Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

Naringin alleviates pneumonia caused by Klebsiella pneumoniae infection by suppressing NLRP3 inflammasome.

Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1ß, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.

[Short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures].

Objective To explore the short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures, and explore the quantification of traditional Chinese medicine manual reduction and personalized improvement of splinting. Methods The clinical data of 50 patients with AO type-A distal radius fractures, who received treatment at the outpatient department of Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province, were retrospective analyzed. The patient cohort included 22 females and 28 males, with ages ranging from 25 to 75 years old. Among them, 27 cases presented with distal radius fractures on the left side, and 24 cases on the right side. The patients were categorized into two groups: treatment group (n=25) and control group(n=25). There were 13 males and 12 females in the treatment group, with an average age of (56.2±5.5) years old. Treatment approach for this group involved several steps. Initially, Mimics Research software was used to conduct comprehensive analysis of complete CT data from the affected limb, resulting in the creation of a three-dimensional model. Subsequently, 3D models of the bones and skin contours, stored as STL format files, were imported into the Materialise Magics 23.0 software for model processing and repair. This facilitated the simulation of reduction and recording of displacement data, effectively generating a "digital prescription" to guide and quantify traditional Chinese medicine manipulation procedures. Finally, a personalized 3D printed splint was applied for fixation treatment. There were 15 males and 10 females in the control group, with an average age of (53.32±5.28) years old. These patients were treated with manualreduction combined with traditional splinting. The clinical efficacy of the two groups was assessed in terms of fracture reduction quality, fracture healing time, Gartland-Werley wrist joint score and X-ray parameters (palminclination angle, ulnar deviation angle, radius height) at 6 weeks post-operatively. Results The treatment group exhibited a shorter duration for achieving clinical healing compared to the control group (P<0.05). Six weeks post-operatively, the treatment group demonstrated higher wrist joint function scores, and a higher proportion of excellent and good outcomes than the control group(P<0.05). The treatment group was superior to the control group in terms of imaging parameters 6 weeks post-operatively (P<0.05). Conclusion By quantifying skin contours through digital simulation prescription reduction, a personalized 3D printed splint is developed to effectively stabilize fractures, enhancing localized fixation while ensuring greater adherence, stability, and comfort. This innovative approach offers personalized treatment for AO type-A distal radius fractures and presents a novel, precise treatment strategy for consideration.

The effect of acupuncture on recovery after colorectal cancer resection: A systematic review meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the efficacy and safety of acupuncture by systematically reviewing the literature on colorectal cancer resection. METHODS: Seven electronic databases were searched from inception to February 28, 2023. Randomized controlled trials on acupuncture in patients after CRC resection were included. Two reviewers independently selected relevant trials, extracted data, and assessed the risk of bias. A random-effects meta-analysis model was used to obtain summary effect estimates. The data were pooled and analyzed using RevMan 5.3. The heterogeneity of selected studies was evaluated by evaluating the I-squared (I2) statistics. RESULTS: Twenty-two studies with 1878 patients were included. Results of the meta-analysis showed there was a low level evidence that acupuncture may improve early postoperative symptoms, such as time to first flatus (n = 876, MD -0.77h, 95% CI -1.22 to -0.33 h, I2 = 89%), time to first bowel movement (n = 671, MD -1.41h, 95% CI -2.20 to -0.63 h, I2 = 95%), time to first defecation (n = 556, MD -1.03h, 95% CI -1.88 to -0.18 h, I2 = 95%), and nausea/vomiting (n = 1488, RR 0.72, 95% CI 0.59-0.89, I2 = 49%) compared with usual care and sham acupuncture. However, there were no statistically significant differences in postoperative pain (n = 1188, MD-0.21, 95% CI -0.59 to 0.17, I2 = 74%). And there was no sufficient evidence of improving long-term functional outcomes. There was substantial heterogeneity across trials. The adverse events associated with acupuncture stimulation were minor in include studies. CONCLUSION SUBSECTIONS: There is currently low-level evidence supporting the use of acupuncture on postoperative symptoms for patients after colorectal cancer resection. More investigations should be established based on the STRICTA statement strictly.

Linear Regression Analysis of Sleep Quality in People with Insomnia in Wuhan City during the COVID-19 Pandemic.

Objective: COVID-19 has evolved into a major global public health event. The number of people reporting insomnia is growing exponentially during the pandemic. This study aimed to explore the relationship between aggravated insomnia and COVID-19-induced psychological impact on the public, lifestyle changes, and anxiety about the future. Methods: In this cross-sectional study, we used the questionnaires from 400 subjects who were obtained from the Department of Encephalopathy of the Wuhan Hospital of Traditional Chinese Medicine between July 2020 and July 2021. The data collected for the study included demographic characteristics of the participants and psychological scales consisting of the Spiegel Sleep Questionnaire, the Fear of COVID-19 Scale (FCV-19S), the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). The independent sample t-test and one-way ANOVA were used to compare the results. Correlation analysis of variables affecting insomnia was performed using Pearson correlation analysis. The degree of influence of the variables on insomnia was determined using linear regression, and a regression equation was derived. Results: A total of 400 insomnia patients participated in the survey. The median age was 45.75 ± 15.04 years. The average score of the Spiegel Sleep Questionnaire was 17.29 ± 6.36, that of SAS was 52.47 ± 10.39, that of SDS was 65.89 ± 8.72, and that of FCV-19S was 16.09 ± 6.81. The scores of FCV-19S, SAS, and SDS were closely related to insomnia, and the influencing degree was in the following order: fear, depression, and anxiety (OR = 1.30, 0.709, and 0.63, respectively). Conclusion: Fear of COVID-19 can be one of the primary contributors to worsening insomnia.

Potential risk of eutrophication in the deepest lake of Southwest China: Insights from phosphorus enrichment in bottom water.

Large deep lakes in plateau regions provide crucial ecosystem services but are susceptible to eutrophication due to their long water residence time. To date, the water quality of deep lakes has not received as much attention as that of shallow lakes owing to logistical challenges. This study investigated the seasonal variation and vertical distribution of phosphorus and related environmental variables in a large deep lake in the Yunnan Plateau, China (Fuxian Lake). Generally, the concentrations of total phosphorus (TP, R2 = 0.862), total dissolved phosphorus (TDP, R2 = 0.922), and dissolved inorganic phosphorus (DIP, R2 = 0.889) exhibited a linear increase with the greater water depth, whereas the pH and dissolved oxygen (DO) showed decreasing trends. The TP, TDP, and DIP values were 0.012, 0.006, and 0.004 mg/L, respectively, in surface waters (0.5 m depth), and increased to 0.074, 0.065, and 0.062 mg/L, respectively, at 140.0 m depth. The averaged over ordering method demonstrated that DO and air temperature accounted for a higher proportion of the explained variance of TP, TDP, and DIP in the shallow water layer (0.5-20.0 m). In contrast, DO and pH accounted for a higher proportion of the explained variance of TP, TDP, and DIP in deeper water layers (40.0-150.0 m). As a warm monomictic lake, the higher observed phosphorus concentrations in deeper water and sediment potentially pose a risk of future eutrophication in the Fuxian Lake. Our findings demonstrate that more efficient technical and management measures should be taken to reduce the external phosphorus load to Fuxian Lake, so that the load to and from the sediment will decrease eventually.

Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy.

Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

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.

Evaluation of an EZH2 inhibitor in patient-derived orthotopic xenograft models of pediatric brain tumors alone and in combination with chemo- and radiation therapies.

Brain tumors are the leading cause of cancer-related death in children. Tazemetostat is an FDA-approved enhancer of zeste homolog (EZH2) inhibitor. To determine its role in difficult-to-treat pediatric brain tumors, we examined EZH2 levels in a panel of 22 PDOX models and confirmed EZH2 mRNA over-expression in 9 GBM (34.6 ± 12.7-fold) and 11 medulloblastoma models (6.2 ± 1.7 in group 3, 6.0 ± 2.4 in group 4) accompanied by elevated H3K27me3 expression. Therapeutic efficacy was evaluated in 4 models (1 GBM, 2 medulloblastomas and 1 ATRT) via systematically administered tazemetostat (250 and 400 mg/kg, gavaged, twice daily) alone and in combination with cisplatin (5 mg/kg, i.p., twice) and/or radiation (2 Gy/day × 5 days). Compared with the untreated controls, tazemetostat significantly (Pcorrected < 0.05) prolonged survival times in IC-L1115ATRT (101% at 400 mg/kg) and IC-2305GBM (32% at 250 mg/kg, 45% at 400 mg/kg) in a dose-dependent manner. The addition of tazemetostat with radiation was evaluated in 3 models, with only one [IC-1078MB (group 4)] showing a substantial, though not statistically significant, prolongation in survival compared to radiation treatment alone. Combining tazemetostat (250 mg/kg) with cisplatin was not superior to cisplatin alone in any model. Analysis of in vivo drug resistance detected predominance of EZH2-negative cells in the remnant PDOX tumors accompanied by decreased H3K27me2 and H3K27me3 expressions. These data supported the use of tazemetostat in a subset of pediatric brain tumors and suggests that EZH2-negative tumor cells may have caused therapy resistance and should be prioritized for the search of new therapeutic targets.

Highland barley Monascus purpureus Went extract ameliorates high-fat, high-fructose, high-cholesterol diet induced nonalcoholic fatty liver disease by regulating lipid metabolism in golden hamsters.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine. AIM OF THE STUDY: This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD). MATERIALS AND METHODS: HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed. RESULTS: Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1). CONCLUSIONS: HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.

[Comparative analysis of chemical compositions of fruits of Perilla frutescens var. arguta and P. frutescens var. frutescens by pre-column derivatization with GC-MS].

The present study compared the appearance and chemical composition of fruits of Perilla frutescens var. arguta(PFA) and P. frutescens var. frutescens(PFF). VHX-6000 3 D depth of field synthesis technology was applied for the appearance observation. The metabolites were qualitatively and quantitatively analyzed by pre-column derivatization combined with gas chromatography-mass spectrometry(GC-MS). Finally, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least-squares discriminant analysis(OPLS-DA) were applied for exploring the differences in their chemical compositions. The results indicated that the size and color of PFA and PFF fruits were different. PFF fruits were significantly larger than PFA fruits. The surface color of PFA fruits was brown, while PFF fruits were in multiple colors, such as white, grayish-white, and brown. Amino acids, saccharides, organic acids, fatty acids, and phenolic acids were identified in PFA and PFF fruits. The results of CA, PCA, and OPLS-DA indicated significant differences in the content of components between PFA and PFF fruits. Three metabolites, including D-glucose, rosmarinic acid, and D-fructose, which were significantly higher in PFA fruits than in PFF fruits, were screened out as differential metabolites. Considering the regulation on the content of rosmarinic acid in Perillae Fructus in the Chinese Pharmacopoeia(2020 edition), the medicinal value of PFA fruits is higher than that of PFF. In conclusion, there are differences in appearance and chemical composition between PFA fruits and PFF fruits. These results are expected to provide fundamental data for specifying plant source and quality control of Perillae Fructus.

[Effects of Bupleurum chinense on the diversity of intestinal flora in depressed mice].

Bupleuri Radix, serving as the sovereign medicinal in many antidepressant compound preparations, has been proved effective in treating depression in mice, but its effect on the intestinal flora remains unclear. The present study aimed to investigate the effects of Bupleurum chinense(one of the original materials of Bupleuri Radix) on the behaviors and the diversity of intestinal flora of depressed mice. A depression mouse model was induced by repeated social defeat stress. Specifically, C57 BL/6 J male mice were exposed to the attack from the CD-1 mice. Then, C57 BL/6 J male mice were divided into a depression group and a B. chinense group, with normal saline and B. chinense administered(ig) respectively. Sucrose preference test and tail suspension test were conducted during and after the experiment respectively, to analyze the effects of B. chinense on the behaviors of the depressed mice. The feces were collected after the experiment. The V3-V4 16 S rDNA regions of intestinal flora of mice in each group were sequenced by Ion S5 TMXL for the analysis of the number of operational taxonomic units(OTUs), richness, alpha and beta diversity indexes, and differential phyla and genera. The results indicated that B. chinense could decrease depressive-like behaviors of mice, increase sucrose preference, and shorten the time of immobility in tail suspension test. After B. chinense intervention, the relative abundance of Firmicutes was significantly decreased, while that of Bacteroidetes was increased at the phylum level. At the genus level, the relative abundance of Lactobacillus and Lachnoclostridium decreased(P<0.05), while that of Bacteroides, Alistopes, etc. was elevated(P<0.05). The findings demonstrate that B. chinense can regulate the intestinal flora and improve the depressive-like behaviors of mice with depression.

[Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant].

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.

A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.

AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors. RESULTS: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.

Clinical observation on horizontal penetration needling combined with rizatriptan monobenzoate tablets for migraine without aura in acute stage / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of horizontal penetration needling combined with rizatriptan monobenzoate tablets, simple horizontal penetration needling and simple rizatriptan monobenzoate tablets for migraine without aura in acute stage.@*METHODS@#A total of 99 patients with migraine without aura in acute stage were randomized into an acupuncture plus medication group, an acupuncture group and a western medication group, 33 cases in each one. In the acupuncture group, horizontal penetration needling was applied once at Hanyan (GB 4) to Xuanli(GB 6), Shenting (GV 24) to Yintang (GV 29), Baihui (GV 20) to Qianding (GV 21), etc. for 2 h. In the western medication group, oral rizatriptan monobenzoate tablets for 10 mg were given once. In the acupuncture plus medication group, treatment of acupuncture combined with rizatriptan monobenzoate tablets were given, the application was the same as the acupuncture group and the western medication group. Before treatment and 0.5, 2, 24 h after treatment, the visual analogue scale (VAS) score was observed, the remission rate and the disappearance rate of migraine of 2, 24 h after treatment were compared in the 3 groups.@*RESULTS@#Compared before treatment, the VAS scores of each time point after treatment were decreased in the 3 groups (@*CONCLUSION@#Horizontal penetration needling combined with rizatriptan monobenzoate tablets have significant therapeutic effect on rapid analgesia and continuous analgesia for migraine without aura in acute stage, its effect is superior to simple horizontal penetration needling and simple rizatriptan monobenzoate tablets.

Review of taste masking techniques in Chinese patent medicine / 中国中药杂志

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

Effect of 9 - PAHSA on cognitive dysfunction in diabetic mice and its possible mechanism.

Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.

Horizontal penetration needling method for headache / 中国针灸

The manipulation and key points of professor

Analysis on relationship between syndrome differentiation of migraine and acupuncture effect / 中国针灸

The problems of the syndrome differentiation of migraine in acupuncture treatment were collected, e.g. inconsistency of syndrome differentiation, unclear staging of syndrome differentiation, lack of standardization in comparison between syndrome differentiation and non-differentiation, insufficient research on the factors of syndrome differentiation. In view of the exiting problems, focusing on two aspects of migraine, namely syndrome differentiation and acupuncture effect, the clinical treatment and research are conducted in migraine treated with acupuncture based on syndrome differentiation. It is believed that the comprehensive observation of the relationship between syndrome differentiation and acupuncture effect, as well as the analysis of the relevant factors of syndrome differentiation of migraine should be the focus in future research.