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In order to establish the standardized processing technology of the hot water washing of Euodiae Fructus, this study, based on the traditional processing method of hot water washing of Euodiae Fructus recorded in ancient works and modern processing specifications of traditional Chinese medicine decoction pieces, took the yield of decoction pieces and the content of main components as the indicators and optimized the processing conditions by orthogonal test based on the results of single factor investigation. At the same time, electronic tongue technology was used to analyze the change law of the taste index of Euodiae Fructus during the hot water washing. The results of the single factor investigation showed that the content of the main components in Euodiae Fructus showed some regular changes during the processing. Specifically, the content of chlorogenic acid, hyperin, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-galactoside, and dehydroevodiamine decreased significantly, with average decreases of-23.75%,-27.80%,-14.04%,-14.03%, and-13.11%, respectively. The content of limonin increased significantly with an average increase of 19.83%. The content of evodiamine, rutaecarpine, evocarpine, and dihydroevocarpine showed fluctuating changes and generally increased, with average variation amplitudes of 0.54%,-3.78%, 2.69%, and 5.13%, respectively. The orthogonal test results showed that the optimum processing parameters for the hot water washing of Euodiae Fructus were as follows: washing time of 2 min, the solid-to-liquid ratio of 1∶10 g·mL~(-1), washing temperature of 80 ℃, washing once, and drying at 50 ℃. After the hot water washing processing, the average yield of Euodiae Fructus pieces was 94.80%. The content of limonin, evodiamine, and rutaecarpine was higher than those of raw pro-ducts, and the average transfer rates were 102.56%, 103.15%, and 105.16%, respectively. The content of dehydroevodiamine was lower than that of the raw products, and the average transfer rate was 83.04%. The results of taste analysis showed that the hot water washing could significantly reduce the salty, astringent, and bitter tastes of Euodiae Fructus. This study revealed the influence of the hot water washing on the content of main components and taste of Euodiae Fructus, and the processing technology of the hot water was-hing of Euodiae Fructus established in this study was stable, feasible, and suitable for industrial production, which laid a foundation for clarifying its processing principle and improving the quality standard and clinical application value of decoction pieces.
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Drugs, Chinese Herbal , Taste , Limonins , Technology , Chromatography, High Pressure Liquid/methodsABSTRACT
Ashi point is one of the three major categories of acupoint in acupuncture-moxibustion theory nowadays. It is originally recorded in Beiji Qianjin Yaofang (Important Formulas Worth a Thousand Gold Pieces for Emergency) as one of the effective folk methods. The theoretic development of ashi point goes through the innovation period of contemporary and modern acupuncture-moxibustion theory, specifically in three aspects, definition, property and status. Through the analysis of historical data, it is found that the bias of ashi point theory results from the misunderstanding of connotation, the distortion of application techniques, the misinterpretation of semantics and the gradual promotion of status. All of these are generally caused by the reform of acupuncture-moxibustion theory in Japan, which covers the essence of ashi point, limits its connotation and clouds the concept of acupoint. It is necessary to re-understand the literal sense and theoretic construction of ashi point and timely update the knowledge system of acupuncture-moxibustion in association with the results of theoretical researches.
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Acupuncture Therapy , Moxibustion , Acupuncture , Acupuncture Points , JapanABSTRACT
ObjectiveTo evaluate the Chinese guidelines and consensus of rehabilitation medicine published in the medical journals in 2022 using Scientific, Transparent and Applicable Rankings (STAR). MethodsGuidelines and consensus which were developed by Chinese institutions or led by Chinese scholars were retrieved in databases of CNKI, Wanfang Data, CBM, Chinese Medical Journal Network, PubMed and Web of Science, in 2022, followed by screening for rehabilitation medicine field. The literature were rated with STAR. ResultsSeven guidelines and eleven consensuses were included. The STAR scores ranged from 11.7 to 69.6, with a median score of 25.9 and mean score of 28.3. There was a significant difference in the total score between guidelines and consensus (U = 12.000, P = 0.014). The score ratio was high in the domains of recommendations (73.6%), evidence (39.5%) and others (33.3%), while it was low in the domains of protocol (1.4%), clinical questions (12.5%) and conflicts of interest (13.9%). The score ratio was high in the items of listing the institutional affiliations of all individuals involved in developing the guideline (94.4%), identifying the references for evidence supporting the main recommendations (94.4%), indicating the considerations (e.g., adverse effects) in clinical practice when implementing the recommendations (88.9%), and making the recommendations clearly identifiable, e.g., in a table, or using enlarged or bold fonts (75%); and it was low in the items of describing the role of funder(s) in the guideline development (0), indicating information about the evaluation and management of conflicts of interest (0), providing tailored editions of the guidelines for different groups of target users (0), presenting the guideline or recommendations visually, such as with figures or videos (0), providing details of the guideline protocol (2.8%), assessing the risk of bias or methodological quality of the included studies (2.8%), describing the responsibilities of all individuals or sub-groups involved in developing the guideline (5.6%), indicating how the clinical questions were selected and sorted (5.6%), formating clinical questions in PICO or other formats (5.6%), making the guideline accessible through multiple platforms (5.6%), and declaring that the funder(s) did not influence the guideline's recommendations (8.3%). ConclusionThe quality of current clinical practice guidelines and consensus of rehabilitation medicine is poor, which should be developed in accordance with the relevant standards.
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a sole viable treatment for acute myeloid leukemia (AML). As the median age of AML is approaching 68 years and the global population is aging, allo-HSCT for is becoming more vital for elderly AML patients (60 years and over). Conditioning regimen is important in determining the clinical outcomes of post-allo-HSCT patients.This review summarized the classic and latest conditioning regimens and evaluated their respective clinical outcomes.Clinicians may appreciate the advantages of each conditioning regimen and formulate optimal options for elderly AML patients.
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Objective:To study the clinical risk factors for osteoporotic fracture (OF) risk prediction in patients with type 2 diabetes mellitus (T2DM) using adjusted fracture risk assessment tool (FRAX) .Methods:A cross-sectional study of 429 patients with T2DM who were hospitalized in the Department of Endocrinology and Geriatrics of the Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University from Sep. 2019 to Sep. 2020 was conducted. Participants were divided into OF low-risk group and OF high-risk group. Participant characteristics (age, gender, height, weight, waist, blood pressure, history of drug treatment, serum glucose, glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) , high-density lipoprotein cholesterol (HDL-C) , triglyceride, serum uric acid, alkaline phosphatase, and thyroid stimulating hormone levels, urine protein/creatinine ratio, urea, creatinine and TPOAB) and dual energy x-ray absorptiometry results were obtained and analyzed. Logistic regression model was used to investigate the relationship between the OF risk of T2DM assessed by adjusted FRAX and clinical risk factors.Results:Patients in the OF high-risk group accounted for 9.09% of the subjects. After adjustment for other variables, the duration of diabetes was still positively associated with significantly elevated risk of OF assessed by adjusted FRAX ( OR 7.660, 95% CI 1.661-35.334, P=0.009) , whereas the blood uric acid was negatively associated with significantly elevated risk of OF assessed by adjusted FRAX ( OR 0.345, 95 % CI 0.128-0.928, P=0.035) .Likewise, LDL-C levels decreased the odds of the risk of OF assessed by adjusted FRAX ( OR 0.316, 95 % CI 0.114-0.881, P=0.028) . There was no significant relationship between alkaline phosphatase ( OR 1.902, 95 % CI 0.904-4.004, P=0.090) as well as total cholesterol ( OR 0.297, 95% CI 0.056~1.560, P=0.151) levels and the elevated risk of OF assessed by adjusted FRAX. Conclusion:Diabetes duration could be a risk factor for OF risk prediction in patients with T2DM using adjusted FRAX, and serum uric acid and LDL-C could be protective factors for OF risk prediction in patients with T2DM using adjusted FRAX.
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Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.
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Humans , Adenocarcinoma/pathology , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/pathology , Inflammation/pathology , Lymphocytes, Tumor-Infiltrating/metabolism , Pancreatic Neoplasms/pathology , Prognosis , Tumor MicroenvironmentABSTRACT
ObjectiveTo provide references for the selection of Zingiberis Rhizoma Recens on the research of famous classical formulas and the reasonable uses for medicines and foods through herbal textural research and quality analysis of Zingiberis Rhizoma Recens from main producing areas in China. MethodBy consulting the ancient and modern literature， the name， origin， producing areas， harvest time， processing methods of Zingiberis Rhizoma Recens were summarized. According to the 2020 edition of Chinese Pharmacopoeia， the contents of 6-gingerol， 8-gingerol， 10-gingerol， and volatile oil in Zingiberis Rhizoma Recens samples were determined. ResultHerbal textural research indicated that medicinal Zingiberis Rhizoma Recens originated from the fresh rhizome of Zingiber officinale. Before Tang dynasty， Zingiberis Rhizoma Recens produced in Sichuan was the best. In the Song dynasty， Zingiberis Rhizoma Recens produced in Sichuan， Zhejiang， and Anhui was of excellent quality. The cultivation of Zingiberis Rhizoma Recens in Shandong developed during the Ming and Qing dynasties. From ancient times to the present， the harvest period extended from the autumnal equinox to the winter solstice. Quality evaluation standards of Zingiberis Rhizoma Recens were essentially the same in ancient and present documents， as those with little gluten or gluten-free and strong pungency were preferred. After determination， the contents of 6-gingerol， 8-gingerol， and 10-gingerol in 44 samples were qualified in 27 samples， with a qualified rate of 61.4%. Among them， 17 samples were unqualified in the total contents of 8-gingerol and 10-gingerol. Among these qualified samples， the content of 6-gingerol ranged from 0.067% to 0.255%， and the total contents of 8-gingerol and 10-gingerol ranged from 0.040% to 0.131%. The content of volatile oil in 36 samples were qualified in 33 samples， with a qualified rate of 91.7%. Among the qualified samples， the content of volatile oil ranged from 0.175% to 0.410%. ConclusionZingiberis Rhizoma Recens has been used as medicines and foods since ancient times， and the genuine producing areas are consistent in ancient and present times， while the quality of the products， especially the medicinal Zingiberis Rhizoma Recens， should be monitored. Medicinal Zingiberis Rhizoma Recens planted in Leshan city of Sichuan province contains high contents of effective components， followed by Qujing and Wenshan cities of Yunnan province. Zingiberis Rhizoma Recens planted in Shandong and other places is mostly edible.
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Wuzhuyu Tang （WZYT）， a classical traditional Chinese medicine （TCM） formula， was first recorded in Treatise on Cold Damage by the prestigious physician ZHANG Zhong-jing in the Eastern Han Dynasty， and included in Catalogue of Ancient Classical Formulas （First Batch）. WZYT is composed of four medcinals： Euodiae Fructus， Ginseng Radix et Rhizoma， Zingiberis Rhizoma Recens， and Jujubae Fructus， which has the effects of warming the middle and tonifying deficiency， dissipating cold and descending adverse qi. Based on data mining， this paper analyzes the modern clinical research literature on WZYT， which is expected to lay a basis for clarifying the "disease-symptom-prescription-medicinal" relationship of WZYT， as well as its modern clinical indications and clinical dosage. With the search term "Wuzhuyu Tang"， 253 complete medical records were retrieved from CNKI， VIP， and Wanfang （2000-2020）， involving 292 TCM prescriptions. Microsoft Excel 2019 was employed to establish the medical record database and the main clinical indications were statistically analyzed. Moreover， the syndromes， incidence law， and medication regularity were summed up. The result indicates WZYT has a wide range of modern clinical applications， mainly including the treatment of headache， dizziness， vomiting， diarrhea， dysmenorrhea， morning sickness， and other diseases， and the "deficiency， cold， and reversal" symptoms， mainly manifested as nausea and vomiting， headache， fatigue and lack of strength， reversal cold of hands and feet， poor appetite， gloomy complexion， dizziness， aversion to wind and cold， abdominal pain， sloppy diarrhea， abdominal distension， poor sleep， pale tongue， white coating， and deep thread wiry pulse. These diseases and symptoms mainly occur in women and middle-aged people. In most cases， medicinals are added or subtracted according to the symptoms， and the common doses of Euodiae Fructus， Zingiberis Rhizoma Recens， Codonopsis Radix or Ginseng Radix et Rhizoma， and Jujubae Fructus in the original prescription are 6-15 g， 10-15 g， 10-15 g or 9-12 g， and 4-6， respectively. The added medicinals are in the descending order of Pinelliae Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhize Radix et Rhizoma， and Chuanxiong Rhizoma according to the frequency.
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Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H2O2 and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT1R) and AT2R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H2O2 and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H2O2. The mRNAs of renal microvascular AT1R and AT2R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.
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Animals , Mice , Angiotensin II/pharmacology , Arterioles/metabolism , Captopril/pharmacology , Hydrogen Peroxide/pharmacology , KidneyABSTRACT
Objective:To explore the relationship between vegetarian diets and vitamin B 12 levels in Chinese pregnant women. Methods:A cross-sectional survey was used to explore the relationship between vegetarian diets and vitamin B 12 levels in Chinese pregnant women based on data from the Chinese National Nutrition and Health Surveillance (2015-2017). Maternal serum vitamin B 12 concentration was determined by electrochemiluminescence. Background and diet information of all subjects were collected using general and food frequency questionnaires. General Linear Model was used to analyze the difference in serum vitamin B 12 levels between vegetarian and non-vegetarian pregnant women and multivariate logistic regression for examining the relationship between vegetarian diets and vitamin B 12 deficiency (vitamin B 12<150 pmol/L) in pregnant women. Results:A total of 8 366 pregnant women were included in the analysis, and vegetarians accounted for 1.2% (102/8 366). The median serum vitamin B 12 concentrations were 155.8(93.6-212.4) pmol/L and 187.2(127.4-267.6) pmol/L ( Z=－4.22, P<0.001), and the vitamin B 12 deficiency rates were 48.0% (49/102) and 35.0% (2 896/8 264) in vegetarian and non-vegetarian women, respectively. The vitamin B 12 deficiency rate in vegetarian women was 0.89-fold higher than in non-vegetarians (95% CI: 1.24-2.89). Among the vegetarian and non-vegetarian pregnant women, vitamin B 12 deficiency rates during the first, second, and third trimesters were 34.8%(16/46), 54.3%(19/35), 66.7%(14/21), and 20.4%(521/2 559), 32.6%(941/2 886), 50.9%(1 430/2 807), noting for an increasing trend ( Z=23.54 and 2.57, P=0.010 and P<0.001). Conclusions:Vegetarian pregnant women are at high risk of vitamin B 12 deficiency. Compared with non-vegetarian women, vegetarian pregnant women in China have lower vitamin B 12 levels and a higher risk of vitamin B 12 deficiency. Moreover, the risk of vitamin B 12 deficiency will gradually increase during pregnancy.
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AIM: To evaluate the influence of slight eye movement during laser scanning on femtosecond laser precision of corneal ablation and postoperative refractive status in small incision lenticule extraction(SMILE). METHODS: Totally 32 patients(62 eyes)who underwent SMILE surgery in our hospital from January 2019 to March 2021 were included and divided into the movement group and the fixation group according to whether the eyeballs were slightly moved during the operation, and select patients with slightly moved monocular eyeballs for binocular pairing. The actual difference of absolute value of corneal absolute cutting error(ACE), astigmatism error(AE), absolute refractive error(ARE)and absolute visual error(AVE)was compared between the movement group and the fixation group and the two eyes of the patients with slight ocular movement in one eye at 1mo after surgery, and the surgical images were quantified to analyze the correlation between the amplitude of ocular movement and AE, and to compare the effects of the area, layer and direction of slight eye movement on ACE.RESULTS: There were no differences in all observed results between movement group and fixation group(P>0.05). Patients with slight movement of one eye had a difference in binocular AE(0.57±0.31D vs 0.33±0.27D, P<0.05), and the amplitude of movement was positively correlated with AE at 1mo after surgery(r=0.564, P<0.05). There was no statistical differences in ACE at 1mo after surgery in patients with slight ocular movement in different regions(central/peripheral), layers(upper/lower lens)and direction(nasal/temporal)(all P>0.05).CONCLUSION:The slight eye movement during laser scanning in SMILE has no significant influence on precision of corneal ablation. It mainly causes decentered ablation and the changes of corneal astigmatism, which has little effect on the spherical equivalent and visual acuity.
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In this study, according to TCM theory of "liver qi stagnation forming fire", emotional stress mice model was employed to evaluate the protective effects of Qingre Xiaoyanning on herpes simplex virus type 1 (HSV-1) induced reactivation. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. BALB/c mice were divided into six groups, including mock group, HSV-1 latency group, HSV-1 reactivation group (HSV-1 latency + stress), low (0.658 g·kg-1·day-1) and high dose (1.316 g·kg-1·day-1) of Qingre Xiaoyanning groups and positive control group (acyclovir, 0.206 g·kg-1·day-1). Except for the normal group and HSV-1 latency group, all mice in other groups received a daily 12-h restraint stress for 4 days. After 7-day treatment of drugs, body weight and recurrent eye infections of mice were recorded. Brain tissues were harvested to monitor HSV-1 antigen distribution by immunohistochemical staining and detect virus titer by plaque assay. In the meantime, the mRNA and protein levels of infected cell polypeptide (ICP27) and glycoprotein B (gB) in the brain tissues were detected by RT-PCR and Western blot, respectively. The level of 4-hydroxynonenal (4-HNE) and expressions of ferroptosis-related proteins were measured by Western blot. The evaluation of malondialdehyde (MDA) content in the brain tissues was conducted by MDA assay commercial kit. The results showed that Qingre Xiaoyanning significantly retarded the decline of body weight of mice induced by HSV-1 reactivation, reduced the activation rate of HSV-1 and recurrent eye infections, declined virus titer of HSV-1, down-regulated gene and protein expressions of ICP27 and gB, and hindered the distribution of HSV-1 antigen in the brain of mice. Meanwhile, Qingre Xiaoyanning also decreased the protein expression of ferroptosis-related proteins, including DMT1, TFR1 and ALOX15 in the brain tissue of HSV-1 reactivated mice. The levels of lipid peroxidation products, 4-HNE and MDA, were also reduced by Qingre Xiaoyanning treatment. All the above results indicate that Qingre Xiaoyanning significantly inhibited HSV-1 reactivation by restraint stress, which might be related to the regulation of ferroptosis. Our findings provide a theoretical basis for the application of "clearing liver-fire" TCM on treatmenting HSV-1 reactivation-related symptoms.
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Objective To investigate the methylation status of ZIC1 gene in peripheral blood and lung cancer tissues of NSCLC patients and its prognostic significance. Methods We took the peripheral blood, cancer tissues and adjacent tissues of 95 NSCLC patients. The peripheral blood of 95 healthy people was taken as control group. MSP was used to compare the detection rate of ZIC1 methylation between peripheral blood and cancer tissues. And we analyzed the correlation of ZIC1 methylation in peripheral blood and cancer tissues with the clinicopathological factors of NSCLC patients. Results The methylation detection rates of ZIC1 in peripheral blood and lung cancer tissues in NSCLC patients were significantly higher than those in peripheral blood of healthy people and adjacent tissues of NSCLC patients (P < 0.05), and the sensitivity and specificity of ZIC1 methylation in the diagnosis of tumor tissues were higher. The positive rate of ZIC1 gene methylation in peripheral blood and tumor tissues of NSCLC patients was significantly correlated with tumor diameter, metastasis, stage and pleural effusion (P < 0.05). Conclusion The methylation of ZIC1 gene is related to the occurrence, development, metastasis and stage of NSCLC. It may be used as a diagnostic and prognostic indicator of NSCLC.
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Objective:To investigate the expression and distribution of human dermal papillary fibroblasts (Fp) , reticular fibroblasts (Fr) , and myofibroblasts (MFB) in keloid tissues.Methods:Keloid tissues were collected from 15 outpatients (including 8 males and 7 females) aged 20-50 years, who were diagnosed in the Department of Dermatology, Renmin Hospital of Wuhan University from May to December 2019. Normal skin tissues were taken from 15 age-matched women who underwent mammoplasty, and served as controls. The distribution of fibroblast activation protein (FAP) , CD90 and alpha-smooth muscle actin (α-SMA) was observed in the keloid tissues and normal skin tissues by dual immunofluorescence staining. Furthermore, fibroblasts were isolated from 3 normal skin and 3 keloid tissue samples, and subjected to primary culture. Subsequently, the fibroblasts were treated with 10 ng/ml transforming growth factor-β1 (TGF-β1) for 48 hours in vitro, during which, changes in fibroblast phenotypes were observed in the 2 groups. Fluorescence-based quantitative RT-PCR and Western blot analysis were performed to determine the mRNA and protein expression of FAP, CD90 and α-SMA. Measurement data were compared between 2 groups by using t test. Results:Immunofluorescence staining of the normal skin tissues revealed that FAP +/CD90 - fibroblasts were predominantly distributed in the superficial dermis, FAP -/CD90 + fibroblasts in the deep dermis, and CD90 + cells hardly expressed α-SMA; however, a large number of FAP + fibroblasts and CD90 + fibroblasts were observed in the deep keloid tissues, and many CD90 + fibroblasts also expressed α-SMA. Dual immunofluorescence staining showed that normal tissue-derived fibroblasts hardly expressed α-SMA, and keloid-derived fibroblasts expressed α-SMA. The fluorescence intensity of α-SMA + cells significantly increased in the normal tissue-and keloid-derived fibroblasts after 24-hour treatment with TGF-β1 (21.058 ± 0.709, 27.112 ± 0.097, respectively) compared with that in the corresponding untreated fibroblasts (11.312 ± 0.636, 21.306 ± 0.464, t=22.430, 13.370, respectively, both P < 0.05) . RT-PCR and Western blot analysis showed that the mRNA and protein expression of FAP, CD90 and α-SMA significantly increased in the keloid-derived fibroblasts after 48-hour treatment with TGF-β1 (mRNA: 92.610 ± 3.667, 1.366 ± 0.105, 3.240 ± 0.141; protein: 0.652 ± 0.073, 1.046 ± 0.119, 0.946 ± 0.117, respectively) compared with the untreated keloid-derived fibroblasts (all P < 0.05) . Conclusion:CD90 + Fr aberrantly proliferated in the deep dermis of keloid tissues, suggesting that directional intervention in aberrantly proliferating FAP -/CD90 + Fr in the deep dermis may promote the efficacy for keloids.
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Chronic inflammatory response syndrome(CIRS)is a chronic, low-grade, systemic inflammatory response, resulting from sustained long-term stimulation of the innate immune system.CIRS is not only associated with certain chronic diseases, but also associated with aging, the development and progression of a variety of diseases in the elderly, and functional decline.Additionally, it is closely related to adverse clinical outcomes and is not uncommon in the elderly.Here we review the characteristics of CIRS and their clinical implications and consider whether CIRS can be classified as a geriatric syndrome, in order to identify new targets for the prevention and treatment of diseases and functional decline in the elderly.
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Objective:To investigate the value of BRAF V600E mutation combined with 2015 American Thyroid Association (ATA) Guidelines ultrasound (US) pattern in fine-needle aspiration (FNA) cytology of thyroid nodules with atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS).Methods:This study retrospectively enrolled 96 consecutive patients with 101 AUS/FLUS thyroid nodules who underwent preoperative US, FNA, and BRAF V600E mutation analysis. All AUS/FLUS nodules were classified based on US pattern-based risk stratification of 2015 ATA Guidelines. With postoperative pathology as the gold standard, the diagnostic value of BRAF V600E mutation, US pattern and the combination of two methods were compared.Results:Postoperative pathology confirmed 33 benign nodules and 68 malignant nodules. The mutation rates of BRAF V600E in AUS/FLUS nodules was 51.5%. The sensitivity, specificity, and accuracy of BRAF V600E in the diagnosis AUS/FLUS nodules were 72.1%, 90.9% and 78.2%, respectively. The ROC curve demonstrated that the best cut-off of US pattern was high suspicion. The sensitivity, specificity, and accuracy of US pattern in the diagnosis of AUS/FLUS nodules were 63.2%, 81.8% and 69.3%, respectively. The accuracy of US pattern in determining AUS/FLUS nodules without BRAF V600E mutation was 70.6%. The sensitivity, specificity, and accuracy of the combination of two methods in the differential diagnosis of AUS/FLUS nodules were 89.7%, 75.8%, and 85.1%, respectively. The combination had the highest sensitivity ( P<0.05). Conclusions:BRAF V600E mutation has a good diagnostic value for differentiating benign and malignant AUS/FLUS nodules. Combined with US pattern, the differential diagnostic value for AUS/FLUS nodules without BRAF V600E mutation can be improved, and the sensitivity can be raised.
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Objective:To explore the applicational value of identifying different types of echogenic foci and distinguishing the lesions between benign and malignant lesions in histopathology classification.Methods:The detailed clinical data of 223 patients (264 thyroid nodules) with echogenic foci in preoperative ultrasound from October 2018 to December 2019 in the Sir Run Run Shaw Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The echogenic foci were categorized as big comet-tail artifact, small comet-tail artifact, microcalcification, coarse calcification, peripheral calcification and eggshell calcification. At the same time, other ultrasonographic features were included in order to comparatively analyze with postoperative pathological findings. Independent samples t test and univariate chi-square test were performed to obtain meaningful information of sex, age, body mass index (BMI), thyroid stimulating hormone (TSH), serum free triiodothyronine (FT 3), serum free thyroxine (FT 4), aspect ratio, composition, margin, echo type, echogenic foci; Logistic regression analysis was performed to screen out the independent influence factors in order to forecast malignant lesions. Spearman correlation analysis was performed to determine the ralationships between the clinical indicators and the pathologic results of thyroid lesions. Results:Among the 264 lesions, there were 219(83.0%) malignant nodules and 45(17.0%) benign nodules. For malignant lesions, except for big comet-tail artifact, other types of echogenic foci were all founded, including 152(69.4%) microcalcification, 41(18.7%) small comet-tail artifact, 17(7.8%) coarse calcification, 7(3.2%) peripheral calcification, 2(0.9%) eggshell calcification. While in benign lesions, there were 13(28.9%) microcalcification, 9(20.0%) coarse calcification, 8(17.8%) peripheral calcification, 6(13.3%) small comet-tail artifact, 6(13.3%) big comet-tail artifact, 3(6.7%) eggshell calcification with all echogenic foci types included. Univariate analysis showed that differences between benign and malignant lesions regarding age, serum FT 4, aspect ratio, composition, margin, echo type, echogenic foci were statistically significant (all P<0.05), Logistic regression analysis indicated that age, serum FT 4, hypoechoic, solid, small comet-tail artifact and microcalcification were independent influence factors for malignancy( OR=0.946, 0.026, 47.656, 9.032, 7.925, 12.767; all P<0.05), age and serum FT 4 were correlated with the pathologic results of thyroid lesions ( rs=-0.259, -0.156; all P<0.05). Conclusions:It is highly suggestive of malignancy when the thyroid lesions are solid, hypoechoic, and echogenic foci type is small comet-tail artifact or microcalcification.
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Objective:To analyze the clinical phenotype, imaging characteristics and genetic characteristics of a family of early-onset dementia caused by a new mutation in the triggerring receptor expressing on myeloid cells 2 gene (TREM2).Methods:Clinical data were collected from a patient with early-onset dementia. Then whole exome sequencing was performed for the proband, followed by Sanger sequencing for the family members.Results:The clinical manifestations of the proband (a 49-year-old female) was personality changes, mental and behavioral abnormalities, memory loss, ataxia, and seizures. Whole-exon sequencing revealed a novel homozygous mutation in exon 2 of TREM2, namely c.154C>T (p.R52C) heterozygosity in four family members, and one patient with similar clinical manifestations was deceased. The proband′s brain magnetic resonance imaging showed bilateral frontotemporal atrophy, bilateral white matter hyperintensity, thin corpus callosum. No bone cysts of the hands and feet were found by digital radiographic imaging.Conclusions:A homozygous mutation in TREM2 gene was detected in a patient with frontotemporal dementia-like dementia, epilepsy, but without bone cysts. This mutation is probably pathogenic. This research highlights the importance of TREM2 gene mutation screening in early-onset dementia, especially in those with atypical presentations.
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Objective:To investigate the relationship of urinary 8-oxoguanosine(8-oxoGsn)with muscle mass, muscle strength, advanced glycation end products(AGEs), trace elements, heavy metals and other health-related indictors in different age groups of the Beijing area.Methods:A cross-sectional research was conducted.Healthy adults aged 25 to 93 years who sought health examination in the Health Examination Center of Beijing Hospital were recruited.Participants were divided into the young and middle-aged group and the elderly group with age 60 as the cutoff.Urinary 8-oxoGsn levels were detected by mass spectrometry and adjusted using urine creatinine values.Body composition was measured by multifrequency bioelectrical impedance analysis(BIA). Grip strength, 6-meter walking speed and 5-times sit to stand test were conducted by experienced team members.Skin autofluorescence was used to detect skin AGEs.A portable optical scanner was used to detect heavy metals and trace elements using reference points of the palm.Levels of fasting blood glucose, glycosylated hemoglobin, high-density lipoprotein and other common blood biochemical indicators were measured.Results:A total of 106 subjects were enrolled, including 68 in the young and middle-aged group and 38 in the elderly group.The proportion of patients with hypertension(14 ases or 36.8% vs.7 ases or 10.3%), systolic blood pressure[130(120, 140) vs.120(110, 126)mmHg], fasting blood glucose[5.7(5.2, 5.9)mmol/L vs.5.2(4.9, 5.5)mmol/L], glycosylated hemoglobin[6.0(5.7, 6.2)% vs.5.7(5.4, 5.9)%], 8-oxoGsn/Cre[1.9(1.4, 2.6) vs.1.3(1.0, 1.6)], AGEs(2.44±0.46 vs.2.01±0.29), 5-times sit to stand test scores[7.8(6.9, 9.8)s vs.6.0(5.0, 6.8)s], magnesium(31.4±7.2 vs.27.7±6.4), mercury(0.013±0.003 vs.0.008±0.003)and silver[0.011(0.010, 0.012) vs.0.010(0.009, 0.011)]were higher in the elderly group than in the young and middle-aged group, while grip strength[28.0(22.0, 35.1)kg vs.36.6(28.5, 49.1)kg], fat-free mass[44.9(37.5, 51.1)kg vs.53.3(42.4, 58.5)kg], trunk muscle mass[21.0(17.5, 23.9)kg vs.25(19.8, 27.4)kg], appendicular skeletal muscle mass[20.9(17.6, 23.9)kg vs.24.9(19.8, 27.3)kg], calcium[273.3(219.1, 480.0) vs.457.8(428.5, 489.1)], cobalt[0.029(0.027, 0.031) vs.0.031(0.028, 0.034)], selenium[1.44(0.93, 1.71) vs.1.61(1.53, 1.68)]and nickel[3.5(3.3, 4.0)*10 -3vs.3.8(3.6, 4.1)*10 -3]were lower in the elderly group than in the young and middle-aged group( P<0.05). Urinary 8-oxoGsn/Cre levels were positively correlated with age, time of 5-times sit to stand test, AGEs, fasting blood glucose, mercury and aluminum( rs=0.443, 0.292, 0.357, 0.205, 0.316 and 0.214, P<0.05), and negatively correlated with trunk muscle mass, appendicular skeletal muscle mass, fat-free mass, grip strength, silicon and manganese( rs=-0.334, -0.333, -0.332, -0.366, -0.246 and -0.234, P<0.05), with statistical significance. Conclusions:Increased urinary 8-oxoGsn/Cre levels are correlated with decreased muscle mass, poor physical function, accumulation of AGEs, decreased trace element levels and increased heavy metal levels.Therefore, 8-oxoGsn has the potential to be a broadly representative and sensitive indicator for health assessment.
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BACKGROUND@#There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment.@*METHODS@#We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes.@*RESULTS@#Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100).@*CONCLUSION@#5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.