[Quality control of Tianwang Buxin Pills based on UPLC fingerprint and multi-component quantification].

Tianwang Buxin Pills have demonstrated therapeutic effects in clinical practice, whereas there is a serious lack of comprehensive quality control to ensure the safety and effectiveness of clinical medication. In this study, ultra-performance liquid chromatography(UPLC) was employed to establish the fingerprint and the method for simultaneously determining the content of seven components of Tianwang Buxin Pills. Furthermore, chemometrics was employed to identify the key factors for the stable quality, which provided a reference for the comprehensive quality control and evaluation of this preparation. There were 25 common peaks in the UPLC fingerprints of 15 batches of Tianwang Buxin Pills, from which thirteen compounds were identified. A quantitation method was established for seven pharmacological components(α-linolenic acid, salvianolic acid B, glycyrrhetinic acid, schisandrin A, ß-asarone, 3,6'-disinapoylsucrose, and ligustilide). The principal component analysis(PCA) and partial least square discriminate analysis(PLS-DA) were performed to determine the key pharmacological components for controlling the quality stability of Tianwang Buxin Pills, which included 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone. The established fingerprint and multi-component content determination method have strong specificity, stability, and reliability. In addition, 3,6'-disinapoylsucrose, α-linolenic acid, and ß-asarone are the key pharmacological components that ensure the quality stability between batches and can be used to comprehensively control the quality of Tianwang Buxin Pills. The findings provide a scientific basis for the quality evaluation and standard establishment of Tianwang Buxin Pills.

Effectiveness of Mobile Health Platform-Based Continuity of Care in Osteoporosis Prevention and Treatment.

Objective: To assess the effectiveness of using mobile health platforms for continuous care in preventing and treating osteoporosis. Methods: 114 patients with osteoporosis admitted to Nantong First People's Hospital from March 2021 to June 2022 were recruited and assigned equally via random number table method to receive either routine care (namely education on osteoporosis disease, dietary guidance, exercise guidance, activity guidance, medication supervision, fall prevention, psychological care, and secondary health education at the time of discharge) (routine group) or mobile health platform-based continuity of care (continuity group), with 57 patients in each group. Outcome measures included treatment compliance, disease knowledge of osteoporosis (diet, exercise, risk factors), quality of life level, and care satisfaction. Results: All eligible patients were followed up for one year after discharge from the hospital. Patients with continuity of care showed higher treatment compliance and disease knowledge of diet, exercise, and risk factors than those with routine care (P = .004). Continuity of care was associated with significantly higher MOS 36-item short-form health survey (SF-36) scores (The SF-36 is a self-administered questionnaire containing 36 items that survey overall health status) and nursing satisfaction in patients versus routine care (P = .004). Conclusion: Mobile health platform-based continuity of care effectively enhances post-discharge compliance and knowledge of osteoporosis in patients with osteoporosis, thereby improving post-discharge quality of life and satisfaction with care. Multi-center studies involving diverse healthcare settings and patient populations would provide more robust evidence. Moreover, these findings highlight the potential benefits of incorporating mobile health platforms into the care continuum for osteoporosis patients. Also, by utilizing mobile health platforms, healthcare providers can extend their reach beyond hospital settings and provide continuous care and support to patients, potentially reducing the burden on healthcare systems and improving overall population health outcomes.

NTPDase1-ATP-P2Y2Rs axis in the sciatic nerve contributes to acupuncture at "Zusanli" (ST36)-induced analgesia in ankle arthritis rats.

BACKGROUND: The efficacy of acupuncture at Zusanli (ST36) in alleviating lower-limb pain is widely acknowledged in clinical practice, while its underlying mechanism remains incompletely elucidated. Our previous research had revealed that the prompt analgesia induced by needling-ST36 was accompanied by expression alterations in certain exco-nucleotidases within the sciatic nerve. Building upon this finding, the current work focused on NTPDase1, the primary ecto-nucleotidase in the human body, which converts ATP into AMP. METHODS: A 20-min acupuncture was administered unilaterally at the ST36 on rats with acute ankle arthritis. The pain thresholds of the injured hind paws were determined. Pharmacological interference was carried out by introducing the corresponding reagents to the sciatic nerve. ATP levels around the excised nerve were measured using a luciferase-luciferin assay. Live calcium imaging, utilizing the Fura 2-related-F340/F380 ratio, was conducted on Schwann cells in excised nerves and cultured rat SCs line, RSC96 cells. RESULTS: The analgesic effect induced by needling-ST36 was impaired when preventing ATP degradation via inhibiting NTPDase1 activities with ARL67156 or Ticlopidine. Conversely, increasing NTPDase1 activities with Apyrase duplicated the acupuncture effect. Similarly, preventing the conversion of AMP to adenosine via suppression of NT5E with AMP-CP hindered the acupuncture effect. Unexpectedly, impeded ATP hydrolysis ability and diminished NTPDase1 expression were observed in the treated group. Agonism at P2Y2Rs with ATP, UTP, or INS365 resulted in anti-nociception. Contrarily, antagonism at P2Y2Rs with Suramin or AR-C 118925xx prevented acupuncture analgesia. Immunofluorescent labeling demonstrated that the treated rats expressed more P2Y2Rs that were predominant in Schwann cells. Suppression of Schwann cells by inhibiting ErbB receptors also prevented acupuncture analgesia. Finally, living imaging on the excised nerves or RSC96 cells showed that agonism at P2Y2Rs indeed led to [Ca2+]i rise. CONCLUSION: These findings strongly suggest that the analgesic mechanism of needling-ST36 on the hypersensation in the lower limb partially relies on NTPDase1 activities in the sciatic nerve. In addition to facilitating adenosine signaling in conjunction with NT5E, most importantly, NTPDase1 may provide an appropriate low-level ATP milieu for the activation of P2Y2R in the sciatic nerve, particularly in Schwann cells.

Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity.

OBJECTIVE: To evaluate if berberine can act on vitamin D receptors (VDR) and thereby regulate the expression of tight junction proteins (TJPs) in irritable bowel syndrame-diarrhea-predominant (IBS-D) rats. METHODS: The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation. After modeling, the model was evaluated and rats were divided into the control group and berberine treatment groups (0.85, 1.7 and 3.4 mg/kg, once a day for 2 weeks). The distal colon was obtained and colonic epithelial cells (CECs) were isolated and cultured after IBS-D model evaluation. The vitamin D receptor response element (VDRE) reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter. VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair, and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs. RESULTS: The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner (P<0.05). The activity of VDRE promoter was also effectively promoted by berberine (P<0.05). Berberine increased the expression of TJPs in IBS-D CECs (P<0.05). VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups (all P<0.05). RT-qPCR and Western blot results showed that compared with the blank group, expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups (all P<0.05). Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1 (P<0.05). CONCLUSION: Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity, and the main site of action is the N-terminal region of VDR.

Pectin alleviates the pulmonary inflammatory response induced by PM2.5 from a pig house by modulating intestinal microbiota.

This study aimed to investigate whether dietary fiber pectin can alleviate PM2.5-induced pulmonary inflammation and the potential mechanism. PM2.5 samples were collected from a nursery pig house. The mice were divided into three groups: the control group, PM2.5 group and PM2.5 + pectin group. The mice in the PM2.5 group were intratracheally instilled with PM2.5 suspension twice a week for four consecutive weeks, and those in the PM2.5 + pectin group were subject to the same PM2.5 exposure, but fed with a basal diet supplemented with 5% pectin. The results showed that body weight and feed intake were not different among the treatments (p > 0.05). However, supplementation with pectin relieved PM2.5-induced pulmonary inflammation, presenting as slightly restored lung morphology, decreased mRNA expression levels of IL-1ß, IL-6 and IL-17 in the lung, decreased MPO content in bronchoalveolar lavage fluid (BLAF), and even decreased protein levels of IL-1ß and IL-6 in the serum (p < 0.05). Dietary pectin altered the composition of the intestinal microbiota, increasing the relative abundance of Bacteroidetes and decreasing the ratio of Firmicutes/Bacteroidetes. At the genus level, short-chain fatty acid (SCFA)-producing bacteria, such as Bacteroides, Anaerotruncus, Prevotella 2, Parabacteroides, Ruminococcus 2 and Butyricimonas, were enriched in the PM2.5 +pectin group. Accordingly, dietary pectin increased the concentrations of SCFAs, including acetate, propionate, butyrate and valerate, in mice. In conclusion, dietary fermentable fiber pectin can relieve PM2.5-induced pulmonary inflammation via alteration of intestinal microbiota composition and SCFA production. This study provides a new insight into reducing the health risk associated with PM2.5 exposure.

Progression of Vascular Calcification and Clinical Outcomes in Patients Receiving Maintenance Dialysis.

Importance: Baseline findings from the China Dialysis Calcification Study (CDCS) revealed a high prevalence of vascular calcification (VC) among patients with end-stage kidney disease; however, data on VC progression were limited. Objectives: To understand the progression of VC at different anatomical sites, identify risk factors for VC progression, and assess the association of VC progression with the risk of cardiovascular events and death among patients receiving maintenance dialysis. Design, Setting, and Participants: This cohort study was a 4-year follow-up assessment of participants in the CDCS, a nationwide multicenter prospective cohort study involving patients aged 18 to 74 years who were undergoing hemodialysis or peritoneal dialysis. Participants were recruited from 24 centers across China between May 1, 2014, and April 30, 2015, and followed up for 4 years. A total of 1489 patients receiving maintenance dialysis were included in the current analysis. Data were analyzed from September 1 to December 31, 2021. Exposures: Patient demographic characteristics and medical history; high-sensitivity C-reactive protein laboratory values; serum calcium, phosphorus, and intact parathyroid hormone (iPTH) values; and previous or concomitant use of medications. Main Outcomes and Measures: The primary outcome was progression of VC at 3 different anatomical sites (coronary artery, abdominal aorta, and cardiac valves) and identification of risk factors for VC progression. Participants received assessments of coronary artery calcification (CAC), abdominal aortic calcification (AAC), and cardiac valve calcification (CVC) at baseline, 24 months, 36 months, and 48 months. Secondary outcomes included (1) the association between VC progression and the risk of all-cause death, cardiovascular (CV)-related death, and a composite of all-cause death and nonfatal CV events and (2) the association between achievement of serum calcium, phosphorus, and iPTH target levels and the risk of VC progression. Results: Among 1489 patients, the median (IQR) age was 51.0 (41.0-60.0) years; 59.5% of patients were male. By the end of 4-year follow-up, progression of total VC was observed in 86.5% of patients; 69.6% of patients had CAC progression, 72.4% had AAC progression, and 33.4% had CVC progression. Common risk factors for VC progression at the 3 different anatomical sites were older age and higher fibroblast growth factor 23 levels. Progression of CAC was associated with a higher risk of all-cause death (model 1 [adjusted for age, sex, and body mass index]: hazard ratio [HR], 1.97 [95% CI, 1.16-3.33]; model 2 [adjusted for all factors in model 1 plus smoking status, history of diabetes, and mean arterial pressure]: HR, 1.89 [95% CI, 1.11-3.21]; model 3 [adjusted for all factors in model 2 plus calcium, phosphorus, intact parathyroid hormone, and fibroblast growth factor 23 levels and calcium-based phosphate binder use]: HR, 1.92 [95% CI, 1.11-3.31]) and the composite of all-cause death and nonfatal CV events (model 1: HR, 1.98 [95% CI, 1.19-3.31]; model 2: HR, 1.91 [95% CI, 1.14-3.21]; model 3: HR, 1.95 [95% CI, 1.14-3.33]) after adjusting for all confounding factors except the presence of baseline calcification. Among the 3 targets of calcium, phosphorus, and iPTH, patients who achieved no target levels (model 1: odds ratio [OR], 4.75 [95% CI, 2.65-8.52]; model 2: OR, 4.81 [95% CI, 2.67-8.66]; model 3 [for this analysis, adjusted for all factors in model 2 plus fibroblast growth factor 23 level and calcium-based phosphate binder use]: OR, 2.76 [95% CI, 1.48-5.16]), 1 target level (model 1: OR, 3.71 [95% CI, 2.35-5.88]; model 2: OR, 3.62 [95% CI, 2.26-5.78]; model 3: OR, 2.19 [95% CI, 1.33-3.61]), or 2 target levels (model 1: OR, 2.73 [95% CI, 1.74-4.26]; model 2: OR, 2.69 [95% CI, 1.71-4.25]; model 3: OR, 1.72 [95% CI, 1.06-2.79]) had higher odds of CAC progression compared with patients who achieved all 3 target levels. Conclusions and Relevance: In this study, VC progressed rapidly in patients undergoing dialysis, with different VC types associated with different rates of prevalence and progression. Consistent achievement of serum calcium, phosphorus, and iPTH target levels was associated with a lower risk of CAC progression. These results may be useful for increasing patient awareness and developing appropriate strategies to improve the management of chronic kidney disease-mineral and bone disorder among patients undergoing dialysis.

The real-time detection of acupuncture-induced extracellular ATP mobilization in acupoints and exploration of its role in acupuncture analgesia.

Our and in vitro studies had confirmed that mechanosensitive ATP release and accumulation in acupoints was elicited by acupuncture (AP), which might be a pivotal step for triggering AP analgesia. But to date, the dynamics of extracellular ATP (eATP) in the interstitial space during AP process was poorly known, mainly due to the low temporal resolution of the current detection approach. This study attempted to capture rapid eATP signals in vivo in the process of needling, and further explored the role of this eATP mobilization in initiating AP analgesic effect. Ipsilateral 20-min needling was applied on Zusanli acupoint (ST36) of complete Freund's adjuvant (CFA)-induced ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in the interstitial space was microdialyzed and real-time quantified by luciferin-luciferase assay at 1-min interval with the aid of the microfluid chip. We revealed in behavioral tests that modulation of eATP levels in ST36 influenced AP analgesic effect on ankle arthritis. A transient eATP accumulation was induced by needling that started to mobilize at 4 min, climbed to the peak of 11.21 nM within 3.25 min and gradually recovered. Such AP-induced eATP mobilization was significantly impacted by ankle inflammation, needling depth, needle manipulation, and the presence of local ecto-nucleotidases. This work reveals that needling elicits a transient eATP mobilization in acupoints, which contributes to initiating AP analgesia. This study will help us better understand the peripheral mechanism of AP analgesia and guide clinicians to optimize the needle manipulations to improve AP efficacy.

Identification of the upstream regulators of KDM5B in gastric cancer.

AIMS: Lysine-specific demethylase 5B (KDM5B) is an epigenetic regulator of chromatin that catalyzes the demethylation of histone 3 lysine 4. It is overexpressed in multiple cancer types and acts as a therapeutic target in cancer therapy. Nevertheless, its upstream regulatory pathway is not completely understood, prompting the search for the underlying biological factors driving KDM5B overexpression. MATERIALS AND METHODS: A comprehensive analysis was performed to examine the association between KDM5B overexpression and copy number variation (CNV), somatic mutation, mRNA expression, miRNA expression, and clinical characters from The Cancer Genome Atlas database. Coexpression and function enrichment analyses were performed with KDM5B-coexpressed genes. The gastric cancer (GC) cell line MKN45 was utilized to verify the regulation of KDM5B using the transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p. KEY FINDINGS: KDM5B was overexpressed and associated with poor prognosis in GC. KDM5B upregulation was driven by CNV amplification and DNA hypomethylation rather than by KDM5B mutations. Enrichment analysis revealed that KDM5B-coexpressed genes were primarily related to the transmembrane transport function and the ubiquitin-mediated proteolysis signaling pathway. As a TF, YY1 might bind to the KDM5B promoter region to regulate KDM5B expression. In addition, miR-29a-3p might bind to and negatively regulate KDM5B expression. SIGNIFICANCE: Our results demonstrate that KDM5B expression is regulated via CNV amplification, DNA hypomethylation, and YY1 and miR-29a-3p; KDM5B expression regulation is associated with patient survival and tumor cell proliferation.

Multiomic Analysis Reveals Core Regulatory Mechanisms underlying Steroidal Glycoalkaloid Metabolism in Potato Tubers.

Steroidal glycoalkaloids (SGAs) present in germinated potato tubers are toxic; however, the mechanisms underlying SGA metabolism are poorly understood. Therefore, integrated transcriptome, metabolome, and hormone analyses were performed in this study to identify and characterize the key regulatory genes, metabolites, and phytohormones related to glycoalkaloid regulation. Based on transcriptome sequencing of bud eyes of germinated and dormant potato tubers, a total of 6260 differentially expressed genes were identified, which were mainly responsible for phytohormone signal transduction, carbohydrate metabolism, and secondary metabolite biosynthesis. Two TCP14 genes were identified as the core transcription factors that potentially regulate SGA synthesis. Metabolite analysis indicated that 149 significantly different metabolites were detected, and they were enriched in metabolic and biosynthetic pathways of secondary metabolites. In these pathways, the α-solanine content was increased and the expression of genes related to glycoalkaloid biosynthesis was upregulated. Levels of gibberellin and jasmonic acid were increased, whereas that of abscisic acid was decreased. This study lays a foundation for investigating the biosynthesis and regulation of SGAs and provides the reference for the production and consumption of potato tubers.

Mechanosensitive TRPV4 Channel-Induced Extracellular ATP Accumulation at the Acupoint Mediates Acupuncture Analgesia of Ankle Arthritis in Rats.

(1) Background: Acupuncture (AP) is a safe and effective analgesic therapy. Understanding how fine needles trigger biological signals can help us optimize needling manipulation to improve its efficiency. Adenosine accumulation in treated acupoints is a vital related event. Here, we hypothesized that extracellular ATP (eATP) mobilization preceded adenosine accumulation, which involved local activation of mechanosensitive channels, especially TRPV4 protein. (2) Methods: AP was applied at the injured-side Zusanli acupoint (ST36) of acute ankle arthritis rats. Pain thresholds were assessed in injured-side hindpaws. eATP in microdialysate from the acupoints was determined by luminescence assay. (3) Results: AP analgesic effect was significantly suppressed by pre-injection of GdCl3 or ruthenium red in ST36, the wide-spectrum inhibitors of mechanosensitive channels, or by HC067047, a specific antagonist of TRPV4 channels. Microdialysate determination revealed a needling-induced transient eATP accumulation that was significantly decreased by pre-injection of HC067047. Additionally, preventing eATP hydrolysis by pre-injection of ARL67156, a non-specific inhibitor of ecto-ATPases, led to the increase in eATP levels and the abolishment of AP analgesic effect. (4) Conclusions: These observations indicate that needling-induced transient accumulation of eATP, due to the activation of mechanosensitive TRPV4 channels and the activities of ecto-ATPases, is involved in the trigger mechanism of AP analgesia.

Acupuncture modulates extracellular ATP levels in peripheral sensory nervous system during analgesia of ankle arthritis in rats.

As an ancient analgesia therapy, acupuncture has been practiced worldwide nowadays. A good understanding of its mechanisms will offer a promise for its rational and wider application. As the first station of pain sensation, peripheral sensory ganglia express pain-related P2X receptors that are involved in the acupuncture analgesia mechanisms transduction pathway. While the role of their endogenous ligand, extracellular ATP (eATP), remains less studied. This work attempted to clarify whether acupuncture modulated eATP levels in the peripheral sensory nerve system during its analgesia process. Male Sprague-Dawley rats underwent acute inflammatory pain by injecting Complete Freund's Adjuvant in the unilateral ankle joint for 2 days. A twenty-minute acupuncture was applied to ipsilateral Zusanli acupoint. Thermal hyperalgesia and tactile allodynia were assessed on bilateral hind paws to evaluate the analgesic effect. eATP of bilateral isolated lumbar 4-5 dorsal root ganglia (DRGs) and sciatic nerves were determined by luminescence assay. Nucleotidases NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were measured by real-time PCR to explore eATP hydrolysis process. Our results revealed that acute inflammation induced bilateral thermal hyperalgesia and ipsilateral tactile allodynia, which were accompanied by increased eATP levels and higher mechano-sensitivity of bilateral DRGs and decreased eATP levels of bilateral sciatic nerves. Acupuncture exerted anti-nociception on bilateral hind paws, reversed the increased eATP and mechanosensitivity of bilateral DRGs, and restored the decreased eATP of bilateral sciatic nerves. NTPDase-2 and -3 in bilateral ganglia and sciatic nerves were inconsistently modulated during this period. These observations indicate that eATP metabolism of peripheral sensory nerve system was simultaneously regulated during acupuncture analgesia, which might open a new frontier for acupuncture research.

Phenolic Compounds, Antioxidant Activities, and Inhibitory Effects on Digestive Enzymes of Different Cultivars of Okra (Abelmoschus esculentus).

In this study, the phenolic profiles and bioactivities of five representative cultivars of okra collected in China were investigated. Noticeable variations of phenolic compounds and their bioactivities were observed among these different cultivars of okra. The contents of total flavonoids (TFC) in "Shuiguo", "Kalong 8", "Kalong 3", "Wufu", and "Royal red" ranged from 1.75 to 3.39 mg RE/g DW, of which "Shuiguo" showed the highest TFC. Moreover, five individual phenolic compounds were found in okra by high performance liquid chromatography analysis, including isoquercitrin, protocatechuic acid, quercetin-3-O-gentiobioside, quercetin, and rutin, while isoquercitrin and quercetin-3-O-gentiobioside were detected as the main phenolic compounds in okra. Moreover, all tested okra exhibited significant antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, 2,2'-azino-bis (3-ethylenzthiazoline-6-sulphonic acid) radical scavenging capacity, and ferric reducing antioxidant power) and inhibitory effects on digestive enzymes (lipase, α-glucosidase, and α-amylase). Indeed, "Shuiguo" exhibited much better antioxidant activities and inhibitory activities on digestive enzymes, which might be attributed to its high TFC. Results suggested that okra, especially "Shuiguo", could be developed as natural antioxidants and inhibitors against hyperlipidemia and hyperglycemia in the fields of functional foods and pharmaceuticals, which could meet the increasing demand for high-quality okra with health-promoting properties in China.

Natural protoberberine alkaloids, identified as potent selective LSD1 inhibitors, induce AML cell differentiation.

Natural protoberberine alkaloids were first identified and characterized as potent, selective and cellular active lysine specific demethylase 1 (LSD1) inhibitors. Due to our study, isoquinoline-based tetracyclic scaffold was identified as the key structural element for their anti-LSD1 activity, subtle changes of substituents attached to the core structure led to dramatic changes of the activity. Among these protoberberine alkaloids, epiberberine potently inhibited LSD1 (IC50 = 0.14 ± 0.01 µM) and was highly selective to LSD1 over MAO-A/B. Furthermore, epiberberine could induce the expression of CD86, CD11b and CD14 in THP-1 and HL-60 cells, confirming its cellular activity of inducing acute myeloid leukemia (AML) cells differentiation. Moreover, epiberberine prolonged the survival of THP-1 cells bearing mice and inhibited the growth of AML cells in vivo without obvious global toxicity. These findings give the potential application of epiberberine in AML treatment, and the isoquinoline-based tetracyclic scaffold could be used for further development of LSD1 inhibitors.

Liuweibuqi capsules improve pulmonary function in stable chronic obstructive pulmonary disease with lung-qi deficiency syndrome by regulating STAT4/STAT6 and MMP-9/TIMP-1.

Context: Liuweibuqi (LWBQ) capsule has been reported to influence symptoms of patients with chronic obstructive pulmonary disease (COPD); however, specific function of LWBQ capsules in COPD with lung-qi deficiency syndrome remains elusive.Objective: This study investigates effect of LWBQ capsules on STAT4/STAT6 and MMP-9/TIMP-1 expression and pulmonary function in stable COPD with lung-qi deficiency syndrome.Materials and methods: Totally, 429 patients diagnosed with stable COPD and lung-qi deficiency syndrome were treated with starch capsules (each time for 9 capsules), or different doses: low (each dose for 8 capsules and 1 LWBQ capsules), medium (each time for 6 capsules and 3 LWBQ capsules), or high (each time for 9 LWBQ capsules) of LWBQ capsules for 30 days, 3 times a day. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% and DLco%pred were evaluated by pulmonary function meter. STAT4/STAT6 and MMP-9/TIMP-1 expression was assessed by RT-qPCR and western blot analysis, and serum concentrations of IL-4, IFN-γ and IL-6 by ELISA.Results: Spearman rank correlation analysis and ROC curve showed that STAT4/STAT6 and MMP-9/TIMP-1 affected pulmonary functions and curative effect of stable COPD with lung-qi deficiency syndrome. After LWBQ capsule treatment, FEV1, FVC, FEV1/FVC% and DLco%pred elevated; STAT4/STAT6, MMP-9/TIMP-1, IFN-γ and IL-6 expression declined whereas IL-4 expression increased (p < 0.05). Logistic regression analysis demonstrated that FEV1/FVC was negatively correlated with STAT4/STAT6 and MMP-9/TIMP-1 expression in COPD patients.Conclusions: LWBQ capsules play a beneficial role in pulmonary function of stable COPD with lung-qi deficiency syndrome via STAT4/STAT6 and MMP-9/TIMP-1.

Besides Photothermal Effects, Low-Level CO2 Laser Irradiation Can Potentiate Skin Microcirculation Through Photobiomodulation Mechanisms.

Background: Improvement of microcirculation is one of the important mechanisms of low-level laser therapy (LLLT) to treat some diseases such as wound healing. Most previous studies have been carried out with multiple lasers other than the 10,600-nm CO2 laser. Recently, the CO2 laser has been used not only as a tool for excision of soft tissues but also for therapeutic applications. Objective: To study whether low-level CO2 laser irradiation can influence microcirculation and further explore the underlying mechanisms. Methods: Seventy-milliwatt (70-mW) CO2 lasers irradiated the forearms of 12 participants and skin blood perfusion (SkBP) was measured with a laser speckle imager. The thermal effect of irradiation was evaluated by measuring the irradiated skin in vivo and the exposed cell suspensions in vitro. Extracellular adenosine triphosphate (eATP) of the human mast cell line (HMC-1) is assessed by luciferin-luciferase assay to explore the potential mechanisms. Results: Irradiation caused dose-dependent increase in SkBP. At a medium dose of 262 J/cm2, SkBP reached its maximum value at 195.8% ± 18.6% of the baseline (n = 12, p < 0.01). Such laser irradiation had a mild thermal effect, heating local skin temperature (SkT) by 6.1°C ± 0.3°C (n = 10) and warming cell suspensions by 4.5°C ± 0.8°C (n = 6). Irradiation dose-dependently lowered eATP levels of HMC-1 cells in vitro. At a medium dose of 262 J/cm2, eATP levels declined to the minimum at 74.8% ± 5.5% of the baseline (n = 12, p < 0.01). This downregulation effect could be significantly inhibited by 100-µM ARL67156, a nonspecific ecto-ATPase inhibitor. On the contrary, heating itself slightly raised the level of eATP. Conclusions: Low-level CO2 laser irradiation can improve microcirculation. Besides the thermal effect, regulation of extravascular eATP by the photobiomodulation mechanism may be involved. This implies that CO2 lasers might be used in LLLT.

Age-induced oxidative stress impairs adipogenesis and thermogenesis in brown fat.

It is well-established that the mass and function of human brown adipose tissue (BAT) declines with age. A key factor involved in age-related impairment of BAT is oxidative stress; however, there is a paucity of studies to date that have explored this relationship. Here, we characterized the age-related molecular and functional alterations in BAT in vivo in mice of different ages, and treated human brown adipocytes with H2 O2 to dissect the direct effect of oxidative stress in vitro. We further explored the structural and functional changes in BAT in an oxidative stress-induced mouse model of aging. We found that the progressive deterioration of BAT was linked to oxidative stress, and observed that the adipogenesis and thermogenic program were significantly impaired upon H2 O2 treatment in vitro. Moreover, antioxidant supplementation (e.g., vitamin E) attenuated oxidative stress and rescued BAT activity decline, suggesting that age-related injury in BAT function can be partly alleviated by antioxidant treatment. Finally, we found that oxidative stress-induced BAT dysfunction is linked to the enhancement of autophagy. These results point to oxidative stress as being an important factor in age-dependent functional impairment of BAT.

Analysis on Composition Rules of Chinese Patent Drugs Treating Pain-Related Diseases Based on Data Mining Method.

OBJECTIVE: To analyze the composition rules of oral prescriptions in the treatment of headache, stomachache and dysmenorrhea recorded in National Standard for Chinese Patent Drugs (NSCPD) enacted by Ministry of Public Health of China and then make comparison between them to better understand pain treatment in different regions of human body. METHODS: Constructed NSCPD database had been constructed in 2014. Prescriptions treating the three pain-related diseases were searched and screened from the database. Then data mining method such as association rules analysis and complex system entropy method integrated in the data mining software Traditional Chinese Medicine Inheritance Support System (TCMISS) were applied to process the data. RESULTS: Top 25 drugs with high frequency in the treatment of each disease were selected, and 51, 33 and 22 core combinations treating headache, stomachache and dysmenorrhea respectively were mined out as well. CONCLUSIONS: The composition rules of the oral prescriptions for treating headache, stomachache and dysmenorrhea recorded in NSCPD has been summarized. Although there were similarities between them, formula varied according to different locations of pain. It can serve as an evidence and reference for clinical treatment and new drug development.

[Lignan glycosides and sucrose esters from roots of Securidaca inappendiculata].

Nine compounds, including five lignan glycosides (1-5), three sucrose esters (6-8), and one organic acid ester (9), were isolated from the ethanol extract of the roots of Securidaca inappendiculata by various chromatographic methods including silica gel, MPLC and preparative HPLC. Their structures were elucidated as acernikol-4″-O-ß-D-glucopyranoside (1), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside (2), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 4-O-ß-D-glucopyranoside (3), (7R, 8S)-dihydrodehydrodiconiferyl alcohol 9'-O-ß-D-glucopyranoside (4), (7R, 8S)-5-methoxydihydrodehy-drodiconiferyl alcohol 4-O-ß-D-glucopyranoside (5), 3, 6'-O-diferuloylsucrose (6), 3-O-feruloyl-6'-O-sinapoylsucrose (7), sibricose A5 (8), and mehyl ferulate (9) on the basis of 1H-, 13C-NMR and MS experiments. Compounds 1-5, 8, and 9 were isolated from the Securidaca genus for the first time. Compounds 2, 3, and 7 exhibited weak cytotoxic activities against Hela and MCF-7 cell lines.

[Screening of active fractions with antithrombotic effect from Caragana jubata].

The antithrombotic effect of Caragana jubata (Pall.)Poir.ethanolic extract (TE)was evaluated by inferior vena cava thrombosis in rats and acute pulmonary thrombosis in mice. To search for the bioactive fractions of TE, comparison on acute pulmonary thrombosis was made between the two main fractions of TE (TE-1 and TE-2). Besides, pharmacological effects of TE, TE-1 and TE-2 on bleeding time and clotting time were also studied. Reference substances combined with UPLC/DAD-q-TOF-MS were applied to identify the main six compounds and other chemical constituents of the TE. The results showed that TE could significantly reduce the rat thrombosis weight in all doses (P<0.01) and improve the protective rate to mice in medium and high doses (P<0.05). TE-2 showed a stronger effect on protecting the mice from paralysis or death and prolonging the bleeding time and clotting time than TE-1. Chemical constituents in TE mainly include isoflavones, pterocarpans and stilbenoids. Constituents in TE-2 were mainly isoflavones and pterocarpans, while those in TE-1 were mainly stilbenoids, which could be inferred that all of these three kinds of constituents may be responsible for the antithrombotic effects of Caragana jubata.