Non-pharmacological therapy for chemotherapy-induced peripheral neurotoxicity: a network meta-analysis of randomized controlled trials.

BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) is the most common adverse effect in patients undergoing chemotherapy, and no effective interventions are currently available for its prevention and treatment. Non-pharmacological therapies appear to be beneficial for the prevention and treatment of CIPN, but it remains unclear which therapy is most effective. The aim of this study was to identify the most effective non-pharmacological therapy for CIPN patients. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were searched for randomized controlled trials on non-pharmacological therapies for CIPN. The primary outcomes included pain and peripheral neuropathological symptoms, and the secondary outcomes included quality of life, sensory and motor symptoms. The pairwise analysis and a network meta-analysis were performed using a random effects model. RESULTS: A total of 46 articles were included in this study, involving 2,878 participants. Our study showed that massage was more effective in pain-alleviating compared with acupuncture [SMD = 0.81, 95%CI (0.04, 1.57)], vitamin and gabapentin [SMD = 2.56, 95%CI (1.39, 3.74)], and usual care and placebo [SMD = 0.9, 95%CI (0.31, 1.49)]. As for attenuating peripheral neuropathological symptoms, massage was more effective than usual care and placebo [SMD = 0.75, 95%CI (0.33, 1.17)], sensorimotor training [SMD = 1.17, 95%CI (0.24, 2.10)], electrostimulation [SMD=-1.18, 95%CI (-2.14, -0.21)], multimodal exercise [SMD=-0.82, 95%CI (-1.57, -0.08)], and resistance training [SMD = 1.03, 95%CI (0.11, 1.95)]. Massage was also more effective than other non-pharmacological therapies in improving quality of life, sensory and motor symptoms. CONCLUSIONS: According to our study, massage has advantages in alleviating pain, improving quality of life, and improving peripheral neuropathological symptoms and has better effect than other non-pharmacological interventions, representing certain clinical significance. However, the results of this study should be interpreted with caution due to the limitations of the included studies. In the future, more high-quality multi arm randomized controlled trials can be attempted to provide direct comparisons of the relative effects of non-pharmacological interventions.

Chemical constituents from Eupatorium fortunei and their anti-inflammatory evaluation by in silico and experimental approaches.

The well-known aromatic and medicinal plant Eupatorium fortunei Turcz. is widely cultivated in China, and previous studies on its bioactive constituents mainly focus on the essential oil ingredients especially thymol derivatives. However, reports on other type of constituents and the potential application are lacking. In the present project, an intensive chemical fractionation on the aerial part extract of E. fortunei led to the isolation and identification of a series of fatty acid derivatives (lipids, 1a/1b-19) including seven pairs of previously undescribed enantiomers (1a/1b-7a/7b), as well as a lignan (brachangobinan A (BBA), 20) and two monoterpenes (8S/8R-9-hydroxythymol, 21a/21b). A preliminary biological evaluation of these compounds in a NO production inhibitory assay model demonstrated compound BBA as the most active one. Network pharmacology analysis was used to predict and explore the possible anti-inflammatory targets and mechanism of BBA, which revealed some potential inflammation-related proteins and signaling pathways. Further experimental investigations validated that the anti-inflammatory effect of BBA could be achieved by suppressing pro-inflammatory factors and blocking the activation of NF-κB signaling pathway. Taken together, our work shows that E. fortunei can serve as a potential resource of lipids and anti-inflammatory agents.

Monoterpene indole alkaloids from the roots of Alstonia rupestris and their anti-inflammatory activity.

Four new monoterpene indole alkaloids (1-4) together with twelve known alkaloids (5-16) were isolated from the roots of Alstonia rupestris. Compound 1 was the first example of C2-symmetric heteroyohimbine-type indole alkaloid homodimer obtained from natural plant resource. Their structures were elucidated on the basis of spectroscopic data. The absolute configuration of 1 was determined by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra. All compounds were evaluated for their anti-inflammatory activities by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Compound 2 showed strong NO inhibition with IC50 value of 4.2 ± 1.3 µM. Moreover, compound 2 could decrease the expressions of cyclooxygenase-2 (COX-2) and transforming growth factor beta-1 (TGF-ß1).

Anti-inflammatory labdane diterpenoids from the aerial parts of Leonurus japonicus.

Twenty-two labdane-type diterpenoids, including ten pairs of 15-epimers and a pair of 13,15-epimers, were obtained from the aerial parts of a well-known medicinal plant Leonurus japonicus Houtt. While these epimers were separated by chiral HPLC, their structures were established mainly via spectroscopic methods especially NMR, X-ray crystallography and ECD techniques. Among them, seventeen compounds, encompassing three pairs of solvolysis artefacts likely due to the use of ethanol as extracting solvent, were reported for the first time in the current work. Our preliminary anti-inflammatory screening demonstrated that seven diterpenoids displayed noteworthy inhibitory effect on the NO production in LPS-induced RAW264.7 cells. In addition, the release of pro-inflammatory factors TNF-α, IL-1ß and IL-6, as well as the expression of iNOS and COX-2 proteins, was also suppressed by the unreported 15,16-epoxy-6ß-hydroxy-15α-methoxy-7,16-dioxolabd-8,13-diene. Further investigation into the preliminary anti-inflammatory mechanism of this compound indicated that it could block the activation of NF-κB signaling pathway.

Inspiratory muscle training improves cardiopulmonary function in patients after transcatheter aortic valve replacement: a randomized clinical trial.

AIMS: Inspiratory muscle training (IMT) can increase the strength or endurance of the diaphragm and accessory muscles of inspiration, yet there is no evidence that endorses the role of IMT in patients of transcatheter aortic valve replacement (TAVR). This study for the first time tested the effects of IMT plus usual cardiac rehabilitation (CR) function in patients after TAVR. METHODS AND RESULTS: A double-blinded, randomized controlled, single-centre clinical trial was undertaken. Participants who had a confirmed diagnosis of valve heart disease and were clinically stable after TAVR were recruited and received a CR programme during the hospital stay. A total of 96 patients were recruited and randomly assigned to the IMT + CR group (n = 48) or the CR group (n = 48) in a 1:1 ratio. The group difference in the primary outcome, the 6-min walk distance at the discharge of the hospital, significantly favoured the IMT + CR group (mean difference -33.52, 95% CI: -64.42 to -2.62, P = 0.034). The significant difference was maintained at the 1-month and 3-month follow-ups (mean difference: 41.51, 95% CI: 1.82-81.21, P = 0.041). In addition, the mean hospital stays of subjects in the IMT + CR group was 11 days, which was significantly shorter than the 12.5 days in the CR group (P = 0.016). Sensitivity analysis using per-protocol analysis supported these findings. No adverse treatment-related events were reported. CONCLUSION: Compared with usual CR, IMT plus CR can effectively improve exercise endurance, pulmonary ventilation function, and inspiratory muscle strength in patients after TAVR and shorten the length of hospital stay.

Methyl 2-naphthoates with anti-inflammatory activity from Morinda officinalis.

Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis, afforded an array of methyl 2-naphthoate derivatives (1-9) including four pairs of enantiomers (1-4), two pimarane diterpenes and two ursane triterpenoids. Among them, eight compounds (1a/1b-3a/3b, 11 and 13) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC50 values of 41.9 and 26.2 µM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.

[Acupotomy relieves pain and improves motor function by regulating autophagy and apoptosis of cartilage in rabbits with knee osteoarthritis apoptosis].

OBJECTIVE: To observe the effect of acupotomy on the expression of Beclin-1, Bcl-2 and Caspase-3 in the cartilage tissue in rabbits with knee osteoarthritis (KOA), so as to explore its mechanism underling improvement of KOA. METHODS: Twenty-four healthy male New Zealand rabbits were randomly and equally divided into blank control, model and acupotomy groups, with 8 rabbits in each group. By using the modified Videman's methods, the KOA model was established by left hind limb immobilization with a plaster cast for 6 weeks. The severity of KOA (knee pain, swelling and motor function) was assessed using Lequesne score, and the rabbits with a score below 4 were excluded. The acupotomy was applied to "Hedingci" (the attachment of the quadriceps tendon to the patella at the upper edge), "Binneixia" (the medial patellar supporting band attachment of medial inferior patellar margin), "Binwaixia" (the lateral patellar supporting band attachment of the lower lateral patellar margin), "Chengfeijian" (the lateral collateral ligament of the knee passes over the lateral joint space), "Weiyangci" (the medial margin of biceps femoris at the lateral end of popliteus), "Yinlingci" (the medial tibial attachment of anserinus tendon) on the left hind limb once a week for 4 weeks. One week after the last intervention, the left knee joint dysfunction severity(pain, maximum walking distance, and some activities of daily living) was evaluated by using modified Lequesne score. Histopathological changes of the cartilage were observed under light microscope after H.E. staining. The apoptosis of chondrocytes was observed after terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labeling (TUNEL) staining. The autophagolysosomes of chondrocytes were observed using transmission electron microscopy. The expression levels of Beclin-1, Bcl-2 and Caspase-3 (related factors of autophagy and apoptosis) were detected using Real-time PCR and Western blot separately. RESULTS: In comparison with the blank control group, the Lequesne score, apoptosis rate, expression levels of Caspase-3 mRNA and protein were significantly increased (P<0.001), and the number of autophagolysosomes, expression levels of Beclin-1 and Bcl-2 mRNAs and proteins considerably decreased (P<0.001) in the model group. Relevant to the model group, the acupotomy group had an obvious decrease in Lequesne score, rate of apoptosis, and expression levels of Caspase-3 mRNA and protein (P<0.001) and an apparent increase in the number of autophagolysosomes and expression levels of Beclin-1 and Bcl-2 mRNAs and proteins (P<0.001). Findings of H.E. staining showed severe damaged cartilage surface, with a large number of exfoliation defects, few chondrocytes on the surface and disordered arrangement of transitional cells in the model group, which was relatively milder in the acupotomy group. CONCLUSION: Acupotomy can mitigate knee-joint pain and improve functional activity in KOA rabbits, which may be associated with its functions in promoting autophagy and suppressing apoptosis by up-regulating expressions of Beclin-1 and Bcl-2 mRNAs and proteins and down-regulation of Caspase-3 mRNA and protein.

Near-infrared light and redox dual-activatable nanosystems for synergistically cascaded cancer phototherapy with reduced skin photosensitization.

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was "double-locked" by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the "double-key", which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.

Protist.guru: A Comparative Transcriptomics Database for Protists.

During the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still largely neglected. To address this gap, we used gene expression data from 17 protist species to create protist.guru: an online database equipped with tools for identifying co-expressed genes, gene families, and co-expression clusters enriched for specific biological functions. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AVAILABILITY: The database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.

Effects of mirror therapy on phantom limb sensation and phantom limb pain in amputees: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effects of mirror therapy on phantom limb sensation and phantom limb pain in amputees. DATA SOURCES: Nine electronic databases (PubMed, EMBASE, MEDLINE, Web of Science, the Cochrane Library, CINAHL, PsycInfo, PreQuest, PEDro) were searched from their inception to May 10th, 2021. METHODS: Two authors independently selected relevant studies and extracted the data. The effect sizes were calculated under a random-effects model meta-analysis, and heterogeneity was assessed using the I2 test. The risk of bias was evaluated by the Cochrane risk of bias tool, and the methodological quality was appraised by the PEDro scale. The GRADE approach was applied to assess the confidence of the effect. RESULTS: A total of 11 RCTs involving 491 participants were included in this review and nine RCTs involving 372 participants were included in meta-analysis. The quality of these studies was from poor to good with scores ranging from 2 to 8 points according to PEDro scale. The pooled SMD showed that mirror therapy reduced the pain with a large effect size (-0.81; 95% CI = -1.36 to -0.25; P = 0.005; I2 = 82%; n = 372) compared with other methods (four covered mirror, one phantom exercise, three mental visualization, one sensorimotor exercise, one transcutaneous electrical nerve stimulation, one tactile stimuli). The quality of evidence for the outcome pain intensity was determined to be fair according to GRADE approach. CONCLUSION: There is fair-quality evidence that MT is beneficial for reducing phantom limb pain.

Combination of Electroacupuncture and Constraint-Induced Movement Therapy Enhances Functional Recovery After Ischemic Stroke in Rats.

Both electroacupuncture and constraint-induced movement therapy have been reported to produce therapeutic effects on the recovery of ischemic stroke. The combined use of these two therapies is not rare clinically, although its effectiveness is not yet clear. We aimed to evaluate the efficacy of the combination of electroacupuncture and constraint-induced movement therapy in ischemic stroke rats, and to explore the potential molecular mechanisms. Ischemic stroke rat models were established by middle cerebral artery occlusion. Then, the rats were assigned to receive one of the following interventions: sole electroacupuncture, sole constraint-induced movement therapy, the combination of both therapies, and no treatment. Functional recovery was assessed with the beam balance test and rotarod test. The infarct volume of the brain and the expression of the molecules Nogo-A, P75NTR, NGF, BDNF, and VEGF in the brain tissue were investigated. The results demonstrated that the combination of the two therapies significantly improved neurological functional recovery in ischemic stroke rats compared to each therapy alone (P < 0.01). We also observed a significant decrease in infarct volume in rats receiving the combined treatment. Nogo-A and P75NTR were downregulated and NGF, BDNF, and VEGF were upregulated in the combined treatment rats compared to the control rats. In conclusion, the combination of electroacupuncture and constraint-induced movement therapy enhanced functional recovery after ischemic stroke in rats, and it is a promising treatment strategy in the rehabilitation of stroke. The anti-Nogo-A effect of electroacupuncture may explain its good compatibility with CIMT in ischemic stroke rats.

Monoterpene indole alkaloids from the roots of Bousigonia mekongensis and their anti-diabetic nephropathy activity.

Four new monoterpene indole alkaloids (1-4) together with six known alkaloids (5-10) were isolated from the roots of Bousigonia mekongensis. Compounds 3 and 4 were the first examples of condylocarpan-adenine type alkaloids obtained from natural plant resource. Their structures were elucidated on the basis of spectroscopic data. All compounds were evaluated for their inhibiting glucose-induced mesanginal cell proliferation and protecting high glucose-evoked podocyte injury activities. (-)-demethoxycarbonyldihydrogambirtannine (5) can significantly antagonize glucose-induced podocyte injury with EC50 value of 6.5 ± 1.2 µM.

Effects of hyperbaric oxygen therapy on patients with spinal cord injury: A systematic review and meta-analysis of Randomized Controlled Trials.

BACKGROUND: The effects of hyperbaric oxygen therapy (HBO) for spinal cord injury (SCI) are controversial. OBJECTIVE: The purpose of this study was to evaluate the effects of HBO therapy on motor function, sensory function, and psychology after SCI. METHOD: We searched the following databases: Medline, Embase, PubMed, Ovid, Cochrane library, China National Knowledge Infrastructure (CNKI), Wan Fang, and VIP up to May 2020. We included Randomized Controlled Trials (RCTs) which investigated patients with SCI received HBO during hospitalization. Motor function, sensory function, and psychology status were measured by commonly used scales including American Spinal Injury Association (ASIA) motor score, Modified Barthel Index (MBI), ASIA sensory score, Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). We performed a meta-analysis by calculating mean difference (MD) to determine the effect of HBO on three levels of function on patients with SCI. We evaluated heterogeneity by I2 test, and I2> 50% was significant. RESULTS: A total of 1746 studies were identified initially, and 11 studies were included, involving 875 participants. HBO therapy significantly improved the ASIA motor score (MD 15.84, 95% CI 9.04 to 22.64, I2= 87%). Six trails suggested that HBO therapy statistically promoted ASIA sensory score (MD 66.30, 95% CI 53.44 to 79.16, I2= 95%). The other four trails suggested that HBO therapy statistically increased the light touch score (MD 9.27, 95% CI 3.89 to 14.65, I2= 91%) and needling score (MD 10.01, 95% CI 8.60 to 11.43, I2= 95%), respectively. HBO therapy was implicated in the significant improvement of MBI (MD 13.80, 95% CI 10.65 to 16.94, I2= 0%). HBO therapy also decreased the HAMA (MD -2.37, 95% CI -2.72 to -2.02, I2= 0%) and HAMD (MD -3.74, 95% CI -5.82 to -1.65, I2= 90%). CONCLUSIONS: HBO therapy may improve motor function, sensory function and psychology after SCI compared to conventional treatments. More high-quality, large sample size RCTs are needed to support these perspectives.

The Effect of Pulsed Electromagnetic Fields on Angiogenesis.

A pulsed electromagnetic field (PEMF) has been used to treat inflammation-based diseases such as osteoporosis, neurological injury, and osteoarthritis. Numerous animal experiments and in vitro studies have shown that PEMF may affect angiogenesis. For ischemic diseases, in theory, blood flow may be richer by increasing the number of blood vessels which supply blood to ischemic tissue. PEMF plays a role in enhancing angiogenesis, and their clinical application may go far beyond the current scope. In this review, we analyzed and summarized the effects and possible mechanisms of PEMF on angiogenesis. Most studies have shown that PEMF with specific parameters can promote angiogenesis, which is manifested by an increased vascular growth rate and increased capillary density. The potential mechanisms consist of promoting vascular endothelial cell proliferation, migration, and tube formation, and increasing the expression level of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), angiopoietin-2 (Ang-2), and other angiogenic growth factors. Additionally, PEMF has an impact on the activation of voltage-gated calcium channels (VGCC). Bioelectromagnetics. © 2021 Bioelectromagnetics Society.

Effect of Therapeutic Ultrasound for Neck Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effects and safety of therapeutic ultrasound in patients with neck pain. DATA SOURCES: The PubMed, EMBASE, CENTRAL, and Physiotherapy Evidence databases were searched for articles published before December 1, 2020. STUDY SELECTION: Randomized controlled trials that compared the effects of therapeutic ultrasound on neck pain were included in this review. The included studies compared therapeutic ultrasound plus other treatments with the other treatments alone or compared therapeutic ultrasound with sham or no treatment. Outcome measures involved the effects on pain, disability, and quality of life. Other treatments included all nonultrasonic therapies (eg, various exercises, massage, electrotherapy). DATA EXTRACTION: Data on the study population, therapeutic ultrasound intervention, combined intervention, outcome measures, and follow-up were extracted. DATA SYNTHESIS: Twelve randomized controlled trials (705 patients) fulfilled the inclusion criteria. Seven studies compared therapeutic ultrasound plus other treatments vs the other treatments alone (449 patients). Therapeutic ultrasound yielded additional benefits for pain, but there was high heterogeneity and we could not draw a clear conclusion. Ultrasound did not have a better effect on disability or quality of life when it was combined with other treatments. Five studies compared therapeutic ultrasound with sham or no treatment (256 patients), and the pooled data showed that therapeutic ultrasound significantly reduced pain intensity. No adverse events of therapeutic ultrasound were reported in the included studies. CONCLUSIONS: Therapeutic ultrasound may reduce the intensity of pain more than sham or no treatment, and it is a safe treatment. Whether therapeutic ultrasound in combination with other conventional treatments produced additional benefits on pain intensity, disability, or quality of life is not clear. The randomized trials included in this review had different levels of quality and high heterogeneity. A large trial using a valid methodology is warranted.

Effects of water therapy on disease activity, functional capacity, spinal mobility and severity of pain in patients with ankylosing spondylitis: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of water therapy for disease activity, functional capacity, spinal mobility, and pain in patients with ankylosing spondylitis. METHODS: PubMed, Ovid, web of science, Cochrane library, Physiotherapy Evidence Database, CNKI, VIP, Wan Fang, and Open Grey were searched for randomized controlled trials that investigated the effects of water therapy on patients with ankylosing spondylitis. Two researchers independently screened the literature databases and then assessed methodological qualities using the Physiotherapy Evidence Database scale and extracted data. Outcomes included were disease activity, functional capacity, spinal mobility, and pain. RESULTS: A total of eight studies (n = 383) met the inclusion criteria. Analysis demonstrated that water therapy had a significant effect on disease activity and pain, but not on spinal mobility, or functional capacity in patients with ankylosing spondylitis. CONCLUSION: Water therapy can benefit patients with ankylosing spondylitis by reducing disease activity and alleviating pain. More well-designed randomized controlled trials are needed to confirm the results.IMPLICATIONS FOR REHABILITATIONWater therapy can reduce disease activity and pain in patients with ankylosing spondylitis, but cannot improve functional capacity or spinal mobility.Due to its analgesic effect both during and after treatment, water therapy remains an alternative for patients with ankylosing spondylitis when land-based therapy is not well tolerated.

[Investigation of active components and mechanism of Pudilan Xiaoyan Oral Liquid based on network pharmacology].

To investigate the active components/ingredients of Pudilan Xiaoyan Oral Liquid based on the network pharmacology technology, and analyze the network data of its potential targets and mechanisms. The active ingredient screening, protein interaction analysis and pathway annotation were used to further optimize its active components and potential targets, and clarify the pharmacodynamic substance basis and mechanism of Pudilan Xiaoyan Oral Liquid. Through this technique, we screened out 41 active ingredients in Pudilan Xiaoyan Oral Liquid, mainly including 16 alkaloid components, 13 organic acid components, 11 flavonoid components and 1 coumarin component such as chicoric acid, chlorogenic acid, oroxindin, rutin, corynoline, and esculetin. In addition, 6 targets for parotitis, 48 targets for tonsillitis, and 22 targets for pharyngitis were screened. A total of 22 disease signaling pathways are involved, including 4 pathways closely related to inflammation. The IL-17 signaling pathway had the highest D(degree) value and may be most closely related to inflammatory diseases. Through network data excavating, we initially explored the main active components/ingredients of Pudilan Xiaoyan Oral Liquid, clarified the pharmacodynamic basis of Pudilan Xiaoyan Oral Liquid treatment-related diseases and its key mechanism of action in this study, hoping to provide a theoretical basis for clinical research, and at the same time, lay the foundation for deep research and promotion of Pudilan Xiaoyan Oral Liquid product.

[Identification of quality markers for Pudilan Xiaoyan Oral Liquid].

On the basis of anti-inflammatory activity, combined with multiple indicators, the quality markers of Pudilan Xiaoyan Oral Liquid were screened and determined for quality control. Lipopolysaccharide(LPS) was used to induce normal human bronchial epithelial cell(NHBE) inflammation model. The anti-inflammatory effects of the main chemical components in Pudilan Xiaoyan Oral Liquid were examined one by one, and the pharmacodynamic basis for the overall anti-inflammatory efficacy of Pudilan Xiaoyan Oral Liquid was clarified to identify the quality markers of Pudilan Xiaoyan Oral Liquid and the contents of the quality markers were determined by high performance liquid chromatography(HPLC). The results showed that adenosine, epigoitrin, chlorogenic acid, caffeic acid, cichoric acid, corynoline, baicalin, wogonoside, wogonin and oroxylin A had a certain regulatory effect on inflammatory factor tumor necrosis factor(TNF-α), interleukin(IL-1ß) and IL-6 at specific concentrations in a dose-dependent manner. Considering the factors such as the IC_(50) value of each monomer component and the comprehensiveness of the quality control components, we proposed to use adenosine, cichoric acid, corynoline, baicalin and wogonin as quality markers of Pudilan Xiaoyan Oral Liquid. The contents of the five components were determined by HPLC, and the results showed that they were relatively stable in three batches of Pudilan Xiaoyan Oral Liquid. In this study, the quality control components selected by the anti-inflammatory activity test have a clear material basis, covering all four active pharmaceutical ingredients, which can fully reflect the quality of Pudilan Xiaoyan Oral Liquid, and effectively improve the quality control standard of Pudilan Xiaoyan Oral Liquid.

[Source control of Pudilan Xiaoyan Oral Liquid--research on quality of Taraxaci Herba based on ultra high performance liquid chromatography fingerprint].

Pudilan Xiaoyan Oral Liquid has been widely used in the clinical treatment of inflammatory diseases such as upper respiratory tract infections. Taraxaci Herba, as the monarch medicine in Pudilan Xiaoyan Oral Liquid, due to its multi-source, multi-origin characteristics, and the difference in the content of active ingredients in different medicinal parts, has become a potential factor for the unstable quality among different batches of Pudilan Xiaoyan Oral Liquid. In this paper, Thermo Scientific Vanquish ultra-high-performance liquid chromatography(UPLC) system was used, and the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2012 Edition) issued by National Pharmacopoeia Commission was used for processing and analysis. The main common peaks were identified and contents were determined by comparison with reference substances. Fingerprints of Taraxaci Herba medicinal materials from different origins were established. 13 common peaks were identified, and 29 batches of samples from five origins had similarities above 0.90. At the same time, an ultra-high performance liquid chromatography method was developed for the determination of monocaffeoyl tartaric acid, chlorogenic acid, caffeic acid, chicoic acid, and luteolin in Taraxaci Herba. The quantitative analysis conditions were verified by methodology, and the average sample recovery was 97.30%-101.8%. The results showed that the content of the same ingredient in Taraxaci Herba from different origins and different medicinal parts was obviously different, and the fluctua-tion range was also different for different ingredients. The establishment of UPLC fingerprints for Taraxaci Herba from different regions combined with multi-component content determination methods provides a reference for improving the quality control of Taraxaci Herba medicinal materials, and also provides a source guarantee for the quality improvement of Pudilan Xiaoyan Oral Liquid.

Efficacy of biofeedback, repetitive transcranial magnetic stimulation and pelvic floor muscle training for female neurogenic bladder dysfunction after spinal cord injury: a study protocol for a randomised controlled trial.

INTRODUCTION: Neurogenic bladder dysfunction is prevalent in female patients with spinal cord injury (SCI), and previous guidelines have recommended pelvic floor muscle training (PFMT) for first-line conservative treatment. However, the actual regimen of PFMT varies widely and the single treatment does not satisfy the need of some patients. Therefore, this study aims to provide a detailed rationale and methodology for comparing the effectiveness of PFMT, biofeedback and repetitive transcranial magnetic stimulation (rTMS) as adjunct treatments for neurogenic bladder dysfunction. METHODS AND ANALYSIS: This trial is a single-centre randomised controlled trial for female patients with urinary incontinence (UI) in phase of chronic SCI. Eligible participants will be randomised to one of four arms: (1) PFMT, (2) PFMT with biofeedback, (3) PFMT and rTMS and (4) PFMT with biofeedback and rTMS. There will be 44 participants in each arm and all the subjects will undergo 20 treatment sessions, five times a week for 4 weeks. The outcomes will be evaluated at 4 weeks, 3 months and 6 months after randomisation. The primary outcome is the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form, and the secondary outcomes include bladder diary, pelvic floor muscle function and the International Spinal Cord Injury Quality of Life Basic Data Set. ETHICS AND DISSEMINATION: The Clinical Research and Biomedical Ethics Committee of the West China Hospital, Sichuan University has approved this trial and the approval number is 2019-885. All participants will be provided written informed consent after verification of the eligibility criteria. The results of this study will be accessible in peer-reviewed publications and be presented at academic conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900026126).