Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

Self-Administered Acupressure for Probable Knee Osteoarthritis in Middle-Aged and Older Adults: A Randomized Clinical Trial.

Importance: The effects of self-administered acupressure (SAA) on knee osteoarthritis (OA) pain remain unclear. Objective: To evaluate the effectiveness of SAA taught via a short training course on reducing knee OA pain in middle-aged and older adults. Design, Setting, and Participants: This randomized clinical trial was conducted among community-dwelling individuals in Hong Kong who were aged 50 years or older with probable knee OA from September 2019 to May 2022. Interventions: The intervention included 2 training sessions for SAA with a brief knee health education (KHE) session, in which participants practiced acupressure twice daily for 12 weeks. The control group (KHE only) received only education about maintaining knee health on the same schedule and duration. Main Outcomes and Measures: The primary outcome was the numerical rating scale (NRS) pain score at 12 weeks. Other outcomes included Western Ontario and McMaster University Osteoarthritis Index, Short Form 6 Dimensions (SF-6D), Timed Up and Go, and Fast Gait Speed tests. Results: A total of 314 participants (mean [SD] age, 62.7 [4.5] years; 246 [78.3%] female; mean [SD] knee pain duration, 7.3 [7.6] years) were randomized into intervention and KHE-only groups (each 157). At week 12, compared with the KHE-only group, the intervention group had a significantly greater reduction in NRS pain score (mean difference [MD], -0.54 points; 95% CI, -0.97 to -0.10 points; P = .02) and higher enhancement in SF-6D utility score (MD, 0.03 points; 95% CI, 0.003 to 0.01 points; P = .03) but did not have significant differences in other outcome measures. The cost-effectiveness acceptability curve demonstrated a greater than 90% probability that the intervention is cost-effective at a willingness to pay threshold of 1 GDP per capita. Conclusions and Relevance: In this randomized clinical trial, SAA with a brief KHE program was efficacious and cost-effective in relieving knee pain and improving mobility in middle-aged and older adults with probable knee OA. Trial Registration: ClinicalTrials.gov Identifier: NCT04191837.

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

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

Qingguang'an-induced autophagy in TFs inhibits scar formation: A follow-up in vivo mechanistic investigation.

Purpose: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). Methods: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1-28. Ultrastructure was observed under a transmission electron microscope (TEM). Real-Time Polymerase Chain Reaction (RT-PCR), Western blot, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining and Immuno-histochemistry (IHC) were performed to assess the harvested blocks. Results: In the Qingguang'an group, intraocular pressure (IOP) on postoperative D28 was significantly lower than values in the no surgery, surgery only and PBS groups (P < 0.05). Its blebs kept better filtering function and less complications in follow-up, which be detected to have less fibroblasts and collagen deposition histologically. Compared with the PBS group, ATG5, Beclin1 and LC3-II mRNA levels were significantly increased while P62 was downregulated in the Qingguang'an group (P < 0.05). Correspondingly, ATG5 and Beclin1 protein amounts in the Qingguang'an group were increased while P62 was downregulated. The LC3-II/Ⅰ ratio tended to rise to the process of autophagy. Abundant autophagosomes were captured under TEM in this condition. Conclusions: Qingguang'an granules can inhibit scar formation in rabbits after GFS and restrain IOP increase by inducing autophagy in TFs.

Effects of traditional Chinese medicine-assisted intervention on improving postpartum lactation: A systematic review and meta-analysis.

Importance: Breast milk is the safest food for infants and has many psychological and physical benefits for infants and mothers. However, problems encountered during the breastfeeding process can reduce postpartum women's willingness to breastfeed. Lactation and engorgement may be improved through Traditional Chinese Medicine auxiliary therapy. However, the overall efficacy of various Traditional Chinese Medicine auxiliary therapies and the relevant meridians and acupuncture points for treating breast milk deficiency remain unclear. Objective: To investigate Traditional Chinese Medicine auxiliary therapy's effectiveness and acupoints for postpartum women who experience problems during the breastfeeding process. Methods: Data were sourced from Embase, Web of Science, CINAHL, Cochrane, CNKI, PubMed, and the Airiti Library Central Register of Controlled Trials and Clinical Trials from the database inception to October 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Main outcome measures: The primary outcomes were overall efficiency, prolactin level, milk volume, and breast engorgement in postpartum women with lactation deficiency after-assisted therapies and the correlation between meridian points and milk secretion. Results: A total of 1,516 studies were initially identified, and 357 articles were assessed. In the final analysis, 20 studies were included, covering various Traditional Chinese Medicine therapies (acupuncture, acupressure, scrapping, moxibustion cupping, etc.) to stimulate relative acupoints without any acupoint stimulation. The overall efficiency (odds ratio [OR] = 14.17, 95% confidence interval [CI] = 6.49 to 30.92), prolactin level (standardized mean difference [SMD] = 0.36, 95% CI = 0.074 to 0.64), improvement of milk volume (SMD = 0.94, 95% CI = 0.59 to 1.29), reduction of engorgement level (OR= 18, 95% CI = 8.34 to 38.82) demonstrated that Traditional Chinese Medicine therapies can effectively improve lactation and breast fullness, thereby helping patients with breast milk deficiency. The most common acupuncture points used to treat agalactia were classified as the Stomach Meridian, Small Intestine Meridian, and Conception Vessel, with the common acupoints CV17: Danzhong, ST18: Rugen, SI1: Shaoze, ST36: Zusanli, and ST16: Yingchuang. Conclusion: Adjuvant Traditional Chinese Medicine therapy can improve lactation and breast engorgement, thereby increasing the willingness to breastfeed. Clinical Finding: 1. The best time for Traditional Chinese Medicine acupoint intervention for breast deficiency treatment is within 24 h 2. The most effective acupuncture points for improving milk deficiency and bloating pain are ST18: Rugen, ST16: Yingchuang, ST36: Zusanli, SI1: Shaoze, CV17: Danzhong. 3. Traditional Chinese Medicine is non-invasive and effective techniques such as scraping, cupping, acupressure and ear peas. 4. Traditional Chinese Medicine can be combined with other different acupuncture points according to the different constitutions of post-partum women. Breast acupressure, ear acupuncture, scrapping, cupping, and moxibustion are noninvasive treatments that can effectively help patients during lactation, and their clinical practice should be considered and widely promoted.

The effects of neurofeedback training for children with cerebral palsy and co-occurring attention deficits: A pilot study.

BACKGROUND: Limited research exists regarding the effectiveness of electroencephalogram (EEG) neurofeedback training for children with cerebral palsy (CP) and co-occurring attention deficits (ADs), despite the increasing prevalence of these dual conditions. This study aimed to fill this gap by examining the impact of neurofeedback training on the attention levels of children with CP and AD. METHODS: Nineteen children with both CP and co-occurring ADs were randomly assigned to either a neurofeedback or control group. The neurofeedback group received 20 sessions of training, lasting approximately 1 h per day, twice a week. Theta/beta ratios of the quantitative electroencephalography (QEEG) recordings were measured pre-training and post-training in the resting state. The Continuous Performance Test (CPT), the Test of Visual Perceptual Skills-3rd Version (TVPS-3) and the Conners' Parent Rating Scale (CPRS) were measured at pre- and post-training. RESULTS: The neurofeedback group showed both decreased theta/beta ratios compared with control group (p = 0.04) at post-training and a within-group improvement during training (p = 0.02). Additionally, the neurofeedback group had a trend of decreased omission rates of the CPT (p = 0.08) and the visual sequential memory and the visual closure subscores in the TVPS-3, compared with the control group (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The results suggested that children with CP and co-occurring AD may benefit from neurofeedback training in their attention level. Further research is needed to explore long-term effects and expand its application in this population.

Usage Patterns of Traditional Chinese Medicine for Patients with Bipolar Disorder: A Population-Based Study in Taiwan.

BACKGROUND: Patients with bipolar disorder (BD) receive traditional Chinese medicine (TCM) for clinical needs unmet with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. METHODS: Data for a total of 12,113 patients with BD between 1996 and 2013 were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000). The chi-square test was used for categorical variables, and the independent t-test was used for continuous variables. A p-value less than 0.05 indicated significance. RESULTS: One thousand three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (n = 1053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herbs and herbal formulae. CONCLUSIONS: Physicians need to be aware of the use of TCM in patients with BD.

Room temperature operation of germanium-silicon single-photon avalanche diode.

The ability to detect single photons has led to the advancement of numerous research fields1-11. Although various types of single-photon detector have been developed12, because of two main factors-that is, (1) the need for operating at cryogenic temperature13,14 and (2) the incompatibility with complementary metal-oxide-semiconductor (CMOS) fabrication processes15,16-so far, to our knowledge, only Si-based single-photon avalanche diode (SPAD)17,18 has gained mainstream success and has been used in consumer electronics. With the growing demand to shift the operation wavelength from near-infrared to short-wavelength infrared (SWIR) for better safety and performance19-21, an alternative solution is required because Si has negligible optical absorption for wavelengths beyond 1 µm. Here we report a CMOS-compatible, high-performing germanium-silicon SPAD operated at room temperature, featuring a noise-equivalent power improvement over the previous Ge-based SPADs22-28 by 2-3.5 orders of magnitude. Key parameters such as dark count rate, single-photon detection probability at 1,310 nm, timing jitter, after-pulsing characteristic time and after-pulsing probability are, respectively, measured as 19 kHz µm-2, 12%, 188 ps, ~90 ns and <1%, with a low breakdown voltage of 10.26 V and a small excess bias of 0.75 V. Three-dimensional point-cloud images are captured with direct time-of-flight technique as proof of concept. This work paves the way towards using single-photon-sensitive SWIR sensors, imagers and photonic integrated circuits in everyday life.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

OBJECTIVE: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. METHODS: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. RESULTS: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). CONCLUSION: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

Validation of traditional Chinese version of Sheffield Profile for Assessment and Referral for Care Questionnaire in Taiwanese patients.

BACKGROUND: Holistic health care considers all aspects of patient care, namely the physical, psychological, spiritual, and social aspects. To assess which patient needs are unmet, a screening questionnaire covering the four aforementioned aspects is required. Therefore, the Sheffield Profile for Assessment and Referral for Care (SPARC), a multidimensional, self-reported questionnaire designed to screen patients regardless of diagnosis, was developed. This study developed a translated and validated traditional Chinese version of the SPARC for patients in Taiwan. METHODS: The original English version of the SPARC was translated into a traditional Chinese version (SPARC-T) through forward-backward translation. Semistructured debriefing interviews were conducted with participants to evaluate the SPARC-T. The reliability and validity of the SPARC-T were assessed through Cronbach's alpha coefficients and a correlation analysis conducted using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. RESULTS: Fifty-three patients were enrolled from our hospital: 22 had cancer but the majority had nonmalignant chronic conditions. About internal consistency, the Cronbach's alpha values for all domains of the SPARC-T were favorable. A correlation analysis of the SPARC-T and FACT-G revealed significant correlations for the domains of physical symptoms, independence and activity, family and social issues, sleep, and treatment issues; no significant correlation was identified for the "psychological issues" domain. CONCLUSION: This study revealed that the SPARC-T is an effective tool for screening Mandarin-speaking patients. Thus, it can be used in hospitals to holistically screen and identify the needs of patients to ensure they can receive appropriate professional support and holistic health care.

Leonurine alleviates rheumatoid arthritis by regulating the Hippo signaling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm. RESULTS: Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes. CONCLUSION: LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.

Factors influencing the effects of the mindfulness-based interventions of patients with substance abuse: A qualitative systematic review and meta-synthesis.

Objective: This article aims to provide the experiences of mindfulness treatments from the perspectives of patients with a history of substance abuse. Data source: Peer-reviewed articles on 5 databases, namely, PubMed, PsychINFO, Medline, CINAHL and the Cochrane Library, between the year of 2000 and 2023. Study Inclusion and Exclusion Criteria: Studies were included if they were published in the English language and reported on qualitative studies that directly engaged patients with experiences of substance abuse and mindfulness treatments. Data extraction: After our initial search, 5355 studies were reviewed by title and abstract, consequently, 10 studies were included. Data synthesis: Meta-ethnography were used in this study. Data were obtained from the quotations from participants and text under the heading "results" or "findings" from the included 10 studies. Results: Effective mindfulness-based interventions (MBI) influence recovery from substance abuse. Four themes were identified as factors influencing the MBI treatment effect. They were (1) engaging in mindfulness: entry and retention, (2) perceived benefits of MBIs, (3) implementation of treatment group and (4) maintenance of treatment effect. Conclusion: This article examines the scientific literature to date and presents the evidence on the factors that influentially impact the effect of MBIs in patients with substance abuse. The findings of this study should be helpful in guiding clinical practice, policy, and future research focused on the treatment effect of MBIs for person with substance use.

Diverse prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with anti-inflammatory and antiviral activities.

Fifteen unreported prenylated C6-C3 derivatives (1-15) were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith, including one bis-prenylated C6-C3 derivative (1), three prenylated C6-C3 derivative-shikimic acid ester hybrids (2-4) and 11 prenylated C6-C3 monomers (5-15). The structures of compounds 1-15 were elucidated by spectroscopic analysis (UV, IR, 1D and 2D NMR, and HRESIMS). The absolute configurations of the compounds were determined using electronic circular dichroism (ECD), induced circular dichroism (ICD), and the modified Mosher's method. Among the isolates, compounds 11, 12, and 15 exhibited significant anti-inflammatory activities by inhibiting the nitric oxide with IC50 values ranging from 1.89 to 24.83 µM in lipopolysaccharide-stimulated murine RAW 264.7 macrophages and murine BV2 microglial cells; compounds 2, 3, and 7 exhibited antiviral activitives against Coxsackievirus B3 with an IC50 value of 33.3, 25.9, and 27.8 µM, respectively.

UPLC-Q-TOF-MS/MS-based urine metabolomics studies on the toxicity and detoxication of Tripterygium wilfordii Hook. f. after roasting.

Tripterygium wilfordii (TW), a well-known traditional Chinese medicine, was widely used in the treatment of autoimmune disorders and inflammatory diseases. However, the clinical use of TW was limited by severe toxicities, such as hepatotoxicity and nephrotoxicity. Our previous studies indicated that roasting was an effective approach for reducing TW-induced toxicity. After roasting, celastrol was completely decomposed, partially converted into 1-hydroxy-2,5,8-trimethyl-9-fluorenone and the total alkaloids content were significantly reduced. However, the detoxication mechanisms of roasting on TW were poorly unknown. This study aimed to explore the toxicity and detoxification mechanisms of TW after roasting based on urine metabolomics. Promising biomarkers were evaluated by multiple comparison analyses. Sixteen toxicity biomarkers were identified between control group and total extract group. Twelve toxicity biomarkers were identified between control group and total alkaloids group. Eight toxicity biomarkers were identified between control group and celastrol group. These metabolites were mainly involved in seven metabolic pathways, summarized as pentose and glucuronate interconversions, lipid metabolism (sphingolipid metabolism, glycerophospholipid metabolisms, fatty acid biosynthesis and steroid hormone biosynthesis) and amino acid metabolism (taurine and hypotaurine metabolism, tryptophan metabolism). After roasting, the toxicities of total extract, total alkaloids and celastrol were relieved by ameliorative serum parameters and pathological changes in hepatic and renal tissues which revealed that the reduction of celastrol and total alkaloids played important roles in the detoxification of roasting on TW. Furthermore, roasting regulated the levels of fourteen potential biomarkers in the total extract group, ten potential biomarkers in the total alkaloids group and seven candidate biomarkers in the celastrol group to normal levels. Biological pathway analysis revealed that roasting may ameliorate TW-induced metabolic disorders in pentose and glucuronate interconversions, lipid metabolism and amino acid metabolism. This study provided evidence for the application of roasting in TW.

[Acupuncture for treatment of tobacco withdrawal syndrome: systematic review and Meta-analysis].

OBJECTIVE: To systematically review the efficacy of acupuncture for the treatment of tobacco withdrawal syndrome. METHODS: The randomized controlled trials (RCTs) regarding acupuncture for treatment of tobacco withdrawal syndrome were searched in CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane, Medline and EMbase databases. The search period was from January 1st of 2011 to December 31st of 2021. After data extraction and bias risk assessment of the included literature, the Meta-analysis was performed using RevMan5.4.1 software. RESULTS: Totally 23 RCTs were included, including 2 120 patients. The Meta-analysis results showed that compared with medication, acupuncture showed no significant difference at improving Fagerström test for nicotine dependence (FTND) score (MD=0.16, 95%CI: -0.08, 0.41), heaviness of smoking index (HSI) score (MD=0.11, 95%CI: -0.13, 0.36), Minnesota nicotine withdrawal scale (MNWS) score (MD=0.12, 95%CI: -0.11, 1.35), questionnaire of smoking urges (QSU) score (MD=-0.30, 95%CI: -2.78, 2.18), Hamilton depression scale (HAMD) score (MD=0.76, 95%CI: -1.54, 3.06), abstinence rate (RR=0.95, 95% CI: 0.82, 1.10) and effective rate (RR=1.01, 95%CI: 0.95, 1.07). Acupuncture was superior to sham acupuncture in reducing MNWS score (MD=-4.88, 95%CI: -5.21, -4.55, P<0.000 01). Acupuncture was superior to cognitive behavioral therapy in reducing FTND score (MD=-1.41, 95%CI: -1.74, -1.08), MNWS score (MD=-4.28, 95%CI: -5.31, -3.25) and increasing abstinence rate (RR=2.19, 95%CI: 1.39, 3.45, P<0.000 01, P<0.001). CONCLUSION: Acupuncture could effectively improve tobacco withdrawal syndrome, increase abstinence rate and effective rate. Limited by the quantity and quality of the included studies, this conclusion needs to be verified by more studies.

Mechanistic Study of Schisandra chinensis Fruit Mixture Based on Network Pharmacology, Molecular Docking and Experimental Validation to Improve the Inflammatory Response of DKD Through AGEs/RAGE Signaling Pathway.

Background: Diabetic kidney disease (DKD) is a major cause of end-stage renal disease (ESRD), and inflammation is the main causative mechanism. Schisandra chinensis fruit Mixture (SM) is an herbal formulation that has been used for a long time to treat DKD. However, its pharmacological and molecular mechanisms have not been clearly elucidated. The aim of this study was to investigate the potential mechanisms of SM for the treatment of DKD through network pharmacology, molecular docking and experimental validation. Methods: The chemical components in SM were comprehensively identified and collected using liquid chromatography-tandem mass spectrometry (LC-MS) and database mining. The mechanisms were investigated using a network pharmacology, including obtaining SM-DKD intersection targets, completing protein-protein interactions (PPI) by Cytoscape to obtain key potential targets, and then revealing potential mechanisms of SM for DKD by GO and KEGG pathway enrichment analysis. The important pathways and phenotypes screened by the network analysis were validated experimentally in vivo. Finally, the core active ingredients were screened by molecular docking. Results: A total of 53 active ingredients of SM were retrieved by database and LC-MS, and 143 common targets of DKD and SM were identified; KEGG and PPI showed that SM most likely exerted anti-DKD effects by regulating the expression of AGEs/RAGE signaling pathway-related inflammatory factors. In addition, our experimental validation results showed that SM improved renal function and pathological changes in DKD rats, down-regulated AGEs/RAGE signaling pathway, and further down-regulated the expression of TNF-α, IL-1ß, IL-6, and up-regulated IL-10. Molecular docking confirmed the tight binding properties between (+)-aristolone, a core component of SM, and key targets. Conclusion: This study reveals that SM improves the inflammatory response of DKD through AGEs/RAGE signaling pathway, thus providing a novel idea for the clinical treatment of DKD.

[Tennis Ball Massage Therapy in Clinical Nurses: Effect on Relieving Musculoskeletal Disorders and Enhancing Self-Efficacy].

BACKGROUND: Musculoskeletal disorders are a common occupational disease. The prevalence of musculoskeletal disorders among nurses is estimated at 65.1%-87.3%, with neck, shoulders, and lower back being most affected. PURPOSE: To explore the effectiveness of tennis ball massage therapy in alleviating muscle soreness and improving pain relief self-efficacy. METHODS: In this quasi-experimental, single-group, pre- and post-test study, 216 nurses in regional teaching hospitals were screened for neck, shoulder, and back pain. Based on the unit attributes, systematic random sampling was employed to recruit 36 nurses to participate in a four-week "fighting pain" intervention program. The "Pain Visual Scale" and "Pain Relief Self-efficacy Scale" were used as the assessment tools. One-way and two-way repeated measure analysis of variance, a signed ranks test, and the Friedman test were used to assess longitudinal change in the data. RESULTS: Shoulders were the most reported site of muscle pain (94.4%), followed by the neck (88.9%) and the upper back (55.6%). The locations of neck, shoulder, and back pain were interacted differently with the four measurement times (F = 2.69, p = .020). In the post hoc comparison, pain relief effectiveness was most significant in the third posttest, followed by the second. The pain relief was significantly different between the pre-test and the third post-test (t = 6.39, 8.68, 6.96, p < .001). There was a significant difference before and after the intervention of the pain relief self-efficacy (F = 53.49, p < .001). The post hoc comparison results revealed that self-efficacy was lowest at pretest and highest at the third posttest. Significant differences were observed between the pre-test and third post-test at the end of the intervention (t = -10.25, p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study shows that tennis ball massage can improve neck, shoulder, and back pain in nurses and improve pain relief self-efficacy. Tennis ball massage is easy to implement, has no time and space restrictions, and requires no assistance to operate. This equipment can be used to effectively reduce muscle pain, improve the comfort of performing regular activities, and raise work efficiency, reducing the negative impact of muscle pain on work.

Effects of Self-Administered Acupressure on Fatigue Following Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Fatigue is a common symptom after a traumatic brain injury (TBI) and may persist for weeks or years. However, nonpharmacological management strategies for fatigue alleviations are almost nonexistent; thus, effective fatigue management programs are needed urgently. PURPOSES: We aimed to evaluate the effects of self-administered acupressure programs on post-TBI fatigue and heart rate variability and identify the possible correlation between the improvements in fatigue symptoms and the changes in heart rate variability. DESIGN: This randomized controlled trial included 2-point acupressure (TPA; n = 27), 5-point acupressure (FPA; n = 27), and usual care (UC, control; n = 27) groups who underwent several assessments before and after the study intervention. Heart rate variability was evaluated at baseline, weeks 2 and 3, and treatment completion. METHODS: The TPA and FPA groups self-administered acupressure (3 minutes per acupoint; bilateral), thrice daily for 4 weeks, whereas the UC group received routine treatment without acupressure. RESULTS: Both the TPA and FPA groups exhibited substantial improvements in fatigue symptoms compared with the baseline findings in the UC group. In addition, the TPA and FPA groups exhibited increased high-frequency power and mean number of times per hour in which the changes in successive normal sinus intervals (RR) gradually exceeded 50 ms (pNN50). Changes in high-frequency power and pNN50 were correlated with improvements in post-TBI fatigue symptoms. CONCLUSION: Acupressure may alleviate chronic fatigue and enhance parasympathetic activity in TBI survivors. The enhancement of parasympathetic activity may be correlated with improvements in post-TBI fatigue symptoms. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should incorporate self-administered acupressure into the care plans for TBI survivors to improve their fatigue symptoms.

[Application prospect of conditional gene editing animals and viral vectors in experimental research of acupuncturology].

Conditional gene editing animals and viral vectors have been widely applied in the research fields of biology and medicine. Recently, they are also used as the effective approaches to reveal the underlying mechanism of acupuncture from the nervous system to the specific molecules. In order to further understand the application of conditional gene editing animals and viral vectors, in this article, we analyze their characteristics, advantages and recent development in the field of acupuncture research and discuss their potential roles and prospect in the future.