[Summary and evaluation of randomized controlled trial on Chinese patent medicine in treatment of diabetic foot ulcer].

This study systematically collected, analyzed, and evaluated randomized controlled trial(RCT) in the treatment of diabetic foot ulcer(DFU). The aim as provide references for future studies and to enhance the application of clinical evidence. The RCT of DFU treated with Chinese Patent Medicine was obtained and analyzed using the AI-Clinical Evidence Database of Chinese Patent Medicine(AICED-CPM). The analysis was supplemented with data from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science. A total of 275 RCTs meeting the requirements were retrieved, with only 7 of them having a sample size of 200 or more. These trials involved 66 different Chinese patent medicine including 25 oral medications, 24 Chinese herbal injections, and 17 external drugs. Among the 33 different intervention/control designs identified, the most common design was Chinese patent medicine + conventional treatment vs conventional treatment(86 cases, 31.27%). Out of the 275 articles included in the literature, 50 did not provide information on the specific course of treatment(18.18%). A total of 10 counting indicators(with a frequency of 426) and 36 measuring indicators(with a frequency of 962) were utilized. The methodological quality of the RCT for the treatment of DFU with Chinese patent medicine was found to be low, with deficiencies in blind methods, other bias factors, study registration, and sample size estimation. There were noticeable shortcomings in the reporting of allocation hiding and implementation bias(blind method application). More studies should prioritize trial registration, program design, and strict quality control during implementation to provide valuable data for clinical practice and serve as a reference for future investigations.

Gegen Qinlian tablets delay Alzheimer's disease progression via inhibiting glial neuroinflammation and remodeling gut microbiota homeostasis.

BACKGROUND: Current therapeutic agents for AD have limited efficacy and often induce undesirable side effects. Gegen Qinlian tablets (GGQLT) are a well-known clearingheat formula used in clinical treatment of inflammatory diseases. Based on traditional Chinese medicine (TCM) theory, the strategy of clearing-heat is then compatible with the treatment of AD. However, it remains unknown whether GGQLT can exert neuroprotective effects and alleviate neuroinflammation in AD. PURPOSE: This study aimed to evaluate the anti-AD effects of GGQLT and to decipher its intricate mechanism using integrative analyses of network pharmacology, transcriptomic RNA sequencing, and gut microbiota. METHODS: The ingredients of GGQLT were analyzed using HPLC-ESI-Q/TOF-MS. The AD model was established by bilateral injection of Aß1-42 into the intracerebroventricular space of rats. The Morris water maze was used to evaluate the cognitive function of the AD rats. The long-term toxicity of GGQLT in rats was assessed by monitoring their body weights and pathological alterations in the liver and kidney. Reactive astrocytes and microglia were assessed by immunohistochemistry by labeling GFAP and Iba-1. The levels of inflammatory cytokines in the hippocampus were evaluated using ELISA kits, RT-PCR, and Western blot, respectively. The potential anti-AD mechanism was predicted by analyses of RNA-sequencing and network pharmacology. Western blot and immunohistochemistry were utilized to detect the phosphorylation levels of IκBα, NF-κB p65, p38, ERK and JNK. The richness and composition of gut bacterial and fungal microflora were investigated via 16S rRNA and ITS sequencing. RESULTS: Typical ingredients of GGQLT were identified using HPLC-ESI-Q/TOF-MS. GGQLT significantly improved the cognitive function of AD rats by suppressing the activation of microglia and astrocytes, improving glial morphology, and reducing the neuroinflammatory reactions in the hippocampus. RNA-sequencing, network and experimental pharmacological studies demonstrated that GGQLT inhibited the activation of NF-κB/MAPK signaling pathways in the hippocampus. GGQLT could also restore abnormal gut bacterial and fungal homeostasis and no longer-term toxicity of GGQLT was observed. CONCLUSIONS: Our findings, for the first time, demonstrate GGQLT exhibit anti-AD effects and is worthy of further exploration and development.

DNA-Binding with One Finger (Dof) Transcription Factor Gene Family Study Reveals Differential Stress-Responsive Transcription Factors in Contrasting Drought Tolerance Potato Species.

DNA-binding with one finger (Dof) proteins comprise a large family that play central roles in stress tolerance by regulating the expression of stress-responsive genes via the DOFCORE element or by interacting with other regulatory proteins. Although the Dof TF has been identified in a variety of species, its systemic analysis in potato (Solanum tuberosum L.) is lacking and its potential role in abiotic stress responses remains unclear. A total of 36 potential Dof genes in potato were examined at the genomic and transcriptomic levels in this work. Five phylogenetic groups can be formed from these 36 Dof proteins. An analysis of cis-acting elements revealed the potential roles of Dofs in potato development, including under numerous abiotic stress conditions. The cycling Dof factors (CDFs) might be the initial step in the abiotic stress response signaling cascade. In potato, five CDFs (StCDF1/StDof19, StCDF2/StDof4, StCDF3/StDof11, StCDF4/StDof24, and StCDF5/StDof15) were identified, which are homologs of Arabidopsis CDFs. The results revealed that these genes were engaged in a variety of abiotic reactions. Moreover, an expression analysis of StDof genes in two potato cultivars ('Long10' (drought tolerant) and 'DXY' (drought susceptible)) of contrasting tolerances under drought stress was carried out. Further, a regulatory network mediated by lncRNA and its target Dofs was established. The present study provides fundamental knowledge for further investigation of the roles of Dofs in the adaptation of potato to drought stress, aiming to provide insights into a viable strategy for crop improvement and stress-resistance breeding.

Comprehensive Analysis of the Complete Mitochondrial Genome of Rehmannia chingii: An Autotrophic Species in the Orobanchaceae Family.

Rehmannia chingii is an important medicinal plant with immense value in scientific research. However, its mitochondrial genome (mitogenome) has not yet been characterized. Herein, based on whole-genome Illumina short reads and PacBio HiFi reads, we obtained the complete mitogenome of R. chingii through a de novo assembly strategy. We carried out comparative genomic analyses and found that, in comparison with the plastid genome (plastome) showing a high degree of structural conservation, the R. chingii mitogenome structure is relatively complex, showing an intricate ring structure with 16 connections, owing to five repetitive sequences. The R. chingii mitogenome was 783,161 bp with a GC content of 44.8% and contained 77 genes, comprising 47 protein-coding genes (CDS), 27 tRNA genes, and 3 rRNA genes. We counted 579 RNA editing events in 47 CDS and 12,828 codons in all CDSs of the R. chingii mitogenome. Furthermore, 24 unique sequence transfer fragments were found between the mitogenome and plastome, comprising 8 mitogenome CDS genes and 16 plastome CDS genes, corresponding to 2.39% of the R. chingii mitogenome. Mitogenomes had shorter but more collinear regions, evidenced by a comparison of the organelles of non-parasitic R. chingii, hemiparasitic Pedicularis chinensis, and holoparasitic Aeginetia indica in the Orobanchaceae family. Moreover, from non-parasitic to holoparasitic species, the genome size in the mitogenomes of Orobanchaceae species did not decrease gradually. Instead, the smallest mitogenome was found in the hemiparasitic species P. chinensis, with a size of 225,612 bp. The findings fill the gap in the mitogenome research of the medicinal plant R. chingii, promote the progress of the organelle genome research of the Orobanchaceae family, and provide clues for molecular breeding.

Water extract of Fagopyrum dibotrys (D. Don) Hara straw increases selenium accumulation in peach seedlings under selenium-contaminated soil.

To promote the selenium (Se) uptakes in fruit trees under Se-contaminated soil, the effects of water extract of Fagopyrum dibotrys (D. Don) Hara straw on the Se accumulation in peach seedlings under selenium-contaminated soil were studied. The results showed that the root biomass, chlorophyll content, activities of antioxidant enzymes, and soluble protein content of peach seedlings were increased by the F. dibotrys straw extract. The different forms of Se (total Se, inorganic Se, and organic Se) were also increased in peach seedlings following treatment with the F. dibotrys straw extract. The highest total shoot Se content was treated by the 300-fold dilution of F. dibotrys straw, which was 30.87% higher than the control. The F. dibotrys straw extract also increased the activities of adenosine triphosphate sulfurase (ATPS), and adenosine 5'-phosphosulfate reductase (APR) in peach seedlings, but decreased the activity of serine acetyltransferase (SAT). Additionally, correlation and grey relational analyses revealed that chlorophyll a content, APR activity, and root biomass were closely associated with the total shoot Se content. Overall, this study shows that the water extract of F. dibotrys straw can promote Se uptake in peach seedlings, and 300-fold dilution is the most suitable concentration.

The water extract of Fagopyrum dibotrys (D. Don) Hara straw promoted the selenium (Se) uptake in peach seedlings under selenium-contaminated soil. The concentration of F. dibotrys straw extract showed a quadratic polynomial regression relationship with the total root and shoot Se. Furthermore, chlorophyll a content, APR activity, and root biomass were closely associated with the total shoot Se. This study shows that water extract of F. dibotrys straw can promote Se uptake in peach seedlings, and 300-fold dilution is the most suitable concentration.

The state of astragaloside IV research: A bibliometric and visualized analysis.

BACKGROUND: Astragaloside IV has emerged as a pharmaceutical monomer with great medical applications and potential. Astragaloside IV has many effects such as improving myocardial ischemia, cerebral ischemia-reperfusion injury, anti-inflammatory, analgesic, antiviral, promoting lymphocyte proliferation, and antitumor effects. However, there are few bibliometric studies on astragaloside IV. OBJECTIVES: We aim to visualize the hotspots and trends in astragaloside IV research through bibliometric analysis to further understand the future development of basic and clinical research. Methods The articles and reviews on astragaloside IV were screened from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace software. Bibliometric analysis was performed on 971 articles published from 1998 to 2022. RESULTS: The number of articles on astragaloside IV increased yearly. These publications came from 42 countries/regions, with China being the largest. The primary research institutions were Shanghai University of Traditional Chinese Medicine and Guangzhou University of Traditional Chinese Medicine. Journal of Ethnopharmacology was the most studied journal and co-cited journal. A total of 473 authors were included, among which Hongxin Wang had the highest number of publications and Zhang Wd had the highest total citation frequency. After analysis, the most common keywords are astragaloside IV, expression, and oxidative stress. Cardiovascular disease, cerebral ischemia, cancer, and kidney disease are current and developing research fields. CONCLUSION: This study used bibliometrics and visualization methods to analyze the research hotspots and trends of astragaloside IV. Astragaloside IV on ischemia-reperfusion injury, cancer, and tumor may become the focus of future research.

The reporting checklist for Chinese patent medicine guidelines: RIGHT for CPM.

Existing reporting checklists lack the necessary level of detail and comprehensiveness to be used in guidelines on Chinese patent medicines (CPM). This study aims to develop a reporting guidance for CPM guidelines based on the Reporting Items of Practice Guidelines in Healthcare (RIGHT) statement. We extracted information from CPM guidelines, existing reporting standards for traditional Chinese medicine (TCM), and the RIGHT statement and its extensions to form the initial pool of reporting items for CPM guidelines. Seventeen experts from diverse disciplines participated in two rounds of Delphi process to refine and clarify the items. Finally, 18 authoritative consultants in the field of TCM and reporting guidelines reviewed and approved the RIGHT for CPM checklist. We added 16 new items and modified two items of the original RIGHT statement to form the RIGHT for CPM checklist, which contains 51 items grouped into seven sections and 23 topics. The new and revised items are distributed across four sections (Basic information, Background, Evidence, and Recommendations) and seven topics: title/subtitle (one new and one revised item), Registration information (one new item), Brief description of the health problem (four new items), Guideline development groups (one revised item), Health care questions (two new items), Recommendations (two new items), and Rationale/explanation for recommendations (six new items). The RIGHT for CPM checklist is committed to providing users with guidance for detailed, comprehensive and transparent reporting, and help practitioners better understand and implement CPM guidelines.

Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

Traditional Chinese medicine for smoking cessation: An umbrella review of systematic reviews and meta-analysis of randomized controlled trials.

INTRODUCTION: Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. METHODS: Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. RESULTS: Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. CONCLUSIONS: Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Saponins from Panax japonicus improve neuronal mitochondrial injury of aging rats.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.

A Programmable Oxygenation Device Facilitates Oxygen Generation and Replenishment to Promote Wound Healing.

Inadequate oxygenation is one of the chief culprits for delayed wound healing. However, current oxygen therapies, such as hyperbaric oxygen therapy and topical oxygen therapy, face hurdles in providing sustained and long-term oxygenation to reverse wound hypoxia. Furthermore, their efficacy in rejuvenating wound injury is restricted by limited penetration of oxygen in the wound bed. Herein, this study proposes a programmable and portable oxygenation device (named GUFO oxydevice) by ingeniously integrating i) a controllable oxygen generation and unidirectional transmission system (COGT-UTS), and ii) a supramolecular assembled perfluorinated hyperbranched polymer/gelatin (GUF) hydrogel in which the perfluorinated hyperbranched polymer (FHBP) acts as an oxygen reservoir to ensure sustained and convenient oxygen replenishment and thus directly regulate the hypoxic wound microenvironment. Accelerating the wound healing process by GUFO oxydevice is achieved in both a diabetic rat and an acute porcine wound model without any secondary tissue damages. The present study demonstrates that the GUFO oxydevice holds promise as a practically feasible candidate for wound treatment.

The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.

Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation.

Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

A CO-mediated photothermal therapy to kill drug-resistant bacteria and minimize thermal injury for infected diabetic wound healing.

With an increasing proportion of drug-resistant bacteria, photothermal therapy (PTT) is a promising alternative to antibiotic treatment for infected diabetic skin ulcers. However, the inevitable thermal damage to the tissues restricts its clinical practice. Carbon monoxide (CO), as a bioactive gas molecule, can selectively inhibit bacterial growth and promote tissue regeneration, which may be coordinated with PTT for drug-resistant bacteria killing and tissue protection. Herein, a CO-mediated PTT agent (CO@mPDA) was engineered by loading manganese carbonyl groups into mesoporous polydopamine (mPDA) nanoparticles via coordination interactions between the metal center and a catechol group. Compared to the traditional PTT, the CO-mediated PTT increases the inhibition ratio of the drug-resistant bacteria both in vitro and in diabetic wound beds by selectively inhibiting the co-chaperone of the heat shock protein 90 kDa (Hsp90), and lowers the heat resistance of the bacteria rather than the mammalian tissues. Meanwhile, the tissue-protective proteins, such as Hsp90 and vimentin (Vim), are upregulated via the WNT and PI3K-Akt pathways to reduce thermal injury, especially with a laser with a high-power density. The CO-mediated PTT unified the bacterial killing with tissue protection, which offers a promising concept to improve PTT efficiency and minimize the side-effects of PTT when treating infected skin wounds.

Nano-composite system of traditional Chinese medicine for ocular applications: molecular docking and three-dimensional modeling insight for intelligent drug evaluation.

The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10-5 mol/m3 and 6.37×10-6 mol/m3. In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

Traditional Chinese Manual Therapy (Tuina) reshape the function of default mode network in patients with lumbar disc herniation.

Purpose: Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes. Methods: Patients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs. Results: In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs. Conclusion: The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.

Transcriptome analysis reveals insight into the protective effect of N-acetylcysteine against cadmium toxicity in Ganoderma lucidum (Polyporales: Polyporaceae).

Ganoderma lucidum is widely cultivated and used as traditional medicine in China and other Asian countries. As a member of macrofungi, Ganoderma lucidum is also prone to bioaccumulation of cadmium and other heavy metals in a polluted environment, which affects the growth and production of Ganoderma lucidum, as well as human health. N-Acetyl-L-cysteine (NAC) is considered a general antioxidant and free radical scavenger that is involved in the regulation of various stress responses in plants and animals. However, whether NAC could regulate cadmium stress responses in macrofungi, particularly edible fungi, is still unknown. In this work, we found that the exogenous NAC could alleviate Cd-induced growth inhibition and reduce the cadmium accumulation in Ganoderma lucidum. The application of the NAC cloud also inhibit cadmium-induced H2O2 production in the mycelia. By using transcriptome analysis, 2920 and 1046 differentially expressed unigenes were identified in "Cd100 vs CK" and "NAC_Cd100 vs Cd100," respectively. These differential unigenes were classified into a set of functional categories and pathways, which indicated that various biological pathways may play critical roles in the protective effect of NAC against Cd­induced toxicity in Ganoderma lucidum. Furthermore, it suggested that the ATP-binding cassette transporter, ZIP transporter, heat shock protein, glutathione transferases, and Cytochrome P450 genes contributed to the increased tolerance to cadmium stress after NAC application in Ganoderma lucidum. These results provide new insight into the physiological and molecular response of Ganoderma lucidum to cadmium stress and the protective role of NAC against cadmium toxicity.

[Evolution of auditory brainstem response in 0-6 years old normal hearing children and characteristics of children with abnormal acoustic conduction].

Objective:To explore the normal reference range of Click-ABR latency and interwave period in 0-6 years old children, and to analyze the clinical characteristics of Click-ABR in children with sound transmission function is abnormal. Methods:A total of 1791（3582 ears） normal hearing children aged 0-6 years and 176（258 ears） conductive hearing loss children were selected for Click-ABR. The differences of Click-ABR parameters in children of different months were analyzed, and the correlation between the degree of conductive hearing loss and Click-ABR parameters was explored. Results:The incubation period of wave Ⅰ was not correlated with the age of month, while the incubation period of wave Ⅲ, wave Ⅴ, waveⅠ-Ⅲ and wave Ⅰ-Ⅴ were highly correlated with the age of month. There was a positive correlation between the latency of wave Ⅰ and hearing threshold in the children with sound transmission function is abnormal under 80 dB nHL stimulation, and there was no difference between the standard values of wave Ⅰ-Ⅲ and Ⅰ-Ⅴ in the children with sound transmission function is abnormal and normal children. Conclusion:The latency of ABR wave Ⅲ and Ⅴ, and the interval between wave Ⅰ-Ⅲ and Ⅰ-Ⅴ shorten with the increase of age in children aged 0-6 years. The normal ABR values of children of different ages should be established in each hearing clinic for children as a reference. Combined with Click-ABR threshold and 80 dB nHL acoustic subwave Ⅰlatency, the abnormal conduction function can be preliminatively screened out, which should be further supplemented with other combinations of hearing diagnosis.