Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Comparison of oxybuprocaine and lidocaine topical anesthesia for pain control in radiofrequency ablation treatment of great saphenous vein insufficiency.

Topical anesthetics have been used for radiofrequency ablation of great saphenous vein insufficiency. A total of 74 patients with great saphenous vein insufficiency treated at our center between February 2021 and August 2022 were enrolled. The patients were selected and divided into an oxybuprocaine group(n = 30) and a lidocaine group (n = 44). The visual analogue scale (VAS) was used to evaluate intraoperative and postoperative pain. Patient satisfaction with anesthesia, maintenance time of anesthesia, and disturbance of the surgeons were also recorded and assessed. The VAS scores and other indices of the 2 groups were compared to assess the effectiveness of anesthesia. Perioperative surgical complications and painkiller use were also recorded. The median VAS score of the patients during the process was 2 in both groups, and the difference between the groups was not statistically significant. In the 2 groups, 93.33% of the patients in the oxybuprocaine group and 93.18% of the patients in the lidocaine group were satisfed with the anesthesia. Nine patients in the lidocaine group and 14 in the oxybuprocaine group received additional anesthetic drugs. The average maintenance time of anesthesia was longer in the lidocaine group. No serious complications occurred in either of the groups. Both oxybuprocaine and lidocaine topical anesthesia combined with tumescent anesthesia could provide effective pain control in radiofrequency ablation treatment of great saphenous vein insufficiency. Although the average maintenance time of anesthesia was longer in the lidocaine group, there was no difference in the associated complications and pain control.

Total tanshinones protect against acute lung injury through the PLCγ2/NLRP3 inflammasome signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a widely used traditional Chinese medicine with anticholinesterase, antitumor, and anti-inflammatory. Total Tanshinones (TTN), the most significant active ingredient of Salvia miltiorrhiza Bunge, exerts anti-inflammatory activity. However, the protective mechanism of total Tanshinones on acute lung injury (ALI) still needs to be explored. AIM OF THIS STUDY: In this study, the underlying mechanisms of TTN to treat with ALI were investigated in vitro and in vivo. MATERIALS AND METHODS: Cell experiments established an in vitro model of LPS-induced J774A.1 and MH-S macrophages to verify the mechanism. The levels of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) were estimated by ELISA. The changes of ROS, Ca2+ and NO were detected by flow cytometry. The expression levels of proteins related to the NLRP3 inflammasome were determined by Western blotting. The effect of TTN on NLRP3 inflammasome activation was examined by immunofluorescence analysis of caspase-1 p20. Male BALB/c mice were selected to establish the ALI model. The experiment was randomly divided into six groups: control, LPS, LPS + si-NC, LPA + si-Nek7, LPS + TTN, and DEX. Pathological alterations were explored by H&E staining. The expression levels of proteins related to the NLRP3 inflammasome were analyzed by Western blotting. RESULTS: TTN decreased pro-inflammatory cytokines levels like TNF-α, IL-6, IL-1ß, NO, and ROS in alveolar macrophages. TTN bound to NIMA-related kinase 7 (NEK7), a new therapeutic protein to modulate NLRP3 inflammasome and PLCγ2-PIP2 signaling pathway. In ALI mice, LPS enhanced IL-1ß levels in the serum, lung tissues, and bronchoalveolar lavage fluid (BALF),which were reversed by TTN. TTN decreased cleaved-caspase-1 and NLRP3 expressions in lung tissues. When Nek7 was knocked down in mice by siRNA, the syndrome of ALI in mice was significantly suppressed, of which the effect was similar to that of TTN. CONCLUSIONS: This research demonstrates that TTN alleviated ALI by binding to NEK7 in vitro and in vivo to modulate NLRP3 inflammasome activation and PLCγ2-PIP2 signaling pathways.

Xiaoketongbi Formula vs pregabalin for painful diabetic neuropathy: A single-center, randomized, single-blind, double-dummy, and parallel controlled clinical trial.

BACKGROUND: We assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN). METHODS: Patients with PDN (n = 68) were included in a single-center, randomized, single-blind, double-dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN). Secondary outcomes evaluated included the reduction of BPI-DPN >50%, changes in the numeric rating scale-11 (NRS-11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events. RESULTS: After 10 weeks of treatment, the BPI-DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group (Ps < 0.001), respectively. The difference in the absolute change in BPI-DPN score between both groups was -1.79 (95% CI: -9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI-DPN reduction >50% (p = 0.038), respectively. There were no significant differences between groups in NRS-11 and DSID (Ps > 0.05). A significantly greater number of patients in the XF group felt "significantly improved" or "improved" than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group -2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group. CONCLUSIONS: XF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.

Extracorporeal Membrane Oxygenation-First Strategy for Acute Life-Threatening Pulmonary Embolism.

Background: Both venoarterial extracorporeal membrane oxygenation (VA-ECMO) and percutaneous mechanical thrombectomy (PMT) are increasingly used to treat acute life-threatening pulmonary embolism (PE). However, there are little data regarding their effectiveness. This study aimed to present the short-term outcomes after managing nine patients with acute life-threatening massive or submassive PE by VA-ECMO with or without complemented PMT and propose a preliminary treatment algorithm. Methods: This study was a single-center retrospective review of a prospectively maintained registry. It included nine consecutive patients with massive or submassive pulmonary embolism who underwent VA-ECMO for initial hemodynamic stabilization, with or without PMT, from August 2018 to November 2021. Results: Mean patient age was 54.7 years. Four of nine patients (44.4%) required cardiopulmonary resuscitation before or during VA-ECMO cannulation. All cannulations (100%) were successfully performed percutaneously. Overall survival was 88.9% (8 of 9 patients). One patient died from a hemorrhagic stroke. Of the survivors, the median ECMO duration was 8 days in patients treated with ECMO alone and 4 days in those treated with EMCO and PMT. Five of nine patients (55.6%) required concomitant PMT to address persistent right heart dysfunction, with the remaining survivors (44.4%) receiving VA-ECMO and anticoagulation alone. For survivors receiving VA-ECMO plus PMT, median hospital lengths of stay were 7 and 13 days, respectively. Conclusions: An ECMO-first strategy complemented with PMT can be performed effectively and safely for acute life-threatening massive or submassive PE. VA-ECMO is feasible for initial stabilization, serving as a bridge to therapy primarily in inoperable patients with massive PE. Further evaluation in a larger cohort of patients is warranted to assess whether VA-ECMO plus PMT may offer an alternative or complementary therapy to thrombolysis or surgical thrombectomy. Type of Research: Single-center retrospective review of a prospectively maintained registry.

Design and Evaluation of Multiplex One-Step Reverse Transcription PCR-Dipstick Chromatography Method for the Analysis of Seven Respiratory Pathogens.

Influenza A, influenza B, severe acute respiratory syndrome coronavirus 2, adenovirus, respiratory syncytial virus, Mycoplasma pneumoniae, and Chlamydophila pneumoniae are common pathogens that can cause severe pneumonia and other symptoms, resulting in acute lower respiratory tract infections. The objective of this study was to design and evaluate a sensitive and specific multiplex one-step reverse transcription PCR (RT-PCR)-dipstick chromatography method for simultaneous rapid detection of these seven pathogens. Streptavidin-coated blue latex particles were used to read out a positive signal. Based on the DNA-DNA hybridization of oligonucleotide sequences (Tag) for forward primer with the complementary oligonucleotide sequence (cTag) on the dipstick and biotin-streptavidin interactions, PCR products were able to be illuminated visually on the dipstick. The specificity and the limit of detection (LOD) were also evaluated. Moreover, the clinical performance of this method was compared with Sanger sequencing for 896 samples. No cross reaction with other pathogens was found, confirming the high specificity of this method. The LOD was 10 copies/µL for each of the tested pathogens, and the whole procedure took less than 40 min. Using 896 samples, the sensitivity and specificity were shown to be no lower than 94.5%. The positive predictive value was higher than 82.1%, and the negative predictive value was higher than 99.5%. The kappa value between the PCR-dipstick chromatography method and Sanger sequencing ranged from 0.869 to 0.940. In summary, our one-step RT-PCR-dipstick chromatography method is a sensitive and specific tool for rapidly detecting multiplex respiratory pathogens.

Rotundic acid reduces LPS-induced acute lung injury in vitro and in vivo through regulating TLR4 dimer.

Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF-κB pathways and enhanced the activity of nuclear factor E2-related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS-induced endotoxin death and had a protective effect on LPS-induced ALI. Our findings collectively indicated that RA has anti-inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.

A case-report of two patients with hereditary protein S deficiency treated by rivaroxaban.

: Hereditary protein S deficiency is an autosomal dominant disorder associated with a high risk of venous thromboembolism (VTE) and usually results from mutations of PROS1. Historically heparin and warfarin have been applied as recommended treatment of VTE. Recent researches showed that rivaroxaban provided more consistent and predictable anticoagulation than warfarin. However, it is unknown whether rivaroxaban is effective for the treatment of VTE in patients with thrombophilia, including protein S deficiency, due to lack of evidence. Here, we report two cases of recurrent VTE in two patients with hereditary protein S deficiency, owing to the same nonsense mutation in PROS1, which were successfully treated by rivaroxaban monotherapy.

Exploration in the mechanism of rhubarb for the treatment of hyperviscosity syndrome based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperviscosity syndrome (HVS) is a major risk factor for thrombotic diseases. Rhubarb, well-known as a traditional Chinese medicine, exhibits multiple pharmacological activities, especially for promoting blood circulation to remove blood stasis (PBRB), which has been become a functional health food for decreasing the risk of cardiovascular diseases. However, due to the complexity of rhubarb components, it is still difficult to clarify the specific targets of effective substances in PBRB, and the pharmacodynamic mechanism needs to be further probed. MATERIALS AND METHODS: The "compound-target-cell-disease" network analysis was initially used to predict potential targets and bioactive compounds. The effect of rhubarb for the treatment of HVS was examined by histopathology and biochemical assays based on the HVS rat model. RESULTS: Through the "compound-target-cell-disease" network analysis, eight potential therapeutic targets were eventually screened out, and platelets were predicted as the main effector cells of rhubarb in PBRB. Among targets coagulation factor II (prothrombin, F2) and fibrinogen gamma chain (FGG) were closely related to platelets, and five compounds associated with F2 and FGG were predicted including emodin-8-O-beta-D-glucopyranoside (Emo), physcion-8-O-beta-D-glucopyranoside (Phy), procyanidin B-5,3'-O-gallate, torachrysone-8-O-beta-D-(6'-oxayl)-glucoside and epicatechin. Furthermore, thoracic aorta histopathology and biochemical examinations showed middle dose of rhubarb (0.42 g/kg/day) significantly ameliorated pathological changes, hemorheology parameters, as well as levels of representative biomarkers such as plasma P-selectin (P-sel) and thromboxane (TXB2) in platelet activation compared to HVS rat model, whose effects were comparable to the positive drug aspirin or even better. Finally, it was further validated F2 and FGG as the major effective targets of rhubarb as well as its two active ingredients Emo and Phy in PBRB. CONCLUSIONS: This study may provide an innovative way and scientific information to further understand the main effective components of rhubarb and its mechanisms about targets of F2 and FGG in PBRB, especially the new therapeutic target FGG, which also provide a basis for establishing a quality control for rhubarb by bioassays that could correlate the clinical efficacy and its mechanism.

Intra-Rater and Inter-Rater Reliability of Tongue Coating Diagnosis in Traditional Chinese Medicine Using Smartphones: Quasi-Delphi Study.

BACKGROUND: There is a growing trend in the use of mobile health (mHealth) technologies in traditional Chinese medicine (TCM) and telemedicine, especially during the coronavirus disease (COVID-19) outbreak. Tongue diagnosis is an important component of TCM, but also plays a role in Western medicine, for example in dermatology. However, the procedure of obtaining tongue images has not been standardized and the reliability of tongue diagnosis by smartphone tongue images has yet to be evaluated. OBJECTIVE: The first objective of this study was to develop an operating classification scheme for tongue coating diagnosis. The second and main objective of this study was to determine the intra-rater and inter-rater reliability of tongue coating diagnosis using the operating classification scheme. METHODS: An operating classification scheme for tongue coating was developed using a stepwise approach and a quasi-Delphi method. First, tongue images (n=2023) were analyzed by 2 groups of assessors to develop the operating classification scheme for tongue coating diagnosis. Based on clinicians' (n=17) own interpretations as well as their use of the operating classification scheme, the results of tongue diagnosis on a representative tongue image set (n=24) were compared. After gathering consensus for the operating classification scheme, the clinicians were instructed to use the scheme to assess tongue features of their patients under direct visual inspection. At the same time, the clinicians took tongue images of the patients with smartphones and assessed tongue features observed in the smartphone image using the same classification scheme. The intra-rater agreements of these two assessments were calculated to determine which features of tongue coating were better retained by the image. Using the finalized operating classification scheme, clinicians in the study group assessed representative tongue images (n=24) that they had taken, and the intra-rater and inter-rater reliability of their assessments was evaluated. RESULTS: Intra-rater agreement between direct subject inspection and tongue image inspection was good to very good (Cohen κ range 0.69-1.0). Additionally, when comparing the assessment of tongue images on different days, intra-rater reliability was good to very good (κ range 0.7-1.0), except for the color of the tongue body (κ=0.22) and slippery tongue fur (κ=0.1). Inter-rater reliability was moderate for tongue coating (Gwet AC2 range 0.49-0.55), and fair for color and other features of the tongue body (Gwet AC2=0.34). CONCLUSIONS: Taken together, our study has shown that tongue images collected via smartphone contain some reliable features, including tongue coating, that can be used in mHealth analysis. Our findings thus support the use of smartphones in telemedicine for detecting changes in tongue coating.

Involvement of macrophage-derived exosomes in abdominal aortic aneurysms development.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is characterized by infiltration of inflammatory cells, extracellular matrix (ECM) degradation, and dysfunction of vascular smooth muscle cells (VSMCs). Recent studies reported that exosomes mediate intercellular communication and are involved in different diseases. Whether exosomes play a role in AAA is poorly understood. Hence, this study evaluated the function of exosomes in AAA development. METHODS: The presence of exosomes in human and calcium phosphate (CaPO4)-induced AAA tissues was determined by immunofluorescence staining of CD63 and Alix. GW4869, an inhibitor of exosome biogenesis, was intraperitoneally injected into CaPO4-induced AAA tissues to evaluate the effects of exosomal inhibition on AAA development. To explore the underlying mechanisms, the human monocytic cell line THP-1 was differentiated into macrophages, and exosomes were collected from macrophages. VSMCs were treated with macrophage-derived exosomes, and the expression of matrix metalloproteinase-2 (MMP-2) was evaluated. The activation of mitogen-activated protein kinases (MAPKs) pathways was also investigated in vitro and in vivo. RESULTS: Exosomes were detected in the adventitia of aneurysmal tissues obtained from humans and mice. They were mainly expressed in clusters of macrophages. Intraperitoneal injection of GW4869 for two weeks significantly attenuated the progression of CaPO4-induced AAA, preserved elastin integrity and decreased MMP-2 expression. Similarly, administration of GW4869 suppressed the systemic and aneurysmal exosome generation. In vitro, treatment with macrophage-derived exosomes elevated MMP-2 expression in human VSMCs, while pre-treatment with GW4869 abolished these effects. It was also found that JNK and p38 pathways mediated the production of MMP-2 in VSMCs following treatment with macrophage-derived exosomes. CONCLUSIONS: This study suggests that exosomes derived from macrophages are involved in the pathogenesis of AAA. Macrophage-derived exosomes trigger MMP-2 expression in VSMC via JNK and p38 pathways. GW4869 supplementation attenuates CaPO4-induced AAA in mice.

Hyaluronic acid-functionalized bilosomes for targeted delivery of tripterine to inflamed area with enhancive therapy on arthritis.

Arthritis treatment has been challenging because of low drug exposure to the articular cavity. This study was intended to develop hyaluronic acid (HA)-functionalized bilosomes for targeted delivery of tripterine (Tri), an antiphlogistic phytomedicine, to the inflamed joint via ligand-receptor interaction. Tri-loaded bilosomes (Tri-BLs) with cationic lipid (DOTAP) were prepared by a thin film hydration method followed by HA coating to form HA@Tri-BLs. HA@Tri-BLs were then characterized by particle size (PS), entrapment efficiency (EE), and structural morphology. The in vitro drug release, hemocompatibility test and cellular uptake were performed to examine the formulation performances of HA@Tri-BLs. The in vivo pharmacokinetics and antiarthritic efficacy were evaluated in arthritic models, respectively. The obtained HA@Tri-BLs possessed a PS of 118.5 nm around with an EE of 99.56%. HA@Tri-BLs exhibited excellent cellular uptake and targeted delivery efficiency for Tri, which resulted in elongation of circulatory residence time and enhancement of intra-arthritic bioavailability (799.9% relative to Tri solution). The in vivo antiarthritic efficacy of HA@Tri-BLs was also significantly superior to uncoated Tri-BLs that gave rise to obvious inflammation resolution. Our findings suggest that HA-functionalized bilosomes are a promising vehicle for articular delivery of antiphlogistic drugs to potentiate their efficacy.

Atypical Nitrogen-Containing Flavonoid in the Fruits of Cumin (Cuminum cyminum L.) with Anti-inflammatory Activity.

The dried seeds of Cuminum cyminum L. have been traditionally used as food and medicine. To explore its chemical composition and anti-inflammatory activity, four new compounds (1-4) along with five known compounds (5-9) were isolated from the seeds in the present study. The chemical structures of the new compounds were identified as follows: methyl 3-((7H-purin-2-yl) amino)-3-(4-isopropylphenyl) propanoate (1), 8-(amino(4-isopropylphenyl)methyl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4-oxo-4H-chromene-6-carboxylic acid (2), (3,4,5-trihydroxy-6-((4-isopropylbenzyl)oxy)tetrahydro-2H-pyran-2-yl)methyl (E)-3-(4-propoxyphenyl)acrylate (3), and (3,4,5-trihydroxy-6-((5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)tetrahydro-2H-pyran-2-yl)methyl 3-(4-isopropylphenyl)-2-methoxypropanoate (4). Compound 2, an atypical nitrogen-containing flavonoid, exhibited the most active inhibitory effect on nitride oxide, with IC50 of 5.25 µM in the lipopolysaccharide-stimulated RAW264.7 cell assay. Compound 2 was found to suppress the expression levels of inducible nitric oxide synthase and cyclooxygenase-2. Furthermore, it was revealed that both nuclear factor κB and mitogen-activated protein kinase were involved in the anti-inflammatory process of compound 2.

Network pharmacology oriented study reveals inflammatory state-dependent dietary supplement hepatotoxicity responses in normal and diseased rats.

Rhubarb, a well-used herbal and dietary supplement, has been widely used as a laxative in many countries. The dietary supplement rhubarb may reveal differential hepatotoxicity responses in normal and diseased subjects; however, its underlying mechanism is unclear. By using a network pharmacology approach, we found that the components contained in rhubarb had associations with a liver disease-related protein network that could be enriched into two subnetworks: a pro-inflammatory protein network associated with liver inflammation and an anti-inflammatory protein network related to liver fibrosis. In addition, macrophages were found to have an association with these subnetworks. Herein, the differential toxicity responses of rhubarb in normal and diseased rats were illustrated by in vivo pharmacology experiments. Rhubarb induced liver injury in normal rats with dose-dependent increases in the pro-inflammatory response; in contrast, it failed to induce hepatotoxic effects in a liver fibrosis rat model and was accompanied by an increase in anti-inflammatory protein expression. Further study showed elevation of high mobility group box-1 (HMGB1) in the sera and liver tissues and remarkable pro-inflammatory activation of Kupffer cells in liver tissue; these phenomena were associated with the hepatotoxic effect of rhubarb and could be blocked by inhibiting either HMGB1 or Kupffer cells through glycyrrhizin or GdCl3, respectively. Interestingly, we also observed attenuated pro-inflammatory activation of Kupffer cells in a liver fibrosis rat model together with a non-hepatotoxic response to rhubarb. These results suggest that the divergent immune states in normal and diseased subjects may contribute to the differential toxicity responses to rhubarb.

Changes in erythrocyte polyunsaturated fatty acids and plasma eicosanoids level in patients with asthma.

BACKGROUND: To investigate the changes of polyunsaturated fatty acids (PUFAs) and their downstream eicosanoids in patients with asthma, the levels of erythrocyte membrane lipids and plasma lipid metabolites were examined. METHODS: Erythrocyte membrane lipids were extracted and esterificated, and then fatty acid compositions were determined by gas chromatography. The concentrations of six eicosanoids of PGE2, TXA2, LTB4, PGE1, 6-k-PGF1α and PGF2α in plasma were measured by ELISA. RESULTS: The results showed that the contents of erythrocyte membrane fatty acids in patients with asthma were mainly composed of C16:0, C18:0, C18:1, C18:2(n-6), and C20:4(n-6). The ratio n-6/n-3 PUFAs in patients and health persons were (4.42 ± 1.33):1 and (3.21 ± 0.79):1 (p < 0.01), showing statistically significant differences. ELISA results showed that the levels of plasma PGE2, TXB2, and PGE1 in patients were higher than health persons; and the levels of eicosanoids of PGF2α and 6-k-PGF1α were significantly lower in patient group than healthy group (p < 0.05), but LTB4 was no obvious difference (p = 0.09). Increased ratio of n-6/n-3 PUFAs is consistent to the increased levels of pro-inflammatory PGE2 and TXB2 and anti-inflammatory PGE1 originated from C20:4(n-6) and C18:2(n-6), indicating that increased ratio of n-6/n-3 PUFAs and eicosanoids from n-6 PUFAs might promote the progress of airway inflammation of asthma. CONCLUSION: Changes of erythrocyte fatty acids, n-6/n-3 PUFAs ratio and the levels of plasma PGE2, TXB2, and PGE1 in patients with asthma were relevant to airway inflammation in some extent. Therefore, it could be proposed that increase of n-3/n-6 PUFAs ratio by diet supplementation of n-3 PUFAs might effectively improve airway inflammation in asthma.

Herbal medicine foot bath for the treatment of diabetic peripheral neuropathy: protocol for a randomized, double-blind and controlled trial.

BACKGROUND: As a common complication of diabetes, the incidence of diabetic peripheral neuropathy (DPN) is 60-70% worldwide. DPN is a major risk factor for diabetic foot, which may lead to foot ulceration and even amputation. The treatment of DPN remains challenging. Our preliminary study demonstrated that the external application of Tangbi Waixi (TW) decoction to the lower extremities relieved clinical symptoms and improved nerve conduction velocity in DPN patients. The aim of this study was to verify the efficacy of TW among DPN patients and evaluate the herb mixture's safety using rigorous methodological designs. METHODS/DESIGN: This study is a multicenter, double-blind, randomized controlled trial. A total of 640 DPN patients will be recruited and randomized to receive a foot bath with either the TW decoction or control drug. Participants will be assessed at baseline and 12 and 24 weeks after treatment. The primary outcome was the change of the Toronto Clinical Scoring System (TCSS). Secondary outcomes were nerve conduction velocity, blood glucose, blood lipids, serum inflammatory cytokines, and the European Quality of Life Five-Dimension Scale (EQ-5D) and TCM symptom scores. DISCUSSION: This multicenter, prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of foot bath treatment with TW decoction. Positive results would provide a novel treatment regimen for DPN patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-16009331 . Registered on 8 October 2016.

[Antiplatelet aggregation bioactivity of Polygoni Multiflori Radix with chemical fingerprints and spectrum-effect correlation analysis].

To explore the active substance of antiplatelet aggregation of Polygoni Multiflori Radix by using chemical fingerprints and antiplatelet aggregation bioactivity test for spectrum-effect correlation analysis. The Polygoni Multiflori Radix was tested by antiplatelet aggregation in vitro, and the results showed that 50% aqueous ethanol extract of Polygoni Multiflori Radix had more potent antiplatelet aggregation effect than 10% or 90% aqueous ethanol extract, and ultrasonic extraction was superior to refluxing extraction in the aspect of antiplatelet aggregation. The antiplatelet aggregation bioactivity of the different Polygoni Multiflori Radix extracts was evaluated and the results showed that the inhibition rate was 32.03%-74.56%. Spectrum-effect correlation analysis indicated that trans-stilbene glucoside, cis-stilbene glucoside and catechinic acid had higher correlation coefficient and they were 0.963 (P<0.01), 0.902 (P<0.01) and 0.656 (P<0.05) respectively; furthermore, all of the above three compounds demonstrated significant antiplatelet aggregation bioactivities. Considering their content difference in Polygoni Multiflori Radix, we calculated the relative active contributions, and the results suggested that trans-stilbene glucoside was the main active substance of Polygoni Multiflori Radix in the aspect of antiplatelet aggregation in vitro.

[Activating blood biological potency assay and chemical fingerprint chromatogram applied to quality evaluation of rhubarb].

The biological potency assay and chemical fingerprint chromatogram were applied to quality evaluation of rhubarb. Using the biological potency as indicators, we evaluated the differences in quality of multiple batches of rhubarbs and related products. Using the platelet aggregation analyzer, we determined platelet aggregation rate in the different rhubarbs preparations, and calculated the biological potency based on the simplified probit principle. UPLC was adopted to establish the fingerprint spectra for rhubarbs. The spectral efficiency correlation analysis between chromatograms and biological potencies were conducted using the double variables of SPSS 22.0 software. We used three chemical composition to verify the potency. The biological potency results suggest that Rheum palmatum has a more potent activity than Rheum tanguticum, and wine-treated rhubarb had a higher potentcy than charred. We identified 10 elements in the Fingerprint Spectrum. The relevant elements including rhein-8-O-ß-D-glucoside, emodin-8-O-ß-D-glucoside and rhein have the strongest activity in the inhibition of platelet aggregation. In conclusion, this study provides a analytical method for rhubarb biological potency based on determination of the maximum antagonism rate model. The rhein may be the effective substance. It may serve as a reference in the quality control of wine processed rhubarb products.

Spectrum-Effect Relationships Between Chemical Fingerprints and Antibacterial Effects of Lonicerae Japonicae Flos and Lonicerae Flos Base on UPLC and Microcalorimetry.

The traditional Chinese medicines Lonicerae Japonicae Flos (LJF, Jinyinhua in Chinese) and Lonicerae Flos (LF, Shanyinhua in Chinese) refer to the flower buds of five plants belonging to the Caprifoliaceae family. Until 2000, all of these were officially listed as a single item, LJF (Jinyinhua), in the Chinese Pharmacopoeia. However, there have recently been many academic controversies concerning the separation and combination of LJF and LF in administrative regulation. Till now there has been little work completed evaluating the relationships between biological activity and chemical properties among these drugs. Microcalorimetry and UPLC were used along with principal component analysis (PCA), hierarchical cluster analysis (HCA), and canonical correlation analysis (CCA) to investigate the relationships between the chemical ingredients and the antibacterial effects of LJF and LF. Using multivariate statistical analysis, LJF and LF could be initially separated according to their chemical fingerprints, and the antibacterial effects of the two herbal drugs were divided into two clusters. This result supports the disaggregation of LJF and LF by the Pharmacopoeia Committee. However, the sample of Lonicera fulvotomentosa Hsu et S. C. Cheng turned out to be an intermediate species, with similar antibacterial efficacy as LJF. The results of CCA indicated that chlorogenic acid and 3,4-Dicaffeoylquinic acid were the major components generating antibacterial effects. Furthermore, 3,4-Dicaffeoylquinic acid could be used as a new marker ingredient for quality control of LJF and LF.

Andrographolide Ameliorates Abdominal Aortic Aneurysm Progression by Inhibiting Inflammatory Cell Infiltration through Downregulation of Cytokine and Integrin Expression.

Abdominal aortic aneurysm (AAA), characterized by exuberant inflammation and tissue deterioration, is a common aortic disease associated with a high mortality rate. There is currently no established pharmacological therapy to treat this progressive disease. Andrographolide (Andro), a major bioactive component of the herbaceous plant Andrographis paniculata, has been found to exhibit potent anti-inflammatory properties by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in several disease models. In this study, we investigated the ability of Andro to suppress inflammation associated with aneurysms, and whether it may be used to block the progression of AAA. Whereas diseased aortae continued to expand in the solvent-treated group, daily administration of Andro to mice with small aneurysms significantly attenuated aneurysm growth, as measured by the diminished expansion of aortic diameter (165.68 ± 15.85% vs. 90.62 ± 22.91%, P < 0.05). Immunohistochemistry analyses revealed that Andro decreased infiltration of monocytes/macrophages and T cells. Mechanistically, Andro inhibited arterial NF-κB activation and reduced the production of proinflammatory cytokines [CCL2, CXCL10, tumor necrosis factor α, and interferon-γ] in the treated aortae. Furthermore, Andro suppressed α4 integrin expression and attenuated the ability of monocytes/macrophages to adhere to activated endothelial cells. These results indicate that Andro suppresses progression of AAA, likely through inhibition of inflammatory cell infiltration via downregulation of NF-κB-mediated cytokine production and α4 integrin expression. Thus, Andro may offer a pharmacological therapy to slow disease progression in patients with small aneurysms.