[Intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain].

OBJECTIVE: To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain. METHODS: A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group，30 cases in each one. In the control group，opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated. RESULTS: The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group (P<0.05). The total equivalent morphine consumption in the observation group was less than the control group (P<0.05). After treatment, the QLQ-C30 scores were increased (P<0.001) and the HAMA scores were decreased (P<0.001) in the both groups, and those in the observation group were superior to the control group (P<0.001). The adverse reaction rates of fatigue, dizziness, nausea and vomiting, constipation in the observation group were lower than the control group (P<0.05). CONCLUSION: Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.

[Study on endpoint determination and process analysis of tablet coating based on near infrared spectroscopy].

To conduct endpoint determination of tablet coating and analyze coating process by near-infrared spectroscopy(NIRS). Firstly, the layered k-fold cross validation was used to discuss the optimal combination of spectral interval and preprocessing method, and the optimal result was used as the modeling condition. Secondly, in above condition, the qualitative model was proposed based on the throught of principal component analysis(PCA) and confidence interval, this model and the conformity test model were established respectively in this study, and the discrimination performance of coating eligibility was calculated. Then, the internal cross validation was used to obtain the coating end-point conforming rate as the threshold for determining the endpoint of tablet coating. Finally, the results of predicted conforming rate and discrimination parameters for the test samples of different batches were calculated with the above models, which were then further used for end-point detection and process analysis. As compared with the conformity test, this method proposed in this study was more accurate and stable in determining the coating conformity, and the coating endpoint can be accurately determined when 95% of the eligibility rate was used as the discriminant threshold. Meanwhile, in the process analysis, the change trend of the process parameters(model discrimination parameters, prediction conforming rate) was basically consistent with that in the conformity test. The results indicate that the method proposed in this study has a good and stable performance, which can be used to determine the endpoint of coating and analyze the process. It is of great significance to reduce the difference between batches and improve the product consistency. Meanwhile, this research method also lays a foundation for the future researches by online near infrared measurements.

Analgesic and anti-inflammatory effects and mechanism of action of borneol on photodynamic therapy of acne.

This study aims to explore the analgesic and anti-inflammatory effects of borneol, a traditional Chinese medicine, on photodynamic treatment of acne. Here, we found that borneol significantly decreased the auricular swelling rate and pain threshold of rats. We also showed that borneol noticeably reduced macrophage and lymphocyte infiltration. The number of Th cells was significantly higher in the control PDT group than in the PDT plus borneol treatment group (P < 0.05). The expression of IL-6, TNF-α, and IL-8 mRNA and proteins were noticeably lower in the treatment group in comparison to those of the PDT control group, while PDT plus borneol activated the p38-COX-2-PGE2 signaling pathway, increasing expression in the treatment group. Borneol has significant analgesic and anti-inflammatory effects on PDT of acne, and enhances the healing of acne by activating p38-COX-2-PGE2 signaling pathway.

Multidrug Resistance-Associated Protein 3 Is Responsible for the Efflux Transport of Curcumin Glucuronide from Hepatocytes to the Blood.

Curcumin, a major polyphenol present in turmeric, is predominantly converted to curcumin-O-glucuronide (COG) in enterocytes and hepatocytes via glucuronidation. COG is a principal metabolite of curcumin in plasma and feces. It appears that the efflux transport of the glucuronide conjugates of many compounds is mediated largely by multidrug resistance-associated protein (MRP) 3, the gene product of the ATP-binding cassette, subfamily C, member 3. However, it is currently unknown whether this was the case with COG. In this study, Mrp3 knockout (KO) and wild-type (WT) mice were used to evaluate the pharmacokinetics profiles of COG, the liver-to-plasma ratio of COG, and the COG-to-curcumin ratio in plasma, respectively. The ATP-dependent uptake of COG into recombinant human MRP3 inside-out membrane vesicles was measured for further identification, with estradiol-17ß-d-glucuronide used in parallel as the positive control. Results showed that plasma COG concentrations were extremely low in KO mice compared with WT mice, that the liver-to-plasma ratios of COG were 8-fold greater in KO mice than in WT mice, and that the ATP-dependent uptake of COG at 1 or 10 µM was 5.0- and 3.1-fold greater in the presence of ATP than in the presence of AMP, respectively. No significant differences in the Abcc2 and Abcg2 mRNA expression levels were seen between Mrp3 KO and WT mice. We conclude that Mrp3 is identified to be the main efflux transporter responsible for the transport of COG from hepatocytes into the blood. SIGNIFICANCE STATEMENT: This study was designed to determine whether multidrug resistance-associated protein (Mrp) 3 could be responsible for the efflux transport of curcumin-O-glucuronide (COG), a major metabolite of curcumin present in plasma and feces, from hepatocytes into the blood using Mrp3 knockout mice. In this study, COG was identified as a typical Mrp3 substrate. Results suggest that herb-drug interactions would occur in patients concomitantly taking curcumin and either an MRP3 substrate/inhibitor or a drug that is predominantly glucuronidated by UDP-glucuronosyltransferases.

The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study.

BACKGROUND: Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. METHODS: Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. RESULTS: Hydrolysis of blood plasma samples prior to extraction and reporting the results as "curcumin" obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. CONCLUSIONS: When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. TRIAL REGISTRATION: ClinicalTrails.gov, trial identifying number NCT04103788 , September 24, 2019. Retrospectively registered.

Antioxidant and Anti-Diabetic Functions of a Polyphenol-Rich Sugarcane Extract.

Objectives: Dysfunctional metabolism of carbohydrates is a fundamental component of many dietary-related disorders. It has been hypothesized that plant extracts containing high levels of antioxidants may have the ability to stabilize carbohydrate regulation. The aim of this study was to assess the effects of a polyphenol-rich sugarcane extract on cellular pathways related to carbohydrate metabolism.Methods: We evaluated the antioxidant activity of a polyphenol-rich sugarcane extract obtained by a patented hydrophobic extract process and its therapeutic potential to regulate carbohydrate metabolism and protect against metabolic disorders such as type 2 diabetes.Results: Quantitative analytical studies support that the polyphenol-rich sugarcane extract has a high concentration of polyphenols and antioxidant compounds. The follow-up cellular studies via Caco-2 cells and dysfunctional ß-cell models suggested that the polyphenol-rich sugarcane extract may help deter glucose and fructose uptake in intestinal cells and restore insulin production in dysfunctional ß-cells-key functions in managing diabetic conditions.Conclusions: These findings suggest that sugarcane polyphenols may modulate cellular mechanism in a manner that is beneficial to health.

Structural Characterization and Immunostimulatory Activity of Polysaccharides from Brassica rapa L. .

Two neutral polysaccharides (BRNP-1, 6.9 kDa; BRNP-2, 4.8 kDa) were purified from the common edible plant Brassica rapa L. via the combined techniques of ion-exchange chromatography and high-performance gel permeation chromatography. Monosaccharide composition analysis showed that BRNP-1 and BRNP-2 were composed of glucosyl residues. Methylation and 1D- and 2D-NMR analyses revealed that both BRNP-1 and BRNP-2 contained a backbone chain that was composed of α-D-(1 → 4)-linked Glcp residues and side chains that were composed of terminally linked Glcp residues attached at the O-6 position of backbone-glycosyl residues. BRNP-1 and BRNP-2, however, differed in branch degree and molecular weight. Bioassay results showed that treatment with the higher dosage (400 µg/mL) of BRNP-1 and BRNP-2 stimulated the proliferation, NO release, and cytokine secretion (IL-6 and TNF-α) of RAW264.7 macrophages. These results suggested that BRNP-1 and BRNP-2 may enhance macrophage-mediated immune responses.

Study on the effect of massage therapy combined with medications on MGD / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To study the effect of tarsal gland massage combined with medication in treatment of meibomian gland dysfunction (MGD).METHODS:Totally 100 patients (189 eyes) with MGD were selected in our hospital from December 2014 to December 2016.The patients were randomly divided into control group and observation group.Patients in the control group were treated with routine drugs,while the patients in the observation group were treated with routine massage.We observed and compared the clinical efficacy of two groups of patients before treatment,1 wk,1 and 3mo after treatment for the subjective symptoms,tear film break-up time,tear secretion test,ocular surface disease index,corneal staining score of the patients in the 3 groups.RESULTS:The total effective rate of the observation group was 93.6％,which was significantly higher than that of the control group (P＜ 0.05).Two groups of patients after treatment of subjective symptoms,ocular surface disease index,corneal staining score decreased,tear break-up time,Schirmer test was increased compared with before treatment (P＜0.05).The decrease of subjective symptoms,ocular surface disease index,corneal staining score,the increase of tear film break-up time,tear secretion test in the observation group were higher than those in the control group (P＜0.05).CONCLUSION:Massage combined with medication can improve the clinical efficacy of MGD.

[Effect of jiedu quyu zishen recipe on TLR9 signal pathway of murine macrophage cells].

OBJECTIVE: To explore efficacy enhancing and detoxification roles of Jiedu Quyu Zishen Recipe (JQZR) in treating systemic lupus erythematosus (SLE) by studying its effect on Toll like receptor 9 (TLR9) signal pathway of murine macrophage cells after JQZR stimulated CpG oligodeoxynucletide (CpG ODN). METHODS: Murine macrophage cells in vitro cultured were randomly divided into 4 groups, i.e., the blank serum group, the CpG ODN stimulus group, the CpG ODN + dexamethasone group, the CpG ODN + medicated serum group. Murine macrophage cells were collected after 24-h intervention. The expression of TLR9, myeloid differentiation factor 88 (MyD88), NF-KB, IFN-α mRNA were analyzed by RT-PCR. The expression of TLR9 and NF-κB protein were analyzed by Western blot. Changes of the NF-KB transcriptional activity were assayed by Dual-Luciferase reporter assay system. RESULTS: mRNA expressions of TLR9, MyD88, NF-κB, and IFN-α, protein expressions of TLR9 and NF-κB, and NF-κB transcriptional activities were enhanced, showing statistical difference when compared with those of the blank serum group (P <0. 05, P <0. 01). Compared with the CpG ODN stimulus group, mRNA expressions of MyD88, NF-κB, and IFN-α, the protein expression of NF-κB and the NF-κB transcriptional activities decreased in the CpG ODN + dexamethasone group with statistical difference (P <0. 01). Compared with the CpG ODN stimulus group, mRNA expressions of TLR9, MyD88, NF-κB, and IFN-α, protein expressions of TLR9 and NF-κB, and NF-κB transcriptional activities were decreased in CpG ODN+ medicated serum group with statistical difference (P <0. 01). CONCLUSION: Efficacy enhancing and detoxification roles of JQZR in treatment of SLE might be realized through regulating TLR9 signal pathways.

[Effects of superphosphate addition on NH3 and greenhouse gas emissions during vegetable waste composting].

To study the effects of superphosphate (SP) on the NH, and greenhouse gas emissions, vegetable waste composting was performed for 27 days using 6 different treatments. In addition to the controls, five vegetable waste mixtures (0.77 m3 each) were treated with different amounts of the SP additive, namely, 5%, 10%, 15%, 20% and 25%. The ammonia volatilization loss and greenhouse gas emissions were measured during composting. Results indicated that the SP additive significantly decreased the ammonia volatilization and greenhouse gas emissions during vegetable waste composting. The additive reduced the total NH3 emission by 4.0% to 16.7%. The total greenhouse gas emissions (CO2-eq) of all treatments with SP additives were decreased by 10.2% to 20.8%, as compared with the controls. The NH3 emission during vegetable waste composting had the highest contribution to the greenhouse effect caused by the four different gases. The amount of NH3 (CO2-eq) from each treatment ranged from 59.90 kg . t-1 to 81.58 kg . t-1; NH3(CO2-eq) accounted for 69% to 77% of the total emissions from the four gases. Therefore, SP is a cost-effective phosphorus-based fertilizer that can be used as an additive during vegetable waste composting to reduce the NH3 and greenhouse gas emissions as well as to improve the value of compost as a fertilizer.

Primary hepatic neuroendocrine tumor with multiple liver metastases: A case report with review of the literature.

We herein present a case involving a 41-year-old woman in whom ultrasound examination revealed multiple liver hemangiomas more than 3 years ago. Follow-up ultrasound examination revealed that the masses had significantly increased; the largest was located in the right lobe (about 8.2 cm × 7.4 cm × 6.0 cm). Abdominal multidetector computed tomography revealed multiple well-circumscribed, heterogeneous, hypodense masses (largest, 6.4 cm × 6.3 cm × 5.0 cm) with significant contrast enhancement during the arterial and portal phases and with contrast wash-out and peripheral enhancement during the delayed phases. Magnetic resonance images demonstrated multiple well-circumscribed, heterogeneous, hypointense hepatic masses with significant contrast enhancement (largest, 6.4 cm × 6.5 cm × 5.1 cm); multiple enlarged porta lymph nodes; and multiple slightly enlarged retroperitoneal lymph nodes. Histological and immunohistochemical examination of the right mass biopsy specimen suggested a malignant neoplasm that had originated from a neuroendocrine cell type (grade 2 well-differentiated neuroendocrine carcinoma). After performing a systemic examination to exclude metastasis from an extrahepatic primary site, we considered that the masses had arisen from a primary hepatic neuroendocrine tumor with multiple liver metastases. The patient underwent transcatheter arterial chemoembolization using a combination of oxaliplatin (150 mg) mixed with one bottle of gelatin sponge particles (560-710 µm) and lipiodol (6 mL). Primary neuroendocrine tumors of the liver are extremely rare. This case is interesting because of the rarity of this neoplasm and previous misdiagnosis as multiple liver hemangiomas. Previously reported cases in the literature are also reviewed.

The effects of Jieduquyuzishen prescription-treated rat serum on the BAFF/BAFF-R signal pathway.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease mainly characterized by B cell hyperactivity. Glucocorticoid (GC) is widely used in SLE for its potent anti-inflammatory and immunosuppressive effects. Despite its important clinical efficacy, high-dose or long-term use of GC can cause severe side effects, such as osteoporosis, osteonecrosis, cataracts, hyperglycemia, coronary heart disease and cognitive impairment. Our early clinical studies have shown that Jieduquyuzishen prescription (JP) can effectively reduce the adverse effects and improve the curative effect of GC in the treatment of SLE. The BAFF/BAFF-R signaling pathway plays an important role in the development of SLE and has been regarded as a potential target for the therapy of SLE. In this study, we attempt to investigate the effect of JP on the BAFF/BAFF-R signaling pathway to explore the mechanism of JP in reducing the toxicity and enhancing the efficacy of GC. YAC-1 cells, isolated rat peripheral blood lymphocytes, polymorphonuclear neutrophils and spleen lymphocytes were treated with drug-containing serum. The results of RT-PCR, Western blot and dual-luciferase reporter gene assays indicate that either JP or GC can inhibit the mBAFF-induced up-regulation of BAFF, BAFF-R, Bcl-2, IL-10 and NF-κB in YAC-1 cells and WEHI-231 cells. Furthermore, MTS, flow cytometry and CFSE results reveal that the proliferation and survival of lymphocytes activated by mBAFF are suppressed by JP, GC and their combination. Contrary to GC, JP can reduce the apoptosis and raise the survival of polymorphonuclear neutrophils and can't increase the apoptosis of the peripheral blood lymphocytes and spleen lymphocytes. Therefore, it is possible that JP can down-regulate the BAFF/BAFF-R signaling pathway as effectively as GC, which may result in the dosage reduction of GC, thus decreasing the toxicity and improving the efficacy of GC-based treatment of SLE.

[Study on the regulation of Jiedu Quyu Zishen Recipe on glucocorticoid receptor alpha in the renal tissue of MRL/lpr mice].

OBJECTIVE: To explore the action mechanism of Jiedu Quyu Zishen Recipe (JQZR) on the signal transduction of glucocorticoid receptor alpha (GRalpha) in the renal tissue of MRL/lpr mice. METHODS: Thirty MRL/lpr mice were randomly divided into three groups, i.e., the model group, the Western medicine group, and the Chinese medicine group, 10 in each. Besides, another 10 Kunming mice was taken as the normal control group. The pathological changes of the renal tissue were observed using HE staining. The expression of GRalpha was analyzed using Real-time PCR and Western blot. The effects of JQZR on the binding power of GRalpha to cyclophilin A were detected using co-immunoprecipitation. RESULTS: The renal injury degree of MRL/lpr mice in the Western medicine group and the Chinese medicine group was alleviated. Compared with the model group, the relative quantitation of GRalpha mRNA and protein expressions in the renal tissue of mice in the Western medicine group decreased, while they increased in the Chinese medicine group, showing statistical difference (P < 0.01). JQZR could significantly elevate the binding potency of GRalpha to cyclophilin A. CONCLUSION: Up-regulating the expression of GRalpha and enhancing mutual actions of GRalpha and cyclophilin A was one of JQZR's effects on improving the lesion of the renal tissue.

[Effect of electroacupuncture on pain threshold and spinal NR2B subunit expression in a rat model of neuropathic pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pain threshold and spinal NR2B subunit expression in a rat model of neuropathic pain due to chronic compression injury (CCI) of the sciatic nerve and explore the analgesic mechanism of EA. METHODS: Male SD rats weighing 200-280 g were randomly divided into 4 groups (n=10), namely the sham-operated group, CCI group, EA+CCI group, and sham EA+CCI group. All the rats underwent tests of the mechanical withdrawal threshold and thermal threshold. On day 13 after the surgery, all the rats were decapitated to collect the L4-6 segments of the spinal cord to examine NR2B expression using Western blotting. RESULTS: The postoperative mechanical withdrawal threshold and thermal threshold were significantly lowered in CCI, EA+CCI and sham EA+CCI groups as compared to those before the surgery (P<0.05). EA obviously alleviated the hypersensitivity in the rats with CCI and inhibited spinal NR2B expressions (P<0.05). No significant differences were found in the mechanical withdrawal threshold, thermal threshold or spinal NR2B subunit expression between CCI group and sham EA+CCI group (P>0.05). CONCLUSION: EA may alleviate neuropathic hypersensitivity partially by inhibiting NR2B expression in the spinal cord of rats with neuropathic pain resulting from CCI of the sciatic nerve.

[Effects of Jinlong Capsule on expressions of interleukin-2 and soluble interleukin-2 receptor in patients with primary liver cancer after transarterial chemoembolization therapy].

OBJECTIVE: To observe and discuss the dynamic changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) and their significance in the patients with primary liver cancer after transarterial chemoembolization (TACE) therapy combined with Jinglong Capsule. METHODS: A total of 48 patients with primary liver cancer, who failed to be treated by major surgery, were randomly divided into two groups: Jinlong Capsule group (TACE therapy plus Jinlong Capsule) and control group (TACE therapy alone). There were 24 cases in each group. The levels of peripheral blood IL-2 and slL-2R were measured before the first TACE and 1, 7 and 15 days after the second TACE respectively by using double-antibody sandwich enzyme-linked immunosorbent assay. The data from Jinlong Capsule group were compared with those from the control group. RESULTS: The level of sIL-2R in Jinlong Capsule group was significantly lower than that in the control group (P<0.05), while the level of IL-2 was significantly higher than that in the control group (P<0.05). CONCLUSION: Jinlong Capsule can significantly improve the lymphocyte function of the patients with primary liver cancer after TACE. The levels of IL-2 and sIL-2R can be considered as the valuable parameters for evaluating the effects on primary liver cancer, and Jinlong Capsule is helpful for the patients with primary liver cancer.