Aldehyde group pendant-grafted pectin-based injectable hydrogel.

Periodate oxidation has been the widely accepted route for obtaining aldehyde group-functionalized polysaccharides but significantly influenced the various physicochemical properties due to the ring opening of the backbone of polysaccharides. The present study, for the first time, presents a novel method for the preparation of aldehyde group-functionalized polysaccharides that could retain the ring structure and the consequent rigidity of the backbone. Pectin was collected as the representative of polysaccharides and modified with cyclopropyl formaldehyde to obtain pectin aldehyde (AP), which was further crosslinked by DL-lysine (LYS) via the Schiff base reaction to prepare injectable hydrogel. The feasibility of the functionalization was proved by FT-IR and 1H NMR techniques. The obtained hydrogel showed acceptable mechanical properties, self-healing ability, syringeability, and sustained-release performance. Also, as-prepared injectable hydrogel presented great biocompatibility with a cell proliferation rate of 96 %, and the drug-loaded hydrogel exhibited clear inhibition of cancer cell proliferation. Overall, the present study showed a new method for the preparation of aldehyde group-functionalized polysaccharides, and the drug-loaded hydrogel has potential in drug release applications.

Efficacy and safety of community-based moxibustion for primary hypertension: A randomized controlled trial with patient preference arms.

Moxibustion has been shown to have a potential antihypertensive effect, but its applicability for the primary care of hypertension is unclear. The authors conducted a multicenter randomized controlled trial (RCT) with patient preference arms to investigate the effect, safety, cost-effectiveness, and compliance of moxibustion in community patients with hypertension. Patients with primary hypertension were enrolled from seven communities randomly or nonrandomly assigned to receive self-administered moxibustion + the original hypertensive regimen or the original hypertensive regimen alone for 6 months. The authors mainly evaluated the effects of moxibustion on hypertensive outcomes and adverse events. As a result, a total of 160 and 240 patients were recruited into the randomized and nonrandomized arms, respectively, with 87.5% completing the follow-up. At month 6, there was a significantly greater reduction in systolic blood pressure (SBP) (difference: -10.57 mmHg), a higher proportion of responders (82.2% vs. 53.7%; odds ratio 4.00), and better improvements in hypertensive symptoms and quality of life (QoL) in the moxibustion group than in the control group in the randomized population, but there was no significant between-group difference in diastolic blood pressure (DBP). The nonrandomized findings showed the same effect direction for all outcomes, except for DBP. All moxibustion-related adverse events were mild. In conclusion, moxibustion can reduce SBP and improve hypertensive symptoms and QoL in community patients with hypertension, with good safety and low cost, although its effect on DBP remains uncertain. The findings suggest that moxibustion may be an appropriate technique for community primary care of hypertension.

A clinical herbal prescription Gu-Shu-Kang capsule exerted beneficial effects on the musculoskeletal system of dexamethasone-treated mice by acting on tissue IGF-1 signalling pathway.

CONTEXT: Gu-Shu-Kang (GSK) is a clinical traditional Chinese medicine prescription for the treatment of primary osteoporosis. OBJECTIVE: This study investigates the protection of GSK against dexamethasone (Dex)-induced disturbance of musculoskeletal system in male mice and to identify the underlying mechanism. MATERIALS AND METHODS: Male C57BL/6 mice in Dex-treated groups were orally administered (i.g.) with vehicle, low dose (0.38 g/kg), middle dose (0.76 g/kg), or high dose (1.52 g/kg) of GSK for 8 weeks. A control group was designed without any treatment. The quadriceps femoris, tibialis anterior and gastrocnemius were harvested. Molecular expression was determined by RT-PCR and immunoblotting. RESULTS: Treatment with GSK enhanced weight-loaded swimming time (from 411.7 ± 58.4 s in Dex group to 771.4 ± 87.3 s in GSK-M) and grip strength (from 357.8 ± 23.9 g in Dex group to 880.3 ± 47.6 g in GSK-M). GSK produced a rise in cross-sectional area of myofibers and promoted a switching of glycolytic-to-oxidative myofiber. The administration with GSK affected expression of muscle regulatory factors shown by the down-regulation in MuRF-1 and atrogin-1 and the up-regulation in myogenic differentiation factor (MyoD) and myosin heavy chain (MHC). GSK stimulated tissue IGF-1 signalling pathway (IGF-1R/PI3K/Akt), not only in skeletal muscle but also in bone associated with the amelioration of trabecular bone mineral density and the improvement of osteogenesis. CONCLUSIONS: These findings revealed the potential mechanisms involved in the beneficial effects of Gu-Shu-Kang on musculoskeletal system in mice with challenging to dexamethasone, and this prescription may have applications in management for muscle atrophy and osteoporosis triggered by glucocorticoid.

External Application of Traditional Chinese Medicine in the Prevention and Treatment of Nausea and Vomiting Caused by Chemotherapy of Non-Small-Cell Lung Cancer: A RCT Study.

Objective: To investigate the external application of traditional Chinese medicine in the prevention and treatment of nausea and vomiting caused by chemotherapy of non-small-cell lung cancer. Methods: This is a prospective trial. A total of 114 patients with non-small-cell lung cancer who were hospitalized in our hospital from October 2020 to March 2022 were selected and randomly divided into the research group and the control group at the ratio of 1 : 1. The control group received chemotherapy + tropisetron 4 mg intravenous drip 30 minutes before chemotherapy./day × 3 days. The research group received chemotherapy + intravenous infusion of tropisetron 4 mg 30 minutes before chemotherapy, once a day for 3 days + external application of traditional Chinese medicine for 5 days. The therapeutic effects of the two groups of patients were compared. Results: After treatment, the serum creatinine, urea nitrogen, and endogenous creatinine in the research group were better than those in the control group (t = 15.943, 12.005, and 13.325; P=0.001, 0.005, and 0.005). After treatment, ALT and TBIL in the research group were superior to those in the control group (t = 11.583, 10.012, and 9.426; P=0.001, 0.002, and 0.001). After treatment, the physiological status, social/family status, emotional status, and family status of the research group were significantly better than those in the control group (t = 16.274, 5.379, 5.142, and 8.153; P=0.005, 0.000, 0.002, and 0.001). After treatment, the ECOG score and KPS score (82.46 ± 4.61) of the research group were significantly different from those of the control group (t = 11.913 and 9.357; P=0.035 and 0.001). The effective rate (χ 2 = 11.724; P=0.000) of the research group was higher but the incidence of adverse reaction (χ 2 = 4.294; P=0.001) was lower than that of the control group. Conclusion: External application of traditional Chinese medicine can significantly reduce nausea and vomiting caused by chemotherapy of non-small-cell lung cancer and can improve the patient's body and quality of life, which is worthy of clinical research and promotion.

Protective effects of Ligularia fischeri root extracts against ulcerative colitis in mice through activation of Bcl-2/Bax signalings.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by high levels of proinflammatory cytokines and epithelial barrier dysfunction. The root of Ligularia fischeri (Ledeb.) Turcz. is a traditional Chinese medicinal herb with diverse therapeutic properties, which has been successfully used to treat inflammation-related diseases. However, little is known about its effect and mechanism against UC. PURPOSE: To investigate the efficacy and mechanism of L. fischeri root extracts against UC. METHODS: L. fischeri root samples were prepared using the alcohol extraction method and liquid-liquid extraction method. A dextran sodium sulfate-induced UC mouse model and a lipopolysaccharide (LPS)-induced inflammatory cell model were employed in the present study. Cell apoptosis was detected by TUNEL staining, and an enzyme-linked immunosorbent assay was used to quantify the abundance of inflammatory factors in tissues. Hematoxylin and eosin staining and Masson staining were employed to analyze drug toxicity to the liver and kidney. A myeloperoxidase (MPO) assay kit was used to detect neutrophil infiltration in colon tissues. RT-qPCR was then employed to quantify the transcriptional levels of proinflammatory and apoptotic-related genes, while tight junction and apoptosis-related proteins were quantified via western blotting. Gas Chromatography/Mass Spectrometry analysis was then performed to identify the natural compounds in L. fischeri root extracts. RESULTS: The water decoction extract, methanol extract, and especially the chloroform extract (CE) exerted potent therapeutic effects in UC mice. Similar to the positive control group (5-aminosalicylic acid), oral administration of CE (30, 60, and 90 mg/kg/d) elicited distinct therapeutic effects on UC mice in the medium- and high-dose groups. CE decreased disease activity index, histopathological score, and MPO level significantly, and effectively retained the colon length. Furthermore, CE significantly reduced the levels of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α and enhanced the expression of tight junction proteins, such as zonula occludens (ZO)-1, ZO-2, claudin-1, and occludin, as well as the transcriptional levels of mucins, such as MUC-1 and MUC-2, in UC mice. Notably, CE prevented apoptosis of colonic epithelial cells by up-regulating Bcl-2 and down-regulating Bax. Also, CE inhibited the secretion of pro-inflammatory cytokines and apoptosis in LPS-induced RAW264.7 macrophages via the activation of Bcl-2/Bax signals. CONCLUSIONS: Collectively, L. fischeri root extracts, especially CE, have obvious therapeutic effects against UC. CE reduces inflammation and protects the intestinal epithelial cells and intestinal epithelial barrier via activation of the Bcl-2/Bax signaling pathway, and may be a promising therapeutic agent for UC treatment.

Community-based heat-sensitive moxibustion for primary hypertension: study protocol for a randomized controlled trial with patient-preference arms.

BACKGROUND: Low- and middle-income countries have a high prevalence of primary hypertension, but its treatment and control are often low. Heat-sensitive moxibustion (HSM), an innovative acupoint stimulation technique, may be effective for treating hypertension and thus used appropriately in primary healthcare. The objective of this study is to investigate whether HSM is effective and safe for the treatment of primary hypertension in the community. METHODS: This study is a multicenter, pragmatic, randomized controlled trial (RCT) with patient-preference arms. Four hundred patients with primary hypertension from seven communities will be enrolled. Initially, the communities will be randomly assigned into two study clusters, one using compulsory randomization and the other allowing treatment selection by patient preferences. Then, patients in the compulsory randomization cluster will be randomized to receive HSM plus their original antihypertensive regimen (HSM group) or only their original antihypertensive regimen (control group) for 6 months. Patients in the patient preference cluster may choose to receive HSM or control if they have a preference; otherwise, patients will be randomly assigned. The primary outcome is the change in systolic blood pressure from baseline; secondary outcomes include change in diastolic blood pressure, dosage of antihypertensive drugs, quality of life (QoL), severity of hypertensive symptoms, and incidence of cardiovascular events. Patient compliance with the HSM regimen, the cost-effectiveness ratio, and safety outcomes will also be evaluated. Outcome data will be collected at 6 monthly visits. DISCUSSION: This trial will provide important evidence regarding HSM as a technique for primary hypertension in primary healthcare settings. Given the randomization with patient preferences considered, the trial will also allow analyzing patient-preference effects and the comparison of randomized and nonrandomized samples, to improve the robustness and extrapolation of study conclusions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04788563 . Registered on March 9, 2021.

Panax Notoginseng Saponins Protect H9c2 Cells From Hypoxia-reoxygenation Injury Through the Forkhead Box O3a Hypoxia-inducible Factor-1 Alpha Cell Signaling Pathway.

ABSTRACT: Panax notoginseng saponins (PNS) are commonly used in the treatment of cardiovascular diseases. Whether PNS can protect myocardial ischemia-reperfusion injury by regulating the forkhead box O3a hypoxia-inducible factor-1 alpha (FOXO3a/HIF-1α) cell signaling pathway remains unclear. The purpose of this study was to investigate the protective effect of PNS on H9c2 cardiomyocytes through the FOXO3a/HIF-1α cell signaling pathway. Hypoxia and reoxygenation of H9C2 cells were used to mimic MIRI in vitro, and the cells were treated with PNS, 2-methoxyestradiol (2ME2), and LY294002." Cell proliferation, lactate dehydrogenase, and malonaldehyde were used to evaluate the degree of cell injury. The level of reactive oxygen species was detected with a fluorescence microscope. The apoptosis rate was detected by flow cytometry. The expression of autophagy-related proteins and apoptosis-related proteins was detected by western blot assay. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway. Furthermore, the protective effects of PNS were abolished by HIF-1α inhibitor 2ME2 and PI3K/Akt inhibitor LY294002. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway.

The efficacy of acupuncture and moxibustion for early and middle-stage osteonecrosis of the femeral head: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Osteonecrosis of the femeral head (ONFH) occurs predominantly in young- and middle-aged people, and the disability rate is high in the late stage of the disease and most patients have to undergo total hip replacement. Clinically, increasing attention is paid to intervening early and middle-stage ONFH so as to delay its progress. Acupuncture and moxibustion (AM) is a unique method for treating ONFH in China. This study aims to summarize the advantages of AM for the treatment of ONFH. METHODS: A comprehensive literature search was conducted on the database with languages of English and Chinese. The medical subject titles used are "Osteonecrosis of the femoral head" and "acupuncture and moxibustion." Related words in the title or abstract including but were not limited to "necrosis of the femoral head," "avascular necrosis of the femoral head," "ischemic necrosis of the femoral head," "caput femoris necrosis," "bone paralysis," "bone erosion," and "bone atrophy." RESULTS: Nine randomized controlled trials were identified in this meta-analysis that included 630 subjects. Meta-analysis showed that the trial group that treated with conventional therapy combined with AM had a higher effective rate (Z = 2.27 P = 0.02) and excellent and good rate (Z = 4.85 P < 0.00001) and Harris hip function score (HHS) (Z = 2.31 P = 0.02) and lower incidence of related adverse reactions during treatment (Z = 2.82 P = 0.005) compared with the control group that treated with conventional therapy alone. CONCLUSIONS: AM for early and middle-stage ONFH is an effective and relatively safe intervention, which can improve the effective rate and excellent and good rate and HHS, and reduce the adverse reaction rate. Clinically, early and middle-stage ONFH can be intervened by combining with AM while taking conventional therapy to improve the efficacy.

The effectiveness and safety of acupuncture for allergic rhinitis: Protocol for an overview of systematic reviews and meta-analyses.

BACKGROUND: Allergic rhinitis (AR) is one of the most common allergic disorders globally. Several systematic reviews and meta-analyses have reported the effectiveness of acupuncture for patients with AR. However, the evidence has not been systematically synthesized. This overview aims to map, synthesize, and assess the reliability of evidence generated from these systematic reviews (SRs) and meta-analyses of acupuncture for AR. METHODS: A Comprehensive literature search will be conducted through the PubMed, Embase, the Cochrane Library of Systematic Reviews, the China National Knowledge Infrastructure Database, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database from inception until January 2020. Additionally, the PROSPERO database and the reference list of included studies will be searched for unpublished, ongoing, or recently completed SRs and meta-analyses. The reviewers will identify reviews independently and extract data according to the methodological guidelines for overviews provided by the Cochrane Collaboration. The risk of bias will be assessed based on the Risk of Bias in Systematic Reviews. The methodological and reporting quality of the included reviews will be assessed using the Assessing the Methodological Quality of Systematic Reviews (V.2) tool and the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. The outcomes of interest include total nasal symptom score, rhinoconjunctivitis quality-of-life questionnaire, immunoglobulin E, visual analog scale, laboratory examination, and side effects. The quality of evidence of outcomes will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation. The evidence will be synthesized where appropriate based on patient subgroups and outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required for overviews. We plan to publish results in peer-reviewed journals and present at international and national academic, clinical, and patient conferences. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This overview will provide comprehensive evidence of acupuncture for patients with AR. PROSPERO REGISTRATION NUMBER: CRD42019140756.

Spatial Divergence of PHR-PHT1 Modules Maintains Phosphorus Homeostasis in Soybean Nodules.

Maintaining phosphorus (Pi) homeostasis in nodules is the key to nodule development and nitrogen fixation, an important source of nitrogen for agriculture and ecosystems. PHOSPHATE-TRANSPORTER1 (PHT1) and its regulator PHOSPHATE-STARVATION-RESPONSE1 (PHR1), which constitute the PHR1-PHT1 module, play important roles in maintaining Pi homeostasis in different organs. However, the PHR1-PHT1 module and its functions in nodules remain unknown. We identified one PHT1 (GmPHT1;11) and four PHR1 (GmPHR1) homologs in soybean (Glycine max) plants, which displayed specific expression patterns in different tissues in nodules, similar to previously reported GmPHT1;1 and GmPHT1;4 Through the integration of different approaches, GmPHR-GmPHT1 modules were confirmed. Combining our results and previous reports, we established multiple GmPHR-GmPHT1 modules acting in the infected or noninfected tissues in nodules. A single GmPHR had more than one GmPHT1 target, and vice versa. Therefore, overlapping and cross-talking modules monitored the wave of available Pi to maintain Pi homeostasis in nodules, which sequentially regulated nodule initiation and development. High levels of GmPHT1;11 enhanced Pi accumulation in nodules, increased nodule size, but decreased nodule number. Nitrogenase activity was also enhanced by GmPHT1;11 Our findings uncover GmPHR-GmPHT1 modules in nodules, which expands our understanding of the mechanism of maintaining Pi homeostasis in soybean plants.

Effectiveness and safety of indirect moxibustion for the treatment of allergic rhinitis: A protocol for systematic review and meta-analysis of RCTs.

BACKGROUND: Allergic rhinitis (AR) is a common allergic disorder worldwide. Western medicine is not optimistic about the therapeutic effect of this disease. However, moxibustion can enhance vital energy or immunity through a great number of clinical trials. Thus, the aim of this systematic review and meta-analysis is to systematically evaluate the effectiveness and safety of indirect moxibustion for treating AR. METHODS: We will conduct a comprehensive literature search in Medline, PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure Database, WanFang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from inception to August 2020 without any language restriction. In addition, we will retrieve the unpublished studies and the references of initially included literature manually. Reviewers will identify studies, extract data, and assess the quality independently. The outcomes of interest include: total effective rate, total nasal symptom score, total non-nasal symptom score, rhinitis quality of life questionnaire, visual analog scale, laboratory indicators (i.e., serum levels of IgE, IgA, or IgG), and adverse events. Randomized clinical trials will be collected, methodological quality will be evaluated using the Cochrane risk-of-bias assessment tool, and the level of evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Meta-analysis will be performed using RevMan 5.3.0 software. The heterogeneity test will be conducted between the studies, and P < .1 and I > 50% are the thresholds for the tests. We will utilize the fixed effects model or the random effects model according to the size of heterogeneity. RESULTS: Because the review is ongoing, no results can be reported. CONCLUSIONS: The results of this review will provide reliable evidence for effectiveness and safety of indirect moxibustion for treating AR. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. This systematic review and meta-analysis will be disseminated online and on paper to help guide clinicians. PROSPERO REGISTRATION NUMBER: CRD42019140944.

[Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats].

OBJECTIVE: To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. METHODS: A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. RESULTS: ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). CONCLUSION: Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.

[Myofascial trigger point: an indicator of acupoint sensitization].

OBJECTIVE: The present study is to investigate the characteristic distribution of primary pain points and referred pain areas in patients with knee-joint pain diseases, therefore revealing the correlation between the myofascial trigger point and acupoint sensitization. METHODS: A total of 483 patients (320 men and 163 women, 36 to 72 years in age) with knee-joint pain recruited from 4 clinical centers were observed from July, 2017 to April, 2019 in the present study. The areas of primary and referred pain in these patients were detected by thumb-pressing and marked on human anatomic atlas. RESULTS: Of the 483 enrolled participants, 336 had lesion sites or tender points around the injured knee joint, and 147 with myofascial pain syndrome showed referred pain spots (zones) in the knee joint area. In 105 patients with patellar tendonitis, epiphysitis of the tibial tubero-sity, or quadriceps tendonitis, the pain area was mainly distributed in the anterior region of the knee. In 76 patients with medial collateral ligament injury, medial meniscal lesion, goose foot bursitis or semimembranosus ending-point inflammation, the pain points mainly occurred in the medial area of the knee. In 127 patients with lateral collateral ligament, lateral meniscus lesion, iliotibial band tendonitis, popliteus or triceps tendinitis, the pain spots were found in the lateral region of the knee. In 28 patients with posterior cruciate ligament injury or popliteal fossa tendonitis, the local pain was found to be at the back of the knee. Referred pain areas were normally detected in the lateral femoral muscles (43 cases), anterior femoral muscles (39 cases), adductor group of femur (26 cases), posterior popliteal fossa muscles group (15 cases), hamstrings (13 cases) and medial leg (11 cases)．. CONCLUSION: The primary pain areas or spots of the knee injury mainly distribute around the joint, whereas those of each muscle group lesion are often located in their respective skeletal muscle. Most of the referred pain areas often occur in the distal end of skeletal muscle and around the knee joint. Primary myofascial trigger points may be considered to be an indicator of acupoint sensitization.

[Clinical observation on the distribution characteristics and rules of pressing sensitive acupoints in bronchial asthma patients].

OBJECTIVE: To compare the distribution characteristics of pressing sensitive acupoints on the body surface between bronchial asthma (BA) patients and healthy subjects, and to analyze the distribution rules of pressing sensitive acupoints in BA patients. METHODS: Seventy BA patients and 70 healthy subjects were selected in this study. The pressing sensitive acupoints were checked with finger pulp and marked on human nerve segment graph. The numbers of pressing sensitive acupoints were counted and the positional relationship between distribution of pressing sensitive acupoints and the position of meridians and nerve segment was observed. RESULTS: (1) The incidence rates of pressing sensitive acupoints in BA patients group and healthy subjects group were 91.4% (64/70) and 15.7% (11/70) respectively, and the BA patients group was higher than the healthy subjects group (P<0.01). (2) The top 3 meridians with pressing sensitive acupoints occuring in BA patients were bladder meridian of foot-taiyang, lung meridian of hand-taiyin and large intestine meridian of hand-yangming, and the most frequent pressing sensitive acupoints were Feishu（BL 13）, Xinshu（BL 15）, Chize（LU 5） and Jueyinshu (BL 14). (3) The pressing sensitive acupoints in BA patients were distributed mainly on C4, C6 and T1-T6 nerve segment. CONCLUSION: Pressing sensitive acupoints have a close correlation with physical condition, and there is a close relation between pressing sensitive acupoints distribution and corresponding meridians and nerve segments in BA patients.

Cyanidin-3-O-Glucoside and Cyanidin Protect Against Intestinal Barrier Damage and 2,4,6-Trinitrobenzenesulfonic Acid-Induced Colitis.

Anthocyanin-rich extracts have shown anti-inflammation activity in mouse colitis models. Cyanidin-3-glucoside (C3G) is one of the widespread anthocyanins in plants, and cyanidin (Cy) is the aglycone of C3G that can be generated in intestine under gut microorganism metabolism. To explore the anti-inflammatory activity of single anthocyanins compound and show the potential mechanism, the protective effects of C3G and its aglycone Cy on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice and lipopolysaccharide (LPS)-stimulated Caco-2 cellular monolayer inflammation were studied. The results showed that both C3G and Cy significantly improved the clinical symptoms and relieved the histological damage in TNBS-challenged mice. The activity of myeloperoxidase and the excretion of inflammatory cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and interferon-γ were also significantly inhibited at the administration dosage of 200 µmol/kg. In vitro studies showed that when LPS-stimulated Caco-2 cells were pretreated with C3G and Cy, the destruction of the intestinal epithelial barrier was ameliorated due to the improvement of the transepithelial electrical resistance and Lucifer yellow flux values, while there were no significant difference between C3G and Cy groups at the same dosage. Similarly, both C3G and Cy suppressed nitric oxide production and inflammatory cytokines secretion of LPS-induced Caco-2 cells. C3G and its aglycone Cy had similar anti-inflammatory activity in both colitis mice and Caco-2 cells. The results suggest that C3G and Cy may exert anti-inflammatory effects by protecting the intestinal barrier as well as by suppressing inflammatory cytokine secretion. Thus, C3G or Cy could be potential preventive agents or supplementary medicines for inflammatory bowel disease.

[Correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases].

OBJECTIVE: To observe the correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases. METHODS: In clinical research, 443 patients from 8 hospitals were recruited, including the outpatients and inpatients of Crohn's disease (n=143), ulcerative colitis (n=108), chronic appendicitis (n=87) and other intestinal diseases (n=105). The site with tenderness on the body surface and the morphological changes of local skin were observed and recorded in the patients. Using a sensory tenderness instrument, the pain threshold at the sensitization point was measured in 60 patients with ulcerative colitis. In animal experiment, SD rats were used and divided into a enteritis group (n=8), in which the enteritis model were established, and a control group (n=3), in which no any intervention was given. After the injection of Evans blue (EB) at caudal vein, the blue exudation points on the body surface were observed and the distribution rule was analyzed statistically. RESULTS: The referred pain on the body surface in the patients with intestinal diseases was mainly located in the lower abdomen (93.9%, 416/443), the lumbar region (70.9%, 314/443) and the lower legs (33.0%, 146/443). The diameter of tenderness region was 1.5 to 2.5 cm. Compared with the region without sensitization, the pain threshold of the sensitization point in the patients with ulcerative colitis was reduced significantly (P<0.001). The referred pain on the body surface in the patients with appendicitis was located in the right lower abdomen (97.7%, 85/87), the waist and back (54.0%, 47/87) and the right lower limbs on the medial side (71.3%, 62/87). The tenderness region was 1 to 2 cm in diameter and was irregular in form. After modeling of enteritis in the rats, the EB exudation points were visible from T12 to L2. CONCLUSION: Intestinal diseases induce referred pain on the body surface where is the same as or adjacent to the location of the spinal segment corresponding to the affected intestinal section. These sensitization regions are related to the locations of acupoints.

Amino acids signatures of distance-related surgical margins of oral squamous cell carcinoma.

BACKGROUND: Histological assessment of resected margins has some drawbacks. We therefore aimed to identify a panel of metabolic markers for evaluating the surgical margins of oral squamous cell carcinoma during surgery. METHODS: A total of 28 case of OSCC samples were enrolled in the study. Gas chromatography-mass spectrometry based untargeted metabolic analysis was employed to acquire the metabolic perturbation of the distance-related surgical margins in the development group. The acquired MS data were then subjected to univariate and multivariate analysis by MetaboAnalyst. Ultra-high performance liquid chromatography-tandem mass spectrometerbased targeted metabolomics for quantitative analysis of the validation group was performed to verify the results of the development group. Another 60 OSCC patients with dysplastic surgical margins were used to further validate the results of the development group by immunohistochemical examination of key enzyme expression, and correlate them with clinicopathological parameters and clinical outcomes. FINDINGS: We finally identified 4 amino acids as negative margin markers, and 6 amino acids as dysplastic margin markers. IHC analysis showed that asparagine synthetase positive expression in dysplastic surgical margins and its higher expression was correlated with tumor recurrence and local relapse-free survival. INTERPRETATIONS: We developed a panel of metabolic molecular markers to supplement the evaluation of negative and dysplastic margins. FUND: This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012); Center of Nanjing Clinical Medicine Tumor (Since 2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

[Distributive regularity of pressing sensitive acupoints in chronic non-atrophic gastritis patients].

OBJECTIVE: To compare the distribution regularity of the pressure-sensitive acupoints in patients with chronic non-atrophic gastritis (CNAG) and healthy subjects, so as to provide suitable acupoint combinations for clinical treatment. METHODS: A total of 120 volunteer subjects including 60 CNAG patients (29 men and 31 women, (40.7±10.3) years at the average age) and 60 healthy subjects (28 men and 32 women, and (40.8±10.2) years at the average age) were enrolled in the present study. The pressure-sensitive acupoints were checked by a fixed operator using his finger pulp along the body trunk and the four limbs and marked on a prepared human dermatome graph. The number of pressing sensitive acupoints were counted, and the relationship between the distribution of the detected sensitive acupoints and the position of meridians and nerve segments was analyzed. RESULTS: The incidence of pressure-sensitive acupoint in CNAG patients and healthy subjects were 86.7% and 15.0%, respectively. In 60 CNAG patients, the most frequently met sensitive acupoints were Xuehai (SP10), Zhongwan (CV13), and Zhongting (CV17) in sequence, mainly covering the Conception Vessel, Spleen Meridian of Foot-Taiyin (SP), and the Stomach Meridian of Foot-Yangming (ST). The sensitive acupoints presented a nerve-segmental distribution within T7-T10 and L3-L5. CONCLUSION: The pressure-sensitive acupoints present a nerve-segmental distribution and have a higher corresponding rate with some meridians related to the stomach, especially under diseased conditions.

Efficacy and safety of moxibustion in patients with chronic prostatitis/chronic pelvic pain syndrome: A systematic review protocol.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urogenital disease. Moxibustion is a complementary treatment option for CP/CPPS. This systematic review will assess the efficacy and safety of moxibustion as a sole or add-on therapy for CP/CPPS. METHODS: We will retrieve randomized controlled trials (RCTs) of moxibustion for CP/CPPS from the following databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, VIP, Chinese Biomedical Database, China National Knowledge Infrastructure Database, Wanfang Data, Chinese Medicine Database System, Google Scholar, Clinicaltrials.gov, and China Clinical Trial Registry from their inception to March 9, 2019, without language restrictions. RCTs comparing moxibustion with active drugs or moxibustion + drugs with these same drugs alone will be included. Primary outcomes will be the change in the total score of the National Institutes of Health's Chronic Prostatic Inflammatory States Index (NIH-CPSI) after moxibustion treatment. Secondary outcomes will include the scores of the individual NIH-CPSI domains, response to treatment of CP/CPPS, leucocyte and phosphatidylcholine corpuscle count in prostatic fluid, incidence of adverse events (AEs), and incidence of moxibustion-related AEs. The Cochrane risk of bias tool will be used for evaluating the risk of bias of individual trials. Heterogeneity will be detected by the Cochran Q test and I-square test. A random-effects model will be used to pool data in the meta-analysis. Risk ratio and weighted or standardized mean difference will be used as the effect measures. Three sets of subgroup analyses will be performed to explore the sources of heterogeneity. Where appropriate, we will assess the likelihood of publication bias based on funnel plots and quantitative tests. RESULTS: This study will produce the systematic review evidence regarding moxibustion for treating CP/CPPS based on current RCTs. CONCLUSION: This study will provide a clear basis for understanding the efficacy and adverse reactions of moxibustion treatment for CP/CPPS. PROSPERO REGISTRATION NUMBER: CRD42019121338.

Nuclear magnetic resonance-based metabolomics approach to evaluate preventive and therapeutic effects of Gastrodia elata Blume on chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.