-0.90), a specificity of 0.79 (0.71-0.85), and an AUC of 0.90 (0.87-0.92). The sensitivity of MR-proADM was 0.84 (0.78-0.88), specificity was 0.86 (0.79-0.91), and AUC was 0.91 (0.88-0.93). The profile of control group, population, and standard reference may be potential sources of heterogeneity. CONCLUSIONS: This meta-analysis demonstrated that presepsin and MR-proADM exhibited high accuracy (AUC ≥ 0.90) in the diagnosis of sepsis in adults, with MR-proADM showing significantly higher accuracy than presepsin.

Diagnosis of invasive pulmonary aspergillosis by lateral flow assay of galactomannan in bronchoalveolar lavage fluid: a meta-analysis of diagnostic performance.

The performance of lateral flow assay (LFA) in diagnosing invasive pulmonary aspergillosis (IPA) has not been well demonstrated. To address this, we conducted a meta-analysis assessing the overall accuracy of LFA in diagnosing IPA using bronchoalveolar lavage fluid (BALF). Over a systematical search and assessment of bias risk, we calculated the pooled specificity, sensitivity, and area under the receiver operating curve (AUC) to assess the diagnostic performance. Our meta-analysis included 11 studies. The combined total sensitivity and specificity for diagnosing IPA were 0.78 (95% confidence interval (CI): 0.71, 0.83) and 0.87 (95% CI: 0.81, 0.91), respectively. The AUC was 0.86 (95% CI: 0.82, 0.89). Our results demonstrate that LFA using galactomannan in BALF exhibits high sensitivity and specificity for diagnosing IPA.

In vivo and in vitro metabolism study of traditional Chinese medicine formula Dingkun Dan in rats by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study.

Subchromosome-Scale Nuclear and Complete Mitochondrial Genome Characteristics of Morchella crassipes.

Morchella crassipes (Vent.) Pers., a typical yellow morel species with high economic value, is mainly distributed in the low altitude plains of Eurasia. However, rare research has been performed on its genomics and polarity, thus limiting its research and development. Here, we reported a fine physical map of the nuclear genome at the subchromosomal-scale and the complete mitochondrial genome of M. crassipes. The complete size of the nuclear genome was 56.7 Mb, and 23 scaffolds were assembled, with eight of them being complete chromosomes. A total of 11,565 encoding proteins were predicted. The divergence time analysis showed that M. crassipes representing yellow morels differentiated with black morels at ~33.98 Mya (million years), with 150 gene families contracted and expanded in M. crassipes versus the two black morels (M. snyderi and M. importuna). Furthermore, 409 CAZYme genes were annotated in M. crassipes, containing almost all plant cell wall degrading enzymes compared with the mycorrhizal fungi (truffles). Genomic annotation of mating type loci and amplification of the mating genes in the monospore population was conducted, the results indicated that M. crassipes is a heterothallic fungus. Additionally, a complete circular mitochondrial genome of M. crassipes was assembled, the size reached as large as 531,195 bp. It can be observed that the strikingly large size was the biggest up till now, coupled with 14 core conserved mitochondrial protein-coding genes, two rRNAs, 31 tRNAs, 51 introns, and 412 ncORFs. The total length of intron sequences accounted for 53.67% of the mitochondrial genome, with 19 introns having a length over 5 kb. Particularly, 221 of 412 ncORFs were distributed within 51 introns, and the total length of the ncORFs sequence accounted for 40.83% of the mitochondrial genome, and 297 ncORFs had expression activity in the mycelium stage, suggesting their potential functions in M. crassipes. Meanwhile, there was a high degree of repetition (51.31%) in the mitochondria of M. crassipes. Thus, the large number of introns, ncORFs and internal repeat sequences may contribute jointly to the largest fungal mitochondrial genome to date. The fine physical maps of nuclear genome and mitochondrial genome obtained in this study will open a new door for better understanding of the mysterious species of M. crassipes.

Interspecific hybridization between cultivated morels Morchella importuna and Morchella sextelata by PEG-induced double inactivated protoplast fusion.

The commercial production of Morchella mushrooms calls for urgent breeding of excellent varieties or strains with appropriate tools, such as protoplast fusion. However, the protoplast fusion in morels has not been studied. In this paper, interspecific hybridization between cultivated morels of M. importuna and M. sextelata by PEG-induced protoplast fusion was conducted. Apart from functional complementation of double inactivated protoplasts, the fusants were characterized by cultural and cultivated characters and molecular markers of random amplified polymorphic DNA (RAPD). The results suggested that the hybrids and their parents showed significant difference in their inoculum recovery time, mycelial growth rate, yield of cultivation and total amino acid content of ascocarps. Moreover, positive barrage reactions were observed between parental strains as well as between each parent and a hybrid line. A dendrogram created on the basis of RAPD fingerprints exhibited three major clusters, in which morel hybrids showed intra-cluster variations, M. sextelata #6 formed an out group, while M. importuna #4 was phylogenetically closer to morel hybrids. All the results demonstrated that real fusants were obtained in our study. Protoplast fusion may provide an ideal alternative for new strain selection, and thus will promote the healthy development of morel industry.

Proteome and Transcriptome Reveal Involvement of Heat Shock Proteins and Indoleacetic Acid Metabolism Process in Lentinula Edodes Thermotolerance.

BACKGROUND/AIMS: Heat stress could cause huge losses for Lentinula edodes in China and other Asian cultivation areas. Yet our understanding of mechanism how to defend to heat stress is incomplete. METHODS: Using heat-tolerant and heat-sensitive strains of L. edodes, we reported a combined proteome and transcriptome analysis of L. edodes response to 40 °C heat stress for 24 h. Meanwhile, the effect of LeDnaJ on the thermotolerance and IAA (indoleacetic acid) biosynthesis in L. edodes was analyzed via the over-expression method. RESULTS: The proteome results revealed that HSPs (heat shock proteins) such as Hsp40 (DnaJ), Hsp70, Hsp90 and key enzymes involved in tryptophan and IAA metabolism process LeTrpE, LeTrpD, LeTam-1, LeYUCCA were more highly expressed in S606 than in YS3357, demonstrating that HSPs and tryptophan as well as IAA metabolism pathway should play an important role in thermotolerance. Over-expression of LeDnaJ gene in S606 strains showed better tolerance to heat stress. It was also documented that intracellular IAA accumulation of S606 (8-fold up) was more than YS3357 (2-fold up), and exogenous IAA enhanced L. edodes tolerance to heat stress. CONCLUSION: Our data support the interest of LeTrpE, LeDnaJ, tryptophan and IAA could play a pivotal role in enhancing organism thermotolerance.

Opposite Polarity Monospore Genome De Novo Sequencing and Comparative Analysis Reveal the Possible Heterothallic Life Cycle of Morchella importuna.

Morchella is a popular edible fungus worldwide due to its rich nutrition and unique flavor. Many research efforts were made on the domestication and cultivation of Morchella all over the world. In recent years, the cultivation of Morchella was successfully commercialized in China. However, the biology is not well understood, which restricts the further development of the morel fungus cultivation industry. In this paper, we performed de novo sequencing and assembly of the genomes of two monospores with a different mating type (M04M24 and M04M26) isolated from the commercially cultivated strain M04. Gene annotation and comparative genome analysis were performed to study differences in CAZyme (Carbohydrate-active enzyme) enzyme content, transcription factors, duplicated sequences, structure of mating type sites, and differences at the gene and functional levels between the two monospore strains of M. importuna. Results showed that the de novo assembled haploid M04M24 and M04M26 genomes were 48.98 and 51.07 Mb, respectively. A complete fine physical map of M. importuna was obtained from genome coverage and gene completeness evaluation. A total of 10,852 and 10,902 common genes and 667 and 868 endemic genes were identified from the two monospore strains, respectively. The Gene Ontology (GO) and KAAS (KEGG Automatic Annotation Serve) enrichment analyses showed that the endemic genes performed different functions. The two monospore strains had 99.22% collinearity with each other, accompanied with certain position and rearrangement events. Analysis of complete mating-type loci revealed that the two monospore M. importuna strains contained an independent mating-type structure and remained conserved in sequence and location. The phylogenetic and divergence time of M. importuna was analyzed at the whole-genome level for the first time. The bifurcation time of morel and tuber was estimated to be 201.14 million years ago (Mya); the two monospore strains with a different mating type represented the evolution of different nuclei, and the single copy homologous genes between them were also different due to a genetic differentiation distance about 0.65 Mya. Compared with truffles, M. importuna had an extension of 28 clusters of orthologous genes (COGs) and a contraction of two COGs. The two different polar nuclei with different degrees of contraction and expansion suggested that they might have undergone different evolutionary processes. The different mating-type structures, together with the functional clustering and enrichment analysis results of the endemic genes of the two different polar nuclei, imply that M. importuna might be a heterothallic fungus and the interaction between the endemic genes may be necessary for its complete life history. Studies on the genome of M. importuna facilitate a better understanding of morel biology and evolution.

Validation of Internal Control Genes for Quantitative Real-Time PCR Gene Expression Analysis in Morchella.

The reliability of qRT-PCR results depend on the stability of reference genes used for normalization, suggesting the necessity of identification of reference genes before gene expression analysis. Morels are edible mushrooms well-known across the world and highly prized by many culinary kitchens. Here, several candidate genes were selected and designed according to the Morchella importuna transcriptome data. The stability of the candidate genes was evaluated with geNorm and NormFinder under three different experimental conditions, and several genes with excellent stability were selected. The extensive adaptability of the selected genes was tested in ten Morchella species. Results from the three experimental conditions revealed that ACT1 and INTF7 were the most prominent genes in Morchella, CYC3 was the most stable gene in different development stages, INTF4/AEF3 were the top-ranked genes across carbon sources, while INTF3/CYC3 pair showed the robust stability for temperature stress treatment. We suggest using ACT1, AEF3, CYC3, INTF3, INTF4 and INTF7 as reference genes for gene expression analysis studies for any of the 10 Morchella strains tested in this study. The stability and practicality of the gene, vacuolar protein sorting (INTF3), vacuolar ATP synthase (INTF4) and14-3-3 protein (INTF7) involving the basic biological processes were validated for the first time as the candidate reference genes for quantitative PCR. Furthermore, the stability of the reference genes was found to vary under the three different experimental conditions, indicating the importance of identifying specific reference genes for particular conditions.

A novel strategy integrating gas phase fractionation with staggered mass range and LC-MS/MS molecular network for comprehensive metabolites profiling of Gui Ling Ji in rats.

Metabolite detection from complex biological samples faces challenges due to interference from endogenous substrates and the inherent limitation of multiple subsequent tandem scanning rates of instruments. Here, a new integrated approach based on gas-phase fractionation with a staggered mass range (sGPF) and a liquid chromatography-tandem mass spectrometry (LC-MS/MS) molecular network was developed to accelerate the data processing of the targeted and untargeted constituents absorbed in rats after oral administration of the traditional Chinese medicine (TCM) prescription Gui Ling Ji (GLJ). Compared with three conventional acquisition methods, sGPF at 3, 5, and 7 mass fractions could enhance MS/MS coverage with an increased MS/MS triggering rate of 29.4-206.2% over data-dependent acquisition (DDA), fast DDA and gas-phase fractionation. A mass range fraction setting of five optimized the performance. Based on the similar diagnostic fragment ions and characteristic neutral loss behaviors in the DDA-MS/MS spectrum, an initial molecular network of GLJ was created with the help of the global natural products social molecular networking (GNPS) platform. Furthermore, to remove the endogenous interference nodes, Cytoscape software was adopted to produce a clean and concise molecular network of prototype compounds and their corresponding metabolites. Using this strategy, a total of 210 compounds, including 59 prototype constituents and 151 metabolites, was unambiguously or tentatively identified in GLJ. This first systematic metabolic study of GLJ in vivo elucidated the potential pharmacodynamic basis of GLJ in clinical treatment. More importantly, this work can serve as a practical example and establish a guide for rapidly identifying TCM metabolites in biological matrices.

Gut microbiota from essential tremor patients aggravates tremors in mice.

Background and objective: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice. Methods: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively. Results: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice. Conclusion: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.

Effects of endogenous capsaicin stress and fermentation time on the microbial succession and flavor compounds of chili paste (a Chinese fermented chili pepper).

Chili paste, is a popular traditional product derived from chili pepper, and its fermentation system is affected by the variable concentration of capsaicin, which originates from the peppers. In the present study, the effects of capsaicin and fermentation time on the microbial community and flavor compounds of chili paste were investigated. After capsaicin supplementation, the total acid was significantly decreased (p < 0.05) along with lower total bacteria, especially lactic acid bacteria. Lactiplantibacillus, Lactobacillus, Weissella, Issatchenkia, Trichoderma, and Pichia were the shared and predominant genera; whereas, the Bacteroides and Kazachstania abundance was significantly increased due to the selection effect of capsaicin over time. Additionally, alterations of the microbial interaction networks and their metabolic preferences led to less lactic acid content with greater accumulation of ethyl nonanoate, methyl nonanoate, etc. This study will provide a perspective for selecting chili pepper varieties and improving the quality of fermented chili paste.

Structure of the Mating-Type Genes and Mating Systems of Verpa bohemica and Verpa conica (Ascomycota, Pezizomycotina).

Verpa spp. are potentially important economic fungi within Morchellaceae. However, fundamental research on their mating systems, the key aspects of their life cycle, remains scarce. Fungal sexual reproduction is chiefly governed by mating-type genes, where the configuration of these genes plays a pivotal role in facilitating the reproductive process. For this study, de novo assembly methodologies based on genomic data from Verpa spp. were employed to extract precise information on the mating-type genes, which were then precisely identified in silico and by amplifying their single-ascospore populations using MAT-specific primers. The results suggest that the MAT loci of the three tested strains of V. bohemica encompassed both the MAT1-1-1 and MAT1-2-1 genes, implying homothallism. On the other hand, amongst the three V. conica isolates, only the MAT1-1-1 or MAT1-2-1 genes were present in their MAT loci, suggesting that V. conica is heterothallic. Moreover, bioinformatic analysis reveals that the three tested V. bohemica strains and one V. conica No. 21110 strain include a MAT1-1-10 gene in their MAT loci, while the other two V. conica strains contained MAT1-1-11, exhibiting high amino acid identities with those from corresponding Morchella species. In addition, MEME analysis shows that a total of 17 conserved protein motifs are present among the MAT1-1-10 encoded protein, while the MAT1-1-11 protein contained 10. Finally, the mating type genes were successfully amplified in corresponding single-ascospore populations of V. bohemica and V. conica, further confirming their life-cycle type. This is the first report on the mating-type genes and mating systems of Verpa spp., and the presented results are expected to benefit further exploitation of these potentially important economic fungi.

Genome Sequencing Highlights the Plant Cell Wall Degrading Capacity of Edible Mushroom Stropharia rugosoannulata.

The basidiomycetous edible mushroom Stropharia rugosoannulata has excellent nutrition, medicine, bioremediation, and biocontrol properties. S. rugosoannulata has been widely and easily cultivated using agricultural by-products showing strong lignocellulose degradation capacity. However, the unavailable high-quality genome information has hindered the research on gene function and molecular breeding of S. rugosoannulata. This study provided a high-quality genome assembly and annotation from S. rugosoannulata monokaryotic strain QGU27 based on combined Illumina-Nanopore data. The genome size was about 47.97 Mb and consisted of 20 scaffolds, with an N50 of 3.73 Mb and a GC content of 47.9%. The repetitive sequences accounted for 17.41% of the genome, mostly long terminal repeats (LTRs). A total of 15,726 coding gene sequences were putatively identified with the BUSCO score of 98.7%. There are 142 genes encoding plant cell wall degrading enzymes (PCWDEs) in the genome, and 52, 39, 30, 11, 8, and 2 genes related to lignin, cellulose, hemicellulose, pectin, chitin, and cutin degradation, respectively. Comparative genomic analysis revealed that S. rugosoannulata is superior in utilizing aldehyde-containing lignins and is possible to utilize algae during the cultivation.

Impacts of Cross-Sectoral Climate Policy on Forest Carbon Sinks and Their Spatial Spillover: Evidence from Chinese Provincial Panel Data.

This paper examines the impact of cross-sectoral climate policy on forest carbon sinks. Due to the complexity of the climate change issue and the professional division of labor among government departments, cross-sectoral cooperation in formulating climate policy is a desirable strategy. Forest carbon sinks play an important role in addressing climate change, but there are few studies focusing on forest carbon sinks and cross-sectoral climate policies. Thus, based on the panel data of 30 provinces and cities in China from 2007 to 2020, this paper establishes a benchmark regression model and a spatial panel model to analyze the impact of cross-sectoral climate policies on forest carbon sinks. We find that cross-sectoral climate policies positively impact forest carbon sinks. Under the influence of the "demonstration effect", we find that cross-sectoral climate policies have a positive impact not only on the forest carbon sinks in the region but also on those in the neighboring region. Further analysis shows that for provinces with less developed forestry industry and small forest areas, the positive effect of cross-sectoral climate policies on forest carbon sinks is more obvious. Overall, this paper can serve as an important reference for local governments to formulate climate policies and increase the capacity of forest carbon sinks.

Serum Lactate Dehydrogenase Is a Sensitive Predictor of Systemic Complications of Acute Pancreatitis.

Background: Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease that can cause various complications, including systemic inflammatory response syndrome (SIRS), pleural effusion, ascitic fluid, myocardial infarction, and acute kidney injury (AKI). However, there is still a lack of rapid and effective indicators to assess the disease. The aim of this study was to investigate the associations of high serum lactate dehydrogenase (LDH) levels with AP severity and systemic complications. Methods: AP patients treated from July 2014 to December 2020 were retrospectively enrolled. They were divided into elevated (n = 93) and normal (n = 143) LDH groups. Their demographic data, clinical data, hospital duration, and hospital expenses were analyzed. Linear and binary logistic regression analyses were used to determine whether elevated LDH is a risk factor for AP severity and complications after adjusting for confounders. Results: There were significant differences in AP severity scores (Ranson, MODS, BISAP, APACHE II, and CTSI), hospital duration, hospital expenses, and the incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI) between the elevated and normal LDH groups. After adjusting for confounders, elevated LDH was associated with AP severity scores and hospital duration and expenses (based on linear regression analyses) and was a risk factor for the occurrence of AP complications and interventions, that is, diuretic and vasoactive agent use (based on binary logistic regression analyses). Conclusions: Elevated LDH is associated with high AP severity scores and high incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI).

The efficacy and safety of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke: systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined. METHODS: Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3. RESULTS: A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke. DISCUSSION: In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.

The effect of anemia on the severity and prognosis of patients with acute pancreatitis: A single-center retrospective study.

Anemia was a risk factor for a worse prognosis of many diseases. This study aims to investigate the relationship between anemia and the severity and prognosis of acute pancreatitis (AP). Inpatients hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University with a primary diagnosis of AP between 1st July 2016 to 31st December 2020 were enrolled. Subsequently, disease severity, the incidence of complications, and the prognosis of patients with AP were compared between the anemic group and the non-anemic group. A total of 282 patients with acute pancreatitis were enrolled; 68.43% of them were also diagnosed with anemia. Notably, these patients had more severe disease (higher RANSON, acute physiologic assessment and chronic health evaluation-II, bedside index for severity in acute pancreatitis, and multiple organ dysfunction syndrome scores); higher incidence of organ failure (acute kidney injury [AKI] and acute heart failure); worse prognosis (higher incidence of vasoactive and diuretic agent use, longer hospital stays, and higher hospital costs) compared to that of patients without anemia (all P < .05). After adjusting for potential confounders, acute physiologic assessment and chronic health evaluation-II, bedside index for severity in acute pancreatitis, multiple organ dysfunction syndrome scores, hospital stay, and hospital costs in anemic patients were higher than those in non-anemic patients; besides, the incidence of AKI and using a diuretic agent in anemic patients was 6.645 and 4.053 times that of non-anemic patients in AP, respectively (all P < .05). Acute pancreatitis patients with anemia have more disease severity, higher incidence of AKI, and worse prognosis compared to those without anemia.

Integrated metabolomics and network pharmacology to reveal the therapeutic mechanism of Dingkun Pill on polycystic ovary syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP), a traditional Chinese medicine prescription, was modified from Bujing decoction and Xusijiangsheng pill by the imperial physician in the Qing dynasty (1700' s). It was believed to treat various gynecological diseases by nourishing qi and blood. Accumulating evidence indicates that it is effective in treating polycystic ovary syndrome (PCOS). However, the therapeutic efficacy and mechanism of action DKP against PCOS need to be further elucidated. AIM OF THE STUDY: To investigate the therapeutic effect and action mechanism of DKP against PCOS using an integrated approach of metabolomics and network pharmacology. MATERIALS AND METHODS: The rat model of PCOS was established by dehydroepiandrosterone. An integrated metabolomics and network pharmacology strategy was applied to systemically clarify the mechanism of DKP against PCOS. Theca cells were prepared to evaluate the effect of DKP and its ingredients on testosterone synthesis in vitro. RESULTS: The pharmacological experiments demonstrated that DKP could effectively convert the disordered estrous cyclicity, decrease the level of testosterone and the luteinizing hormone/follicle stimulating hormone ratio, and inhibit abnormal follicle formation in PCOS rats. By metabolomics analysis, 164 serum endogenous differential metabolites and 172 urine endogenous differential metabolites were tentatively identified. Steroid hormone biosynthesis and ovarian steroidogenesis were the most significantly impacted pathways. Based on network pharmacology and metabolomics studies, the ingredient-target-pathway network of DKP in the treatment of PCOS was constructed. Among the 10 key targets, CYP17A1, CYP19A1, STS, AR, ESR1, and MYC were closely involved in ovarian androgen synthesis. In theca cell-based assay of testosterone synthesis, DKP and its two active compounds (ligustilide and picrocrocin) showed inhibitory effects. CONCLUSION: DKP effectively improved symptoms in rats with dehydroepiandrosterone-induced PCOS. The mechanism of DKP in the treatment of PCOS is related to the CYP17A1 enzyme required for androgen synthesis.

Washed Microbiota Transplantation Lowers Blood Pressure in Patients With Hypertension.

Background: Although transplantation of the fecal microbiota from normotensive donors has been shown to have an antihypertensive effect in hypertensive animal models, its effect on blood pressure in patients with hypertension is unclear. This study aimed to assess the effect of washed microbiota transplantation (WMT) from normotensive donors on blood pressure regulation in hypertensive patients. Methods: The clinical data of consecutive patients treated with washed microbiota transplantation (WMT) were collected retrospectively. The blood pressures of hypertensive patients before and after WMT were compared. The factors influencing the antihypertensive effect of WMT in hypertensive patients and fecal microbial composition of donors and hypertensive patients were also analyzed. Results: WMT exhibited an antihypertensive effect on blood pressure: the blood pressure at hospital discharge was significantly lower than that at hospital admission (change in systolic blood pressure: -5.09 ± 15.51, P = 0.009; change in diastolic blood pressure: -7.74 ± 10.42, P < 0.001). Hypertensive patients who underwent WMT via the lower gastrointestinal tract (ß = -8.308, standard error = 3.856, P = 0.036) and those not taking antihypertensive drugs (ß = -8.969, standard error = 4.256, P = 0.040) had a greater decrease in systolic blood pressure, and hypertensive patients not taking antihypertensive drugs also had a greater decrease in diastolic blood pressure (ß = -8.637, standard error = 2.861, P = 0.004). After WMT, the Shannon Diversity Index was higher in six of eight hypertensive patients and the microbial composition of post-WMT samples tended to be closer to that of donor samples. Conclusion: WMT had a blood pressure-lowering effect in hypertensive patients, especially in those who underwent WMT via the lower gastrointestinal tract and in those not taking antihypertensive drugs. Therefore, modulation of the gut microbiota by WMT may offer a novel approach for hypertension treatment.