Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Study of oxygen-deficient W18O49-based drug delivery system readily absorbed through cellular internalization pathways in tumor-targeted chemo-/photothermal therapy.

W18O49-mediated photothermal therapy (PTT) is affected by the easily oxidized property and its direct exposure to physiological environment can cause biological events, which limit its development in the biomedical field. Herein, a composite nanoparticle PVP-W18O49@C (PW@C), with significant antioxidant and excellent biocompatibility, was constructed to overcome the limitations of W18O49 in the medical field. Oxygen-deficient W18O49, with irregular defect structure, was combined with hollow carbon nanospheres treated by reflux to obtain W18O49@C (W@C) similar to sea urchins. Compared with W18O49, W@C shows stronger antioxidant properties, and it still has the ability to convert light energy to heat energy after 6 months. In addition, polyvinyl pyrrolidone is coated on the surface of W@C to construct PW@C, which significantly improves biocompatibility of W@C. The photothermal conversion efficiency of PW@C was 42.9 ± 1.3. PWD (PW@C loaded with DOX·HCl) showed controllable drug release behavior under pH and NIR stimulation, and the drug release rate reached 69.1 ± 1.6% at pH = 5.0. Notably, PWD was readily absorbed by cells through clathrin/caveolae-mediated internalization channels, and the viability of HeLa cells treated with PWD + NIR was only 21.5 ± 1.0%. Through photothermal, drug delivery/release and cytotoxicity evaluation, PWD was proved to be an effective platform for chemo-/photothermal combinational tumor therapy.

Head Acupuncture Plus Schuell's Language Rehabilitation for Post-Stroke Aphasia: A Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I2=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I2=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I2=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I2=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I2=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I2=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I2=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I2=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I2=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I2=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I2=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I2=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I2=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION: HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).

Engineering Bio-MOF/polydopamine as a biocompatible targeted theranostic system for synergistic multi-drug chemo-photothermal therapy.

In this study, a biodegradable multifunctional photothermal drug delivery nanoparticles (MPH NPs) using curcumin (Cur) as the ligand coated with hyaluronic acid (HA) was successfully prepared, which could simultaneously deliver Cur and doxorubicin hydrochloride (DOX·HCl) to overcome the common drug resistance in cancer cells. Polydopamine (PDA) as a protective shell prevents premature degradation of Cur in physiological environment and enables it to play effective medicinal value. MPH NPs can specifically recognize CD44 receptors on the surface of cancer cells for tumor targeting, with the damage of the partially released DOX to the superficial tumor cells, and then the positively charged Cur released may gradually penetrate into the cells through electron interaction to improve the problem of low permeability. In vitro cell experiments showed that hydrophobic/hydrophilic drugs co-loaded MPDH (MPH loaded with DOX·HCl) could enter the cancer cells through the endocytosis mediated by clathrin / caveolin, and the inhibition rate of MPDH on HeLa cells reached 79.28 % irradiation under 808 nm laser. MPH were composed of safe materials that have been proven to be biodegradable in human body, which avoided the disadvantages that NPs were difficult to discharge and caused damage to normal organs during long-term use.

Zingiber officinale: A Systematic Review of Botany, Phytochemistry and Pharmacology of Gut Microbiota-Related Gastrointestinal Benefits.

Ginger (Zingiber officinale Rosc.) is a traditional edible medicinal herb with a wide range of uses and long cultivation history. Fresh ginger (Zingiberis Recens Rhizoma; Sheng Jiang in Chinese, SJ) and dried ginger (Zingiberis Rhizoma; Gan Jiang in Chinese, GJ) are designated as two famous traditional Chinese herbal medicines, which are different in plant cultivation, appearances and functions, together with traditional applications. Previous researches mainly focused on the differences in chemical composition between them, but there was no systematical comparison on the similarity concerning research achievements of the two herbs. Meanwhile, ginger has traditionally been used for the treatment of gastrointestinal disorders, but so far, the possible interaction with human gut microbiota has hardly been considered. This review comprehensively presents similarities and differences between SJ and GJ retrospectively, particularly proposing them the significant differences in botany, phytochemistry and ethnopharmacology, which can be used as evidence for clinical application of SJ and GJ. Furthermore, the pharmacology of gut microbiota-related gastrointestinal benefits has also been discussed in order to explore better ways to prevent and treat gastrointestinal disorders, which can be used as a reference for further research.

Mechanisms and molecular targets of the Yu-Ping-Feng powder for allergic rhinitis, based on network pharmacology.

ABSTRACT: In traditional Chinese medicine (TCM), Yu-Ping-Feng powder (YPFP) has been used to treat allergic rhinitis (AR) for centuries. However, the mechanisms underlying its effects or its molecular targets in AR treatment are yet to be elucidated. Therefore, the active compounds of YPFP and their targets were collected and identified from the Traditional Chinese Medicine Systems Pharmacology database. Moreover, AR-associated targets were acquired from the GeneCards and Online Mendelian Inheritance in Man database. Proteins interactions network of YPFP presumed targets and AR-associated targets were examined and merged to reveal the candidate YPFP targets against AR.Cytoscape software and BisoGenet Database were employed to perform the Visualization and Integrated Discovery (Cluster Profiler R package, version: 3.8.1). Kyoto Encyclopedia of Genes and Genomes and genome pathway analyses. To identify the key target genes, a gene-pathway network has been constructed.We identified 44 effective active compounds and 622 YPFP targets. Also 1324 target genes related to AR were identified. Twenty pathways, including those of AGE-RAGE signaling, fluid shear stress, atherosclerosis, PI3K-Akt signaling, and tumor necrosis factor signaling was enriched significantly. MAPK1 was identified as the core gene, while others including RELA, AKT1, NFKBIA, IL6, and JUN, were also important in the gene-pathway network. Clearly, network pharmacology can be applied in revealing the molecular targets and mechanisms of action of complex herbal preparations.These findings suggested that YPFP could treat AR by regulating immunological functions, diminishing inflammation, and improving immunity through different pathways.

Metabolomics of Spleen-Yang deficiency syndrome and the therapeutic effect of Fuzi Lizhong pill on regulating endogenous metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Spleen-Yang deficiency (SYD) is one of the primary causes of many digestive diseases, such as ulcerative colitis (UC), and irritable bowel syndrome (IBS), but its endogenous metabolic characteristics are still unclear. Fuzi Lizhong pill (FLZP) is well-known for its powerful capacity for treating SYD; however, its mechanisms require further study. AIM OF THE STUDY: Herein, our present study aimed to investigate the essence of SYD from the perspective of metabolomics, and tried to reveal the anti-SYD action mechanisms of FLZP. MATERIALS AND METHODS: Firstly, the compound factor modeling method with the principle of "indiscipline in diet + excessive fatigue + intragastric administration of Senna water extracts" was used to establish Sprague Dawley (SD) rats as SYD model. Then, the visceral index, motilin (MTL), malonaldehyde (MDA), Interleukin 1 alpha (IL-1α), and Interleukin 6 (IL-6) levels were used to verify the anti-SYD effect of FLZP. In addition, serum samples were analyzed by UPLC-QE/MS metabolomics technique. Finally, the metabolic pathways associated with specific biomarkers were analyzed to research the possible mechanism underlying the action of FLZP. RESULTS: The expression of MTL, MDA, IL-1α, and IL-6 were regulated by FLZP, which suggested that it has relieved diarrhea and gastrointestinal motility disorder caused by SYD and had an anti-peroxidation, anti-inflammatory, and immune regulation effect. A total of 75 metabolites were found to be the potential biomarkers of SYD. Moreover, FLZP regulates 21 metabolites and 10 vital pathways including the tricarboxylic acid (TCA) cycle, sphingolipid metabolism, and histidine metabolism. CONCLUSION: SYD primarily causes disorders of amino acid metabolism, lipid metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, nucleotide metabolism, and translation. In addition, FLZP regulated carbohydrate, lipid, and amino acid metabolisms, gastrointestinal motility, digestive juice secretion, immune regulation, as well as antioxidant effects. Hence, FLZP had a good therapeutic effect on treatment of SYD. It might be a promising therapeutic agent for the treatment of SYD-related diseases.

Efficacy and Safety of Guizhi Decoction AssociatedFormulas for Allergic Rhinitis: A Systematic Review.

In this study, we aim to evaluate the efficacy and safety of Guizhi Decoction associated formulas for the treatment of allergic rhinitis. A total of seven online databases were searched to collect studies published up to Feb 23rd, 2020. Study quality of each included article was evaluated by the Cochrane Collaboration risk of bias tool. Systematic reviews were conducted based on the Cochrane systematic review method by using RevMan 5.3 Software. Among the included trials, Guizhi Decoction associated formulas alone (or plus Western medicine, or acupoint-based therapy) were main therapies in experimental groups. Interventions in control groups include Western medicine, Guizhi Decoction associated formulas alone, Chinese patent medicine, and placebo control. Primary outcomes in this study include recovery rate, accumulative marked effective rate, accumulative effective rate, and recurrence rate. Finally, 23 trials involving 2281 participants were included. Results of systematic reviews show that Guizhi Decoction and associated formulas alone, plus Western medicine or plus acupoint-based therapies, were significantly better compared with using Western medicine alone in terms of efficacy. In addition, the formulas plus nasal TCM fumigation therapy could improve effective rate for AR treatment compared to using the formulas alone. More types and cases of adverse events were reported in the control groups (Western medicine alone), but events of included trials were all mild and did not need specific medical intervention. More RCTs of high quality, and large sample size, with appropriate blinding methods or nonblinded pragmatic trials of Guizhi Decoction and associated formulas for AR are needed.

Efficacy and Safety of Acupoint Catgut Embedding for Diarrhea-Predominant Irritable Bowel Syndrome and Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

In this study, we aim to evaluate the efficacy and safety of acupoint catgut embedding for the treatment of diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome. We searched seven online databases to collect studies published up to Feb 29th, 2020. Study quality of each included article was evaluated by the Cochrane Collaboration Risk of Bias Tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.3 software. Among the included trials, acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapies, or plus oral traditional Chinese medicine were the main therapies in the experimental groups. Interventions in control groups mainly include oral western medicine alone, other acupoint-based therapies alone, or other acupoint-based therapies alone. Primary outcomes in this study include recovery rate, accumulative marked effective rate, accumulative effective rate, and recurrence rate. Finally, 30 trials involving 1889 participants were included. The results of systematic reviews and meta-analyses show that acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapy or plus oral traditional Chinese medicine was significantly better compared with using oral western medicine alone in terms of efficacy for IBS-C and IBS-D. In addition, acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapy or plus oral traditional Chinese medicine could improve the effective rate and decrease the recurrence rate for IBS-D compared with using oral western medicine, other acupoint-based therapies, or oral traditional Chinese medicine alone. Adverse events of acupoint catgut embedding include local induration, redness, swelling, and itchiness, but they were all mild and disappeared swiftly with ordinary local interventions. There is an urgent need for RCTs of high quality and large sample size and with longer treatment duration and follow-up periods of acupoint catgut embedding for IBS.

Congrong Shujing Granule-Induced GRP78 Expression Reduced Endoplasmic Reticulum Stress and Neuronal Apoptosis in the Midbrain in a Parkinson's Disease Rat Model.

The main pathological changes inherent in Parkinson's disease (PD) are degeneration and loss of dopamine neurons in the midbrain and formation of Lewy bodies. Many studies have shown that the pathogenesis of PD is closely related to endoplasmic reticulum (ER) oxidative stress. This study combined various traditional Chinese medicines to prepare Congrong Shujing granules (CSGs). The optimal dose combination of the ingredients was identified by experimental intervention in SH-SY5Y cells in vitro. A PD rat model was established by intraperitoneal injection of rotenone sunflower oil emulsion. The suspension tests were performed on the 14th day after modeling and also on the 14th day after CSG intervention (5.88 g/kg, 11.76 g/kg, and 23.52 g/kg). We evaluated the changes in motor function and the expression of neuronal cell functional marker proteins, ER stress (ERS) marker proteins, and apoptosis-related pathway proteins of neuronal cells. Changes in cellular ultrastructure were observed by electron microscopy. Our results showed that CSG treatment lengthened the duration of PD rats' gripping to the wire. 78 kDa glucose-regulated protein (GRP78) expression in the substantia nigra was significantly upregulated in the middle- and high-dose CSG groups after 14 days of treatment compared with the model group. The expression of the key dopaminergic neuron functional enzyme tyrosine hydroxylase (TH) and cerebral dopamine neurotrophic factor (CDNF) was elevated. The expression of c-Jun N-terminal kinase (JNK) and phosphorylated c-Jun decreased, and cell apoptosis was significantly reduced. Compared with the model group, the treatment groups had fewer ER fragmentation and degranulation (ribosome shedding) and abundant ER and mitochondria suggesting that CSG reduced ER stress and neuronal apoptosis in the midbrain of a PD rat model by inducing the expression of molecular chaperone GRP78.

Efficient Synthesis of Structured Phospholipids Containing Short-Chain Fatty Acids over a Sulfonated Zn-SBA-15 Catalyst.

Catalytic production of structured phospholipids (SPLs) containing short-chain fatty acids (SCFAs) in an efficient heterogeneous manner is of great importance from the standpoint of food engineering. Herein, a bifunctionalized sulfonated Zn-SBA-15 catalyst was studied for SPL synthesis through interesterification of soybean lecithin with ethyl propionate or methyl butyrate. Various characterization techniques such as pyridine Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and ultraviolet-visible diffuse reflectance spectroscopy were conducted to determine the physicochemical properties, so as to build the possible structure-reactivity relationship of the catalyst. In screening tests with commercial Amberlyst-15 or other SBA-15-type materials, the as-prepared sample showed promising catalytic performance probably owing to its mesoporous structure and cooperative role of Brönsted and Lewis acid sites. Notably, the sample was easily separated and recycled without obvious deactivation. In general, the investigated catalyst was regarded as one of the promising alternatives to otherwise expensive biocatalysts for SCFA-containing SPL production.

The efficacy and safety of acupoint application combined with western medicine for allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupoint application combined with western medicine has been used for treating allergic rhinitis widely. However, the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis are unclear. This study aims to evaluate the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis. METHODS: Randomized controlled trials of acupoint application combined with western medicine for allergic rhinitis will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of acupoint application combined with western medicine for the treatment of allergic rhinitis. CONCLUSIONS: The findings of the study will provide helpful evidence for the efficacy and safety of acupoint application combined with western medicine in the treatment of allergic rhinitis, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/NSGJH.

The efficacy and safety of Chinese herbal compound in pediatric patients with allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: We design this study to assess the efficacy and safety of Chinese herbal compound for allergic rhinitis in children. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) will be searched from the establishment of each database to July 2020. Randomized controlled trials of Chinese herbal compound for the treatment of allergic rhinitis in children will be included. Two researchers will screen the literature, extract data, and assess the risk of bias independently. Statistical analysis will be performed in RevMan 5.3. RESULTS: This study will summarize high quality evidence of randomized controlled trials on exploring the efficacy and safety of Chinese herbal compound for allergic rhinitis in children. CONCLUSIONS: The findings of study will provide scientific evidence of the efficacy and safety of Chinese herbal compound for allergic rhinitis in children for clinician and further studies. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/Q5TRZ.

Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules () in Patients with Parkinson's Disease and Syndrome of Shen (Kidney) Essence Deficiency.

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS: CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

Traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy: A systematic review and meta-analysis of 31 RCTs.

In this study, we aim to evaluate the efficiency and safety of traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy. A total of eight online databases were searched to collect studies published up to February 2019. Study quality of each included article was evaluated by the Cochrane Collaboration risk of bias tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using the RevMan 5.3 software. Traditional Chinese medicine foot bath combined with acupoint massage was the main therapy in experimental group. Interventions in control groups include western medicine, oral traditional Chinese medicine, other symptomatic treatment of western medicine, and blank control. Primary outcomes in this study include sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), total effective rate, and neuropathic syndrome score. Finally, 31 trials involving 3284 participants were included. The results of systematic reviews and meta-analyses showed that traditional Chinese medicine foot bath combined with acupoint massage was significantly better compared with the control groups in terms of the total effective rate, SNCV, MNCV, and neuropathic syndrome score. No case of adverse effect was reported. These findings show that traditional Chinese medicine foot bath combined with acupoint massage may be safer and more effective for the treatment of DPN. However, due to the low methodological quality, further research with randomized controlled trials (RCTs) of higher quality is required to prove its efficacy and better evidence for clinical treatment.

An "essential herbal medicine"-licorice: A review of phytochemicals and its effects in combination preparations.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Gancao in Chinese, GC), the dried root and rhizome of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L., is an "essential herbal medicine" in traditional Chinese medicine (TCM). There is a classic traditional Chinese medicine theory says that "nine out of ten formulas contain licorice" and licorice is considered as one of the most important herbal medicine which can reduce toxicity and increase efficacy of certain herbal medicine while it is combined application. In addition, it is a "medicine food homology" herbal medicine and also be widely used as a health food product and natural sweetener. However, no systematic literature review has been compiled to reveal its superiority. Herein, the aim of this work is to develop an overview of the state on phytochemicals, as well as effects of licorice in combination preparations, which can provide better understand the superiority of licorice and the special position in the application of TCM. Besides, ethnobotany, ethnopharmacological uses, quality control and toxicology of licorice have also been researched, which would provide reference for future clinical and basic research needs. MATERIALS AND METHODS: The information about licorice was collected from various sources including classic books about Chinese herbal medicine, and scientific databases including scientific journals, books, and pharmacopoeia. A total of 124 bibliographies, which are published from 1976 to 2019, have been searched and researched. RESULTS: In this study, the interaction of chemical compounds between licorice and toxic herbal medicine, pharmacological effect of licorice, and the effect of licorice on pharmacokinetics of toxic compounds are considered as the main mechanisms underlying the effects of licorice in combination preparations. Besides, ethnobotany, ethnopharmacological uses and chemical constituents have been summarized. CONCLUSION: This work comprehensively reviews the state on ethnobotany, ethnopharmacological uses, phytochemicals, combined applications, quality control and toxicology of licorice. It will provide systematic insights into this ancient drug for further development and clinical use.

Rapid discovery of chemical constituents and absorbed components in rat serum after oral administration of Fuzi-Lizhong pill based on high-throughput HPLC-Q-TOF/MS analysis.

BACKGROUND: Fuzi-Lizhong pill (FZLZP), which was first recorded in the Classic-"Taiping Huimin Heji Ju Fang" of the Song Dynasty, has been widely used to treat gastrointestinal disease in clinic for thousands of years in China. However, an in-depth understanding of the chemical constituents of FZLZP and its potential bioactive constituents is lacking. METHODS: A simple, sensitive and selective method of high-performance liquid chromatography coupled with quadrupole-time-of-flight high-definition mass spectrometry (HPLC-Q-TOF/MS) and automated data analysis (Agilent MassHunter Qualitative Analysis B.06.00 Workstation Software) was developed to simultaneously identify the chemical constituents of FZLZP and the absorbed prototypes as well as the metabolites in rat serum after the oral administration of FZLZP. RESULTS: Sixty-seven compounds, including alkaloids, flavonoids, triterpenes, gingerols, phenylpropanoids and volatile oil, in the FZLZP extract were tentatively characterized by comparing the retention time and mass spectrometry data and retrieving the reference literatures. Additionally, 23 prototype compounds and 3 metabolites in the rat serum samples were identified after oral administration of FZLZP, which might be the potential active components in vivo. In addition, the absorption of alkaloids decreased when Aconitum carmichaeli Debx. was in the form of combined application as a prescription compared to when it was in the form of herb powder. CONCLUSIONS: Herein, the chemical constituent in vitro and the absorbed compounds in the serum of a traditional Chinese formula, Fuzi-Lizhong pill, were fully characterized using a rapid and comprehensive analysis approach based on high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry coupled to MassHunter Qualitative Analysis software data processing approach. The results provide helpful chemical information on FZLZP for further pharmacology and active mechanism research. In view of the bioactive constitutes that basically were derived from these absorbed compounds in vivo, this work could provide a useful strategy to explore the bioactive substances of traditional Chinese medicine.

Catgut Implantation at Acupoint Reduces Immune Reaction in a Rat Model of Allergic Rhinitis.

Allergic rhinitis (AR), an IgE-mediated response, is characterized by a Th2-type immunological pattern together with mast cells activation. Acupuncture, with the use of implanted catgut, is a traditional therapy that has been widely applied for the treatment of AR. However, the exact mechanism of the immunomodulatory effects of catgut implantation at acupoint (CIAA) remains unclear, in part due to the lack of a suitable laboratory animal model. We developed and optimized a rat model of ovalbumin- (OVA-) induced allergic inflammation, characterized by increased IL-4, sIgE, and SP and reciprocal decrease of IFN-γ. In the present study, we have further used this model to address the immunomodulatory effects of CIAA stimulation at Yingxiang (LI20) and Zusanli (ST36) acupoints and to elucidate the mechanisms involved in the regulation of SP, sIgE, IL-4, IFN-γ, TLR2, and TLR4. After AR model was established via OVA challenge, the rats were randomized as follows: control, model, sham-operated, 1-week CIAA (C1), 2-week CIAA (C2), and Budesonide nasal spray. The C1 and C2 groups were subjected to the bilateral acupoint Yingxiang (LI20) and Zusanli (ST36), respectively. Multiple analyses and quantifications were performed, which revealed that due to the persistent stimulus to acupoints by embedding catgut, the C2 group improved AR symptoms, compared to the C1 group. We conclude that CIAA at the Yingxiang (LI20) and Zusanli (ST36) acupoints effectively reduces allergic symptoms and inflammatory parameters in the rat model of AR. Thus, CIAA treatment is potentially an alternative therapeutic modality in AR.

Novel hemostatic biomolecules based on elastin-like polypeptides and the self-assembling peptide RADA-16.

BACKGROUND: Safe and effective hemostatic materials are important for reducing mortality resulting from excessive hemorrhage. In this work, new biomaterials with hemostatic effects were created by fusing the gene coding for RADA-16, a self-assembling peptide with the sequence RADARADARADARADA, to the 3'-end of the open reading frame (ORF) encoding elastin-like polypeptides through gene recombination. RESULTS: The fusion proteins, termed 36R, 60R and 96R, were solubly over-expressed in Escherichia coli BL21 (DE3) based on genetic manipulation of the high-efficiency prokaryotic expression vector pET28a (+) and bacterial transformation. Western Blot analysis showed that the over-expressed proteins were the target fusion proteins. The target proteins 36R with 94.72% purity, 60R with 96.91% purity and 96R with 96.37% purity were prepared using an inverse phase transition cycle at 65 °C followed by His-tag affinity chromatography. The proliferation results of the mouse fibroblast cell line L929 and hippocampus neuron cell line HT22 indicated that the fusion proteins did not cause obvious cell toxicity. The lyophilized spongy film of the purified 36R, 60R and 96R could stop the hemorrhage of a 2 × 2 mm bleeding wound in the mouse liver after 27.21 ± 1.92 s, 18.65 ± 1.97 s and 15.85 ± 1.21 s, respectively. The hemostasis time was 21.23 ± 1.84 s for rat-tail collagen and 14.44 ± 1.33 s for RADA-16 lyophilized on gauze. The hemostatic time of three treated groups were all significantly superior to that of the negative control without any hemostasis treatment, which spontaneously stopped bleeding after 37.64 ± 1.34 s. Statistical analysis showed that the spongy film with purified 96R exhibited an exciting hemostatic effect that was superior to rat-tail collagen and close to that of RADA-16 lyophilized on gauze. CONCLUSIONS: These results revealed that the fusion proteins achieved by gene recombination technology could serve as a promising hemostatic material.