Learning from circadian rhythm to transform cancer prevention, prognosis, and survivorship care.

Circadian timekeeping mechanisms and cell cycle regulation share thematic biological principles in responding to signals, repairing cellular damage, coordinating metabolism, and allocating cellular resources for optimal function. Recent studies show interactions between cell cycle regulators and circadian clock components, offering insights into potential cancer treatment approaches. Understanding circadian control of metabolism informs timing for therapies to reduce adverse effects and enhance treatment efficacy. Circadian adaptability to lifestyle factors, such as activity, sleep, and nutrition sheds light on their impact on cancer. Leveraging circadian regulatory mechanisms for cancer prevention and care is vital, as most risk stems from modifiable lifestyles. Monitoring circadian factors aids risk assessment and targeted interventions across the cancer care continuum.

Insulin-like growth factor 1 in heat stress-induced neuroinflammation: novel perspective about the neuroprotective role of chromium.

Heat stress (HS) can cause a series of stress responses, resulting in numerous negative effects on the body, such as the diminished food intake, carcass quality and reproductive capacity. In addition to the negative effects on the peripheral system, HS leads to central nervous system (CNS) disorders given its toll on neuroinflammation. This neuroinflammatory process is mainly mediated by microglia and astrocytes, which are involved in the activation of glial cells and the secretion of cytokines. While the regulation of inflammatory signaling has a close relationship with the expression of heat shock protein 70 (Hsp70), HS-induced neuroinflammation is closely related to the activation of the TLR4/NF-κB pathway. Moreover, oxidative stress and endoplasmic reticulum (ER) stress are key players in the development of neuroinflammation. Chromium (Cr) has been widely shown to have neuroprotective effects in both humans and animals, despite the lack of mechanistic evidence. Evidence has shown that Cr supplementation can increase the levels of insulin-like growth factor 1 (IGF-1), a major neurotrophic factor with anti-inflammatory and antioxidant effects. This review highlights recent advances in the attenuating effects and potential mechanisms of Cr-mediated IGF-1 actions on HS-induced neuroinflammation, providing presently existing evidence supporting the neuroprotective role of Cr.

Effects of comfort nursing on pain and quality of life in children undergoing tonsillectomy.

OBJECTIVE: To observe the effect of comfort nursing on pain, quality of life, and nutritional status in children undergoing tonsillectomy. METHODS: In this retrospective study, a total of 114 children who underwent tonsillectomy in Chun'an Hospital of Traditional Chinese Medicine were divided into a research group and a control group according to the nursing methods, with 57 cases in each group. The control group received routine nursing care, and the research group received additional comfort nursing. We compared the pain level (assessed by visual analogue scale (VAS) scale), quality of life (assessed by Generic Quality of Life Inventory-74 (GQOLI-74)), relevant clinical indicators (postoperative swallowing recovery time, wake-up time, and hospital stay), nutrition indicators (total blood protein and albumin), sleep quality (assessed by Pittsburgh Sleep Quality Index (PAQI)), nursing satisfaction, and postoperative complications between the two groups. RESULTS: After postoperative nursing, the VAS scores and PSQI scores were significantly decreased (both P<0.05), and the GQOLI-74 scores were significantly increased (P<0.05) in both groups. The postoperative swallowing recovery time, wake-up time, and hospital stay in the research group were significantly shorter than those in the control group (all P<0.05). The levels of total serum protein and albumin in the research group were significantly higher than those in the control group (both P<0.05). The research group showed a significantly higher satisfaction rate and lower incidence of complications as compared with the control group (both P<0.05). The results of the logistic regression analysis showed that postoperative upper respiratory infection and the degree of tonsillar embedment were independent risk factors for hemorrhage after tonsillectomy (P<0.05). CONCLUSION: In children undergoing tonsillectomy, providing comfort nursing can significantly reduce pain and improve their quality of life.

Inhalation of L-arginine-modified liposomes targeting M1 macrophages to enhance curcumin therapeutic efficacy in ALI.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), characterized by uncontrolled lung inflammation, is one of the most devastating diseases with high morbidity and mortality. As the first line of defense system, macrophages play a crucial role in the pathogenesis of ALI/ARDS. Therefore, it has great potential to selectively target M1 macrophages to improve the therapeutic effect of anti-inflammatory drugs. l-arginine plays a key role in regulating the immune function of macrophages. The receptors mediating l-arginine uptake are highly expressed on the surface of M1-type macrophages. In this study, we designed an l-arginine-modified liposome for aerosol inhalation to target M1 macrophages in the lung, and the anti-inflammatory drug curcumin was encapsulated in liposomes as model drug. Compared with unmodified curcumin liposome (Cur-Lip), l-arginine functionalized Cur-Lip (Arg-Cur-Lip) exhibited higher uptake by M1 macrophages in vitro and higher accumulation in inflamed lungs in vivo. Furthermore, Arg-Cur-Lip showed more potent therapeutic effects in LPS-induced RAW 264.7 cells and the rat model of ALI. Overall, these findings indicate that l-arginine-modified liposomes have great potential to enhance curcumin treatment of ALI/ARDS by targeting M1 macrophages, which may provide an option for the treatment of acute lung inflammatory diseases such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome and middle east respiratory syndrome.

Effects of Silage Diet on Meat Quality through Shaping Gut Microbiota in Finishing Pigs.

With increasing demand for high-quality pork, development of green and healthy feed for finishing pigs is urgently needed. In this study, the effects and mechanisms of mulberry and paper mulberry silages on growth performance, meat quality, and intestinal health of finishing pigs were explored. Intestinal microbiota were profiled, and microbially produced short-chain fatty acids (SCFAs) were measured. The average daily gain (ADG) and feed conversion rate (FCR) with mulberry and paper mulberry silages were not significantly different from those of the control. Meat quality as measured by pork marbling and fatty acids in the longissimus dorsi was better with mulberry silage. The highest concentration of SCFAs was also with mulberry silage. According to 16S rRNA sequencing, Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae, which are important in SCFA production, were biomarkers of mulberry silage. PICRUSt functional analysis of intestinal microbes indicated that galactose metabolism, starch and sucrose metabolism, and carbohydrate digestion and absorption decreased significantly in silage treatments but increased in the control. Correlations between intestinal microbes and SCFAs and fatty acids indicated Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA and fatty acid contents. The results indicated that mulberry silage could increase SCFA content through shaping intestinal microbes to affect the deposition of fatty acids, which laid a solid theoretical foundation for improving pork quality. IMPORTANCE To avoid competition between people and animals for food, it is essential to develop nontraditional feeds. In this study, the effects of the silages of the unconventional feed resources mulberry and paper mulberry on meat quality of finishing pigs were examined. With mulberry silage in the diet, meat quality improved as indicated by meat color, marbling score, and beneficial fatty acids in the longissimus dorsi muscle. Pigs fed mulberry silage had the highest concentrations of short-chain fatty acids (SCFAs), and 16S rRNA sequencing identified Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae as biomarkers, which are important in SCFA production. Functions of intestinal microbes in the two silage groups primarily involved amino acid metabolism and SCFA production. Correlations between intestinal microbes and SCFAs and fatty acids indicated that Clostridium_sensu_stricto-1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA contents in the intestine and fatty acids in the longissimus dorsi.

"King of the forage"-Alfalfa supplementation improves growth, reproductive performance, health condition and meat quality of pigs.

As one kind of high-quality feed with rich nutrients, including high quality protein and amino acids, dietary fiber, enriched vitamins and mineral elements and bioactive molecules, alfalfa has been widely used in the production of ruminant livestock. As the understanding of alfalfa becomes more and more comprehensive, it is found that the high-quality nutrients in alfalfa could have positive effects on pigs. An increasing number of researches have shown that supplementing dietary alfalfa to the diet of gestating sows reduced constipation, alleviated abnormal behavior, improved satiety and reproductive performance; supplementing dietary alfalfa to the diet of piglets improved growth performance and intestinal barrier function, reduced intestinal inflammatory response and diarrhea; supplementing dietary alfalfa to the diet of growing-fattening pigs improved production performance and pork quality. Moreover, the mechanisms by which various nutrients of alfalfa exert their beneficial effects on pigs mainly including dietary fiber stimulating intestinal peristalsis, enhancing the activity of digestive enzymes, and promoting the colonization of beneficial bacteria in the intestinal tract through fermentation in the intestine, producing short-chain fatty acids and thus improving intestinal health; high quality protein and amino acids are beneficial to improve animal health condition; rich vitamins and mineral elements play an important role in various physiological functions and growth and development of the body; and bioactive molecules can improve the antioxidant and anti-inflammatory level. Therefore, alfalfa could be used as pig feed ingredient to alleviate various problems in the pig industry and to improve pig production performance. In this review, we detail the current application of alfalfa in pigs and discuss the potential mechanisms involved in how alfalfa improves growth and reproductive performance, pork quality, and intestinal health of the animals, thus laying the foundation for the increased application of high-quality forage in pig production.

Water quality criteria and ecological risk assessment for copper in Liaodong Bay, China.

The establishment of water quality criteria (WQC) for copper (Cu) was used as the basis for an ecological risk assessment of marine Cu pollution in Liaodong Bay, China. Published ecotoxicity data for Cu were obtained and supplemented with the results of acute Cu toxicity tests. The marine WQC for Cu in Liaodong Bay was developed using a species sensitivity distribution method with a safety factor of 2.0 and the USEPA acute-to-chronic ratio method. The ecological risk of Cu in Liaodong Bay was assessed by comparing the seawater Cu concentrations with the developed WQC. The results of this study showed that the acute and chronic Cu concentrations in Liaodong Bay were 3.31 and 2.18 µg/L, respectively. Comparison of the WQC to Cu concentrations in the bay resulted in risk quotients slightly >1.0 and typically ≤2.0. These data suggest that certain organisms in Liaodong Bay are at risk. These results can assist in the development of a pollution control management approach for the bay.

Aqueous extract of Scrophularia ningpoensis improves insulin sensitivity through AMPK-mediated inhibition of the NLRP3 inflammasome.

BACKGROUND: Scrophularia ningpoensis Hemsl. is a commonly used medicinal plant in China for the treatment of diabetes mellitus (DM), but its mechanism of action remains poorly described. Type 2 diabetes mellitus (T2DM) accounts for > 90% of all DM cases and is characterized by insulin resistance. PURPOSE: The aim of this study was to investigate whether the insulin sensitivity can be improved by treatment with aqueous extract of S. ningpoensis (AESN) and further explore its mechanism(s) of activity. METHODS: Primary mouse hepatocytes and human HepG2 hepatocytes were used to investigate the effects of AESN on cell viability, AMP-activated protein kinase (AMPK) activation and glucose output under normal culture conditions. To mimic hyperglycemia and insulin resistance in vitro, hepatocytes were exposed to high glucose (HG), and the influences of AESN on AMPK phosphorylation, NLRP3 inflammation activation, insulin signaling, lipid accumulation and glucose output were investigated. Increasing doses of AESN (50, 100 and 200 mg/kg/day) were administered by gavage to db/db mice for 8 weeks, and then biochemical analysis and histopathological examinations were performed. RESULTS: AESN significantly activated AMPK and inhibited glucose output in hepatocytes, but did not impact cell viability under normal culture conditions. Moreover, in HG-treated hepatocytes, AESN protected against aberrant AMPK activity, NLRP3 inflammasome activation, insulin signaling, and lipid accumulation. AMPK inhibition abolished the regulatory effects of AESN on the NLRP3 inflammasome, insulin signaling, lipid accumulation, and glucose output of hepatocytes following HG exposure. Furthermore, AESN administration reduced blood glucose and serum insulin levels, improved lipid profiles and insulin resistance, and corrected the aberrant AMPK activity and NLRP3 inflammasome activation in liver tissues. CONCLUSION: AESN improves insulin sensitivity via AMPK-mediated NLRP3 inflammasome inhibition.

Dietary alfalfa powder supplementation improves growth and development, body health, and meat quality of Tibetan sheep.

The application of alfalfa powder (AP) in Tibetan sheep to explore its healthy effects and meat quality improvement potential has not been reported. Our study found that AP improved the growth performance, serum metabolism, and antioxidation of Tibetan sheep. The edible quality, sensory quality, and nutritional quality of longissimus dorsi (LD) were analyzed. We observed lower drip loss and hue angle of meat after AP supplementation. AP also increased the cooked meat percentage, pH24h, a*24h, chroma24h, and the contents of protein and fat. The targeted metabolomics profiling revealed that the contents of essential amino acids and flavor amino acids in mutton increased by AP treatments. AP also promoted the deposition of MUFA and PUFA. Therefore, as a promising botanical supplement, AP has a positive effect on the growth, development, and body health of Tibetan sheep, and is also conductive to providing healthy and nutritious high-quality livestock products.

Integrating network pharmacology and experimental models to investigate the efficacy of QYHJ on pancreatic cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear. AIM OF THE STUDY: This study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro. MATERIALS AND METHODS: The bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting. RESULTS: A total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment. CONCLUSIONS: QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.

Eucommiae cortex polysaccharides mitigate obesogenic diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism.

Rationale: The high fat and sucrose diet, known as the obesogenic diet (OD), has been related to low-grade chronic inflammation and neurodevelopmental disorders. Emerging evidence suggests that OD influences cognitive and social function via the gut-brain axis. However, the effects of OD during adolescence on future health have been unclear. Meanwhile, the underlying mechanisms and effective interventions are not fully understood. Polysaccharides, one of the most abundant substances in the Eucommiae cortex, exhibit potential immunomodulatory and neuroprotective effects. Here, we aimed to investigate the impact of OD on adolescents, explore the modulating roles of Eucommiae cortex polysaccharides (EPs) on OD-induced behavioral dysfunction, and elucidate the underlying molecular mechanisms. Methods: In the present study, four-week-old mice were fed with OD for four weeks to simulate persistent OD in adolescents. The behavioral features were accessed by open field test and Morris water maze. The gut bacterial structure was identified by 16S rRNA gene amplicon sequencing. The gene and protein expression in colonic tissues and hippocampus were detected by qRT-PCR, immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Detection of biological metabolites in serum and hippocampal tissues was performed by widely targeted metabolomics and targeted metabolomics. Results: We found that OD-fed mice showed cognitive and social-behavioral deficits accompanied by gut dysbiosis and systematic tryptophan (Trp) metabolism disorders, which increased kynurenine (Kyn) concentration in the hippocampus. Bacteria-derived lipopolysaccharide (LPS, endotoxin) induced microglia-mediated neuroinflammation, directing the metabolism of Kyn in the hippocampus toward quinolinic acid (QA), which led to glutamate-mediated hyperactivation of mossy cells (MCs) in hippocampal hilus. Furthermore, OD impaired parvalbumin (PV) interneurons-related local circuits in the hippocampal granule cell layer. These resulted in hippocampal neurogenesis deficits and related behavioral dysfunction in mice. EPs supplementation ameliorated OD-induced gut dysbiosis, as evidenced by inhibiting the expansion of Escherichia coli (E.coli) and reducing the concentration of LPS in colonic contents and serum, thereby inhibiting the subsequent neuroinflammation. In addition, oral EPs suppressed the peripheral Kyn pathway to reduce the concentration of QA and glutamic acid in the hippocampus of OD-fed mice, thereby rescuing the glutamic acid-triggered neuroexcitotoxicity. These contributed to remodeling the rhythm of hippocampal neurogenesis and mitigated behavioral dysfunction in OD-fed mice. Conclusions: The present study addresses a gap in the understanding of neuronal dysfunction associated with OD during adolescence and provides the first evidence that EPs improved cognitive and social behavior via modulation of gut microbiota and tryptophan metabolism in adolescent mice fed with OD, which may represent novel preemptive therapy for neurodevelopmental disorders via manipulation of the tryptophan metabolite.

Coagulants put phosphate-accumulating organisms at a competitive disadvantage with glycogen-accumulating organisms in enhanced biological phosphorus removal system.

Enhanced biological phosphorus removal (EBPR) process is susceptible to the changed operation condition, which results in an unstable treatment performance. In this work, long-term effect of coagulants addition, aluminum salt for the reactor R1 and iron salt for the reactor R2, on EBPR systems was comprehensively evaluated. Results showed that during the initial 30 days' coagulant addition, effluent chemical oxygen demand and phosphorus can be reduced below 25 and 0.5 mg·L-1, respectively. Further supply of metal salts would stimulate microbial extracellular polymeric substance excretion and induce reactive oxygen species accumulation, which destroyed the cell membrane integrity and deteriorated the phosphorus removal performance. Moreover, coagulants would decrease the relative abundance of Candidatus Accumulibacter while increase the relative abundance of Candidatus Competibacter, leading phosphors accumulating organisms in a disadvantage position. The results of this work might be valuable for the operation of chemical assisted biological phosphorus removal bioreactor.

Baicalin Ameliorates Inflammatory Response in a Mouse Model of Rhinosinusitis via Regulating the Treg/Th17 Balance.

OBJECTIVE: Rhinosinusitis is a global health problem affecting millions of people around the world. Baicalin is a bioactive compound isolated from medicinal plant Scutellaria baicalensis Georgi. The present study aims to investigate potential effects of baicalin on clinicopathological changes in nasal/sinus mucosa in a mouse model. METHODS: A mouse model of sinonasal inflammation induced by high dose of ovalbumin was applied to evaluate effects of baicalin. Rhinosinusitis symptoms, histopathological features, levels of histamine, immunoglobulin E (IgE), IL-17A, IL-10, and balance of regulatory T cell (Treg)/T-helper 17 (Th17) responses were examined. RESULTS: Baicalin significantly relieved rhinosinusitis symptoms in mice, reduced histopathological changes, and suppressed serum levels of histamine and IgE in a dose-dependent manner. In lymphocytes of mice, baicalin modulated balance of Treg/Th17 proportions by attenuating Th17 cells and enhancing Treg cells, respectively. The serum IL-17A was decreased and IL-10 was increased in mice treated by baicalin. In addition, baicalin promoted levels of Smad protein 3 (p-Smad3) and forkhead box P3 (FOXP3) to promote Treg cells while suppressed levels of p-Stat3 and retineic-acid-receptor-related orphan nuclear receptor γt (RORγt) to inhibit Th17 cells. CONCLUSIONS: These data demonstrate that baicalin effectively ameliorates sinonasal inflammation in a mouse model by recovering the immunological balance of Treg/Th17 responses. Our finding highlights the potential value of baicalin for the treatment of rhinosinusitis.

Protective effects of alfalfa saponins on oxidative stress-induced apoptotic cells.

As is known, alfalfa saponins can be used as a feed additive in a pig's diet and the addition of alfalfa saponins to a pig's diet could improve its antioxidant capacity. However, the mechanism by which alfalfa saponins exert their antioxidant effects has not been studied. To address this issue, H2O2-induced rat intestinal epithelial cells were used to establish an oxidative stress model to explore the protective mechanism of alfalfa saponins in this study. The results demonstrated that alfalfa saponins could rescue the cell proliferation activity, elevate the amount of antioxidant enzymes and downregulate the release of MDA and LDH in H2O2-induced cells. The antioxidant activity of alfalfa saponins was achieved by restoring GSH homeostasis. Further results demonstrated that alfalfa saponins could inhibit cell apoptosis through activating the MAPK signaling pathway. These results elucidated the mechanism by which alfalfa saponins exert their antioxidant effects and provided a potential strategy for alleviating oxidative stress in monogastric animals.

[Effect of long-snake moxibustion on nonspecific low back pain with symptom of cold and dampness].

OBJECTIVE: To compare the clinical therapeutic effect of long-snake moxibustion and ginger-partitioned moxibustion at ashi point on nonspecific low back pain (NLBP) with symptom of cold and dampness. METHODS: A total of 120 patients were randomized into a long-snake moxibustion group, an ashi point group and a waiting for treatment group, 40 cases in each one. Ginger-partitioned moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) of governor vessel in the long-snake moxibustion group, and was applied at ashi point of affected area in the ashi point group, 40 min each time, once every other day and totally 8 times were required. No intervention was adopted in the waiting for treatment group, and after the trial, long-snake moxibustion was applied. Before and after treatment, the visual analogue scale (VAS) scores of rest and activity, the Oswestry disability index (ODI) score and the score of cold and dampness symptom were observed in the 3 groups. RESULTS: Compared before treatment, the VAS scores of rest and activity, the ODI scores and the scores of cold and dampness symptom after treatment were decreased in the long-snake moxibustion group and the ashi point group (P<0.05). After treatment, the variations of the above indexes in the long-snake moxibustion group and the ashi point group were larger than those in the waiting for treatment group (P<0.05), and the variations of the above indexes in the long-snake moxibustion group were larger than those in the ashi point group (P<0.05). CONCLUSION: Long-snake moxibustion can effectively improve the pain, dysfunction and the symptom of cold and dampness in patients with nonspecific low back pain, and the improvement is superior to the ginger-partitioned moxibustion at ashi point.

[Clinical effectiveness of "long snake moxibustion" for cold-dampness type chronic non-specific low back pain patients with negative emotions].

OBJECTIVE: To observe the clinical efficacy of long snake moxibustion and Ashi-point moxibustion in the treatment of cold-dampness type chronic non-specific low back pain (CNLBP) patients. METHODS: A total of 120 cold-dampness type CNLBP patients who signed the informed consent were randomly and equally divided into control, long snake moxibustion and Ashi-point moxibustion groups. Ginger-separated moxibustion was applied to the region between Dazhui (GV14) and Yaoshu (GV2) for patients of the long-snake moxibustion group, or to the tenderness spot of the waist for patients of the Ashi-point moxibustion group. The treatment was conducted for 40 min each time, once every other day for a total of 8 sessions. Patients of the control group did not receive any intervention. The visual analogue scale (VAS) was used to assess low back pain severity. The Oswestry Disability Index (ODI) was employed to assess ten aspects of patients' daily-life activities (pain intensity, personal care, lif-ting, walking, sitting, standing, sleeping, sex life, social life, and traveling). The cold-damp syndrome scores (pain property, symptoms, ranges of motion, waist palpation, tongue and pulse condition) were achieved by consulting the textbook "Differential Diagnostics of Traditional Chinese Medicine Syndromes". The Hospital Anxiety and Depression Scale (HADS, a self-made assessment instrument) was used to assess the patients' severity of emotional disorder.The plasma cortisol level was detected by ELISA. RESULTS: Before treatment, there were no significant differences among the three groups in the levels of all the indexes (P>0.05). After moxibustion, the VAS scores during rest and movement, ODI score, cold-damp syndrome score and anxiety score in both long snake moxibustion and Ashi-point moxibustion groups, and the HADS depression score and plasma cortisol content in the long snake moxibustion group were significantly reduced compared with their own pre-treatment (P<0.05). The difference values between pre and post-treatment of VAS scores during rest and movement, ODI score, cold-damp syndrome score, anxiety score, depression score and cortisol content were obviously higher in the long snake moxibustion and Ashi-point moxibustion groups than those in the control group. The difference values between pre- and post-treatment of VAS scores during rest and movement, ODI score, cold-damp syndrome score, anxiety score, depression score and cortisol content were obviously higher in the long snake moxibustion group than in the Ashi-point group (P<0.05). CONCLUSION: Both ginger-separated long snake moxibustion and Ashi-point moxibustion can relieve low back pain, daily-life activities, cold-damp syndrome, negative emotions, and reducing cortisol level in cold-dampness type CNLBP patients，and the therapeutic efficacy of long snake moxibustion is obviously better.

Effect of substituents on Stokes shift of BODIPY and its application in designing bioimaging probes.

BODIPY-based probes have excellent fluorescence properties. However, small Stokes shifts approximately 5-15 nm greatly affect their detection sensitivity. In this study, we compared the Stokes shifts of reported BODIPY-based probes with various of substituents, and found that the phenyl groups on the specific position of BODIPY core could expand the Stokes shift of BODIPY-based probes, and methoxy groups on these phenyl substituents could enhance such effects. Then, by quantum chemical calculations, we found that the number of methoxy groups might also have obvious effect on the Stokes shift of BODIPY. Taking nitric oxide (NO) as analyte, 4,4-difluoro-8-(3,4-diaminophenyl)-3,5-bis(2,4-dimethoxyphenyl)-4-bora-3a,4a-diaza-s-indancene (DMOPB) with diaminophenyl substituents has been designed and synthesized. Compared with monomethoxy-phenyl substituted BODIPY-based probes (MOPBs) in our previous work, Stokes shift of DMOPB was expanded by 10 nm when using dimethoxyphenyl instead of monomethoxyphenyl, which is basically consistent with the quantum chemistry calculation of 11 nm. DMOPB can react with NO in only 2 min to form the triazole DMOPB-T with a fluorescence quantum yield of 0.32. An excellent linear relationship was observed in the range of NO concentration from 0.5 µM to 4 µM and the detection limit was 1 nM. The experimental results indicate that DMOPB with high sensitivity, excellent selectivity, low toxicity and dark background can be a great candidate for imaging NO in cells and tissues. Considering the lack of practical way to increase Stokes shift of small-molecule fluorescent probes based on specific fluorophore, the proposed strategy has great potential for the designing of probes with large Stokes shift.

Nobiletin attenuates adverse cardiac remodeling after acute myocardial infarction in rats via restoring autophagy flux.

BACKGROUND: Our previous study showed that autophagy flux was impaired with sustained heart ischemia, which exacerbated adverse cardiac remodeling after acute myocardial infarction (AMI). Here we investigated whether Nobiletin, a citrus polymethoxylated flavonoids, could restore the autophagy flux and improve cardiac prognosis after AMI. AMI was induced by ligating left anterior descending (LAD) coronary artery in rats. Nobiletin improved the post-infarct cardiac dysfunction significantly and attenuated adverse cardiac remodeling. Meanwhile, Nobiletin protected H9C2 cells against oxygen glucose deprivation (OGD) in vitro. The impaired autophagy flux due to ischemia was ameliorated after Nobiletin treatment by testing the autophagy substrate, LC3BⅡ and P62 protein level both in vivo and in vitro. GFP-mRFP-LC3 adenovirus transfection also supported that Nobiletin restored the impaired autophagy flux. Specifically, the autophagy flux inhibitor, chloroquine, but not 3 MA, alleviated Nobiletin-mediated protection against OGD. Notably, Nobiletin does not affect the activation of classical upstream autophagy signaling pathways. However, Nobiletin increased the lysosome acidation which also supported that Nobiletin accelerated autophagy flux. Taken together, our findings suggested that Nobiletin restored impaired autophagy flux and protected against acute myocardial infarction, suggesting a potential role of autophagy flux in Nobiletin-mediated myocardial protection.

Acupuncture for cancer-related fatigue in lung cancer patients: a randomized, double blind, placebo-controlled pilot trial.

BACKGROUND: Cancer-related fatigue (CRF) is a distressing symptom that is the most common unpleasant side effect experienced by lung cancer patients and is challenging for clinical care workers to manage. METHODS: We performed a randomized, double-blind, placebo-controlled pilot trial to evaluate the clinical effect of acupuncture on CRF in lung cancer patients. Twenty-eight patients presenting with CRF were randomly assigned to active acupuncture or placebo acupuncture groups to receive acupoint stimulation (LI-4, Ren-6, St-36, KI-3, and Sp-6) twice per week for 4 weeks, followed by 2 weeks of follow-up. The primary outcome was the change in intensity of CFR based on the Chinese version of the Brief Fatigue Inventory (BFI-C). As the secondary endpoint, the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) was adopted to assess the influence of acupuncture on patients' quality of life (QOL). Adverse events and safety of treatments were monitored throughout the trial. RESULTS: Our pilot study demonstrated feasibility among patients with appropriate inclusion criteria and good compliance with acupuncture treatment. A significant reduction in the BFI-C score was observed at 2 weeks in the 14 participants who received active acupuncture compared with those receiving the placebo (P < 0.01). At week 6, symptoms further improved according to the BFI-C (P < 0.001) and the FACT-LCS (P = 0.002). There were no significant differences in the incidence of adverse events in either group (P > 0.05). CONCLUSION: Fatigue is a common symptom experienced by lung cancer patients. Acupuncture may be a safe and feasible optional method for adjunctive treatment in cancer palliative care, and appropriately powered trials are warranted to evaluate the effects of acupuncture.

Moxifloxacin is an effective and safe candidate agent for tuberculosis treatment: a meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of the introduction of moxifloxacin into the recommended regimen for tuberculosis (TB) treatment. METHODS: A meta-analysis was performed of nine eligible studies regarding the effect of moxifloxacin plus the recommended regimen compared to the recommended regimen alone for the treatment of TB. RESULTS: In the efficacy analysis, the overall odds ratio (OR) for sputum culture conversion was 1.895 (95% confidence interval (CI) 1.355-2.651, p=0.000), indicating that when moxifloxacin is combined with the recommended regimen, the rate of sputum culture conversion is elevated compared to the recommended regimen alone. The overall OR for recurrence was 0.516 (95% CI 0.342-0.920, p=0.022), suggesting that the introduction of moxifloxacin into the recommended regimen reduces TB relapse after treatment. In the safety analysis, the overall OR was estimated to be 1.001 (95% CI 0.855-1.172, p=0.989), demonstrating that adding moxifloxacin to the recommended regimen does not cause more adverse events during TB treatment. CONCLUSIONS: This meta-analysis suggests that the introduction of moxifloxacin into the recommended regimen for the treatment of non-drug resistant TB improves the clinical outcome by elevating the culture conversion rate and reducing the recurrence rate.