Higenamine inhibits acute and chronic inflammatory pain through modulation of TRPV4 channels.

Pain is the cardinal symptom of many debilitating diseases and results in heavy health and economic burdens worldwide. Asarum (Asarum sieboldii Miq.) is a commonly used analgesic in Chinese medicine. However, the analgesic components and mechanisms of asarum in acute and chronic pain mice model remain unknown. In this study, we first generated asarum water extract and confirmed strong analgesic properties in mice in both the acute thermal and mechanical pain models, as well as in the complete Freund's adjuvant (CFA) induced chronic inflammatory pain model. Second, we identified higenamine as a major component of asarum and found that higenamine significantly inhibited thermal and mechanical induced acute pain and CFA induced chronic inflammatory pain. Then, using Trpv4-/- mice, we found that TRPV4 is necessary for CFA induced thermal and mechanical allodynia, and demonstrated that higenamine analgesia in the CFA model is partly through TRPV4 channel inhibition. Finally, we found that GSK1016790A, a TRPV4 agonist, induced calcium response was significantly inhibited by higenamine in both cultured DRG neurons and TRPV4 transfected HEK293 cells. Consistent with calcium imaging results, higenamine pretreatment also dose-dependently inhibited GSK1016790A induced acute pain. Taken together, our behavior and calcium imaging results demonstrate that the asarum component higenamine inhibits acute and chronic inflammatory pain by modulation of TRPV4 channels.

Risk-taking in consumers' online purchases of health supplements and natural products: a grounded theory approach.

BACKGROUND: Health supplements and natural products are widely used by the general public to support physical function and prevent disease. Additionally, with the advent of e-commerce, these products have become easily accessible to the general public. Although several theoretical models have been used to explain the use of health supplements and natural products, empirical evidence on how consumers make decisions to purchase online health supplements and natural products remains limited. METHODS: In this study, a grounded theory approach was used to develop a substantive theoretical model with the aim of investigating the decision-making process of consumers when purchasing health supplements and natural products online. Malaysian adult consumers who had purchased these products via the Internet were either purposively or theoretically sampled. A total of 18 virtual in-depth interviews (IDIs) were conducted to elicit participants' experiences and priorities in relation to this activity. All the IDIs were audio-recorded and transcribed verbatim. The data were analysed using open coding, focus coding and theoretical coding. The analytical interpretations and theoretical concepts were recorded in research memos. RESULTS: Consumers' decisions to purchase a health supplement or natural product over the Internet are based on a series of assessments regarding the perceived benefits and risks of this activity, which may be related to the product or the process. In the online marketplace, consumers attempt to choose products, online sellers, sales platforms and/or purchase mechanisms with lower perceived risk, which ultimately enhances their confidence in five elements related to the purchase: (1) product effectiveness, (2) product safety, (3) purchase convenience, (4) fair purchase and (5) online security. Consumers take an acceptable level of risk to purchase these products online, and this acceptable level is unique to each individual and is based on their perception of having control over the potential consequences if the worst-case scenario occurs. CONCLUSIONS: In this study, a substantive theoretical model is developed to demonstrate how consumers decide to purchase online health supplements and natural products by accepting an acceptable level of risk associated with the product or process. The emerging model is potentially transferable to other populations in similar contexts.

[Rapid determination of aesculin and aesculetin in Fraxini Cortex by high performance liquid chromatography-ultraviolet at equal absorption wavelength].

Fraxini Cortex is a traditional Chinese herbal medicine that has been used for thousands of years to treat dampness-heat diarrhea, dysentery, red or white vaginal discharge, painful swelling or redness of the eyes, and nebula. It contains various chemical components, including coumarins, iridoids, phenolic acids, and flavonoids. Coumarins are important active ingredients in Fraxini Cortex and have antibacterial, anti-inflammatory, antioxidant, antitumor, and antiviral activities. Aesculin and aesculetin are two major coumarin components of Fraxini Cortex that are widely used in its quality evaluation. Previous HPLC methods for determination of aesculin and aesculetin present several limitations, such as long analysis times and high solvent and reference compound consumption. In this study, a rapid, eco-friendly and cost saving HPLC method for the determination of aesculin and aesculetin in Fraxini Cortex was established by using the core-shell column and equal absorption wavelength (EAW). Different factors influencing the extraction process, such as the extraction solvent, temperature, and time, were assessed to obtain the optimal extraction conditions. The results showed that Fraxini Cortex samples could be well extracted by ultrasonic extraction for 5 min with a 25% ethanol aqueous solution. A core-shell column was used, and different mobile phases and flow rates were investigated to obtain the best rapid-HPLC separation conditions. The optimized HPLC conditions were as follows: a Poroshell 120 EC-C18 column (50 mm×4.6 mm, 2.7 µm), acetonitrile-0.1% formic acid aqueous solution (6∶94, v/v) as the eluent, a flow rate of 1.5 mL/min, and a column temperature of 25 ℃. The EAW of aesculin and aesculetin was a key factor in their determination using a single reference compound. EAW selection was performed in two steps. First, the UV spectra of two equimolar concentrations of the reference compounds (aesculin and aesculetin) were compared to determine the EAW of the two analytes. The EAW results were then verified by the HPLC analysis of the reference compound solutions. The final EAW of aesculin and aesculetin was 341 nm. The determination of aesculin and aesculetin using only one reference compound (i. e., aesculin) was achieved by HPLC-UV at this EAW. The newly developed HPLC method revealed a good linear relationship between the two target analytes (r=1.0000). The limits of detection (LODs) and limits of quantification (LOQs) were 1.5 µmol/L and 3.0 µmol/L, respectively, and the average recoveries of aesculin and aesculetin were 99.0% and 97.5%. The stabilities of the sample solutions were examined, and the two analytes demonstrated good stability for 24 h. The contents of the target analytes in 10 batches of Fraxini Cortex were determined using the proposed EAW method and the classic external standard method (ESM), and comparable concentrations were obtained. The contents of aesculin and aesculetin in the 10 batches of Fraxini Cortex were 0.26%-2.80% and 0.11%-1.47%, respectively. A t-test was conducted to compare the results of the proposed EAW technique with those obtained via the method reported in the Chinese Pharmacopoeia, and no significant difference between the two assay methods was noted (P>0.05). Comparison of the newly established EAW method with those reported in the literature revealed that our method required only 10 min to complete and used as little as 0.5 mL of the solvent and only one standard. Therefore, the developed EAW method is a rapid, simple, eco-friendly, and cost-effective analytical method that is suitable for the determination of aesculin and aesculetin in Fraxini Cortex and its related products. The proposed technique is an improved method for determining aesculin and aesculetin and contributes to the enhancement of the quality evaluation of Fraxini Cortex.

A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes.

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.

Rapid detection of adulteration of olive oil with soybean oil combined with chemometrics by Fourier transform infrared, visible-near-infrared and excitation-emission matrix fluorescence spectroscopy: A comparative study.

Several spectroscopic techniques have been used to detect olive oil adulteration. To evaluate the performance of these spectral techniques on this issue, this work performed a comparative study on identifying adulterated olive oil with different concentrations of soybean oil based on Fourier-transform infrared (FTIR), visible-near-infrared (Vis-NIR) and excitation-emission matrix fluorescence spectroscopy (EEMs) combined with chemometrics. Principal component analysis (PCA)/ multi-way-PCA analysis showed the feasibility of the three spectral methods for the identification of olive oil adulteration. The accuracy of FTIR and Vis-NIR based on partial least squares discriminant analysis (PLS-DA) for adulterated olive oil was 100%, while the accuracy of EEMs based on unfold-PLS-DA was only 73%. The accuracy of EEMs combined with back-propagation artificial neural network based on self-weighted alternating trilinear decomposition is 100%. In comparison, FTIR and Vis-NIR are superior for the detection of olive oil adulteration due to the convenience of instrument operation and modeling.

Rapid detection and quality evaluation of Shuang-Huang-Lian injection by ATR-IR and NIR spectroscopy combined with chemometrics.

Quality evaluation and consistency evaluation of drugs are the keys to ensure the therapeutic effect and safety of drugs. In this study, attenuated total refraction infrared (ATR-IR) spectroscopy and near-infrared (NIR) spectroscopy combined with chemometrics were used for rapid detection and quality evaluation of active components of Shuang-Huang-Lian injection (SHLI), a traditional Chinese medicine preparation commonly used in China. Taking the chromatographic detection results as a reference, the partial least squares (PLS) model based on ATR-IR and NIR data was constructed by removing the bands with serious noise interference and low signal frequency band. The results showed that the PLS model achieved satisfactory results for the prediction of the three active components (chlorogenic acid, baicalin and phillyrin) in SHLI, indicating that the two spectral techniques combined with the PLS regression method could be successfully used for rapid quantitative analysis of the three active ingredients in SHLI. Relatively, the PLS model based on the ATR-IR spectrum has higher R2 and smaller RMSE than it based on the NIR spectrum. Furthermore, based on the rapid quantitative analysis of the three active ingredients in SHLI, the quality of 140 SHLI samples from seven manufacturers was evaluated by TOPSIS (technique for order preference by similarity to the ideal solution) analysis, and the consistency of different batches of SHLI products from the same manufacturer was evaluated. The results showed that there were differences in the quality of SHLI produced by different manufacturers, and the quality of different batches of SHLI produced by the same manufacturer was not completely consistent. In conclusion, ATR-IR and NIR spectroscopy combined with chemometrics can be used for accurate and rapid quantitative analysis and quality evaluation of SHLI. This study provides a good idea for the rapid quantitative analysis and quality evaluation of drugs or food based on spectroscopic technology and chemometrics.

The Prevalence of Online Natural Health Products Purchase: A Systematic Review

@#Aim and design: This systematic review aimed to estimate the prevalence of online natural health products (NHPs) purchases among consumers. Data Sources: Four databases (PubMed, Science Direct, Scopus and Web of Sciences) were searched for articles published up to July 1, 2021. Review Method: Studies included were those reporting the prevalence of online NHPs purchases, those excluded were case reports, commentaries, letters, editorials, review articles, theses and non-English studies. The risk of bias of selected studies was assessed using the Joanna Briggs Institute’s checklist, and the pooled prevalence of online NHPs purchases was generated using the random-effect model. Results: A total of 30 studies were included in the meta-analysis, representing a total of 40,535 respondents. The pooled prevalence of online NHPs purchases was estimated at 7.60% (95% CI: 5.49, 10.01). Prevalence was higher in studies conducted in recent years, among physically active populations and when sports nutrition was included within the scope of NHPs. More than half of the selected studies have a moderate risk of bias, and considerable heterogeneity was observed across the selected studies. Conclusion and Impact: Online purchases of NHPs are not common among consumers, but they have become more common in recent years. A wide range of NHPs were investigated across studies, which may have contributed to the considerable heterogeneity reported in this review. It is suggested that future studies investigating online NHPs purchases consider reporting individual prevalence statistics specific to each NHP type, to facilitate meaningful comparisons between studies.

A comparative study on classification of edible vegetable oils by infrared, near infrared and fluorescence spectroscopy combined with chemometrics.

Driven by economic benefits like any other foods, vegetable oil has long been plagued by mislabeling and adulteration. Many studies have addressed the field of classification and identification of vegetable oils by various analysis techniques, especially spectral analysis. A comparative study was performed using Fourier transform infrared spectroscopy (FTIR), visible near-infrared spectroscopy (Vis-NIR) and excitation-emission matrix fluorescence spectroscopy (EEMs) combined with chemometrics to distinguish different types of edible vegetable oils. FTIR, Vis-NIR and EEMs datasets of 147 samples of five vegetable oils from different brands were analyzed. Two types of pattern recognition methods, principal component analysis (PCA)/multi-way principal component analysis (M-PCA) and partial least squares discriminant analysis (PLS-DA)/multilinear partial least squares discriminant analysis (N-PLS-DA), were used to resolve these data and distinguish vegetable oil types, respectively. PCA/M-PCA analysis exhibited that three spectral data of five vegetable oils showed a clustering trend. The total correct recognition rate of the training set and prediction set of FTIR spectra of vegetable oil based on PLS-DA method are 100%. The total recognition rate of Vis-NIR based on PLS-DA are 100% and 97.96%. However, the total correct recognition rate of training set and prediction set of EEMs data based on N-PLS-DA method is 69.39% and 75.51%, respectively. The comparative study showed that FTIR and Vis-NIR combined with chemometrics were more suitable for vegetable oil species identification than EEMs technique. The reason may be concluded that almost all chemical components in vegetable oil can produce FTIR and NIR absorption, while only a small amount of fluorophores can produce fluorescence. That is, FTIR and NIR can provide more spectral information than EEMs. Analysis of EEMs data using self-weighted alternating trilinear decomposition (SWATLD) also showed that fluorophores were a few and irregularly distributed in vegetable oils.

Integrating network pharmacology and experimental models to investigate the efficacy of QYHJ on pancreatic cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear. AIM OF THE STUDY: This study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro. MATERIALS AND METHODS: The bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting. RESULTS: A total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment. CONCLUSIONS: QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor.

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

[Distribution and enrichment characteristics of soil nutrients in the nebkhas profile of Nitraria tangutorum in Gahai Lake Area, Qaidam Basin.] / æŸ´è¾¾æœ¨ç›†åœ°å°•æµ·æ¹–åŒºç™½åˆºçŒä¸›æ²™å †å‰–é¢åœŸå£¤å »åˆ†çš„åˆ†å¸ƒå’Œå¯Œé›†ç‰¹å¾.

As a special bio-geomorphic landscape in the Qaidam desert area, Nitraria tangutorum nebkhas play a critical role in fixing quicksand, improving soil quality, and maintaining the stability of regional ecological environment. Taking the N. tangutorum nebkhas with coverage of approximately 15%, 25%, 45% and 60% in Gahai Lake area of Qaidam Basin as the research objects, we analyzed the vertical distribution and enrichment characteristics of soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP) and available potassium (AK). The results showed that the contents of SOM, TN, TP, TK, AN, AP and AK varied in the range of 1.67-10.22 g·kg-1, 0.05-0.42 g·kg-1, 0.31-0.54 g·kg-1, 15.87-18.84 g·kg-1, 2.26-11.68 mg·kg-1, 0.80-15.00 mg·kg-1 and 45-161 mg·kg-1, respectively. Vertically, soil nutrients in the N. tangutorum nebkhas with 15% coverage showed a decreasing trend first then increased, and then decreased again with the increase of soil depth, except for TP, which did not show any significant change. In the nebkhas with 25%, 45% and 60% coverage, SOM, TN, AN, TP and AP all showed a decreasing trend with increasing soil depth ,whereas TK and AK did not change significantly with soil layer. Above the nebkhas ground level of N. tangutorum, SOM, TN, TK, AN, AP and AK were all enriched, especially in the surface layer.Aamong all the nutrients, the enrichment rate of AN reached 5.19. In addition, below the nebkhas ground level of N. tangutorum, TN, AN, TK, AK and AP also showed enrichment. SOM, TN, AN, TP, AP, TK and AK were all significantly positively correlated with soil water content, and negatively correlated with altitude. All nutrients except TP were mainly affected by altitude. In conclusion, soil nutrient content of N. tangutorum nebkhas was the highest in the surface layer, the enrichment effect of which was not only reflected in the interior of the nebkhas, but also below the ground level of the nebkhas. Our results could provide reference for the scientific utilization of N. tangutorum nebkhas and ecological environment protection in Qaidam Basin area.

Oral administration of processed Cassia obtusifolia L. seed powder May reduce body weight and cholesterol in overweight patients with schizophrenia: A 36-week randomized, double-blind, controlled trial of high and low doses.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity in patients with schizophrenia is related to antipsychotic drug use, hypertension, diabetes, and dyslipidemia, which are critical risk factors for cardiovascular disease. Cassia seed is a traditional Chinese medicine that can be used to treat various eye disorders. Anthraquinone-containing Cassia seed were used to lower serum levels of fat and cholesterol. AIM OF STUDY: The effects of Cassia seed powder on body weight and lipids were investigated in overweight or obese patients with schizophrenia. METHODS: The present study was designed as a double-blind, randomized, controlled trial. Ninety-four patients with schizophrenia who were overweight or obese were assigned to a control group (CG, 47 patients) and treatment group (TG, 47 patients) that received low dose Cassia seed power (0.3 g once daily) and Cassia seed powder (3.0 g once daily), respectively, for 36 weeks. The main outcome was the change in body mass index and waist circumference (WC). The secondary outcome was the change in serum lipids, C-reactive protein, interleukin-6, and glycated hemoglobin. RESULTS: Seventy-four patients completed the study (n = 36, CG; n = 38, TG). WC was significantly lower at the second (24 weeks, 98.63 ± 9.44 vs 95.80 ± 10.26 cm, p = 0.023), third (36 weeks, 98.35 ± 9.46 vs 95.05 ± 10.07 cm, p = 0.002), and fourth (48 weeks, 98.78 ± 9.48 vs 93.73 ± 10.28 cm, p < 0.001) follow-ups than at baseline in the TG, but only significantly lower than baseline at the fourth follow-up (100.78 ± 13.98 vs 94.03 ± 9.74 cm, p = 0.006); no significant difference in CG was observed at both the second (101.03 ± 13.62 vs 97.35 ± 8,29 cm, p = 0.08) and third (100.55 ± 13.69 vs 96.55 ± 8.29 cm, p = 0.066) follow-up. The difference in serum total cholesterol and low-density lipoprotein levels between the baseline and the third follow-up was greater in the TG than in the CG (149.68 ± 34.85 vs 179.08 ± 75.87 mg/dL, p = 0.033; 84.40 ± 28.06 vs102.08 ± 34.12 mg/dL, p = 0.015, respectively). CONCLUSION: In patients with schizophrenia who were overweight or obese, oral administration of Cassia seed powder (3.0 g) for 24 weeks and 36 weeks reduced WC, and oral administration of Cassia seed powder for 36 weeks reduced total cholesterol and low-density lipoprotein levels, suggesting that Cassia seed powder aids the management of patients with schizophrenia who are overweight or obese. However, these results are preliminary, and future studies should use larger sample sizes, multiple testing centers, and multiple dosing.

[Effect of electroacupuncture on gut microbiota and serum IL-1ß and IL-18 in rats with vascular dementia based on principle of "curing brain disorders by treating intestines"].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui"(GV20), "Dazhui"(GV14), "Shenshu" (BL23)and "Zusanli"(ST36) on the intestinal flora and serum interleukin (IL)-1ß and IL-18 contents in vascular dementia (VD) rats. METHODS: SD rats were randomized into sham operation, VD model, GV20+GV14+BL23 (EA-basic acupoints), and EA-basic acupoints+ST36 and EA-basic acupoints+probiotics groups (n=10 in each group). EA (10 Hz/50 Hz) was conducted for 30 min, once daily for 4 consecutive weeks. Rats of the EA-basic acupoints+probiotics received gavage of probiotics (2 mL/d containing 2.0×109 CFU of live bifidobacterium), once a day for 4 weeks, and those of the EA-basic acupoints and EA-basic acupoints+ST36 groups received gavage of the same dose of normal saline. The Morris water maze test was used to evalua-te the rats' lear-ning and memory ability before and after the treatment. The serum IL-1ß and IL-18 levels were determined by ELISA, and the histopathological changes of the intestinal mucosa were observed by H.E. staining. The ultrastructural changes of hippocampal neurons were observed by using transmission electron microscopy and 16S rDNA sequencing technique was used to analyze the composition of intestinal microbiome. RESULTS: Compared with the sham operation group, the escape latency, serum levels of IL-1ß and IL-18, as well as the relative abundance of harmful bacteria (including Catabacter, obinsoniella and Desulfovibrio) in the intestine were significantly increased (P<0.01). In comparison with the model group, the escape latency, serum levels of IL-1ß and IL-18 in the three treatment groups, and the relative abundance of harmful bacteria (such as the Catabacter, Robinsoniella and Desulfovibrio) in the EA-basic acupoints+ST36 group were down-regulated obviously(P<0.05,P<0.01), and the relative abundance of Clostridiales-unclassified in both EA-basic acupoints+probiotics and EA-basic acupoints+ST36 groups was significantly up-regulated (P<0.05). The effects of EA-basic acupoints+ST36 and EA-ba-sic acupoints+probiotics were significantly superior to that of EA-basic acupoints in down-regulating IL-18 content (P<0.05). H.E. staining showed atrophy of the whole mucosal layer, loss of goblet cells, destruction of glands, infiltration of a large number of inflammatory cells, and transmission microscope displayed fuzziness of the nucleus membrane boundary, cystic dilation of the rough endoplasmic reticulum with unclear structure swelling of the mitochondria, and disordered arrangement or dissolution of the inner cristae in the model group, which was relatively milder in the EA-basic acupoints+ST36 and EA-basic acupoints+probiotics groups. CONCLUSION: EA of GV20+GV14+BL23+ ST36 can improve the cognitive dysfunction of VD model rats, which may be related to its function in regulating the imbalance of intestinal microbiota, thereby inhibiting the peripheral inflammatory factor.

Matrine injection inhibits pancreatic cancer growth via modulating carbonic anhydrases- a network pharmacology-based study with in vitro validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Matrine injection is a complex mixture of plant bioactive substances extracted from Sophora flavescens Aiton and Smilax glabra Roxb. Since its approval by the Chinese Food and Drug Administration (CFDA) in 1995, Matrine injection has been clinically used as a complementary and alternative treatment for various cancers; however, the underlying mechanism of pancreatic cancer treatment is yet to be elucidated. AIM OF THE STUDY: The present study explores the potential mechanism of matrine injection on pancreatic cancer through network pharmacology technique and in vitro experimental validation. MATERIALS AND METHODS: Genes differentially expressed in pancreatic cancer were obtained from the Gene Expression Omnibus (GEO) database (GSE101448). The potential active components of matrine injection were selected following a literature search, and target prediction was performed by the SwissTarget Prediction database. Overlapping genes associated with survival were screened by the Gene Expression Profiling Interactive Analysis (GEPIA) database. In vitro experimental validation was performed with cell counting kit-8 (CCK-8) assay, apoptosis detection, cell cycle analysis, immunoblotting, and co-immunoprecipitation of the identified proteins. RESULTS: One thousand seven hundred genes differentially expressed among pancreatic tumor and non-tumor tissues were screened out. Sixteen active components and 226 predicted target genes were identified in matrine injection. A total of 25 potential target genes of matrine injection for the treatment of pancreatic cancer were obtained. Among them, the prognostic target genes carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) based on the GEPIA database are differently expressed in tumors compared to adjacent normal tissue. In vitro experiments, the results of CCK-8 assay, apoptosis and cell cycle analysis, immunoblotting, and co-immunoprecipitation showed that matrine injection inhibited Capan-1 and Mia paca-2 proliferation, arrested the cell cycle at the S phase, and induced apoptosis through up-regulated CA12 and down-regulated CA9. CONCLUSIONS: In this study, bioinformatics and network pharmacology were applied to explore the treatment mechanism on pancreatic cancer with matrine injection. This study demonstrated that matrine injection inhibited proliferation, arrested the cell cycle, and induced apoptosis of pancreatic cancer cells. The mechanism may be related to the induction of CA12 over-expression, and CA9 reduced expression. As novel targets for pancreatic cancer treatment, Carbonic anhydrases require further study.

Deep learning-based auto-segmentation of clinical target volumes for radiotherapy treatment of cervical cancer.

OBJECTIVES: Because radiotherapy is indispensible for treating cervical cancer, it is critical to accurately and efficiently delineate the radiation targets. We evaluated a deep learning (DL)-based auto-segmentation algorithm for automatic contouring of clinical target volumes (CTVs) in cervical cancers. METHODS: Computed tomography (CT) datasets from 535 cervical cancers treated with definitive or postoperative radiotherapy were collected. A DL tool based on VB-Net was developed to delineate CTVs of the pelvic lymph drainage area (dCTV1) and parametrial area (dCTV2) in the definitive radiotherapy group. The training/validation/test number is 157/20/23. CTV of the pelvic lymph drainage area (pCTV1) was delineated in the postoperative radiotherapy group. The training/validation/test number is 272/30/33. Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD) were used to evaluate the contouring accuracy. Contouring times were recorded for efficiency comparison. RESULTS: The mean DSC, MSD, and HD values for our DL-based tool were 0.88/1.32 mm/21.60 mm for dCTV1, 0.70/2.42 mm/22.44 mm for dCTV2, and 0.86/1.15 mm/20.78 mm for pCTV1. Only minor modifications were needed for 63.5% of auto-segmentations to meet the clinical requirements. The contouring accuracy of the DL-based tool was comparable to that of senior radiation oncologists and was superior to that of junior/intermediate radiation oncologists. Additionally, DL assistance improved the performance of junior radiation oncologists for dCTV2 and pCTV1 contouring (mean DSC increases: 0.20 for dCTV2, 0.03 for pCTV1; mean contouring time decrease: 9.8 min for dCTV2, 28.9 min for pCTV1). CONCLUSIONS: DL-based auto-segmentation improves CTV contouring accuracy, reduces contouring time, and improves clinical efficiency for treating cervical cancer.

Desensitization of TRPV1 Involved in the Antipruritic Effect of Osthole on Histamine-Induced Scratching Behavior in Mice.

Osthole has been isolated from the fruits of Cnidium monnieri (L.) Cusson, which has been used in Chinese traditional medicine to treat pruritic disorders for a long time. However, the antipruritic mechanism of osthole is not fully understood. In the present study, using calcium imaging, molecular docking, and animal scratching behavior, we analyzed the pharmacological effects of osthole on transient receptor potential vanilloid 1 (TRPV1). The results showed that osthole significantly induced calcium influx in a dose-dependent manner in dorsal root ganglion (DRG) neurons. Osthole-induced calcium influx was inhibited by AMG9810, an antagonist of TRPV1. Osthole and the TRPV1 agonist capsaicin-induced calcium influx were desensitized by pretreatment with osthole. Furthermore, molecular docking results showed that osthole could bind to TRPV1 with a hydrogen bond by anchoring to the amino acid residue ARG557 in the binding pocket of TRPV1. In addition, TRPV1 is a downstream ion channel for the histamine H1 and H4 receptors to transmit itch signals. Osthole attenuated scratching behavior induced by histamine, HTMT (histamine H1 receptor agonist), and VUF8430 (histamine H4 receptor agonist) in mice. These results suggest that osthole inhibition of histamine-dependent itch may be due to the activation and subsequent desensitization of TRPV1 in DRG neurons.

Effects of Selenium Auricularia cornea Culture Supplementation on Growth Performance, Antioxidant Status, Tissue Selenium Concentration and Meat Quality in Growing-Finishing Pigs.

Selenium Auricularia cornea culture (SAC) is a new source of organic selenium. Two experiments were conducted to determine the available energy of SAC fed to pigs and to evaluate the effects of dietary SAC supplementation on growth performance, serum biochemical profiles, fecal short chain fatty acids (SCFA), meat quality, tissue selenium concentration, and oxidative stability of fresh meat in growing-finishing pigs. In Experiment (Exp.) 1, 12 barrows with average body weight (BW) of 42.40 ± 5.30 kg were randomly allotted to two groups and fed the basal diet and SAC-supplemented diet, individually. In Exp. 2, 96 growing-finishing pigs (BW: 91.96 ± 7.55 kg) were grouped into four dietary treatments; each treatment contained six replicates with four pigs per replicate. The four treatments fed a control diet and three experimental diets supplemented with 0.6%, 1.2%, and 2.4% SAC, respectively. The trial lasted for 45 days. The results revealed that digestible energy (DE) of SAC was 11.21 MJ/kg. The average daily gain (ADG) was improved in pigs fed 1.2% and 2.4% SAC during day 24 to 45 and the overall period. Dietary 1.2% and 2.4% SAC supplementation had a lower F/G (p < 0.05) than the control diet during different stages. Dietary SAC supplementation increased fecal butyrate contents (p < 0.05), and pigs fed 1.2% and 2.4% SAC diets had a higher MCT1 mRNA expression (p = 0.04) in the colon. Pigs fed 2.4% SAC had higher GSH-Px contents (p < 0.05) in serum, liver, and longissimus dorsi muscle (LDM) than those in the control group. The 2.4% SAC-supplemented group revealed a higher Se content (p < 0.05) in LDM and a lower MDA concentration (p < 0.05) in fresh meat during the simulated retail display on day six. In conclusion, this study suggested that SAC was more effective in improving growth, enhancing the antioxidant status, depositing Se in muscle, and increasing meat oxidative stability of pigs.

[Effects of ERα gene overexpression on bone mineral density and calcium and phosphorus metabolism inovariectomized osteoporosis mice].

Objective: To investigate the effects of estrogen receptor α (ERα) gene overexpression on bone metabolism and calcium and phosphorus metabolism in ovariectomized osteoporosis mice, and to provide experimental basis for targeted gene therapy of osteoporosis. Methods: Thirty SPF female mice were randomly divided into sham operation group, model group and ERα overexpression group with 10 mice in each group. After the model was established, the ERα overexpression group was transfected with recombinant adenovirus vector carrying mouse ERα gene by intraspinal injection. The model group was transfected with empty virus, and the sham operation group was not treated. The expression of ERα gene in bone tissue of mice was detected by quantitative Real-time PCR (qRT-PCR). Bone mineral density (BMD) of mouse femur was measured after modeling. Trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular segregation (Tb.Sp), bone volume fraction (BV/TV) and biomechanical strength of femur were measured by micro-CT scanning. Serum levels of calcium (Ca), phosphorus (P), osteocalcin (BGP) and alkaline phosphatase (ALP) were measured by automatic biochemical analyzer. The expressions of tissue inhibitor of metalloproteinases 1 (TIMP-1) and monocyte chemotactic protein 1 (MCP-1) in bone homogenate were detected by Immunohistochemistry. Results: Compared with sham operation group, the expression level of ERα gene in bone tissue of model group was decreased significantly, the levels of BMD, BV/TV, Tb. Th, maximum load, rigidity coefficient, Ca and P were decreased, while the levels of Tb. Sp, BGP and ALP were increased significantly (P＜0.05). Compared with the sham operation group, the expression level of TIMP-1 protein in the bone tissue of the model group was significantly decreased, while that of MCP-1 protein was increased, while that of the ERα overexpression group was increased while that of MCP-1 was decreased (P＜0.05).The levels of ERα gene expression, BMD, BV/TV, TB. Th, maximum load, rigidity coefficient, Ca and P in the ERα overexpression group were significantly higher than those in the model group, while Tb. Sp, BGP and ALP were significantly lower (P＜0.05). Compared with the sham operation group, mean optical density of TIMP-1 in the bone tissue of the model group was significantly decreased, while that of MCP-1 was significantly increased, and that of the ERα overexpression group was significantly increased while that of MCP-1 was significantly decreased (P＜0.05). Conclusion: ERα gene overexpression can improve osteoporosis by regulating bone mineral density, bone parameters, bone metabolism, calcium and phosphorus metabolic indicators and the expression levels of TIMP-1 and MCP-1 in tissues.

Treatment effect and mechanism of Fu's subcutaneous needling among patients with shoulder pain: A retrospective pilot study.

Fu's subcutaneous needling (FSN) is a new acupuncture therapy developed from acupuncture and Traditional Chinese Medicine models. The aim of this study was to investigate the effect of FSN on shoulder pain. In this retrospective comparative study, patient case files with shoulder pain (Group A) treated with FSN were analyzed and compared with the same number of patients with shoulder pain (Group B) treated with conventional acupuncture and physical therapy. Motion-related pain (MRP), pain under pressure (PUP), and Range of motion (ROM) were collected before and after intervention. In the 68 patients, there were 39 males and 29 females, aged 21-53 years old (mean ± SD = 36.4 ± 8.15) with onset time ranging from 1 day to 7 days (mean ± SD = 3.15 ± 1.73). MRP, PUP, and ROM scores were improved after FSN intervention (p < .05). There were significant differences between group A and group B in MRP, PUP, and ROM scores after FSN intervention and 1 week follow-up (p < .05). No adverse events, such as fainting and sharp pain, occurred during the treatment process. FSN can be an effective rehabilitation intervention for improving shoulder pain and shoulder range of motion.