Effects of Patient-Controlled Transcutaneous Electrical Acupoint Stimulation on Cancer Induced Bone Pain Relief in Patients with Non-Small Cell Lung Cancer: Study Protocol for a Randomized Controlled Trial.

Background: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC). Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight. Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP. Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Preparation of phosphorus containing products by co-incineration of sludge ash and calcium-based additives: Focusing one-step and multi-step method.

Due to the irreplaceable nature of phosphorus (P) in biological growth and the shortage of P rock, it is necessary to recover P from waste, such as sludge ash. P-containing products were prepared using sludge ash and calcium-based additives (CaCO3 and eggshell). In addition, the effects of different incineration methods (one-step method (OSM) and multi-step method (MSM)), additive doses, and incineration temperature on the P content and species in the products were investigated. The results indicated that as the dose of calcium-based additives increased, total P (TP) content in P-containing products reduced, apatite P (AP) content increased, non-apatite P (NAIP) content declined, and P solubility in citric acid content decreased. The amount of AP increased, NAIP reduced, and P solubility in citric acid decreased as the incineration temperature climbed. Although P in P-containing products prepared by OSM and MSM changed in a similar way at different additive doses and temperatures, P-containing products prepared by MSM had at least a 6.1% increase in P solubility in citric acid. Compared with OSM, MSM could save 10% of calcium-based additives when reaching the maximum AP value. Additionally, pure materials were employed to investigate how P species changed during the incineration procedure. The advantage of the MSM-prepared product over the OSM-prepared product may be explained by the high concentration of Ca3(PO4)2 and low concentration of amorphous calcium bound P (Ca-P). Overall, MSM is an effective method to reduce the dose of calcium-based additives and increase the bioavailability of P in P-containing products.

Structurally Diverse Coumarins from Peucedanum praeruptorum and their Anti-Inflammatory Activities via NF-κB Signaling Pathway.

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.

Prepared Radix Polygoni Multiflori and emodin alleviate lipid droplet accumulation in nonalcoholic fatty liver disease through MAPK signaling pathway inhibition.

As one of the most common liver diseases, nonalcoholic fatty liver disease (NAFLD) affects almost one-quarter of the world's population. Although the prevalence of NAFLD is continuously rising, effective medical treatments are still inadequate. Radix Polygoni Multiflori (RPM) is a traditional Chinese herbal medicine. As a processed product of RPM, prepared Radix Polygoni Multiflori (PRPM) has been reported to have antioxidant and anti-inflammatory effects. This study investigated whether PRPM treatment could significantly improve NAFLD. We used recent literature, the Herb database and the SwissADME database to isolate the active compounds of PRPM. The OMIM, DisGeNET and GeneCards databases were used to isolate NAFLD-related target genes, and GO functional enrichment and KEGG pathway enrichment analyses were conducted. Moreover, PRPM treatment in NAFLD model mice was evaluated. The results indicate that the target genes are mainly enriched in the AMPK and de novo lipogenesis signaling pathways and that PRPM treatment improves NAFLD disease in model mice. Here, we found the potential benefits of PRPM against NAFLD and demonstrated in vivo and in vitro that PRPM and its ingredient emodin downregulate phosphorylated P38/P38, phosphorylated ERK1/2 and genes related to de novo adipogenesis signaling pathways and reduce lipid droplet accumulation. In conclusion, our findings revealed a novel therapeutic role for PRPM in the treatment of NAFLD and metabolic inflammation.

Functions and targets of miRNAs in pharmacological and toxicological effects of major components of Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) has a long history of use as a traditional Chinese medicine and has been widely administered to treat various inflammatory and autoimmune diseases. MicroRNAs (miRNAs) are endogenous, short, non-coding RNAs that regulate gene expression post-transcriptionally. They participate in the efficacies and even toxicities of the components of TwHF, rendering miRNAs an appealing therapeutic strategy. This review summarizes the recent literature related to the roles and mechanisms of miRNAs in the pharmacological and toxicological effects of main components of TwHF, focusing on two active compounds, triptolide (TP) and celastrol (CEL). Additionally, the prospects for the "You Gu Wu Yun" theory regarding TwHF nephrotoxicity are presented.

Comprehensive effects of thiamethoxam from contaminated soil on lettuce growth and metabolism.

The second-generation neonicotinoid thiamethoxam, is prevalent in soils because of its extensive application and persistence. However, the comprehensive effects of thiamethoxam residue in soils on cultivated plants are still poorly understood. This study examined variations of growth state, physiological parameters, antioxidant activity, and metabolites in lettuce after thiamethoxam exposure; the removal effects of different washing procedures were also investigated. The results indicated that thiamethoxam in soils significantly increased the fresh weight, seedling height and chlorophyll content in lettuce, and also altered its lipid, carbohydrate, nucleotide and amino acids composition based on untargeted metabolomics. KEGG pathway analysis uncovered a disruption of lipid pathways in lettuce exposed to both low and high concentrations of thiamethoxam treatments. In addition, the terminal residues of thiamethoxam in lettuce were below the corresponding maximum residue limits stipulated for China. The thiamethoxam removal rates achieved by common washing procedures in lettuce ranged from 26.9% to 42.6%. This study thus promotes the understanding of the potential food safety risk caused by residual thiamethoxam in soils.

Unusual triterpenoids and steroids from Cipadessa baccifera and their biological activities.

Five undescribed triterpenoids and steroids (1-5), as well as ten known compounds, were purified from the branches and leaves of Cipadessa baccifera. Notably, 1 and 2 are rare cipadesin-type limonoids with an unusual 8,30-epoxide ring and 1,8-ether linkage, respectively. Compound 5 possessed pregnane steroid skeleton with an uncommon 5/6/6/6/5-fused ring system. Their structures were constructed by extensive spectroscopic analysis (NMR, IR, UV, and HRESIMS), and their absolute configurations were confirmed by ECD calculations and quantum chemical calculations. All the isolates were in vitro assayed for their antimicrobial potentials against 6 pathogenic microorganisms and antiproliferation activities against five human cancer cell lines. As a result, compounds 5, 12, 13, and 14 exhibited moderate antibacterial activities (MIC: 25-50 µg/mL). Moreover, 5 showed cytotoxicity against five cancer cell lines with IC50 values ranging from 8.0 to 19.9 µM.

Effect of acupuncture or moxibustion at Acupoints Weizhong (BL40) or Chize (LU5) on the change in lumbar temperature in healthy adults: A study protocol for a randomized controlled trial with a 2 × 2 factorial design.

BACKGROUND: Low back pain is a common complaint among adults, and moxibustion and acupuncture are commonly used treatments. In traditional theory, Weizhong (BL40) is a popular acupoint, as supported by the saying "Yao Bei Wei Zhong Qiu." However, the difference in efficacy between acupuncture and moxibustion remains unclear. Therefore, this trial will compare the thermal effects of acupuncture and moxibustion at BL40 and Chize point (LU5) in healthy adults to provide more objective evidence regarding the relationship between the lumbar and BL40. METHOD/DESIGN: The trial will use a two-by-two factorial design, randomly assigning 140 participants to four groups (acupuncture at Weizhong (BL40), acupuncture at Chize (LU5), moxibustion at Weizhong (BL40), and moxibustion at Chize (LU5)) at a ratio of 1:1:1:1. Each group will undergo a 30-minute intervention, with the primary outcome being mean temperature in the lumbar region at the last minute of the intervention period. Secondary outcomes include maximum lumbar temperature in the lumbar region at the last minute of the intervention, average lumbar temperature and average bladder meridian temperature at specific time points during and after the intervention, and scores on the warming sensation questionnaire. Data will be analyzed on an intention-to-treat basis. DISCUSSION: This study will be the first to compare the thermal effect difference in the lumbar area between acupuncture and moxibustion in healthy individuals. The findings of this study will provide new insights for the "Yao Bei Wei Zhong Qiu" theory of traditional Chinese medicine. TRIAL REGISTRATION: ClinicalTrials.gov, Trial number: NCT05665426. Registered on 26 December 2022.

Hosimosines A-E, structurally diverse cytisine derivatives from the seeds of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils (Fabaceae family) is an arbor species endemic to China. The seeds of O. hosiei have been used as traditional Chinese medicine to treat hernia, abdominal pain, blood stasis and amenorrhea. Cytisine-like and angustifoline type alkaloids were main components identified from this plant. In our research on the bioactive alkaloids from the promising Chinese medicinal plants, four new angustifoline type alkaloids (1-4) and a new cytisine-like alkaloid (5), named hosimosine A-E, together with 13 known analogues (6-18) were isolated from the seeds of O. hosiei. Their structures were elucidated by the extensive spectroscopic methods, especially the interpretation of NMR spectra and specific rotations, along with the methods of NMR and ECD calculation. Compounds 1-4 were identified as two pairs of epimers, whose relative configurations were deduced from density functional theory (DFT) calculations of NMR chemical shifts and DP4+ analysis, and absolute configurations were determined by comparison of their experimental and theoretical ECD spectra. Compound 5 displayed two sets of NMR data caused by the existence of tautomeric forms. Compounds 14, 17 and 18 were determined to be enantiomers of literature compounds. Some of the isolates exhibited moderate cytotoxic effects against HepG2, A2780 and MCF-7 cells.

Anti-inflammatory strategies for photothermal therapy of cancer.

High temperature generated by photothermal therapy (PTT) can trigger an inflammatory response at the tumor site, which not only limits the efficacy of PTT but also increases the risk of tumor metastasis and recurrence. In light of the current limitations posed by inflammation in PTT, several studies have revealed that inhibiting PTT-induced inflammation can significantly improve the efficacy of cancer treatment. In this review, we summarize the research progress made in combining anti-inflammatory strategies to enhance the effectiveness of PTT. The goal is to offer valuable insights for developing better-designed photothermal agents in clinical cancer therapy.

Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice.

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.

Linear Regression Analysis of Sleep Quality in People with Insomnia in Wuhan City during the COVID-19 Pandemic.

Objective: COVID-19 has evolved into a major global public health event. The number of people reporting insomnia is growing exponentially during the pandemic. This study aimed to explore the relationship between aggravated insomnia and COVID-19-induced psychological impact on the public, lifestyle changes, and anxiety about the future. Methods: In this cross-sectional study, we used the questionnaires from 400 subjects who were obtained from the Department of Encephalopathy of the Wuhan Hospital of Traditional Chinese Medicine between July 2020 and July 2021. The data collected for the study included demographic characteristics of the participants and psychological scales consisting of the Spiegel Sleep Questionnaire, the Fear of COVID-19 Scale (FCV-19S), the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). The independent sample t-test and one-way ANOVA were used to compare the results. Correlation analysis of variables affecting insomnia was performed using Pearson correlation analysis. The degree of influence of the variables on insomnia was determined using linear regression, and a regression equation was derived. Results: A total of 400 insomnia patients participated in the survey. The median age was 45.75 ± 15.04 years. The average score of the Spiegel Sleep Questionnaire was 17.29 ± 6.36, that of SAS was 52.47 ± 10.39, that of SDS was 65.89 ± 8.72, and that of FCV-19S was 16.09 ± 6.81. The scores of FCV-19S, SAS, and SDS were closely related to insomnia, and the influencing degree was in the following order: fear, depression, and anxiety (OR = 1.30, 0.709, and 0.63, respectively). Conclusion: Fear of COVID-19 can be one of the primary contributors to worsening insomnia.

Phosphorus recovery from incinerated sewage sludge ash using electrodialysis coupled with plant extractant enhancement technology.

Phosphorus (P) is an integral mineral nutrient for the growth of plants and animals. As the increasing population worldwide, the demand for P resources keeps increasing. Therefore, it is necessary to recover P from secondary resources. Unlike conventional P recovery processes, this work focused on the recovery of P from incinerated sewage sludge ash (ISSA) using electrodialysis as the main technology coupled with plant extractants. In this study, Amaranthus and hydrolyzed polymaleic anhydride (HPMA) were used as P extractants, investigating the effects of HPMA concentration and pH of the compound agent on the migration of P and heavy metals from ISSA. The results showed that the concentration of HPMA and pH of the compound agent had a significant influence on the mobility of P and heavy metals. Meanwhile, the impacts of eggshell additions and voltage on the recovery efficiency of P was also studied by using waste eggshells as calcium sources. We found that when eggshells were added at 10 g/L and the voltage was 10 V, the recovery efficiency of P reached 96.05%. Moreover, XRD patterns revealed that the mineral phase of recovered P-containing products was predominantly hydroxyapatite, which had good environmental benefits. Generally, the favorable results have been achieved in the recovery efficiency of P and has practical implications for P recovery from ISSA.

A hypoxia-activated photothermal agent inhibits multiple heat shock proteins for low-temperature photothermal therapy.

A near-infrared (NIR) organic photothermal agent (PTA) to inhibit three types of heat shock proteins (HSPs) was synthesized, which could be activated under hypoxic conditions for low-temperature photothermal therapy (PTT) of cancer.

[Challenges and choices: translational acupuncture research spectrum-a proposal].

For more than half a century，the modern bioresearch in acupuncture has made remarkable advancements, proving scientific basis underlying the traditional, intuitive treatment, as well as leading to some new discoveries with the potential to enhance the effectiveness of acupuncture as we know it. Meanwhile, the clinical researches have started to shift its paradigm from traditional individual observation to modern evidence-based medicine. However, there is little interaction between basic and clinic researches, which are like two separate worlds, not benefiting each other. Also the education and training of acupuncture are still traditional style, little combining with modern studies. To bridging the large gap, we need translational science involving in. In this article, with a critical reviews of the limitations of the traditional methods of acupuncture, the challenges faced by clinic practices and placebo-control studies, and the advantages and disadvantages of basic research, we propose a methodological paradigm of the translational research, Translational Acupuncture Research Spectrum, that meets the current situation of acupuncture researches, hoping to give insights into this field and to promote modern acupuncture to move towards a new stage.

Advances in photobiomodulation for cognitive improvement by near-infrared derived multiple strategies.

Cognitive function is an important ability of the brain, but cognitive dysfunction can easily develop once the brain is injured in various neuropathological conditions or diseases. Photobiomodulation therapy is a type of noninvasive physical therapy that is gradually emerging in the field of neuroscience. Transcranial photobiomodulation has been commonly used to regulate neural activity in the superficial cortex. To stimulate deeper brain activity, advanced photobiomodulation techniques in conjunction with photosensitive nanoparticles have been developed. This review addresses the mechanisms of photobiomodulation on neurons and neural networks and discusses the advantages, disadvantages and potential applications of photobiomodulation alone or in combination with photosensitive nanoparticles. Photobiomodulation and its associated strategies may provide new breakthrough treatments for cognitive improvement.

Low expression of the intestinal metabolite butyric acid and the corresponding memory pattern regulate HDAC4 to promote apoptosis in rat hippocampal neurons.

After intensive research on the gut-brain axis, intestinal dysbiosis is considered to be one of the important pathways of cognitive decline. Microbiota transplantation has long been thought to reverse the behavioral changes in the brain caused by colony dysregulation, but in our study, microbiota transplantation seemed to improve only behavioral brain function, and there was no reasonable explanation for the high level of hippocampal neuron apoptosis that remained. Butyric acid is one of the short-chain fatty acids of intestinal metabolites and is mainly used as an edible flavoring. It is commonly used in butter, cheese and fruit flavorings, and is a natural product of bacterial fermentation of dietary fiber and resistant starch in the colon, acting similarly to the small-molecule HDAC inhibitor TSA. The effect of butyric acid on HDAC levels in hippocampal neurons in the brain remains unclear. Therefore, this study used rats with low bacterial abundance, conditional knockout mice, microbiota transplantation, 16S rDNA amplicon sequencing, and behavioral assays to demonstrate the regulatory mechanism of short-chain fatty acids on the acetylation of hippocampal histones. The results showed that disturbance of short-chain fatty acid metabolism led to high HDAC4 expression in the hippocampus and regulated H4K8ac, H4K12ac, and H4K16ac to promote increased neuronal apoptosis. However, microbiota transplantation did not change the pattern of low butyric acid expression, resulting in maintained high HDAC4 expression in hippocampal neurons with continued neuronal apoptosis. Overall, our study shows that low levels of butyric acid in vivo can promote HDAC4 expression through the gut-brain axis pathway, leading to hippocampal neuronal apoptosis, and demonstrates that butyric acid has great potential value for neuroprotection in the brain. In this regard, we suggest that patients with chronic dysbiosis should pay attention to changes in the levels of SCFAs in their bodies, and if deficiencies occur, they should be promptly supplemented through diet and other means to avoid affecting brain health.

A heat shock protein-inhibiting molecular photothermal agent for mild-temperature photothermal therapy.

A heat shock protein-inhibiting photothermal agent (PTA) with endoplasmic reticulum targeting was synthesized to reduce the thermal resistance and enhance the effect of mild-temperature photothermal therapy (PTT).

Superior Gait Symmetry and Postural Stability among Yoga Instructors-Inertial Measurement Unit-Based Evaluation.

This study investigates gait symmetry and single-leg stance balance of professional yoga instructors versus age-matched typically developed controls using inertial measurement unit (IMU)-based evaluation. We recruited twenty-five yoga instructors and twenty-five healthy control subjects to conduct the walking experiments and single-leg stance tests. Kinematic data were measured by attaching IMUs to the lower limbs and trunk. We assessed the asymmetry of swing phases during the normal-walk and tandem-walk tests with eyes open and closed, respectively. The subjects subsequently conducted four single-leg stance tests, including a single-leg stance on both legs with eyes open and closed. Two balance indexes regarding the angular velocities of the waist and chest were defined to assess postural stability. The gait asymmetry indexes of yoga instructors were significantly lower than those of the typically developed controls. Similarly, the yoga instructors had better body balance in all four single-leg stance tests. This study's findings suggest that yoga improves gait asymmetry and balance ability in healthy adults. In the future, further intervention studies could be conducted to confirm the effect of yoga training.