Characterization of CYP82 genes involved in the biosynthesis of structurally diverse benzylisoquinoline alkaloids in Corydalis yanhusuo.

Benzylisoquinoline alkaloids (BIAs) represent a significant class of secondary metabolites with crucial roles in plant physiology and substantial potential for clinical applications. CYP82 genes are involved in the formation and modification of various BIA skeletons, contributing to the structural diversity of compounds. In this study, Corydalis yanhusuo, a traditional Chinese medicine rich in BIAs, was investigated to identify the catalytic function of CYP82s during BIA formation. Specifically, 20 CyCYP82-encoding genes were cloned, and their functions were identified in vitro. Ten of these CyCYP82s were observed to catalyze hydroxylation, leading to the formation of protopine and benzophenanthridine scaffolds. Furthermore, the correlation between BIA accumulation and the expression of CyCYP82s in different tissues of C. yanhusuo was assessed their. The identification and characterization of CyCYP82s provide novel genetic elements that can advance the synthetic biology of BIA compounds such as protopine and benzophenanthridine, and offer insights into the biosynthesis of BIAs with diverse structures in C. yanhusuo.

Jianpi Antai formula prevents miscarriage by repressing M1 polarization of decidual macrophages through ubiquitination of NLRP3 mediated by MARCH7.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Antai Formula (JAF) is an ancient formula from He's gynecology, which has been used clinically for more than 30 years and has significant therapeutic effects on spontaneous abortion (SA). Both macrophage polarization and NLRP3 inflammasome correlate with the occurrence of SA in women with recurrent or threatened miscarriage. Whether JAF prevent SA via mediating activation of decidual macrophage (dMφ) and ubiquitination-associated degradation of NLRP3 remains uncertain. AIM OF THE STUDY: This study aimed to clarify the effects of JAF on pregnancy outcomes and dMφ polarization at the maternal-fetal interface in an SA mouse model, and use in vivo and invitro methods to explore whether JAF can inhibit M1 polarization of dMφ by up-regulating MARCH7-mediated NLRP3 ubiquitination, thereby preventing SA. MATERIALS AND METHODS: The CBA/J × DBA/2 mating method was used to establish an SA model and the dMφs of SA mice were isolated and cultured. Th1-, Th2-, Th17- and Treg-related cytokine levels were evaluated using ELISA. qRT-PCR was used to detect the levels of M1/M2 macrophage-related cytokine mRNA in the decidua, and western blotting was used to detect the expression of NLRP3 inflammasome-related proteins in the decidua and placenta. The expression of M1/M2 markers of dMφ was detected using flow cytometry, ASC speck formation was observed using immunofluorescence, and the ubiquitination level of MARCH7-NLRP3 was detected using co-immunoprecipitation. RESULTS: JAF increased the survival rate of fetuses and the levels of estradiol and progesterone in SA model mice. It also reduced the serum Th1 and Th17-associated cytokine levels and decidual M1 macrophage-associated cytokine levels, while elevating the M2 macrophages in SA mice. NLRP3, caspase-1, ASC, and IL-1ß protein expression in the decidua and placenta were also reduced. si-MARCH7 transfection reversed the effect of JAF on inhibiting the formation of the NLRP3 inflammasome and the activation of macrophages in dMφs of SA mice. CONCLUSION: JAF could effectively prevent and treat SA by repressing M1 polarization of dMφs through NLRP3 ubiquitination and pyroptosis inhibition, which were mediated by MARCH7.

QiShenYiQi pill inhibits atherosclerosis by promoting TTC39B-LXR mediated reverse cholesterol transport in liver.

BACKGROUND: Tetranucleotide repeat domain protein 39B (TTC39B) was found to combine with ubiquitin ligase E3, and promote the ubiquitination modification of liver X receptor (LXR), which led to the inhibition of reverse cholesterol transport and development of atherosclerosis. QiShenYiQi pill (QSYQ) is a modern Chinese patent drug for treating ischemic cardiovascular diseases, the underlying mechanism is found to promote the expression of LXR-α/ ATP-binding cassette transporter G5 (ABCG5) in the liver of atherosclerotic mice. PURPOSE: The aim of this study is to investigate the effect of QSYQ on TTC39B-LXR mediated reverse cholesterol transport in atherosclerotic mice. STUDY DESIGN AND METHODS: Male apolipoprotein E gene knockout mice (7 weeks old) were fed with high-fat diet and treated with low dose of QSYQ (QSYQ-l, 0.3 g/kg·d), high dose of QSYQ (QSYQ-H, 1.2 g/kg·d) and LXR-α agonist (LXR-A, GW3965 10 mg/kg·d) for 8 weeks. C57BL/6 J mice were fed with normal diet and used as negative control. Oil red O staining, HE staining, ELISA, RNA sequencing, western blot, immunohistochemistry, RT-PCR, cell culture and RNA interference were performed to analyze the effect of QSYQ on atherosclerosis. RESULTS: HE staining showed that QSYQ reduced the atherosclerotic lesion significantly when compared to the control group. ELISA measurement showed that QSYQ decreased serum VLDL and increased serum ApoA1. Oil Red O staining showed that QSYQ reduced the lipid content of liver and protect liver function. Comparative transcriptome RNA-sequence of liver showed that DEGs after QSYQ treatment enriched in high-density lipoprotein particle, ubiquitin ligase complex, bile secretion, etc. Immunohistochemical staining and western blot proved that QSYQ increased the protein expression of hepatic SR-B1, LXR-α, LXR-ß, CYP7A1 and ABCG5. Targeted inhibiting Ttc39b gene in vitro further established that QSYQ inhibited the gene expression of Ttc39b, increased the protein expression of SR-B1, LXR-α/ß, CYP7A1 and ABCG5 in rat hepatocyte. CONCLUSION: Our results demonstrated the new anti-atherosclerotic mechanism of QSYQ by targeting TTC39B-LXR mediated reverse cholesterol transport in liver. QSYQ not only promoted reverse cholesterol transport, but also improved fatty liver and protected liver function.

Therapeutic Efficacy of Head Gusha Combined with Kaitianmen in the Management of Insomnia.

Objective: This study aimed to analyze the therapeutic efficacy of a combined treatment approach involving specialized head scraping (Guasha) in conjunction with Kaitianmen to manage insomnia. Methods: We conducted a study involving 90 individuals with insomnia who received treatment at our hospital between March 2022 and March 2023. These participants were selected and randomly assigned to either a research group (n = 45) or a control group (n = 45). The control group received oral Diazepam (DZ), while the research group underwent specialized head scraping and Kaitianmen therapy. Comparative assessments were made between the two groups, considering clinical efficacy, pre-and post-treatment Traditional Chinese Medicine (TCM) symptom scores, as well as evaluations of sleep quality and negative emotions (NEs) using the Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety/Depression Scale (SAS/SDS), respectively. Additionally, a treatment satisfaction survey was administered at discharge. Results: The research group exhibited a significantly higher overall response rate compared to the control group (P < .05). Both groups displayed substantial reductions in TCM symptom scores, PSQI scores, and SAS/SDS scores following treatment, with the research group achieving even lower scores (P < .05). The treatment satisfaction survey indicated a greater degree of satisfaction among participants in the research group compared to the control group (P < .05). Conclusions: The combination of specialized head scraping and Kaitianmen therapy has demonstrated effectiveness in the treatment of insomnia and offers a valid means of alleviating patients' negative emotions. These findings suggest promising prospects for clinical applications.

Enhancing Quality Control in Continuous Renal Replacement Therapy Through ICU Specialist Nursing Care Management Program.

Objective: This study aims to investigate the impact of a specialized intensive care unit (ICU) nursing quality control team management program on continuous renal replacement therapy (CRRT). Our goal is to provide insights for enhancing the clinical outcomes of CRRT and improving patient satisfaction. Methods: We conducted this study at The First People's Hospital of Linping District in Hangzhou, China, from January 2018 to December 2021. The study comprised 519 critically ill patients in need of CRRT. Among them, 265 patients received routine bedside care management for CRRT (control group), while 254 patients received specialized quality control management for CRRT (experimental group). We compared several key parameters between the two groups, including the unplanned downtime rate, average downtime duration, compliance with continuous treatment for >24 hours and scheduled downtime for 72 hours, daily hemodialysis cost per patient, duration of single filter usage, unplanned extubation rate, and incidence of catheter-associated bloodstream infections. Additionally, we assessed nursing satisfaction, blood biochemical markers, and coagulation indices for both groups. Results: Compared to the control group, the experimental group demonstrated a reduced occurrence of unplanned events, an increase in average downtime duration, greater compliance with continuous treatment (>24 hours) and scheduled downtime (72 hours), lower daily hemodialysis costs per patient, extended duration of single filter usage, reduced rates of unplanned extubation and catheter-related bloodstream infections. Furthermore, patients in the experimental group reported significantly higher nursing satisfaction. In terms of blood potassium, sodium, BUN, and SCr levels, the experimental group exhibited lower values compared to the control group. In the investigation of blood coagulation indices, the numerical values for patients in the experimental group were notably better than those in the control group. Conclusions: The ICU specialized nursing quality control team management program for continuous renal replacement therapy outperforms conventional nursing management.

The tuber-specific StbHLH93 gene regulates proplastid-to-amyloplast development during stolon swelling in potato.

In potato, stolon swelling is a complex and highly regulated process, and much more work is needed to fully understand the underlying mechanisms. We identified a novel tuber-specific basic helix-loop-helix (bHLH) transcription factor, StbHLH93, based on the high-resolution transcriptome of potato tuber development. StbHLH93 is predominantly expressed in the subapical and perimedullary region of the stolon and developing tubers. Knockdown of StbHLH93 significantly decreased tuber number and size, resulting from suppression of stolon swelling. Furthermore, we found that StbHLH93 directly binds to the plastid protein import system gene TIC56 promoter, activates its expression, and is involved in proplastid-to-amyloplast development during the stolon-to-tuber transition. Knockdown of the target TIC56 gene resulted in similarly problematic amyloplast biogenesis and tuberization. Taken together, StbHLH93 functions in the differentiation of proplastids to regulate stolon swelling. This study highlights the critical role of proplastid-to-amyloplast interconversion during potato tuberization.

Optimization of sequence and chiral content enhances therapeutic potential of tilapia piscidin peptides.

Because antimicrobial peptides (AMPs) often exhibit broad-spectrum bactericidal potency, we sought to develop peptide-based antimicrobials for potential clinical use against drug-resistant pathogens. To accomplish this goal, we first optimized the amino acid sequence of a broad-spectrum AMP known as Tilapia Piscidin 4 (TP4). Then, we used the optimized sequence to create a pair of heterochiral variants (TP4-α and TP4-ß) with different percentages of D-enantiomers, as poly-L peptides often exhibit poor pharmacokinetic profiles. The conformations of the peptide pair exhibited inverted chirality according to CD and NMR spectroscopic analyses. Both heterochiral peptides displayed enhanced stability and low hemolysis activities. Irrespective of their different d-enantiomer contents, both heterochiral peptides exhibited bactericidal activities in the presence of human serum or physiological enzymes. However, the peptide with higher d-amino acid content (TP4-ß) caused better bacterial clearance when tested in mice infected with NDM-1 K. pneumoniae. In addition, we observed a relatively higher hydrogen bonding affinity in a simulation of the interaction between TP4-ß and a model bacterial membrane. In sum, our results demonstrate that the current design strategy may be applicable for development of new molecules with enhanced stability and in vivo antimicrobial activity.

Mulches assist degraded soil recovery via stimulating biogeochemical cycling: metagenomic analysis.

Soil degradation of urban greening has caused soil fertility loss and soil organic carbon depletion. Organic mulches are made from natural origin materials, and represent a cost-effective and environment-friendly remediation method for urban greening. To reveal the effects of organic mulch on soil physicochemical characteristics and fertility, we selected a site that was covered with organic mulch for 6 years and a nearby lawn-covered site. The results showed that soil organic matter, total nitrogen, and available phosphorus levels were improved, especially at a depth of 0-20 cm. The activities of cellulase, invertase, and dehydrogenase in soil covered with organic mulch were 17.46%, 78.98%, and 283.19% higher than those under lawn, respectively. The marker genes of fermentation, aerobic respiration, methanogenesis, and methane oxidation were also enriched in the soil under organic mulch. Nitrogen cycling was generally repressed by the organic mulch, but the assimilatory nitrate and nitrite reduction processes were enhanced. The activity of alkaline phosphatase was 12.63% higher in the mulch-covered soil, and functional genes involved in phosphorus cycling were also enriched. This study presents a comprehensive investigation of the influence of organic mulch on soil microbes and provides a deeper insight into the recovery strategy for soil degradation following urban greening. KEY POINTS: • Long-term cover with organic mulches assists soil recovery from degradation • Soil physical and chemical properties were changed by organic mulches • Organic mulches enhanced genes involved in microbially mediated C and P cycling • Soil organic matter was derived from decomposition of organic mulch and carbon fixation • N cycling was repressed by mulches, except for assimilatory NO2- and NO3- reductions.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Virtual screening combined with experimental verification reveals the potential mechanism of Fuzitang decoction against Gouty Arthritis.

Background: and Purpose: Fuzitang decoction (FZT), a classic prescription of traditional Chinese medicine (TCM), has excellent efficacy in treating gouty arthritis (GA). However, the underlying molecular mechanism remains obscure. In the present study, we aimed to explore the underlying mechanisms of FZT in treating GA by virtual screening combined with experimental verification. Methods: In this study, the active components of FZT and their corresponding targets were screened from the TCMSP database and TargetNet database. Then, the potential targets of FZT against GA were retrieved from multiple databases to generate a network. Protein-protein interaction, herbal-component-target, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were applied to identify potential targets and related signaling pathways. Furthermore, molecular docking simulation was applied to identify the interactions between the drug and targets. Finally, in vitro experiments were conducted to validate the potential targets and signaling pathways. Results: In the present study, several crucial components, including kaempferol, luteolin, catechin, deoxyandrographolide, and perlolyrine in FZT, were obtained through network pharmacology, and several potential targets to treat GA were developed, such as PPARG, CYP3A4, PTGS2 (known as COX2), VEGFA, and CYP1A1. Experimental validation suggested that deoxyandrographolide significantly suppressed the expression of IL-1ß, COX2, NLRP3 and IL-6 in inflammatory monocyte cells. Conclusions: Our results identified a novel anti-inflammatory compound, deoxyandrographolide, which helps to explain the potential mechanism of FZT in treating GA and provides evidence to support FZT's clinical use.

[Preparation of vitexin albumin nanoparticles and its pharmacokinetic study].

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Background: Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods: We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results: Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions: CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration: PROSPERO, CRD42023396828.

Assessing Left Ventricular Systolic Function in Patients with Pregnancy-Induced Hypertension Using Three-Dimensional Speckle Tracking Technology.

Objective: This study investigates the clinical utility of three-dimensional speckle tracking technology in assessing left ventricular systolic function in pregnancy-induced hypertension syndrome (PIH). Methods: We retrospectively enrolled 70 patients with diagnosed PIH treated at our institution between July 2019 and August 2021 as the study group. A total of 70 healthy pregnant women undergoing routine antenatal examinations at the same institution during the same period were included in the control group. Two-dimensional conventional echocardiography measured left ventricular parameters in both groups. Three-dimensional speckle tracking technology analyzed Left Ventricular Global Longitudinal Peak Strain (LVGLS), Left Ventricular Global Radial Peak Strain (LVGRS), and Left Ventricular Global Circumferential Peak Strain (LVGCS). Differences in left ventricular systolic function and pregnancy outcomes were compared. Results: In the study group, LVEDD, LVPWTd, and IVSTd (47.67±4.88, 10.68±1.21, 11.24±1.03) exceeded those in the control group (45.21±5.65, 8.17±0.98, 8.91±0.37). LVEF (62.12±5.63) was lower than the control group (65.25±5.17) (all P < .05). LVGLS, LVGCS, and LVGAS in the study group (-15.66±1.07, -20.17±2.89, -23.17±3.43) were higher than the control group (-20.14±1.27, -25.17±1.36, -37.68±3.29), while LVGRS (30.29±3.61) was lower than the control group (34.18±4.08) (all P < .05). The study group had 72.86% natural deliveries and 27.14% cesarean sections; the control group had 31.43% natural deliveries and 68.57% cesarean sections (all P < .05). Weeks of delivery and birth weight in the study group (36.87±1.23, 2.71±0.41) were lower than the control group (38.96±1.54, 3.41±0.78) (both P < .05). Conclusions: Compared to traditional methods, three-dimensional speckle tracking technology more sensitively detects left ventricular strain and rotation in PIH patients. It holds clinical relevance in early left ventricular dysfunction detection, effectively mitigating adverse pregnancy outcomes and warranting clinical adoption and application.

Anti-inflammatory and analgesic effects of Streblus indicus.

The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1ß, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.

Efficacy and safety of acupoint application in the treatment of ulcerative colitis: A systematic review and meta-analysis.

BACKGROUND: The efficacy of acupoint application in the treatment of ulcerative colitis (UC) is still controversial. The purpose of this study is to systematically evaluate the clinical efficacy and safety of acupoint application in the treatment of ulcerative colitis. METHODS: The databases of China National Knowledge Infrastructure (CNKI), Chinese Biology Medicine (CBM), VIP, Wanfang, Embase, PubMed, the Cochrane Library and Web of Science were searched. The time limit was from the establishment of the database to July 2022. The published randomized controlled trials of acupoint application in the treatment of UC were analyzed by meta-analysis and trial sequential analysis. RESULTS: A total of 13 studies were included, with a total sample size of 878 cases. Compared with conventional western medicine, acupoint application can effectively improve the effective rates of clinical comprehensive (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.06-1.20, P = .0003), syndrome (RR 1.13, 95% CI 1.03-1.24, P = .009), and interleukin-4 (IL-4) (mean differences 2.62, 95% CI 1.96-3.28, P < .00001) in the treatment of UC, and reduce interferon-γ (mean differences -5.38, 95% CI -6.81 to -3.94, P < .00001). The effective rates of colonoscopy (RR 0.94, 95% CI 0.84-1.05, P = .25), pathological examination (RR 1.04, 95% CI 0.90-1.20, P = .60) and rate of adverse reaction (RR 0.55, 95% CI 0.25-1.21, P = .14) were the same. Trial sequential analysis indicated that the benefits of effective rates of clinical comprehensive and syndrome, IL-4, and interferon-γ were conclusive. Harbord regression showed no publication bias (P = .98). The evaluation of evidence quality suggested that the evidence quality of effective rates of clinical comprehensive and syndrome was moderate and the evidence quality of other indicators was low or very low. CONCLUSION: Acupoint application is a safe and effective method for the treatment of UC, and has the prospect of clinical application.

Investigation of the Mechanisms and Experimental Verification of Yulin Formula in the Treatment of Diminished Ovarian Reserve via Network Pharmacology.

Purpose: The aim of this study is to examine, using network pharmacology analysis and experimental validation, the pharmacological processes by which Yulin Formula (YLF) reduces cyclophosphamide-induced diminished ovarian reserve (DOR). Methods: First, information about the active components, associated targets, and related genes of YLF and DOR was gathered from open-access databases. The primary targets and pathways of YLF to reduce DOR were predicted using studies of functional enrichment from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Protein-Protein Interaction (PPI) networks. Second, we built a cyclophosphamide-induced diminished ovarian reserve (DOR) rat model to verify the primary target proteins implicated in the predicted signaling pathway to explore the mechanism of improve ovarian function of YLF. Results: 98 targets met the targets of the 82 active ingredients in YLF and DOR after searching the intersection of the active ingredient targets and DOR targets. Fourteen targets, including AKT and Caspase-3 among others, were hub targets, according to the PPI network study. The PI3K/AKT pathway was revealed to be enriched by numerous targets by the GO and KEGG enrichment studies, and it was used as a target for in vivo validation. Animal studies showed that YLF administration not only reduced the number of atretic follicles, the proportion of TUNEL-positive ovarian cells, the rate of apoptosis of granulosa cells (GCs) and the proportion of abnormal mitochondria in DOR rats, but also reversed the high expression of Caspase-3, Caspase-9, BAX, cytochrome C, PI3K and P-AKT, improving the ovarian reserve in cyclophosphamide (CTX)-induced DOR rats. Conclusion: Our research results predicted the active ingredients and potential targets of YLF-interfering DOR by an integrated network pharmacology approach, and experimentally validated some key target proteins participated in the predicted signaling pathway. A more comprehensive understanding of the pharmacological mechanism of YLF for DOR treatment was obtained.

Neutrophil extracellular trap production and CCL4L2 expression influence corticosteroid response in asthma.

The association between neutrophil extracellular traps (NETs) and response to inhaled corticosteroids (ICS) in asthma is unclear. To better understand this relationship, we analyzed the blood transcriptomes from children with controlled and uncontrolled asthma in the Taiwanese Consortium of Childhood Asthma Study using weighted gene coexpression network analysis and pathway enrichment methods. We identified 298 uncontrolled asthma-specific differentially expressed genes and one gene module associated with neutrophil-mediated immunity, highlighting a potential role for neutrophils in uncontrolled asthma. We also found that NET abundance was associated with nonresponse to ICS in patients. In a neutrophilic airway inflammation murine model, steroid treatment could not suppress neutrophilic inflammation and airway hyperreactivity. However, NET disruption with deoxyribonuclease I (DNase I) efficiently inhibited airway hyperreactivity and inflammation. Using neutrophil-specific transcriptomic profiles, we found that CCL4L2 was associated with ICS nonresponse in asthma, which was validated in human and murine lung tissue. CCL4L2 expression was also negatively correlated with pulmonary function change after ICS treatment. In summary, steroids fail to suppress neutrophilic airway inflammation, highlighting the potential need to use alternative therapies such as leukotriene receptor antagonists or DNase I that target the neutrophil-associated phenotype. Furthermore, these results highlight CCL4L2 as a potential therapeutic target for individuals with asthma refractory to ICS.

Phenolic Characterization and Antioxidant Activity of Chrysanthemum indicum and Opisthopappus Shih during Different Growth Stages.

Recently, much attention has been devoted to natural phenolics because of their ideal structure and chemistry for free radical scavenging activities, which may play important roles in long-term health and a reduction in the risk of developing chronic degenerative diseases. Chrysanthemum indicum (C. indicum) has been widely used as a health food and as a popular herb in China for many centuries. Opisthopappus Shih (O. shih) often takes the place of its related genera, C. indicum, in functional tea or medicine prescriptions in place of origin. In this article, a comparative study on the phenolics and antioxidant activity of C. indicum and O. shih during different growth stages was investigated. The antioxidant properties of plant extracts were tested using DPPH and ABTS assays. The characterization of potential phytochemicals was carried out using Fourier transform infrared (FT-IR) spectroscopy. Total phenolics (TPC) and total flavonoid content (TFC) were measured using Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. An HPLC method was used to simultaneously quantify five phenolic compounds, including chlorogenic acid, luteolin, rutin, quercetin, and apigenin. Results indicated that the Trolox equivalent antioxidant activity (TEAC) values of C. indicum and O. shih had extremely large variations at different growth stages. The most abundant phenolics and potent antioxidant activity of two related plants appear at the early vegetative and then flowering stages. Antioxidant activities and phenolic content of O. shih were higher than those of corresponding organs of C. indicum at the same collection time. The whole plant of O. shih, especially its leaves and flowers, are good candidates for obtaining nutraceuticals and functional food ingredients.

[Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency. METHODS: A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups. RESULTS: After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01). CONCLUSION: Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.