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Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
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Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ2=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.
Subject(s)
Male , Female , Humans , Thyroid Cancer, Papillary/surgery , Retrospective Studies , Quality of Life , Thyroid Neoplasms/pathology , Endoscopy , Thyroidectomy/methodsABSTRACT
BackgroundChronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease, and patients with COPD often experience substantially emotional difficulties, such as anxiety and depression, all of which may cause serious detriment to the prognosis of patients. As a non-pharmacological intervention in clinical practice, group mindfulness-based stress reduction therapy (MBSR) is beginning to emerge, while has rarely been studied in COPD patients with concurrent emotional difficulties. ObjectiveTo evaluate the effects of group MBSR on depression, state of mindfulness and pulmonary function in stable COPD patients, so as to provide references for the application of group MBSR in patients with COPD. MethodsA total of 97 patients with stable COPD who were followed up in the Department of Respiratory and Critical Care Medicine of Mianyang Third People's Hospital from January to October 2019 were selected as the study objects, and they were assigned into study group (n=50) and control group (n=47) by random number table method. All individuals received routine medication therapy and an 8-week health education, based on this, participants in study group partook an 8-week intervention comprising group MBSR. At the baseline, 4 weeks and 8 weeks of intervention, participants were assessed with Self-rating Depression Scale (SDS), Five Facet Mindfulness Questionnaire (FFMQ) and COPD Assessment Test (CAT), as well as the pulmonary function testing. ResultsThere were 41 patients in study group and 42 cases in control group completed the study. The group * time interaction was interpreted as significant between two groups for SDS, FFMQ and CAT scores (F=54.858, 86.161, 69.862, P<0.01). Baseline SDS, FFMQ and CAT scores of the two groups yielded no statistical difference between two groups (F=0.240, 0.052, 0.019, P>0.05), while study group scored lower on SDS and CAT (F=12.900, 38.511, 7.797, 28.824, P<0.01) and higher on FFMQ (F=27.324, 82.412, P<0.01) than those of the control group after 4 and 8 weeks of intervention. With the prolongation of intervention time in study group, participants demonstrated an overall reduction in SDS and CAT scores (F=109.753, 124.144, P<0.01), and an increase in FFMQ scores (F=228.194, P<0.01). There were no between-group differences in forced expiratory volume in one second as percentage of predicted volume (FEV1%pred) after 4 and 8 weeks of intervention (F=0.104, P=0.748) , and the within-group changes in FEV1%pred value over the intervention period in study group was not statistical (F=0.561, P=0.458). ConclusionGroup MBSR may help relieve depressive symptoms, enhance mindfulness level, and alleviate clinical symptoms in stable COPD patients, but has no effect on pulmonary function. [Funded by Mianyang Health and Health Commission Scientific Research Project (number, 201916)]
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To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated. After modeling, they were randomly divided into a model group, high-dose, medium-dose, and low-dose Zhenwu Decoction groups(33.8, 16.9, and 8.45 g·kg~(-1)·d~(-1)), and an irbesartan group(25 mg·kg~(-1)·d~(-1)), with at least 15 animals in each group. The intervention lasted for eight weeks. After the intervention, body weight and food intake were measured. Serum crea-tinine(Scr), blood urea nitrogen(BUN), fasting blood glucose(FBG), urinary albumin(uALb), and urine creatinine(Ucr) were determined. The uALb/Ucr ratio(ACR) and 24 h urinary protein(UTP) were calculated. Renal pathological morphology was evaluated by HE staining and Masson staining. The levels of key molecular proteins in the ROCK/IKK/NF-κB pathway were detected by Western blot. Enzyme-linked immunosorbent assay(ELISA) was used to detect interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Compared with the blank group, the model group showed increased content of BUN, uALb, and SCr, increased values of 24 h UTP and ACR, decreased content of Ucr(P<0.05), enlarged glomeruli, thickened basement membrane, mesangial matrix proliferation, inflammatory cell infiltration, and collagen fiber deposition. The protein expression of ROCK1, ROCK2, IKK, NF-κB, phosphorylated IKK(p-IKK), phosphorylated NF-κB(p-NF-κB), and phosphorylated inhibitor of NF-κB(p-IκB) increased(P<0.05), while the protein expression of inhibitor of NF-κB(IκB) decreased(P<0.05). The levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α increased(P<0.05), while the level of IL-10 decreased(P<0.05). Compared with the model group, the groups with drug treatment showed decreased levels of BUN, uALb, SCr, 24 h UTP, and ACR, increased level of Ucr(P<0.05), and improved renal pathological status to varying degrees. The high-and medium-dose Zhenwu Decoction groups and the irbesartan group showed reduced protein expression of ROCK1, ROCK2, IKK, NF-κB, p-IKK, p-NF-κB, and p-IκB in the kidneys(P<0.05), increased protein expression of IκB(P<0.05), decreased levels of serum inflammatory factors IL-1β, IL-6, IL-8, and TNF-α(P<0.05), and increased level of IL-10(P<0.05). Zhenwu Decoction can significantly improve renal function and renal pathological damage in DN mice of spleen-kidney Yang deficiency syndrome, and its specific mechanism may be related to the inhibition of inflammatory response by down-regulating the expression of key molecules in the ROCK/IKK/NF-κB pathway in the kidney.
Subject(s)
Mice , Male , Animals , NF-kappa B/metabolism , Interleukin-8 , Interleukin-10 , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6 , I-kappa B Kinase , Spleen , Irbesartan , Uridine Triphosphate , Yang Deficiency/drug therapy , Kidney/pathologyABSTRACT
Head and neck squamous cell carcinoma (HNSCC) still lacks effective targeted treatment. Therefore, exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC. Here, we reported that the expression levels of family with sequence similarity 64, member A (FAM64A) were significantly higher in HNSCC tissues and cell lines. In addition, FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC. Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells, and vice versa. Moreover, we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model. Mechanistically, a physical interaction was found between FAM64A and forkhead box protein M1 (FOXM1) in HNSCC cells. FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1, but also, more importantly, by modulating FOXM1 expression via the autoregulation loop. Furthermore, a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts. Taken together, our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC, and FAM64A might be a promising molecular therapeutic target for treating HNSCC.
Subject(s)
Animals , Mice , Carcinogenesis , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic , Head and Neck Neoplasms/genetics , Homeostasis , Squamous Cell Carcinoma of Head and NeckABSTRACT
Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.
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Objective:To investigate the efficacy of additional treatment (chemoradiotherapy or esophagectomy) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma.Methods:Clinicopathological data of 97 patients of esophageal squamous cell carcinoma with infiltration depth of M3-SM3 who underwent ESD in Zhongda Hospital from July 2014 to April 2019 were reviewed. There were 57 patients in the additional treatment group and 40 patients in the observation group. The rate of relapse-free survival (RFS) was evaluated by Kaplan-Meier method (used log-rank test).Results:In the additional treatment group, 15 underwent esophagectomy after ESD, and no tumor metastases were found, but 1 patient died of upper gastrointestinal bleeding after surgery; 42 underwent chemoradiotherapy, and all patients were alive, but 3 patients experienced distant metastases. In the observation group, 13 patients experienced local recurrence, 2 patients died of tumor recurrence and 1 patient died of cerebrovascular disorder. Kaplan-Meier analysis showed that the RFS rate of the additional treatment group was higher than that of the observation group ( P=0.001). Conclusion:ESD followed by additional chemoradiotherapy or esophagectomy has good clinical efficacy and can improve prognosis for superficial esophageal squamous cell carcinoma (M3-SM3) patients.
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ObjectiveTo establish a simple, fast and accurate method for locating the volatile oil in Angelicae Sinensis Radix based on frozen section and fluorescence imaging technology, and to reveal the distribution and accumulation of volatile oil in the roots of this herbal medicine. MethodAngelicae Sinensis Radix was used as the research material, the best frozen section conditions for the research material were established by comparing the effects of different cryoprotectants on the quality of frozen sections of Angelicae Sinensis Radix. The suitability of Sudan Ⅲ chemical staining and fluorescence localization for positioning the volatile oil were compared according to the loss of volatile oil and the complexity of operation process. ResultA new method for evaluating the quality of frozen sections of Angelicae Sinensis Radix was established. According to the evaluation equation, it was found that the highest score was obtained when the head, body and tail positions of Angelicae Sinensis Radix were treated with 20% glycerol, 15% glycerol and 20% sucrose, respectively. There was yellowish-brown oily substance in the oil chambers of phelloderm and secondary phloem, and oil canal of the secondary xylem of Angelicae Sinensis Radix, which could be stained orange red or orange yellow by Sudan Ⅲ, and there was green spontaneous fluorescence in the same part under the fluorescence microscope. ConclusionThe relatively complete section of Angelicae Sinensis Radix can be obtained after being treated with cryoprotectant. The volatile oil exists in the oil chambers of phelloderm and secondary phloem, and oil canal of the secondary xylem of Angelicae Sinensis Radix. This study can provide reference for observation of the accumulation sites of volatile oil in other plants.
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Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.
Subject(s)
Animals , Rats , Analgesia , Ganglia, Spinal , Growth Differentiation Factor 15 , Sensory Receptor Cells , Sodium Channels , Tetrodotoxin/pharmacologyABSTRACT
Objective: To compare the recovery and quality of life of patients with oral and oropharyngeal tumors treated with three kinds of free soft tissue flaps. Methods: The clinical data of 103 patients, including 66 males and 37 females, aged 26-74 years, who underwent primary repair of defects after resection of oral and oropharyngeal tumors in Sichuan Tumor Hospital from July 2014 to August 2020 were analyzed. Anterolateral thigh flap (ALTF) was used in 43 patients, radial forearm free flap (RFFF) in 45 patients, and lateral arm free flap (LAFF) in 15 patients. Postoperative qualities of life of patients were evaluated by the university of Washington quality of life questionnaire and oral health impact scale (HIP-14 Chinese edition). SPSS 23.0 software was used for statistical analysis. Results: The T staging of RFFF or LAFF group was significantly lower than that of ALTF group (P<0.05). There was no significant difference in mean flap areas between ALTF group ((55.87±27.38) cm2) and LAFF group ((49.93±19.44) cm2), while RFFF group had smaller mean flap area ((33.18±6.05) cm2) than ALTF group (t=5.311, P<0.001) and LAFF group (t=3.284, P=0.005). In terms of oral functions including swallowing, mastication, taste and spitmouth, there were no significant differences between LAFF group and RFFF group (P>0.05), but both groups had better oral functions than ALTF group (P<0.05). There was no significant difference in appearance scores between LAFF group (75(75, 75)) and ALTF group (75(75,75) vs.75(75,75),Z=-1.532, P=0.126), and both groups had higher scores than RFFF group (50(50, 75),Z values were -3.447 and -3.005 respectively, P<0.05). RFFF group had higher speech score (100(67, 100)) than LAFF group (67(50, 76),Z=-2.480, P<0.05) and ALTF group (67(33, 67),Z=-5.414, P<0.05). ALTF group had lower mean score of quality of life than RFFF group [72(56,77) vs.79(69, 89),Z=-3.070, P<0.05), but there was no statistical difference in the mean scores of qualities of life between ALTF group and LAFF group (Z=1.754, P=0.079). According to the evaluation of oral health impact scale (HIP-14 Chinese version) 1 year after surgery, individual item scores and the average score of all items in ALTF group were lower than those in RFFF and LAFF groups (P<0.05), with no significant difference between RFFF group and LAFF group (P>0.05). Conclusions: RFFF has unique advantages for small tissue defects, while ALTF is suitable for large tissue defects, such as buccal penetrating defect, whole tongue and near whole tongue defect, and LAFF is a compromise choice between ALTF and RFFF. ALTF is inferior to RFFF and LAFF in oral functional reconstruction, including swallowing, chewing, taste and spittle. ALTF and LAFF are superior to RFFF in postoperative appearance.
Subject(s)
Female , Humans , Male , Forearm/surgery , Free Tissue Flaps , Oropharyngeal Neoplasms/surgery , Quality of Life , Plastic Surgery Procedures , Thigh/surgeryABSTRACT
Objective:To study the change of soil environment and yield of <italic>Angelica sinensis </italic> when cultivated on the film side and and open field sides,and to explore the influence of garlic volatiles and film-side cultivation on continuous cropping <italic>A. sinensis</italic>,so as to provide some certain theoretical basis for the saying that the <italic>A. sinensis</italic> garlic intercropping mode and film-side cultivation could alleviate continuous cropping <italic>A. sinensis</italic>. Method:In this study, the effects of garlic on soil environment and yield of <italic>A. sinensis</italic> cultivated on film side and crop rotation were discussed through the determination and analysis of soil microorganism quantity,soil enzyme activity and yield of Angelica sinensis in the rhizosphere of <italic>A. sinensis</italic>. Result:The number of bacteria and actinomycetes in the rhizosphere soil of <italic>A. sinensis </italic>increased significantly, while the number of fungi decreased significantly. Among them, the number of bacteria and actinomycetes in the intercropping of <italic>A. sinensis</italic> and garlic on the film side increased by 104% and 146.89% on average as compared with that of the control (monoculture under continuous cropping open field),and the number of fungi decreased by 39.28% on average as compared with that of control group. When the enzyme activity in the rhizosphere soil was significantly increased under the condition of intercropping with garlic on the film side,the soil urease,sucrase,alkaline phosphatase and acid phosphatase activities under the intercropping of <italic>A. sinensis</italic> and gralic on the rotation film side were increased by 61.60%,51.09%,203.48% and 76.19% respectively as compared with those in control group. The yield of <italic>A. sinensis</italic> significantly increased under the condition of intercropping with garlic on the film-side,and the yield of Angelica sinensis under the rotation film-side intercropping with garlic increased by 39.37% as compared with that of control group. Conclusion:Under the mode of film-side cultivation,the interplanting of <italic>A. sinensis </italic>with garlic can change the number of soil microorganism,improve the activity of soil enzyme,improve the physical and chemical properties of soil, alleviate the obstacle of continuous cropping and guarantee the healthy growth of <italic>A. sinensis</italic> more effectively.
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Objective:To evaluate the efficacy and safety of oral prednisone acetate and oral prednisone acetate combined with local injection of triamcinolone acetonide for the prevention of esophageal stricture after endoscopic submucosal dissection (ESD) for early esophageal cancer and precancerous lesions.Methods:Data of 52 patients with early esophageal cancer or precancerous lesions hospitalized from December 2014 to February 2019 in Zhongda Hospital of Southeast University were analyzed retrospectively. They were divided into the control group (group A, n=20), oral hormone group (group B, n=17) and oral medication combined with local injection group (group C, n=15). The rates of stenosis and refractory stenosis, endoscopic dilatation times after ESD, time interval of first dilation after ESD and adverse events related to the operation and administration of glucocorticoids were compared among the three groups. Results:The differences in stenosis rates [85.0% (17/20) VS 47.1% (8/17) VS 46.7% (7/15), P<0.01], rates of refractory stenosis [75.0% (15/20) VS 23.5% (4/17) VS 20.0% (3/15), P<0.01], and endoscopic dilatation times [3.50 (2.25, 6.00) VS 0.00 (0.00, 2.50) VS 0.00 (0.00, 2.00), P<0.01] were statistically significant among the three groups. In pairwise comparison, the above indicators in group B and group C were significantly lower or less than those in group A ( P<0.05), but there were no statistical differences between group B and group C ( P>0.05). The time intervals of the first dilation after ESD were significantly different among the three groups (27.7±9.4 d VS 110.1±46.0 d VS 147.4±9.4 d, P<0.01). In pairwise comparison, the first dilation intervals in group B and group C were longer than that in group A ( P<0.01), and this indicator in group C was longer than that in group B ( P<0.01). Two patients in the control group developed perforation after ESD but they were treated actively and recovered finally. No severe ESD, steroid, or perforation related adverse events occurred in any other patient of the three groups. Conclusion:Both oral prednisone and oral prednisone combined with local injection of triamcinolone acetonide after ESD can effectively and safely prevent esophageal stricture after ESD. Oral administration combined with local injection of corticosteroids can prolong the time interval of the first dilation after ESD, which is beneficial to the psychological recovery and the improvement of patients’ life quality after the operation.
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This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.
Subject(s)
Animals , Rats , Biological Transport , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Hyperlipidemias/metabolism , Liver/metabolism , Rats, Sprague-Dawley , Triglycerides/metabolismABSTRACT
Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.
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As the most common symptomatic reason to seek medical consultation, pain is a complex experience that has been classified into different categories and stages. In pain processing, noxious stimuli may activate the anterior cingulate cortex (ACC). But the function of ACC in the different pain conditions is not well discussed. In this review, we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain, neuropathic pain, and cancer pain in the ACC, and discuss the cellular receptors and signaling molecules from animal studies. We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management. The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.
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Objective:To clarify the effect of Fangfeng Tongshengtang on early-stage serum endotoxin (ET) and programmed death-1/programmed ligand-1(PD-1/PD-L1) in patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)(early-stage), and exploring the mechanism of Fangfeng Tongshengtang in the treatment of early stage HBV-ACLF. Method:The 69 patients with early stage HBV-ACLF were enrolled in the study and all of them received antiviral drugs, liver protection and jaundice relieving drugs as well as supporting therapy. According to the random number table, 35 patients were randomly assigned to observation group (to take Fangfeng Tongshengtang, and 34 patients were assigned to control group to take placebo. The observation period was 3 weeks in both groups. Before treatment and 1, 2, and 3 weeks after treatment, theserum ET, expression of PD-1/PD-L1 in serum CD4+ and CD8+ T cells, liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total bilirubin (TBIL), and direct bilirubin (DBIL)], coagulation function [prothrombin time (PT), and prothrombin activity (PTA)] were detected to verify the effect of Fangfeng Tongshengtang on HBV-ACLF (early-stage). Result:After 3 weeks of treatment, ET, expression of serum CD4+PD-1+, CD4+PD-L1+, CD8+PD-1+, CD8+PD-L1+, ALT, AST, TBIL, DBIL, and PT decreased significantly (P<0.01), while Alb and PTA increased significantly(P<0.01)in both groups. As compared with the control group, the ET in observation group was lower at 1st, 2nd and 3rd week after treatment (P<0.01), the CD4+PD-1+, CD4+PD-L1+, CD8+PD-1+ and CD8+PD-L1+ in observation group were lower at 2nd week and 3rd week(P<0.05, P<0.01), the ALT, AST, TBIL and DBIL in observation group were lower at 1st, 2nd and 3rd week(P<0.05, P<0.01), the PT in observation group was lower at 2nd and 3rd week(P<0.05), and the PTA in observation group was higher at the 2nd and 3rd week(P<0.01). Conclusion:Fangfeng Tongshengtang can achieve the therapeutic effect for HBV-ACLF (early-stage) probably by reducing the serum ET and the expression of PD-1 / PD-L1 in serum CD4 +, CD8 + T cells.
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Objective:To explore the allelopathic effect of garlic volatiles on Angelica sinensis by studying the allelopathic effect of both living garlicand isolated garlic sprout volatiles on A. sinensis, and provide certain theoretical basis for Angelica garlic interplanting mode to alleviate the stress of continuous cropping A. sinensis. Method:Through the determination and analysis of the growth indexes and leaf protective enzyme system of A. sinensis,the adaptability of A. sinensis to continuous cropping stress and non-continuous cropping stress environment under the influence of the volatiles of living garlic and isolated garlic sprout as well as the mechanism of resistant growth and development were discussed. Result:The overall analysis showed that the growth index and leaf protective enzyme activity of isolated garlic sprout with alleloinductive treatment(DC2)under continuous cropping stress were increased by 17.51% and 48.34% respectively as compared with those under single cropping(CK1). The growth index and leaf protective enzyme activity of angelica under continuous cropping and intercropping(LC2)were increased by 16.63% and 36.65% as compared with those under monocrop cropping(CK2). Those indicated that the volatiles of isolated garlic sprout had more significant effect than those of live garlic on alleviating the stress of continuous cropping of A. sinensis. Conclusion:Regardless of the presence of continuous cropping obstacle,appropriate concentrations of living garlic and isolated garlic sprout volatiles had an allelopathic promoting effect on angelica root growth index and leaf protective enzyme activity,and the effect was more obvious in continuous cropping stress conditions,so intercropping garlic has a certain role in alleviating angelica's continuous cropping stress.
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Objective::To explore the clinical efficacy of modified Sanzi Yangqintang combined with colon hydrotherapy in the treatment of non-alcoholic fatty liver disease (NAFLD) with phlegm-dampness. Method::Totally 100 patients with NAFLD were selected and randomly divided into treatment group (50 cases) and control group (50 cases). Both groups were orally given silybin and glycyrrhizic acid diamine capsules.The treatment group was also added with modified Sanzi Yangqintang and colon hydrotherapy.The treatment lasted for 7 days.The control group was also added with saline colon hydrotherapy.Main traditional Chinese medicine (TCM) syndrome scores and liver function indexes before and after treatment [alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamate transpeptidase (GGT)], blood lipid routine [cholesterol (TCH), triglyceride (TG)], inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], FibroScan measurement [liver stiffness measurement (LSM), controlled attenuation parameters (CAP)], uric acid and body weight changes were observed.Adverse reactions were observed, and the patient's medication safety was evaluated. Result::TCM syndrome score, liver enzyme index, blood lipid index, inflammatory factor index, FibroScan CAP, uric acid and body weight of the two groups were significantly reduced than those before treatment(P<0.05, P<0.01) .There was no significant difference in liver enzymes, TCH, IL-6 and LSM between treatment group and control group.And TCM syndrome scores, UA, TNF-α, FibroScan CAP decreased were significantly different from control group (P<0.05). Conclusion::Modified Sanzi Yangqintang combined with colon hydrotherapy can not only alleviate NAFLD with phlegm-dampness symptoms, but also significantly reduce triglyceride, tumor necrosis factor and FibroScan CAP and body mass, with certain clinical efficacy in a short term.
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Objective::To define the clinical efficacy of modified Taohe Chengqitang combined with colon hydrotherapy in patients with severe nonalcoholic fatty liver disease (NAFLD) accompanied by phlegm-heat stagnation syndrome and its mechanism. Method::Totally 100 patients with severe NAFLD by phlegm-heat stagnation syndrome were enrolled in the study.They were all given Shanzha Xiaozhi capsule.According to the random number table, the patients were randomly divided into the observation group (50 patients, colon hydrotherapy combined with traditional Chinese medicine) and the control group (50 patients, Shanzha Xiaozhi capsule alone). The observation period was 4 weeks.The therapeutic effect of colon hydrotherapy was verified through determinations of the liver function, blood lipid, insulin resistance index (IRI), controlled attenuation parameter (CAP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) before and after treatment.The mechanism of colon hydrotherapy combined with modified Taohe Chengqitang was preliminarily analyzed based on changes of IR, TNF-α and IL-6. Result::Alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase (γ-GT), total cholesterol (TCH), triglyceride (TG), fasting plasma glucose (FPG), fasting insulins (FINS), IRI, CAP, TNF-αand IL-6 of NAFLD patients in both of two groups were significantly lower than those before treatment (P<0.01). ALT, AST, γ-GT, TCH, TG, FPG, IRI, CAP, TNF-α and IL-6 in observation group were significantly lower than those in the control group after treatment (P<0.01). FINS in observation group was significantly lower than that in the control group (P<0.05). Conclusion::Colon hydrotherapy combined with modified Taohe Chengqitang is an effective method for treating NAFLD accompanied by phlegm-heat stagnation syndrome.Its mechanism may be mainly correlated with the reduction of IRI, serum TNF-α and IL-6.The course of colon hydrotherapy, the therapeutic mechanism and the long-term efficacy need to be further studied in the future.
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OBJECTIVE: To establish the TLC identification and HPLC quantitative analysis method of Artemisia ordosica. METHODS: TLC and HPLC were used for qualitative and quantitative analysis of A. ordosica collected from five different regions. The TLC conditions were as follows: the reference substance was spathulenol, the adsorbent was silica gel G, the developing agent was petroleum ether (60-90 ℃)-acetone (5∶1) and the chromogenic color reagent was alcoholic solution of sulfuric acid (10%). The reference substance was 5,4′-dihydroxy-7-methoxyflavanone, the adsorbent was silica gel G, the developing agent was dichloromethane-ethyl acetate-formic acid (15∶1∶0.1) and the chromogenic reagent was ultraviolet lamp. The HPLC separation was set at performed on Topsil C18 (4.6 mm×250 mm,5 μm); the mobile phase was composed of water (A) and acetonitrile (B) and the gradient elution program was as follows: 0-15 min,25%-38% B;15-40 min,38%-45% B. The detection wavelength was 275 nm with column temperature kept at 30 ℃. RESULTS: The spots of reference substances (spathulenol and 5,4′-dihydroxy-7-methoxyflavanone) and A. ordosica in TLC had good repeatability and were easy to be identified. Under the HPLC conditions adopted in this study, all calibration curves exhibited good linearity (r>0.999 3). The recoveries of the method were 97.75%, 96.00%, 98.20%, 97.00%, 95.50%, 99.33%, 97.50%, 96.50%, and 97.33%, respectively. The RSDs were less than 2.0%. Compounds 1, 2, 5 and 8 were not detected in some samples, while compounds 3, 4, 6, 7 and 9 were detected and their content changes in different samples were (0.998±0.013)-(1.263±0.018), (0.108±0.002)-(0.301±0.005), (1.201±0.018)-(1.457±0.023), (0.635±0.011)-(0.801±0.013), (1.150±0.018)-(1.222±0.023) mg•g-1, respectively. CONCLUSION: The TLC identification and HPLC quantitative analysis of A. ordosica are established and can be used for the quality control of A. ordosica.