Application and thinking of musculoskeletal ultrasound in diagnosis and treatment of musculoskeletal diseases with acupuncture and moxibustion. / è‚Œéª¨è¶ å£°åœ¨é’ˆç¸è¯Šæ²»è‚Œè‚‰éª¨éª¼ç–¾ç— ä¸­çš„è¿ç”¨ä¸Žæ€è€ƒ.

Musculoskeletal ultrasound (MSUS) is characterized as the dynamic, real-time and continuous visualization, the quantitative and qualitative localization,the simple operation and the absence of use contraindication. As a tool for auxiliary examination, treatment, evaluation and research, in acupuncture and moxibustion, MSUS may improve the accuracy of acupoint location, guide the direction and depth of needle insertion, monitor the reactions of deqi, guarantee the safety of operation and quantify the effect evaluation. Hence, it may provide an objective basis for acupuncture and moxibustion research and be conductive to display the operation techniques of acupuncture and moxibustion by means of objective approaches such as imaging and data.

Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice.

The hypothalamic supramammillary nucleus (SuM) plays a crucial role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find that approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from non-rapid-eye movement or rapid-eye movement sleep, and chemogenetic activation of SuMMS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for the modulation of wakefulness by this hypothalamic-septal projection.

Construction of hierarchical SiO2 microcapsule towards flame retardation, low toxicity and mechanical enhancement of epoxy resins.

A novel approach for improving the flame retardancy, smoke suppression and mechanical properties of epoxy resins (EPs) has been proposed by incorporating functionalized hollow mesoporous silica microcapsules (SHP) loaded with phosphorous silane flame retardants (SCA) and coated with polydopamine (PDA) and transition metals. The proposed approach involves a multi-level structure that combines several mechanisms to enhance the flame-retardant properties of EP. The physical barrier provided by silica serves to impede heat and mass transfer during combustion, while the catalytic carbonization effect of phosphorus and transition metals promotes the formation of a protective char layer, which acts as a barrier to further flame propagation. Incorporating a low loading amount of 3 wt% SHP into the epoxy matrix resulted in EP/SHP-3 composites with significantly improved flame retardancy, as evidenced by a limiting oxygen index of 31.5% and a V-1 rating, in contrast to the values obtained for unmodified EP, which were 23.8% and no rating, respectively. In addition, cone calorimeter test (CCT) results indicated that the total heat release, peak heat release rate and total smoke production of EP/SHP-3 decreased by 18.2%, 25.2% and 18.4%, respectively. Moreover, the improved interfacial compatibility facilitated by polydopamine assists in the dispersion and compatibility of the SHP with the epoxy matrix, leading to better mechanical properties. Herein, the addition of 1 wt% SHP to EP significantly improved its mechanical performance, with a 16.7% increase in tensile strength and a 19.2% increase in impact strength. The design of the multi-level structural approach has the potential to provide new ideas for the simultaneous improvement of fire safety as well as mechanical properties of polymers.

Comparison of different adjuvant therapy regimen efficacies in patients with high risk of recurrence after radical resection of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high recurrence rate even after radical surgery. Postoperative adjuvant transhepatic arterial chemoembolization (PA-TACE), postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC), postoperative adjuvant radiotherapy (PA-RT), and postoperative adjuvant molecular targeted therapy have been demonstrated to be effective in reducing the postoperative recurrence rate. The present network meta-analysis was conducted to compare the effects of PA-TACE, PA-HAIC, PA-RT and postoperative adjuvant molecular targeted therapy on the overall survival (OS) and disease-free survival (DFS) in HCC patients after radical resection and to determine the optimal treatment strategy. METHODS: Network meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane Library, and Web of Science were used to collect eligible studies up to December 25, 2022. Studies related to PA-TACE, PA-HAIC, and postoperative adjuvant molecular targeted therapy after radical HCC resection was included. The endpoints were OS and DFS, and the effect size was determined using hazard ratio with a 95% confidence interval. R software and "gemtc" package were employed to analyze the results. RESULTS: A total of 38 studies involving 7079 patients with HCC after radical resection were ultimately enrolled to be analyzed. Four postoperative adjuvant therapy measures and two oncology indicators were evaluated. In this study, OS-related investigations validated that PA-Sorafenib and PA-RT markedly enhanced the OS rates in patients after radical resection when compared to PA-TACE and PA-HAIC. However, statistical analysis revealed no significant difference between PA-Sorafenib and PA-RT, as well as PA-TACE and PA-HAIC. In the DFS-related investigations, PA-RT demonstrated superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC. Additionally, PA-Sorafenib displayed better efficacy than PA-TACE. Nevertheless, there was no statistical significance between PA-Sorafenib and PA-HAIC, as well as PA-TACE and PA-HAIC. We also performed a subgroup analysis of studies focusing on HCC complicated by microvascular invasion after radical resection. In terms of OS, both PA-RT and PA-Sorafenib demonstrated a noteworthy improvement over PA-TACE, whereas no statistical significance was detected between PA-RT and PA-Sorafenib. Likewise, for DFS, both PA-Sorafenib and PA-RT exhibited superior efficacy compared to PA-TACE. CONCLUSION: In patients with HCC after radical resection and a high risk of recurrence, both PA-Sorafenib and PA-RT significantly improved OS and DFS when compared to PA-TACE and PA-HAIC. Notably, PA-RT exhibited superior efficacy over PA-Sorafenib, PA-TACE, and PA-HAIC in terms of DFS. Similarly, PA-Sorafenib appeared to be more effective than PA-TACE for DFS.

Development of alternative herbals remedy for gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis.

Objective: Screening out potential herbal medicines and herbal ingredients for the treatment of gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis. Methods: Gene expression profiles of gastric tumour tissues and normal tissue samples were obtained from the GEO database and the samples were analysed for immune cell infiltration condition and differential expressed genes of ferroptosis. Key genes were screened by protein-protein interaction (PPI) and enrichment analysis, and molecular docking was used to predict and preliminary validate potential herbal and traditional Chinese medicine components for gastric cancer based on the key genes. Finally, RT-QPCR was used to validate the prediction results. Results: Immune cell infiltration analysis revealed high levels of infiltration of activated CD4 memory T cells, monocytes, M0 macrophages in gastric tumor tissues, while plasma cells and resting mast cells had higher levels of infiltration in the paraneoplastic tissues. Differential gene expression analysis identified 1,012 upregulated genes and 880 downregulated genes, of which 84 immune related differentially expressed genes such as CTSB, PGF and PLAU and 10 ferroptosis-related differentially expressed genes such as HSF1, NOX4 and NF2 were highly expressed in gastric cancer tissues. The results of enrichment analysis showed that they mainly involve 343 biological processes such as extracellular matrix organization and extracellular structural organization; 37 cellular components such as complexes of collagen trimer and basement membrane; 35 molecular functions such as signal receptor activator activity and receptor ligand activity; 19 regulatory pathways such as cytokine-cytokine receptor interactions and retinol metabolism. Finally, two key genes, TLR4 and KRAS, were selected and 12 herbal medicines such as Radix Salviae liguliobae, Rhizoma Coptidis, Rhizoma Polygoni cuspidati and 27 herbal ingredients such as resveratrol, salvianolic acid b were predicted on the basis of key genes. Molecular docking results showed that KRAS binds tightly to coumarin and magnolol, while TLR4 can bind tightly to resveratrol, curcumin, salvianolic acid b, shikonin. Subsequently, the effect of resveratrol and magnolol was experimentally verified. Conclusion: Herbal medicines such as S. liguliobae, Rhizoma Coptidis, Rhizoma P. cuspidati and herbal ingredients such as resveratrol, curcumin, salvianolic acid b may provide research directions and alternative therapeutic approaches for immunomodulation of TME and ferroptosis of tumour cells in gastric cancer.

Low-intensity exercise combined with sodium valproate attenuates kainic acid-induced seizures and associated co-morbidities by inhibiting NF-κB signaling in mice.

Sodium valproate (VPA) is a broad-spectrum anticonvulsant that is effective both in adults and children suffering from epilepsy, but it causes psychiatric and behavioral side effects in patients with epilepsy. In addition, 30% of patients with epilepsy develop resistance to VPA. At present, regular physical exercise has shown many benefits and has become an effective complementary therapy for various brain diseases, including epilepsy. Therefore, we wondered whether VPA combined with exercise would be more effective in the treatment of seizures and associated co-morbidities. Here, we used a mouse model with kainic acid (KA)-induced epilepsy to compare the seizure status and the levels of related co-morbidities, such as cognition, depression, anxiety, and movement disorders, in each group using animal behavioral experiment and local field potential recordings. Subsequently, we investigated the mechanism behind this phenomenon by immunological means. Our results showed that low-intensity exercise combined with VPA reduced seizures and associated co-morbidities. This phenomenon seems to be related to the Toll-like receptor 4, activation of the nuclear factor kappa B (NF-κB), and release of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), and IL-6. In brief, low-intensity exercise combined with VPA enhanced the downregulation of NF-κB-related inflammatory response, thereby alleviating the seizures, and associated co-morbidities.

Evaluation of water quality and its driving forces in the Shaying River Basin with the grey relational analysis based on combination weighting.

The water quality of the Shaying River Basin and even the entire Huai River Basin has been widely concerned. Based on the water quality data acquired in flood and non-flood seasons from 2012 to 2016, the Shaying River Basin was selected as the research object. First, the principal component analysis method was used to identify the main pollution indices. Then, grey relational analysis combined with an analytic hierarchy process and entropy weight method was used to evaluate the water quality of the upper, middle, and lower reaches of the Shaying River Basin, while the single factor evaluation method was used for comparative analysis. Finally, the driving forces of water quality were analyzed and discussed from natural and human aspects. The results show that the main pollutants in the Shaying River Basin are total nitrogen, total phosphorus, and ammonium nitrogen. While the basin is seriously polluted by nitrogen and phosphorus, the spatial and temporal distribution of the pollution varies, although the overall trend toward improving water quality conditions is significant. The midstream region had the poorest water quality, which fluctuated between Classes III and V. The downstream region had generally good water quality, which could be ranked as Class III most of the time. And the upstream region had the best water quality with well-developed ecological conditions; all the water samples were ranked as Class I or II. The water quality improves significantly during the flood season when compared with that in the non-flood season. Seasonal climate variation, non-point source pollution emissions, the release of water from sluices and dams, and water resource management activities are the main reasons for the variations in water quality across the Shaying River Basin.

Activating BK channels ameliorates vascular smooth muscle calcification through Akt signaling.

Vascular calcification (VC) is characterized by pathological depositions of calcium and phosphate in the arteries and veins via an active cell-regulated process, in which vascular smooth muscle cells (VSMCs) transform into osteoblast/chondrocyte-like cells as in bone formation. VC is associated with significant morbidity and mortality in chronic kidney disease (CKD) and cardiovascular disease, but the underlying mechanisms remain unclear. In this study we investigated the role of large-conductance calcium-activated potassium (BK) channels in 3 experimental VC models. VC was induced in vascular smooth muscle cells (VSMCs) by ß-glycerophosphate (ß-GP), or in rats by subtotal nephrectomy, or in mice by high-dosage vitamin D3. We showed that the expression of BK channels in the artery of CKD rats with VC and in ß-GP-treated VSMCs was significantly decreased, which was functionally confirmed by patch-clamp recording. In ß-GP-treated VSMCs, BK channel opener NS1619 (20 µM) significantly alleviated VC by decreasing calcium content and alkaline phosphatase activity. Furthermore, NS1619 decreased mRNA expression of ostoegenic genes OCN and OPN, as well as Runx2 (a key transcription factor involved in preosteoblast to osteoblast differentiation), and increased the expression of α-SMA protein, whereas BK channel inhibitor paxilline (10 µM) caused the opposite effects. In primary cultured VSMCs from BK-/- mice, BK deficiency aggravated calcification as did BK channel inhibitor in normal VSMCs. Moreover, calcification was more severe in thoracic aorta rings of BK-/- mice than in those of wild-type littermates. Administration of BK channel activator BMS191011 (10 mg· kg-1 ·d-1) in high-dosage vitamin D3-treated mice significantly ameliorated calcification. Finally, co-treatment with Akt inhibitor MK2206 (1 µM) or FoxO1 inhibitor AS1842856 (3 µM) in calcified VSMCs abrogated the effects of BK channel opener NS1619. Taken together, activation of BK channels ameliorates VC via Akt/FoxO1 signaling pathways. Strategies to activate BK channels and/or enhance BK channel expression may offer therapeutic avenues to control VC.

Effect of Nigella sativa in the treatment of nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

The effectiveness of Nigella sativa (NS) treatment for nonalcoholic fatty liver disease (NAFLD) remains controversial. This systematic review, and meta-analysis, was conducted to evaluate potential benefits of NS for NAFLD. Up to June 11, 2020, randomized controlled trials (RCTs) evaluating NS for the treatment of NAFLD were searched and included from PubMed, Embase, Cochrane Library, and Web of science. Mean differences (MD) or risk ratio (RR) and 95% confidence intervals (CI) were calculated. Six articles from five trails with a total of 358 participants were included. Although NS has no beneficial effect on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL), triglyceride (TG), insulin, and tumor necrosis factor α (TNF-α), its supplementation did improve the levels of alanine transaminase (ALT), aspartate transaminase (AST), fasting blood sugar (FBS), high-density lipoprotein cholesterol (HDL), high-sensitivity C reactive protein (hs-CRP), and grade of fatty liver compared with placebo. In summary, this study showed that NS supplementation was effective in the treatment of NAFLD and could improve the levels of ALT, AST, FBS, HDL, and hs-CRP in patients with NAFLD, as well as the severity of NAFLD. High-quality large sample RCTs are necessary to confirm the benefit of NS supplementation for NAFLD.

Confirmation of potential neuroprotective effects of natural bioactive compounds from traditional medicinal herbs in cerebral ischemia treatment.

Ischemic brain injury is a prevalent disease with high disability and mortality, but no efficient therapeutics for the disease are currently available mainly due to the narrow therapeutic window. The treatment of cerebrovascular disease by using herbal medicine has been applied for a long time, from which large amounts of medical experience and knowledge have been accumulated. Numerous natural bioactive compounds extracted from Chinese medicines exhibit neuroprotective activities, especially protecting the brain from ischemic injury. This review summarizes the mechanisms underlying cerebral ischemic pathophysiology, including excitotoxicity, generation of free radical, inflammation, astrocytic influence, apoptosis, blood-brain barrier dysfunction, and discusses neuroprotective activities of the representative natural bioactive compounds extracted from traditional medicinal herbs, with targeting one or more signal molecules. Confirmation of potential neuroprotective activities of bioactive compounds derived from Chinese medicine in ischemic stroke treatment is discussed.

Anticonvulsant Effects of Dingxian Pill in Pentylenetetrazol-Kindled Rats.

Dingxian pill has been used as an antiepilepsy agent in China from ancient to modern times, of which the concrete pharmacological characterization and the underlying molecular mechanism remain unclear. The present study was undertaken to investigate them by animal behavior, electroencephalogram (EEG), Morris water maze, immunohistochemistry, transcriptomics, and real-time PCR. In our results, the treatment of Dingxian pill dose-dependently inhibited PTZ-induced seizure-like behavior and reduced the seizure grades, LFP power spectral density, and brain wave of the epileptiform EEG component induced by PTZ. In Morris water maze tests, the learning and memory ability of kindled epileptic rats could be attenuated more efficiently by Dingxian pill. For the immediate early gene c-fos, the expression was reduced after Dingxian pill treatment, and the difference was significant between the treatment and the model group. Through the transcriptome analysis of the gene expression in hippocampus, Egr3, Nrg, Arc, and Ptgs2, closely related to epilepsy, had been proved to be downregulated by application of Dingxian pill. All of the results not only highlight the antiepileptic effects of Dingxian pill and its molecular mechanism, but also provide a modern validity theory for the clinical application of traditional Chinese medicine (TCM).

The Zuo Jin Wan Formula increases chemosensitivity of human primary gastric cancer cells by AKT mediated mitochondrial translocation of cofilin-1 / 中国天然药物

Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.

The Yin and Yang of BK Channels in Epilepsy.

BACKGROUND & OBJECTIVE: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled "excitatory" or "inhibitory", the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in epilepsy is controversial so far, and a growing area of intense investigation. CONCLUSION: Here, this review aims to highlight recent discoveries on the dichotomous role of BK channels in epilepsy, focusing on relevant BK-dependent pro- as well as antiepileptic pathways, and discuss the potential of BK specific modulators for the treatment of epilepsy.

Zuo Jin Wan Reverses DDP Resistance in Gastric Cancer through ROCK/PTEN/PI3K Signaling Pathway.

Gastric cancer (GC) is the third leading cause of cancer-related death. Chemotherapy resistance remains the major reason for GC treatment failure and poor overall survival of patients. Our previous studies have proved that Zuo Jin Wan (ZJW), a traditional Chinese medicine (TCM) formula, could significantly enhance the sensitivity of cisplatin (DDP)-resistant gastric cancer cells to DDP by inducing apoptosis via mitochondrial translocation of cofilin-1. However, the underlying mechanism remains poorly understood. This study aimed to evaluate the effects of ROCK/PTEN/PI3K on ZJW-induced apoptosis in vitro and in vivo. We found that ZJW could significantly activate the ROCK/PTEN pathway, inhibit PI3K/Akt, and promote the apoptosis of SGC-7901/DDP cells. Inhibition of ROCK obviously attenuated ZJW-induced apoptosis as well as cofilin-1 mitochondrial translocation, while inhibition of PI3K had the opposite effects. In vivo, combination treatment of DDP and ZJW (2000 mg/kg) significantly reduced tumor growth compared with DDP alone. Moreover, the combined administration of ZJW and DDP increased the expression of cleaved ROCK and p-PTEN while it decreased p-PI3K and p-cofilin-1, which was consistent with our in vitro results. These findings indicated that ZJW could effectively inhibit DDP resistance in GC by regulating ROCK/PTEN/PI3K signaling and provide a promising treatment strategy for gastric cancer.

[Study on the measurement of residual stresses around indentations in SiC/Al2O3 nanocomposite using fluorescence].

The residual stresses induced by an indentation were studied in 5% SiC/Al2O3 nanocomposite using fluorescence spectroscopy in this work. It was found that within the indentation and the region of about 10 microm outside the impression, the broadening of the R-lines is obvious, and that the compression shift is a strong function of the distance from the indentation centre. From the observed frequency shifts, the hydrostatic stresses in regions sampled in the indentation, and in the complex stress field surrounding it were measured. The same variation regularity of stresses exists along the diagonal direction and the side vertical bisector direction. The symmetry of the residual stress field around the indentation was also found.