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BACKGROUND: Clinically, most patients with lung cancer (LC) die from tumor spread and metastasis. Specific metastasis-related molecules can provide reference for clinical prediction of efficacy, evaluation of prognosis, and search for the best treatment plan. Troponin T1 (TNNT1) is highly expressed in various cancer tissues, which affects malignant behavior of tumor cells and is related to patients' survival and prognosis. However, the role and molecular mechanism of TNNT1 in LC invasion and metastasis have not yet been investigated. METHODS: Gene expression profiling interactive analysis (GEPIA) online analysis was used to analyze TNNT1 expression in LC tissues. Quantitative real-time-polymerase chain reaction (qRT-PCR) or western blot were performed to measure TNNT1 or epithelial-to-mesenchymal transition (EMT)-related and Wnt/ß-catenin pathway-related protein expression in LC cells. After TNNT1 knockdown, cell scratch healing and transwell assays were introduced to assess cell migration and invasion, respectively. RESULTS: TNNT1 expression in LC tissues and cells was increased. TNNT1 knockdown notably impaired LC cell migration, invasion and EMT. TNNT1 knockdown inhibited Wnt/ß-catenin pathway of LC cells. Lithium chloride (LiCl) addition partially restored the inhibition of TNNT1 knockdown on migration, invasion, EMT and Wnt/ß-catenin of LC cells. CONCLUSION: TNNT1 knockdown attenuated LC migration, invasion and EMT, possibly through Wnt/ß-catenin signaling.

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Leukemia-initiating cells (LICs) are regarded as the origin of leukemia relapse and therapeutic resistance. Identifying direct stemness determinants that fuel LIC self-renewal is critical for developing targeted approaches. Here, we show that the RNA-editing enzyme ADAR1 is a crucial stemness factor that promotes LIC self-renewal by attenuating aberrant double-stranded RNA (dsRNA) sensing. Elevated adenosine-to-inosine editing is a common attribute of relapsed T cell acute lymphoblastic leukemia (T-ALL) regardless of molecular subtype. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL patient-derived xenograft models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA to avoid detection by the innate immune sensor melanoma differentiation-associated protein 5 (MDA5). Moreover, we uncover that the cell-intrinsic level of MDA5 dictates the dependency on the ADAR1-MDA5 axis in T-ALL. Collectively, our results show that ADAR1 functions as a self-renewal factor that limits the sensing of endogenous dsRNA. Thus, targeting ADAR1 presents an effective therapeutic strategy for eliminating T-ALL LICs.

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Leukemia initiating cells (LICs) are regarded as the origin of leukemia relapse and therapeutic resistance. Identifying direct stemness determinants that fuel LIC self-renewal is critical for developing targeted approaches to eliminate LICs and prevent relapse. Here, we show that the RNA editing enzyme ADAR1 is a crucial stemness factor that promotes LIC self-renewal by attenuating aberrant double-stranded RNA (dsRNA) sensing. Elevated adenosine-to-inosine (A-to-I) editing is a common attribute of relapsed T-ALL regardless of molecular subtypes. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL PDX models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA and retains unedited nuclear dsRNA to avoid detection by the innate immune sensor MDA5. Moreover, we uncovered that the cell intrinsic level of MDA5 dictates the dependency on ADAR1-MDA5 axis in T-ALL. Collectively, our results show that ADAR1 functions as a self-renewal factor that limits the sensing of endogenous dsRNA. Thus, targeting ADAR1 presents a safe and effective therapeutic strategy for eliminating T-ALL LICs.

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Acupuncture plays a vital anti-inflammatory action in sepsis by activating autonomic nerve anti-inflammatory pathways, such as sympathoadrenal medullary pathway, but the mechanism remains unclear. This study aims to explore the optimum parameter of electroacupuncture (EA) stimulation in regulating the sympathoadrenal medullary pathway and evaluate EA's anti-inflammatory effect on sepsis. To determine the optimum parameter of EA at homotopic acupoint on adrenal sympathetic activity, the left adrenal sympathetic nerve firing rate evoked by different intensities of single shock electrical stimulation (ES) at ST25 in healthy male Sprague-Dawley rats were evaluated by in vivo electrophysiological recording, and the levels of norepinephrine (NE) and its metabolites normetanephrine (NMN) were also examined using mass spectrometry. To verify the role of EA at ST25 in sepsis, the rats were given an intraperitoneal injection of lipopolysaccharide (LPS) to induce sepsis model, and survival rate, clinical score, and the level of interleukin (IL)-6, IL-1ß, and IL-10 were evaluated after EA application. We observed that 3 mA is the optimal intensity for activating adrenal sympathetic nerve, which significantly elevated the level of NE in the peripheral blood. For LPS-treated rats, EA at the ST25 apparently increased the survival rate and improved the clinical score compared to the control group. Furthermore, 3 mA EA at ST25 significantly decreased pro-inflammatory cytokines IL-6 and IL-1ß and upregulated anti-inflammatory cytokine IL-10 compared to the LPS-treated group. Overall, our data suggested that 3 mA is the optimal EA intensity at ST25 to activate the sympathoadrenal medullary pathway and exert an anti-inflammatory effect in sepsis.

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The basic biological research of acupuncture originates from clinical practice and serves clinical application. It is the fundamental idea of "acupuncture translational medicine". The animal experiment is indispensable in acupuncture translational medicine, which contributes to simplifying the complex factors affecting the clinical efficacy of acupuncture, observing the effect of the nociceptive stimuli and obtaining the invasive and off-body biomarkers. Focusing on animal experiment, the basic biological research can objectively reveal the structure and function of acupoints, obtain the parameters required by different stimulation methods and clarify the material basis which acupuncture works, so as to provide the references and evidences for acupoint combination and the selection of appropriate stimulation in clinical practice, as well as the development of medical instruments and new drugs.

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Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.

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Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology. Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats. Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within <100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection. Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.

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Fibroblast-like synoviocytes (FLSs) play a crucial role in rheumatoid arthritis (RA) pathogenesis. While miRNA (miR)-506 has been implicated in the progression of multiple diseases, its role in RA remains to be explored. The present study evaluated the function of miR-506 in the regulation of RA-FLSs. FLSs were prepared from RA and healthy synovial tissues. The expression of miR-506 was measured by quantitative real time PCR (qRT-PCR). The effects of miR-506 on RA-FLSs proliferation and apoptosis were detected by cell counting Kit-8 and flow cytometry assays, respectively. The determination of TNF-α, IL-6, and IL-1ß concentrations in RA-FLSs supernatant were done by ELISA. The levels of miR-506 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-506 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell cycle arrest at the G0/G1 phase. The overexpression of miR-506 induced apoptosis, along with an increase in activities of caspase-3 and -8. A target gene Toll-like receptor 4 (TLR4) under the direct regulation of miR-506 was identified through the luciferase assay, qRT-PCR and western blot analysis. Forced overexpression of TLR4 in the rescue experiments showed that TLR4 effectively reversed the effect on proliferation and apoptosis in miR-506-overexpressing RA-FLSs. Thus, miR-506 may be a potential target for RA prevention and therapy of RA.

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OBJECTIVE: To explore the clinical efficacy of herbal-partitioned moxibustion on moderate and severe persistent allergic rhinitis (AR) with spleen-qi deficiency syndrome. METHODS: With prospective case series study method, forty-seven patients of moderate and severe persistent AR with spleen-qi deficiency syndrome were treated with herbal-partitioned moxibustion at Yintang (GV 29), Shenque (CV 8), Hegu (LI 4) and Zusanli (ST 36), once every two days, three treatments a week, continuously for 8 weeks. The visual analogue scale (VAS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and scores of spleen-qi deficiency syndrome were recorded before treatment, 2 weeks, 4 weeks and 8 weeks into treatment as well as 4 weeks after treatment; in addition, the improvement rate of each index was compared before and after treatment. RESULTS: Compared before treatment, the VAS, RQLQ and scores of spleen-qi deficiency syndrome were significantly reduced 2 weeks, 4 weeks and 8 weeks into treatment as well as 4 weeks after treatment (P<0.05, P<0.01). The efficacy was gradually increased 2 weeks, 4 weeks and 8 weeks into treatment (all P<0.01). On the 8 weeks into treatment, the improved and markedly effective rate was 59.6% (28/47) for VAS, 19.1% (9/47) for RQLQ and 14.9% (7/47) for scores of spleen-qi deficiency syndrome; the total effective rate was all 85.1% (40/47). Compared with 4 weeks after treatment, there was no significant difference (all P>0.05). CONCLUSIONS: The herbal-partitioned moxibustion has superior efficacy for moderate and severe persistent allergic rhinitis with spleen-qi deficiency syndrome.

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Postherpetic neuralgia is manifested as drastic lingering pain, which seriously impacts the survival quality of patient. In the paper, focusing on the time of postherpetic neuralgia and in association with the characteristics of symptoms such as the location and nature of pain and skin lesion, the etiology, location of sickness, nature of sickness and pathogenesis were differentiated, and the laws of acupoint selection and therapeutic operations were explored in the treatment with acupuncture. Regarding the apparent pain at night, especially during 23:00 to 3:00, Ashi points (Extra) and Jiaji (EX-B 2) were selected in terms of location differentiation. The acupoints on the liver and gallbladder meridians were specially selected and the supplementary acupoints were used according to general symptoms based on syndrome and symptom differentiation to improve the therapeutic effects. Regarding the therapeutic operation, the bloodletting puncture was used in terms of blood stagnation in collaterals. Additionally, the other operations were selected individually, such as filiform needle therapy, fire needling therapy, plum-blossom needle therapy and bleeding and cupping therapy.

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To discuss the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis. In clinic, we take the "principle, method, prescription, acupoint and technic" as the outline, paying attention to identify disease location and establishing the method of "promoting blood to remove stasis, regulating thoroughfare vessel and conception vessel" on the basis of the pathogenesis of "stasis obstructing uterus, disharmony of thoroughfare vessel and conception vessel". The prescription combines "dredging" with "conditioning", and the emphasis should be different in different periods. In menstrual period, we put emphasis on activating the circulation of qi and blood as well as clearing meridians to relieve pain and choose the acupoints on the spleen meridian of foot-taiyin and experimental points, such as Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32), Shiqizhui (EX-B 8). In the intermenstrual period, we regulate the qi and blood of thoroughfare vessel and conception vessel, and the function of viscera. The acupoints for the disease root are mainly at spleen meridian of foot-taiyin and conception vessel, such as Sanyinjiao (SP 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36). And the reinforcing and reducing technic are applied accordingly.

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