An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Efficacy and safety of yoga for the management of chronic low back pain: an overview of systematic reviews.

Background: Yoga is a non-pharmacological conservative therapeutic modality that can be employed for the management of chronic low back pain (CLBP). In this overview, we have summarized and evaluated data from current systematic reviews (SRs) on the use of yoga for CLBP. Methods: We comprehensively searched SRs on the use of yoga for CLBP in nine electronic databases from inception to September 2023. The methodological quality was evaluated using the Assessment of Multiple Systematic Review Scale-2 (AMSTAR-2). The reporting quality of the included SRs was evaluated using the Preferred Reporting Item for Systematic Review and Meta-Analysis-2020 (PRISMA-2020), and the quality of data was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers performed the screening, data extraction, and quality assessment process of SRs. Results: A total of 13 SRs were included. The results of the AMSTAR-2 indicated that the methodological quality of the included studies was relatively low. The PRISMA-2020 checklist evaluation results indicated that methodological limitations in reporting, especially regarding data processing and presentation, were the main weaknesses. The GRADE assessment indicated that 30 outcomes were rated moderate, 42 were rated low level, and 20 were rated very low level. Downgrading factors were mainly due to the limitations of the included studies. Conclusion: Yoga appears to be an effective and safe non-pharmacological therapeutic modality for the Management of CLBP. Currently, it may exhibit better efficacy in improving pain and functional disability associated with CLBP. However, the methodological quality and quality of evidence for SRs/MAs in the included studies were generally low, and these results should be interpreted cautiously.

Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I (1, 4-11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Lactobacillus rhamnosus GG aggravates vascular calcification in chronic kidney disease: A potential role for extracellular vesicles.

AIMS: Lactobacillus rhamnosus GG (LGG) is a probiotic with great promise in future clinical application, which can significantly promote bone formation. However, the effect of LGG on CKD-related vascular calcification is unclear. In this study, we aimed to investigate the effect of LGG on CKD-related vascular calcification. MATERIALS AND METHODS: After 2 weeks of 5/6 nephrectomy, CKD rats received a special diet (4 % calcium and 1.8 % phosphate) combined with 1,25-dihydroxyvitamin D3 to induce vascular calcification. Meanwhile, CKD rats in the LGG group were gavaged orally with LGG (1 × 109 CFU bacteria/day). 16S RNA amplicon sequencing was performed to analyze the effect of LGG treatment on gut microbiota composition. Furthermore, differential ultracentrifugation was utilized to extract EVs. The effects of EVs on vascular calcification were evaluated in rat VSMCs, rat aortic rings, and CKD rat calcification models. In this study, vascular calcification was assessed by microcomputed tomography analysis, alizarin red staining, calcium content determination, and the expression of osteogenic transcription factors RUNX2 and BMP2. KEY FINDINGS: LGG remarkably aggravated vascular calcification. LGG supplementation significantly altered gut microbiota composition in CKD rats, particularly increasing Lactobacillus. Interestingly, EVs presented a significant promoting effect on the development of calcification. Finally, mechanistic analysis proved that EVs aggravated vascular calcification through PI3K/AKT signaling. SIGNIFICANCE: These results do not support the supplementation of LGG in CKD-associated vascular calcification patients. Our study presented a fresh perspective on LGG with potential risks and adverse effects. CKD patients should use specific probiotic strains cautiously.

[Acupuncture at "umbilical four-acupoints" for chronic insomnia and its comorbid symptoms].

OBJECTIVE: To observe the effects of acupuncture at "umbilical four-acupoints" on chronic insomnia and its comorbid symptoms. METHODS: A total of 120 patients with chronic insomnia were randomly divided into an observation group (60 cases, 8 cases dropped off) and a control group (60 cases, 5 cases dropped off). The patients in the observation group were treated with acupuncture at regular acupoints (Baihui [GV 20] and bilateral Shenmen [HT 7], Neiguan [PC 6], Anmian [Extra]) and "umbilical four-acupoints", while the patients in the control group were treated with acupuncture at regular acupoints. Acupuncture was given once a day, 6 times a week, for a total of 3 weeks in the two groups. The Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI) scores were observed before treatment, after treatment and in follow-up of one month after treatment completion; the Beck anxiety inventory (BAI), Beck depression inventory (BDI), fatigue severity scale (FSS), and Epworth sleepiness scale (ESS) scores were observed before and after treatment; the sleep parameters of polysomnography (PSG), including sleep latency (SL), awake-up time (AT), sleep efficiency (SE) and total sleep time (TST), were observed before and after treatment using polysomnography monitor in the two groups. RESULTS: Compared with those before treatment, the PSQI and ISI scores in both groups were reduced after treatment and in follow-up (P<0.05), and the PSQI and ISI scores in the observation group were lower than those in the control group after treatment and in follow-up (P<0.05). Compared with those before treatment, the BAI, BDI, FSS and ESS scores in both groups were reduced after treatment (P<0.05), and the BAI, BDI, FSS and ESS scores in the observation group were lower than those in the control group after treatment (P<0.05). Compared with those before treatment, the SL and AT in both groups were reduced after treatment (P<0.05), while SE and TST were increased after treatment (P<0.05); after treatment, the SL and AT in the observation group were lower than those in the control group (P<0.05), while SE and TST in the observation group were higher than those in the control group (P<0.05). CONCLUSION: On the basis of regular acupoint selection, acupuncture at "umbilical four-acupoints" could improve sleep quality, alleviate the severity of insomnia, and improve the comorbid symptoms i.e. anxiety, depression, fatigue and lethargy in patients with chronic insomnia.

Efficacy and safety of Yaobitong capsule for acute lumbar disc herniation: A protocol for a multi-center randomized controlled trial.

BACKGROUND: There are few effective conservative therapies for acute lumbar disc herniation (LDH), and the choice of nonsteroidal anti-inflammatory drugs is not recommended for all patients. The purpose of this study was to compare the effect of Yaobitong capsule with celecoxib capsule, and to further confirm the safety and efficacy of Yaobitong capsule. METHODS: This study is a large sample multicenter randomized controlled trial. Eight hospitals served as sub centers to recruit patients. A total of 258 patients are divided into Yaobitong group and celecoxib group according to the ratio of 1:1. Celecoxib or Yaobitong capsule was taken orally for 14 days. Patients will complete the trial after 3 months of follow-up, and independent statisticians who are blinded to random assignment will analyze the data using SAS 9.3 software. The primary outcome was the visual analogue scale (VAS) score after 14 days of treatment, and Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and SF-12 will be regarded as secondary outcomes. Safety indexes will be recorded before and after treatment, and adverse events (AEs) will be recorded throughout this trial. DISCUSSION: This study will evaluate the efficacy and safety of Yaobitong capsule in treating LDH. The experimental results will provide evidence support to treat LDH with Yaobitong capsule.

Efficacy and safety of Daoyin and massage for lumbar disc herniation: A protocol for overview of systematic reviews.

BACKGROUND: Lumbar disc herniation (LDH) is a common disease, which can cause low back pain, sciatica, and even disability. The treatment of LDH is a global challenge. Conservative therapy with non-drugs is considered to be the first choice for patients with LDH. In recent years, an increasing number of systematic reviews and meta analyses on Daoyin and massage interventions in lumbar disc herniation have been implemented. However, the evidence quality and methodological quality of these systematic reviews/meta analyses are unknown and need to be systematically evaluated. This overview aims to systematically summarize and critically appraise the current evidence on Daoyin and massage for LDH. METHODS: Eight electronic data will be retrieved, including China National Knowledge Infrastructure (CNKI), Wanfang database (WF), China Biomedical database (CBM), Chinese Scientific Journals Database (VIP), PubMed, Cochrane Library, Web of Science (WOS), and EMBASE from their inception to March 1, 2022. The reporting quality, methodological quality, risk of bias, quality of evidence will be assessed by using The Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 (PRISMA 2020), the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Review (ROBIS), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers conducted literature screening, data extraction, and quality evaluation process. In addition, we will establish an overlap matrix and calculate the corrected covered area to evaluate the impact of overlapping areas on conclusions. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This overview will provide comprehensive evidence of Daoyin and massage for treating lumbar disc herniation. SYSTEMATIC REVIEW REGISTRATION: INPLASY202210019.

Self-Propelled and Near-Infrared-Phototaxic Photosynthetic Bacteria as Photothermal Agents for Hypoxia-Targeted Cancer Therapy.

Hypoxia can increase the resistance of tumor cells to radiotherapy and chemotherapy. However, the dense extracellular matrix, high interstitial fluid pressure, and irregular blood supply often serve as physical barriers to inhibit penetration of drugs or nanodrugs across tumor blood microvessels into hypoxic regions. Therefore, it is of great significance and highly desirable to improve the efficiency of hypoxia-targeted therapy. In this work, living photosynthetic bacteria (PSB) are utilized as hypoxia-targeted carriers for hypoxic tumor therapy due to their near-infrared (NIR) chemotaxis and their physiological characteristics as facultative aerobes. More interestingly, we discovered that PSB can serve as a kind of photothermal agent to generate heat through nonradiative relaxation pathways due to their strong photoabsorption in the NIR region. Therefore, PSB integrate the properties of hypoxia targeting and photothermal therapeutic agents in an "all-in-one" manner, and no postmodification is needed to achieve hypoxia-targeted cancer therapy. Moreover, as natural bacteria, noncytotoxic PSB were found to enhance immune response that induced the infiltration of cytotoxicity T lymphocyte. Our results indicate PSB specifically accumulate in hypoxic tumor regions, and they show a high efficiency in the elimination of cancer cells. This proof of concept may provide a smart therapeutic system in the field of hypoxia-targeted photothermal therapeutic platforms.

CoAl-layered double hydroxide nanosheet-based fluorescence assay for fast DNA detection.

In the study, CoAl-layered double hydroxide (CoAl-LDH) was prepared as a fluorescence quenching agent to detect DNA molecules. Because of its simple preparation for a large scale, excellent surface effect, good biocompatibility and high fluorescence quenching capability, the effective, rapid, and sensitive DNA detection was realized. The fluorescence quenching efficiency of LDH to 5(6)-carboxyfluorescein attached to single stranded DNA (FAM-ssDNA) was as high as 88%, and after FAM-ssDNA hybridized with the complementary DNA oligonucleotide, that to FAM-dsDNA was about 33%. The quenching mechanisms of LDH for ssDNA and dsDNA were discussed. Phosphate exposed of ssDNA played an important role in quenching effect. Compared to dsDNA, more exposed phosphate groups in ssDNA resulted in the stronger electrostatic interaction between ssDNA and LDH, and thus the higher quenching efficiency. Under optimal conditions, the linear equation was y = 38.26 + 3.37x in a linear relationship of 1-50 nM, and the correlation coefficient R2 corresponded to 0.999, and the limit of detection was calculated to be 0.79 nM (3σ). Cytotoxicity studies have shown that LDH has good biocompatibility. The study provides an effective, sensitive and safe approach for DNA detection and gives an insight for the design of LDH-based biosensing materials.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Multifunctional Magnetic Nanoplatform Eliminates Cancer Stem Cells via Inhibiting the Secretion of Extracellular Heat Shock Protein 90.

Cancer stem cells (CSCs) are responsible for malignant tumor initiation, recurrences, and metastasis. Therefore, targeting CSCs is a promising strategy for the development of cancer therapies. A big challenge for CSC-based cancer therapy is the overexpression of therapeutic stress protein, heat shock protein 90 (Hsp90), which protects CSCs from further therapeutic-induced damage, leading to the failure of treatment. Thus, efficient strategies to target CSCs are urgently needed for cancer therapy. To this end, a multifunctional nanoparticle (MNP) for CSC-based combined thermotherapy and chemotherapy is reported. This strategy dramatically suppresses tumor growth in breast CSC xenograft-bearing mice. Furthermore, a new mechanism is present that the MNP exerts its striking effects on CSCs by inhibiting the secretion of extracellular Hsp90 (eHsp90), resulting in the interruption of several key signaling pathways. These findings open new perspectives on the use of an MNP for effective CSC-based cancer treatment by inhibiting the function of eHsp90.

Nucleus-targeted nano delivery system eradicates cancer stem cells by combined thermotherapy and hypoxia-activated chemotherapy.

Many efforts have focused on the cancer stem cell (CSC) targeting nano delivery system, however, the anticancer therapy efficacy is relative low due to the highly drug-resistance and drug efflux. Nucleus-targeted drug delivery is a promising strategy for reverse the drug resistance and drug efflux of CSCs, but in vivo nucleus-targeted drug delivery has been challenging. Herein, we designed a mesoporous silica nanoparticle (MSN)-based nucleus-targeted system, which could directly target the CSCs and further enter the nucleus by the surface modification of anti-CD133 and thermal-triggered exposure of TAT peptides under an alternating magnetic field (AMF). The nucleus-targeted drug release ultimately leads to an exhaustive apoptosis of the CSCs through combined thermotherapy and hypoxia-activated chemotherapy. In vivo, the nucleus-targeted nano delivery system efficiently inhibits the tumor growth without notable side effects during the course of treatment. Molecular mechanism study illustrates that the system effectively eliminates the CSCs by blocking the hypoxia signaling pathway. This designed nucleus-targeted nano delivery system is expected to provide new insights for developing efficient platforms for CSC-targeted cancer therapy.

Porous Organic Polymer-Coated Band-Aids for Phototherapy of Bacteria-Induced Wound Infection.

Band-Aids have been widely used for wound care. For most adhesive bandages, however, they have a limited capacity to speed up the wound healing process, which in turn may cause serious wound infections. In this study, antibacterial Band-Aids, combining porphyrin-based porous organic polymers (POPs) with commercial antibiotic-free Band-Aids, are designed. Under white light irradiation, POPs can produce effective photothermal heat, as well as highly reactive oxygen species (ROS), thereby triggering the potent hyperthermia and simultaneous ROS increase on wounds. Additionally, white light is similar to sunlight, which makes POP-based Band-Aids (PBAs) ideal wound dressings for wound disinfection.

Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) decoction Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with diarrhea (IBS-D). METHOD: A multicenter, randomized, double-blind, placebo-controlled clinical trial was designed. Based on the order of inclusion, the IBS-D patients were randomly assigned to the treatment group or the placebo control group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times daily, for 8 weeks. The primary indices of efficacy included the effective rates of IBS symptom severity score (IBS-SSS) and the differences in adequate relief (AR) responder; the secondary indexes of efficacy included the changes in scores of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD) scales. The safety indices included adverse events and related laboratory tests. RESULTS: A total of 216 patients were included, with 109 in the treatment group and 107 in the control group, and finally 206 were included in the full analysis set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total effective rate was 67.6% and 40.2% for the treatment and control groups, respectively, with 95% confidence interval (CI) for difference in the effective rates between the two groups of 14.4%-40.2%; while in PPS, the total effective rate was 71.3% and 41.2% for the treatment and control groups, respectively (95% CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better efficacy in the treatment group. Both FAS and PPS showed higher AR responder in the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL, the total score and scores in various dimensions of IBS-QOL were not significantly different between the two groups (P>0.05). Both anxiety and depression scales of HAD were not significantly different between the two groups (P>0.05). No adverse events or laboratory abnormalities were found to be obviously related to the tested drugs or clinically significant. CONCLUSION: Chang'an I Recipe was more effective than placebo in the treatment of IBS-D, with no obvious adverse reactions. (No.ChiCTR-TRC-09000328).

Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study.

AIM: To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS: We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME III criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2:1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 °C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS: Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION: Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.

Metal-carbenicillin framework-based nanoantibiotics with enhanced penetration and highly efficient inhibition of MRSA.

The development of effective therapies to control methicillin-resistant Staphylococcus aureus (MRSA) infections is challenging because antibiotics can be degraded by the production of certain enzymes, for example, ß-lactamases. Additionally, the antibiotics themselves fail to penetrate the full depth of biofilms formed from extracellular polymers. Nanoparticle-based carriers can deliver antibiotics with better biofilm penetration, thus combating bacterial resistance. In this study, we describe a general approach for the construction of ß-lactam antibiotics and ß-lactamase inhibitors co-delivery of nanoantibiotics based on metal-carbenicillin framework-coated mesoporous silica nanoparticles (MSN) to overcome MRSA. Carbenicillin, a ß-lactam antibiotic, was used as an organic ligand that coordinates with Fe3+ to form a metal-carbenicillin framework to block the pores of the MSN. Furthermore, these ß-lactamase inhibitor-loaded nanoantibiotics were stable under physiological conditions and could synchronously release antibiotic molecules and inhibitors at the bacterial infection site to achieve a better elimination of antibiotic resistant bacterial strains and biofilms. We confirmed that these ß-lactamase inhibitor-loaded nanoantibiotics had better penetration depth into biofilms and an obvious effect on the inhibition of MRSA both in vitro and in vivo.

Norcantharidin Inhibits SK-N-SH Neuroblastoma Cell Growth by Induction of Autophagy and Apoptosis.

Norcantharidin, a low-toxic analog of the active anticancer compound cantharidin in Mylabris, can inhibit proliferation and induce apoptosis of multiple types of cancer cells. However, the anticancer activities of norcantharidin with respect to neuroblastoma, and its underlying mechanisms, have not been investigated. Therefore, our study was designed to determine the efficacy of norcantharidin on SK-N-SH neuroblastoma cell death and to elucidate detailed mechanisms of activity. In the present study, norcantharidin suppressed the proliferation and cloning ability of SK-N-SH cells in a dose-dependent manner, apparently by reducing the mitochondrial membrane potential and arresting SK-N-SH cells at the G2/M stage, accompanied by elevated expressions of p21 and decreased expressions of cyclin B1 and cell division control 2. Treatment by norcantharidin induced significant mitophagy and autophagy, as demonstrated by a decrease in Translocase Of Outer Mitochondrial Membrane 20 (TOM20), increased beclin1 and LC3-II protein expression, reduced protein SQSTM1/p62 expression, and accumulation of punctate LC3 in the cytoplasm of SK-N-SH cells. In addition, norcantharidin induced apoptosis through regulating the expression of B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 and B-cell lymphoma 2-associated X protein/myeloid cell leukemia 1 and activating caspase-3 and caspase-9-dependent endogenous mitochondrial pathways. We also observed an increase in phosphor-AMP-activated protein kinase accompanied with a decrease in phosphor-protein kinase B and mammalian target of rapamycin expression after treatment with norcantharidin. Subsequent studies indicated that norcantharidin participates in cellular autophagy and apoptosis via activation of the c-Jun NH2-terminal kinases/c-Jun pathway. In conclusion, our results demonstrate that norcantharidin can reduce the mitochondrial membrane potential, induce mitophagy, and subsequently arouse cellular autophagy and apoptosis; the AMP-activated protein kinase, protein kinase B/mammalian target of rapamycin, and c-Jun NH2-terminal kinases/c-Jun signaling pathways are widely involved in these processes. Thus, the traditional Chinese medicine norcantharidin could be a novel therapeutic strategy for treating neuroblastoma.

A preparation model of Chinese medicine decoction placebo.

Chinese medicine (CM) decoction placebo is one of the key factors restricting the placebo-controlled clinical trial of CM. In this article, based on the analysis of the diffificulties in preparing CM placebo, the production requirements for placebo were put forward. Moreover, in accordance with clinical practices, a production method and evaluation process of CM decoction placebo was proposed, to provide a reference for clinical research.

A multifunctional upconverting nanoparticle incorporated polycationic hydrogel for near-infrared triggered and synergistic treatment of drug-resistant bacteria.

Recently, antibiotic drug-resistant therapies have become very important due to the emergence of antibiotic-resistant bacterial strains. The development of novel antibacterial materials has received significant attention. Here, quaternized chitosan hydrogels incorporated with NaYF4:Er/Yb/Mn@photosensitizer-doped silica (UCNPs/MB) were synthesized for effective killing of both gram-positive oxacillin-resistant S. aureus (DR-S. aureus) and gram-negative kanamyclin-resistant E. coli (DR-E. coli) bacteria upon near-infrared (NIR) laser irradiation. In this system, the cationic macroporous nature of the hydrogel acts as a molecular 'anion sponge', which sucks the outer part of the anionic microbe membrane into the gel interior voids and causes microbe membrane disruption. By incorporating UCNPs/MB-doped silica into the hydrogel, we have combined photodynamic therapy (PDT) with quaternized chitosan to obtain a high therapeutic index via a synergistic effect. In vitro experiments have demonstrated that our system had excellent antibacterial efficiency to both DR-S. aureus and DR-E. coli bacteria. More importantly, our new synergistic treatment modality provided an excellent therapy platform for drug-resistant bacteria, which could improve antimicrobial efficiency.

[Analysis of Response of IBS-SSS, AR, and IBS-QOL in IBS Clinical Effect Evaluation].

Objective To observe the response of common indices for clinical effect evaluation on irritable bowel syndrome (IBS), thereby providing reference for IBS related clinical indices in clinical trials of Chinese medicine (CM). Methods A randomized, double-blinded, placebo control trial was set up. Totally 58 diarrhea-predominant IBS (IBS-D) patients were randomly assigned to the test group (28 cases) and the control group (30 cases). Patients in the test group took Chang'an Recipe I (CR I), while those in the control group took CR I placebo. The therapeutic course for all was 8 weeks. Defeca- tion related symptoms was taken as significance in clinics. Principal component analysis was performed in symptoms index. IBS symptom severity score (IBS-SSS) and IBS quality of life (IBS-QOL) were taken as dependent variables. Main component value and the integral of hospital anxiety and depression scale a (HADa) and hospital anxiety and depression scale d (HADd) were taken as independent variables. Their linear correlation was analyzed. Adequate relief (AR) value was taken as dependent variable, while symptoms index was taken as independent variable. Their Logistic regression correlation was analyzed. Main component value A and B of symptoms index were taken as measurement index. A group with effi- cacy was selected from the test group or the control group, and response analyzed in patients of this group. Results There was statistical difference in main component value of A and B in the test group after treatment (P <0.05). So data of the test group were taken as referential standard, the responsibili- ties of IBS-SSS, AR, IBS-QOL were observed. (1) The score of IBS-SSS had a linear regression with defecation related symptoms and anxiety scores, and its responsibility was higher with an effect size of 1.59. (2) Response to each AR was linearly related to defecation related symptoms.(3) The score of IBS-QOL was not obviously correlated with defecation related symptoms, but with moderate response to anxiety state (an effect size of 0. 61). Domains of dysphoria and worries about health could reflect clinical changes with the effect size of 0. 50 and 0. 70 respectively. Conclusions IBS-SSS had better clinical response, which was suitable for IBS clinical effect evaluation. Response to each AR was related with defe- cation related symptoms. But attention should be paid to its clinical meaning. IBS-QOL had a moderate effect size. It was suggested to be used in long-term clinical research.