The effect of physical interventions on pain control after orthodontic treatment: A systematic review and network meta-analysis.

OBJECTIVE: Pain is a frequent adverse reaction during orthodontic treatment, which can significantly reduce treatment compliance and compromise the expected treatment effect. Physical interventions have been used to alleviate pain after orthodontic treatment, but their effectiveness is controversial. This study used a network meta-analysis to assess the efficacy of various physical interventions typically used in managing pain after orthodontic treatment, with a view to provide evidence-based recommendations for representative interventions for orthodontic pain relief during peak pain intensity. METHODS: A systematic search of six electronic databases, from their respective inception dates, was conducted to identify relevant literature on the efficacy of various typical physical interventions for managing pain after orthodontic treatment. Literature screening was performed according to the Cochrane System Evaluator's Manual. Stata 16.0 was used to assess heterogeneity, inconsistency, publication bias, and sensitivity to generate an evidence network diagram and conduct a network meta-analysis. RESULTS: In total, 771 articles were reviewed to collect literature on interventions, including low-level laser therapy (LLLT), vibration, acupuncture, and chewing. Of these, 28 studies using a visual analog scale (VAS) as an outcome indicator were included. The results showed that LLLT, vibration, acupuncture, and chewing effectively relieved the pain symptoms in patients after orthodontic treatment. At 24 h post-treatment, LLLT (surface under the cumulative ranking curve [SUCRA] = 80.8) and vibration (SUCRA = 71.1) were the most effective interventions. After 48 h of treatment, acupuncture (SUCRA = 89.6) showed a definite advantage as the best intervention. CONCLUSION: LLLT, vibration, acupuncture, and chewing can alleviate pain associated with orthodontic treatment. Among these interventions, acupuncture was found to be the most effective at 48 h after orthodontic treatment. In addition, acupuncture demonstrated long-lasting and stable pain-relieving effects. However, further studies are needed to determine the most suitable equipment-specific parameters for acupuncture in relieving pain associated with orthodontic treatment.

Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup.

Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis. In mice with hematopoietic dysfunction, SZEK (gavage, 0.3 mL/25 g) alleviated pathological damage to the bone marrow and spleen; increased the number of naïve cells (Lin-), hematopoietic stem cells (Lin-Sca-1+c-Kit+), long-term self-renewing hematopoietic stem cells (Lin-Sca-1+c-Kit+CD48-CD150+), B lymphocytes (CD45+CD19+), and macrophages (CD11b+F4/80+) in the bone marrow; and reduced inflammation. Preliminary intestinal flora and serum metabolome analyses indicated that the pro-hematopoietic mechanism of SZEK was associated with macrophage differentiation. Further validation revealed that SZEK promoted hematopoiesis by decreasing the number of M2 macrophages and inhibiting the secretion of negative hematopoietic regulatory factors in mice with hematopoietic dysfunction.

Aroma and taste analysis of pickled tea from spontaneous and yeast-enhanced fermentation by mass spectrometry and sensory evaluation.

Anaerobically fermented pickled tea (PT) can be produced by spontaneous fermentation (SF) or yeast-enhanced fermentation (YF). Aroma and taste characteristics of PT during YF and SF were investigated using sensory evaluation, odour activity, aroma character impact values, HS-SPME-GC-MS, UPLC-QQQ-MS/MS, and spectrophotometry, annotating 198 volatile and 115 non-volatile components. The main contributing volatile components were ß-ionone, and 1-octanol, promoted by YF and SF, and yielding floral and fruity aromas respectively. Additionally, compared with SF, YF promoted the formation of citronellol yielding a floral aroma, inhibited the stale aroma of methoxybenzenes, and reduced bitter, astringent, and sour tastes. Furthermore, partial least-squares regression analysis identified the main components related to the 'acides aroma' of PT as linalool oxide, n-decanoic acid, hexanoic acid, 3,7-dimethyl-2,6-octadienoic acid, 3-methyl-1-dodecyn-3-ol, and nerolidol. This application could be used as methodology for the comprehensive analysis of tea aroma and taste and these results can act as guidelines for PT production and quality control.

A novel mechanism for regulating lung immune homeostasis: Zukamu granules alleviated acute lung injury in mice by inhibiting NLRP3 inflammasome activation and regulating Th17/Treg cytokine balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a severely acute lung inflammation with high morbidity and mortality. Zukamu granules (ZKMG) is one of the Uygur patent drugs commonly used in clinic, which is included in the National Essential Drugs List (2018 edition). Clinical studies have shown that ZKMG has a significant effect on acute upper respiratory tract infection, and has better anti-inflammatory and antipyretic effects. However, the immunomodulatory mechanism of ZKMG on ALI is still not clear. AIM OF THE STUDY: The aim of this study is to investigate the lung protective effect and immunomodulatory mechanism of ZKMG on lipopolysaccharide (LPS) -induced ALI mice, and to provide an important basis for the treatment strategy and theoretical basis of ALI. MATERIALS AND METHODS: First, network pharmacology was used to predict the potential signaling pathways and biological processes of ZKMG related to immunology. Molecular docking technique was used to predict the possibility between the core components of ZKMG acting on NLRP3 protein. In addition, protein levels of F4/80 in lung tissues were assessed by Immunohistochemistry (IHC). The contents of IL-1ß, IL-18, IL-17A and IL-10 in the lung tissue and serum, MPO in the lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR analysis (RT-qPCR) was used to detect NLRP3 mRNA in lung tissue. Protein levels of NLRP3, Caspase-1, Cleaved caspase-1 p20, ASC, and GSDMD were detected by Western blot (WB). RESULTS: The results of network pharmacology showed that the immune pathways of ZKMG were mainly Th17 signaling pathway, IL-17 signaling pathway, NOD-like receptor signaling pathway, etc. Molecular docking results showed that the core components of ZKMG had good binding ability to NLRP3 protein. The verification experiments showed that ZKMG can reduce the degree of lung injury, and reduce the level of inflammatory infiltration of neutrophils and macrophages by reducing the content of MPO and F4/80. In addition, ZKMG can reduce NLRP3 mRNA, inhibit the expression of NLRP3/Caspase-1/GSDMD and other related pathway proteins, and reduce inflammatory factors such as IL-1ß and IL-18. It can also reduce the content of pro-inflammatory cytokine IL-17A, increase the content of anti-inflammatory cytokine IL-10 in lung tissue. CONCLUSION: ZKMG can reduce the degree of lung tissue injury in ALI by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway and restoring the IL-17A/IL-10 cytokine balance, and its protective mechanism may be related to the regulation of lung immune homeostasis. It will provide a new strategy for studying the regulation of lung immune homeostasis.

Extraction, structural characterization and biological activities of polysaccharides from mulberry leaves: A review.

In recent years, plant polysaccharides have garnered attention for their impressive biological activity. Mulberry leaves have a long history of medicinal and edible use in China, polysaccharide is one of the main active components of mulberry leaves, mainly consist of xylose, arabinose, fructose, galactose, glucose and mannose, etc. The extraction methods of mulberry leaves polysaccharides (MLPs) mainly include hot water extraction, microwave-assisted extraction, ultrasonic extraction, enzyme-assisted extraction, and co-extraction. The separation and purification of MLPs involve core steps such as decolorization, protein removal, and chromatographic separation. In terms of pharmacological effects, MLPs exhibit excellent activity in reducing blood glucose, anti-oxidation, immune regulation, anti-tumor, antibacterial, anti-coagulation, and regulation of gut microbiota. Currently, there is a considerable amount of research on MLPs, however, there is a lack of systematic summarization. This review summarizes the research progress on the extraction, structural characterization, and pharmacological activities of MLPs, and points out existing shortcomings and suggests reference solutions, aiming to provide a basis for further research and development of MLPs.

Dietary methionine supplementation during the estrous cycle improves follicular development and estrogen synthesis in rats.

The follicle is an important unit for the synthesis of steroid hormones and the oocyte development and maturation in mammals. However, the effect of methionine supply on follicle development and its regulatory mechanism are still unclear. In the present study, we found that dietary methionine supplementation during the estrous cycle significantly increased the number of embryo implantation sites, as well as serum contents of a variety of amino acids and methionine metabolic enzymes in rats. Additionally, methionine supplementation markedly enhanced the expression of rat ovarian neutral amino acid transporters, DNA methyltransferases (DNMTs), and cystathionine gamma-lyase (CSE); meanwhile, it significantly increased the ovarian concentrations of the metabolite S-adenosylmethionine (SAM) and glutathione (GSH). In vitro data showed that methionine supply promotes rat follicle development through enhancing the expression of critical gene growth differentiation factor 9 and bone morphogenetic protein 15. Furthermore, methionine enhanced the relative protein and mRNA expression of critical genes related to estrogen synthesis, ultimately increasing estrogen synthesis in primary ovarian granulosa cells. Taken together, our results suggested that methionine promoted follicular growth and estrogen synthesis in rats during the estrus cycle, which improved embryo implantation during early pregnancy. These findings provided a potential nutritional strategy to improve the reproductive performance of animals.

Development and comparison of parallel reaction monitoring and data-independent acquisition methods for quantitative analysis of hydrophilic compounds in white tea.

In the present work, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) methods were developed for the accurate quantitation of amino acids, alkaloids nucleosides and nucleotides in tea. The quality peaks were significantly enhanced by optimizing the LC elution procedure, HCD voltage, MS resolution, and scanning event. Both methods were validated with good liner linearity (0.004-200 µg/mL), LODs (0.001-0.309 µg/mL for PRM and 0.001-0.564 µg/mL for DIA). Applied to white tea sample, the contents of these hydrophilic compounds were range from 34,655.39 to 70,586.14 mg/kg, and caffeine (32,529.02 mg/kg) and theanine (5483.46 mg/kg) were determined as the most abundant ones. Based on the quantitation data set, the white tea samples from Puer, Lincang and Xishuangbanna were clearly discriminated using multivariate data analysis. The results of the present works show that PRM and DIA have great potential in quantitative analysis of multiple hydrophilic compounds in food samples.

Ganoderma lucidum ethanol extracts ameliorate hepatic fibrosis and promote the communication between metabolites and gut microbiota g_Ruminococcus through the NF-κB and TGF-ß1/Smads pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum, a traditional edible medicinal mushroom, has been widely reported to improve liver diseases as a dietary intervention for people. Ganoderma lucidum extracts, primarily total triterpenoids (GLTTs), are one of the bioactive ingredients that have excellent beneficial effects on hepatic fibrosis. Therefore, its prevention and reversal are particularly critical due to the increasing number of patients with chronic liver diseases worldwide. AIM OF THE STUDY: The study aimed to evaluate whether GLTTs had a hepatoprotective effect against hepatic fibrosis through metabolic perturbations and gut microbiota changes and its underlying mechanisms. MATERIALS AND METHODS: The compound compositions of GLTTs were quantified, and carbon tetrachloride (CCl4)-induced hepatic fibrosis rats were used to investigate the cause of the improvement in various physiological states with GLTTs treatment, and to determine whether its consequent effect was associated with endogenous metabolites and gut microbiota using UPLC-Q-TOF-MSE metabolomics and 16S rRNA gene sequencing technology. RESULTS: GLTTs alleviated physical status, reduced liver pathological indicators, proinflammatory cytokines, and deposition of hepatic collagen fibers via regulating the NF-κB and TGF-ß1/Smads pathways. The untargeted metabolomics analysis identified 16 potential metabolites that may be the most relevant metabolites for gut microbiota dysbiosis and the therapeutic effects of GLTTs in hepatic fibrosis. Besides, although GLTTs did not significantly affect the α-diversity indexes, significant changes were observed in the composition of microflora structure. In addition, Spearman analysis revealed strong correlations between endogenous metabolites and gut microbiota g_Ruminococcus with hepatic fibrosis. CONCLUSION: GLTTs could provide a potential target for the practical design and application of novel functional food ingredients or drugs in the therapy of hepatic fibrosis.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

Combinatorics-based chemical characterization and bioactivity comparison of different parts of traditional Chinese medicinal plants through LC-Q-TOF-MS/MS, multivariate statistical analysis and bioassay: Marsdenia tenacissima as an example.

Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima, it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima, are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima. Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima, respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima, but also provides a paradigm for the research of other similar medicinal plants.

[Qualitative and quantitative study of flavonoids in Notoginseng Radix et Rhizoma based on UPLC-Q-TOF-MS and HPLC-DAD].

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-ß-D-xylosyl)-ß-D-galactoside was the highest with the average content in the tested samples of 161.0 µg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 µg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 µg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.

[Correlation between active component content and color of Atractylodes Lancea and A. chinensis based on color difference principle].

We explored the correlations between the color difference values [ΔL~*(lightness), Δa~*(red-green), Δb~*(yellow-blue)] and the content of four active components(including sesquiterpenoids and polyacetylenes) in the powder of Atractylodes lancea and A. chinensis, aiming to provide reference for the quality evaluation of Atractylodis Rhizoma and establish a qualitative model that can distinguish between A. lancea and A. chinensis based on the chromatic values. The tristimulus values(L~*, a~*, and b~*) of 23 batches of A. lancea and A. chinensis were measured by a color difference meter. The content of atractylenolide Ⅱ, ß-eudesmol, atractylodin, and atractylone in the 23 batches of samples were measured by high performance liquid chromatography(HPLC). Principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were performed to establish the qualitative models for distinguishing between A. lancea and A. chinensis. SPSS was employed to analyze the correlations between the tristimulus values and the content of the four index components. The results showed that the established PCA and PLS-DA models can divide the A. lancea and A. chinensis samples into two regions, and the tristimulus values of A. lancea and A. chinensis were positively correlated with the content of ß-eudesmol and atractylodin. Therefore, the PCA and PLS-DA models can successfully identify A. lancea and A. chinensis, and the appearance color can be used to quickly predict the internal quality of Atractylodis Rhizoma. This study provides a reference for the quality evaluation of Atractylodis Rhizoma and the modern research on the color of Chinese medicinal materials.

Protective effects and mechanisms of opuntia polysaccharide in animal models of diabetes mellitus: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia speciesis used in traditional medicine to treat diabetes mellitus (DM). Polysaccharide is one of the main components of Opuntia. Opuntia polysaccharide (OPS) is a kind of natural active macromolecular substance, numerous animal experiments have been conducted to treat DM, however, its protective effect and mechanism in animal models of DM has not been clarified. AIM OF THE STUDY: The aim of this study is to evaluate the efficacy of OPS on DM through a stematic review and meta-analysis of animal models, and whether its improves blood glucose (BG) levels, body weight (BW), food intake, water intake, and lipid levels, and to summarize the potential mechanism of OPS in the treatment of DM. MATERIALS AND METHODS: We searched relevant Chinese and English databases from the date of construction to March 2022, including PubMed (MEDLINE), Embase, Cochrane Library, Scopus and Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedicine Literature Database (CBM), Chinese Science and Technology Periodicals Database (VIP), Wanfang Database. 16 studies were included for meta-analysis. RESULTS: The results showed that compared with the model group, the OPS significantly improved BG, BW, food intake, water intake, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Meta-regression and subgroup analysis showed that intervention dose, animal species, duration and modeling method may be the source of the heterogeneity. There was no statistical difference between the positive control group and the OPS treatment group in improving BW, food intake, water intake, TC, TG, HDL-C, and LDL-C. CONCLUSIONS: OPS can effectively improve the symptoms of hyperglycemia, polydipsia, polyphagia, low body weight, and dyslipidemia in DM animals. The possible protective mechanisms of OPS on DM animals are immune regulation, repair of damaged pancreatic ß cells, and inhibition of oxidative stress and cell apoptosis.

Human factors engineering of BCI: an evaluation for satisfaction of BCI based on motor imagery.

Existing brain-computer interface (BCI) research has made great progress in improving the accuracy and information transfer rate (ITR) of BCI systems. However, the practicability of BCI is still difficult to achieve. One of the important reasons for this difficulty is that human factors are not fully considered in the research and development of BCI. As a result, BCI systems have not yet reached users' expectations. In this study, we investigate a BCI system of motor imagery for lower limb synchronous rehabilitation as an example. From the perspective of human factors engineering of BCI, a comprehensive evaluation method of BCI system development is proposed based on the concept of human-centered design and evaluation. Subjects' satisfaction ratings for BCI sensors, visual analog scale (VAS), subjects' satisfaction rating of the BCI system, and the mental workload rating for subjects manipulating the BCI system, as well as interview/follow-up comprehensive evaluation of motor imagery of BCI (MI-BCI) system satisfaction were used. The methods and concepts proposed in this study provide useful insights for the design of personalized MI-BCI. We expect that the human factors engineering of BCI could be applied to the design and satisfaction evaluation of MI-BCI, so as to promote the practical application of this kind of BCI.

[Clinical observational study on the treatment of oligozoospermia with Shizi Sanhua decoction combined with Nuoyu].

OBJECTIVE: To study the clinical therapeutic effect as well as drug effectiveness and safety of Shizi Sanhua decoction combined with Nuoyu in the treatment of oligozoospermia in men. METHODS: 102 patients with oligozoospermia diagnosed at Longhua Hospital of Shanghai University of Traditional Chinese Medicine from February 2022 to March 2023 were selected and randomly divided into 3 groups. The treatment group was treated with Shizi Sanhua Decoction + Nuoyu; the traditional Chinese medicine group was treated with Shizi Sanhua Decoction; and the Nuoyu nutrient group was treated with Nuoyu nutrient. A review assessment and record were made after one course of treatment (3 months). RESULTS: A total of 102 patients completed the trial due to the treatment process. There were 34 cases in each of the traditional Chinese medicine group, the Nuoyu nutrient group, and the treatment group. Clinical efficacy: total effective rate of 52.94% in the traditional Chinese medicine group; 58.82% in the Nuoyu nutrient group; 82.35% in the treatment group. The clinical efficacy of the treatment group was better than that of the traditional Chinese medicine group and the Nuoyu nutrient group (P<0.05), which was statistically significant. Semen routine: the treatment group was better than the traditional Chinese medicine group and Nuoyu nutrient group in improving the total number of sperm and sperm concentration. CONCLUSION: The semen concentration and forward sperm count of patients with oligozoospermia treated with Shizi Sanhua Decoction combined with Nuoyu improved more significantly, and the clinical efficacy was remarkable. And the clinical efficacy is not affected by age and disease duration. It can be popularized and applied as a treatment for oligozoospermia.

A paraventricular thalamus to central amygdala neural circuit modulates acute stress-induced heightened wakefulness.

Heightened wakefulness in response to stressors is essential for survival but can also lead to sleep disorders like insomnia. The paraventricular thalamus (PVT) is both a critical thalamic area for wakefulness and a stress-sensitive brain region. However, whether the PVT and its neural circuitries are involved in controlling wakefulness in stress conditions remains unknown. Here, we find that PVT neurons projecting to the central amygdala (CeA) are activated by different stressors. These neurons are wakefulness-active and increase their activities upon sleep to wakefulness transitions. Optogenetic activation of the PVT-CeA circuit evokes transitions from sleep to wakefulness, whereas selectively silencing the activity of this circuit decreases time spent in wakefulness. Specifically, chemogenetic inhibition of CeA-projecting PVT neurons not only alleviates stress responses but also attenuates the acute stress-induced increase of wakefulness. Thus, our results demonstrate that the PVT-CeA circuit controls physiological wakefulness and modulates acute stress-induced heightened wakefulness.

The Combined Use of Medium- and Short-Chain Fatty Acids Improves the Pregnancy Outcomes of Sows by Enhancing Ovarian Steroidogenesis and Endometrial Receptivity.

Fatty acids play important roles in maintaining ovarian steroidogenesis and endometrial receptivity. Porcine primary ovarian granulosa cells (PGCs) and endometrial epithelial cells (PEECs) were treated with or without medium- and short-chain fatty acids (MSFAs) for 24 h. The mRNA abundance of genes was detected by fluorescence quantitative PCR. The hormone levels in the PGCs supernatant and the rate of adhesion of porcine trophoblast cells (pTrs) to PEECs were measured. Sows were fed diets with or without MSFAs supplementation during early gestation. The fecal and vaginal microbiomes were identified using 16S sequencing. Reproductive performance was recorded at parturition. MSFAs increased the mRNA abundance of genes involved in steroidogenesis, luteinization in PGCs and endometrial receptivity in PEECs (p < 0.05). The estrogen level in the PGC supernatant and the rate of adhesion increased (p < 0.05). Dietary supplementation with MSFAs increased serum estrogen levels and the total number of live piglets per litter (p < 0.01). Moreover, MSFAs reduced the fecal Trueperella abundance and vaginal Escherichia-Shigella and Clostridium_sensu_stricto_1 abundance. These data revealed that MSFAs improved pregnancy outcomes in sows by enhancing ovarian steroidogenesis and endometrial receptivity while limiting the abundance of several intestinal and vaginal pathogens at early stages of pregnancy.

Application of network composite module analysis and verification to explore the bidirectional immunomodulatory effect of Zukamu granules on Th1 / Th2 cytokines in lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. RESULTS: The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.

A novel therapeutic approach for IPF: Based on the "Autophagy - Apoptosis" balance regulation of Zukamu Granules in alveolar macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu Granules (ZKMG) is one of the representative Uygur patent drugs widely used in China, which is included in the National Essential Drugs List (2018 edition). As the first choice for common cold treatment in Uygur medicine theory, it has unique anti-inflammatory and antitussive efficacy. AIM OF THE STUDY: According to the recent inflammatory hypothesis, the abnormal proliferation, autophagy and apoptosis process of lung cells especially alveolar macrophages (AMs) may play an important role in the progress of idiopathic pulmonary fibrosis (IPF). Therefore, we came up with a novel treatment approach for IPF by regulating the balance of AMs "autophagy - apoptosis", and took ZKMG as the sample drug for our research. MATERIALS AND METHODS: Network pharmacology approach was conducted to predict the active components and intersected targets between ZKMG and inflammation. PPI network, GO and KEGG enrichment analysis were screened and analyzed to predict the anti-inflammatory mechanism of ZKMG. Biological experiment adopted from 128 rats, and hematoxylin-eosin staining, flow cytometry and RT-PCR were performed to examine the pathological morphology, HYP contents in lung tissue, AMs counting, AMs apoptosis, AMs phagocytosis rate, mRNA relative quantity determination of 3 key factors associated with AMs "autophagy - apoptosis" and mRNA relative quantity determination of AMs surface receptor signaling pathway. RESULTS: The predicted results showed that the mechanism of ZKMG in anti-inflammatory was related to the response and elimination of inflammatory stimuli, the intervention of apoptosis and surface receptor signaling pathways of cells. The verification experiments showed that excessive apoptosis and insufficient autophagy of AMs always existed in the progression of IPF. ZKMG could inhibit AMs proliferation, significantly reduce AMs apoptosis rate, intervene the binding of the Bcl-2 to Beclin 1, inhibit the Caspase 3 activation, stimulate the enhancement of AMs phagocytosis, and inhibit the high expression of TLR4/MyD88/NF-κB surface receptor signaling pathway, which may partly retard the fibrosis process. CONCLUSION: By inhibiting proliferation, enhancing phagocytosis, inhibiting the formation of Bcl-2 complex, and inhibiting the high expression of MYD88-dependent TLR4 signaling pathway, ZKMG can regulate the balance of AMs "autophagy - apoptosis" in the alveolitis stage to retard the fibrosis process partly. With a comprehensive strategy of "target prediction - experimental verification", we have demonstrated that inhibiting the apoptosis and promoting autophagy activity of AMs may suggest a new perspective for IPF treatment, which would provide reference for the subsequent development.

Integrated metabolomic and transcriptomic analysis reveals variation in the metabolites and genes of Platycodon grandiflorus roots from different regions.

INTRODUCTION: Platycodon grandiflorum root (PG), a popular traditional Chinese medicine, contains considerable chemical components with broad pharmacological activities. The complexity and diversity of the chemical components of PG from different origins contribute to its broad biological activities. The quality of southern PG is superior to that of northern PG, but the mechanisms underlying these differences remain unclear. OBJECTIVES: In order to study variation in the differentially accumulated metabolites (DAMs), differentially expressed genes (DEGs), as well as their interactions and signalling pathways among PG from Anhui and Liaoning. METHODS: The metabolomes based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the transcriptome based on high-throughput sequencing technology were combined to comprehensively analyse PGn and PGb. RESULTS: A total of 6515 DEGs and 83 DAMs from the comparison of PG from Anhui and Liaoning were detected. Integrated analysis of metabolomic and transcriptomic data revealed that 215 DEGs and 57 DAMs were significantly enriched in 48 pathways according to KEGG pathway enrichment analysis, and 15 DEGs and 10 DAMs significantly enriched in the main pathway sesquiterpenoid and triterpenoid and phenylpropanoid biosynthesis might play a key role in complex response or regulatory processes. CONCLUSION: Differences in PG from southern and northern China might thus stem from differences in environmental factors, such as precipitation, light duration, and humidity. The results of our study provide new insight into geographic variation in gene expression and metabolite accumulation and will enhance the utilisation of PG resources.