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The study aims to investigate the anti-hepatic fibrosis and anti-inflammatory activities of palbinone, and to explore the internal regulatory mechanism, so as to lay an active foundation for its development as an anti-non-alcoholic steatohepatitis (NASH) candidate. First, sulforhodamine B (SRB) method was used to detect the effect of palbinone on the proliferation of human hepatic stellate cells LX-2 and rat hepatic stellate cells HSC-T6. Following, in the in vitro hepatic fibrosis cell model that activated by transforming growth factor beta 1 (TGF-β1), quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the inhibitory effect of different concentrations of palbinone on the transcription level and protein expression level of hepatic fibrosis markers. And the regulating mechanism of palbinone on fibrosis-related genes was analyzed at the same time. In addition, in the inflammatory cell model that induced by lipopolysaccharide (LPS) and nigericin, ELISA was used to detect the effect of palbinone on the released interleukin-1β (IL-1β) level. At the same time, Western blot was used to detect the effect of palbinone on the related proteins of inflammatory pathway. The results showed that palbinone could significantly inhibit the proliferation activity of LX-2 and HSC-T6, and their half maximal inhibitory concentration (IC50) values were (375.11 ± 55.45) and (260.27 ± 36.81) nmol·L-1, respectively. In addition, palbinone showed a dose-dependent inhibitory effect on the expression levels of TGF-β1-induced fibrosis-related genes, including collagen type Ⅰ α 1 (COL1A1), TGF-β1, α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase 1 (TIMP1). Mechanism study showed that palbinone may decrease the expression level of Yes-associated protein (YAP), thereby weakening its activation effect on the downstream fibrosis pathway. In addition, palbinone also exerted an anti-inflammatory effect by inhibiting the activity of nuclear factor kappa-B (NF-κB) signaling pathway and reducing inflammatory factors cysteinyl aspartate specific proteinase-1 (caspase-1) and IL-1β release. In conclusion, palbinone can not only inhibit the proliferation and activation of hepatic stellate cells by inhibiting the expression of YAP, but also inhibit the expression and release of inflammatory factors at the same time. All these studies provide theoretical support for the development of palbinone as an anti-nonalcoholic steatohepatitis drug.
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@#Protein corona is a protein layer that adsorbs on the surface after nonspecific interactions between nanoparticles and plasma proteins.In recent years, studies have shown that modification of specific plasma proteins on the surface of nanoparticles to construct protein corona can prolong the blood half-life of nanoparticles and promote the targeted delivery of nanoparticles, which has attracted widespread attention to the study of drug-carrying systems, among which, albumin corona, the most abundant protein in blood, is the most widely studied.Based on the above, this paper systematically summarized the method of constructing albumin corona and its application in the research on pharmaceutical preparations, in order to provide reference for the construction of albumin corona in the process of drug preparation.
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Objective:To explore the effects of "rain classroom" wisdom teaching on geriatric students′ autonomous learning ability and self-efficacy.Methods:From June to August, 2021, 61 nursing students who practiced in the department of gerontology of the Second Xiangya Hospital, Central South University were selected as research subjects, and divided into experimental group (30 students) and control group (31 students) by random number table method. In the experimental group, wisdom teaching based on "Rain classroom" was carried out at the same time as conventional teaching, while in the control group, conventional teaching was carried out, and the teaching effect was evaluated by the independent learning ability measurement scale and academic self-efficacy scale of nursing students.Results:The score of autonomous learning ability of nursing students in the experimental group was 68.55 ± 11.06, and that in the control group was 74.29 ± 9.16. The difference between the two groups was statistically significant ( t = -2.01, P<0.05). The academic self-efficacy scores of nursing students in experimental group and control group were 52.27 ± 11.56 and 52.64 ± 9.28 respectively. There was no significant difference between the two groups ( P>0.05). Conclusions:The wisdom teaching of "rain classroom" improves the independent learning ability of geriatric nursing students, and attaches importance to the cultivation of self-efficacy of nursing students, and the improvement of self-efficacy needs further research.
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Objective:To explore the mediating effect of nurses′ self-efficacy in palliative care between the past behavioral experience of end-of-life care and core competence, and provide theoretical reference for improving the core competence of clinical nurses in palliative care.Methods:579 clinical nurses from 2 tertiary general hospitals in Shandong Province were investigated by convenience sampling method using general information questionnaire, nurses′ self-efficacy questionnaire for palliative care and palliative care nurses′ core competency questionnaire. The data were analyzed by SPSS 25.0.Results:The total score of core competence of hospice care of 579 nurses was (71.41 ± 22.74), nurses′ self-efficacy of palliative care was positively correlated with their core competence ( r = 0.648, P<0.01), past behavior experience was positively correlated with self-efficacy ( r = 0.479, P<0.01), positively correlated with core competence ( r = 0.427, P<0.01). Nurses′ self-efficacy of palliative care played a partial mediating role between the pastbehavioral experience and core competence, which accounted for 64.67% of the total effect. Conclusions:The past behavioral experience of end-stage nursing can directly or indirectly affect the core competence of nurses in palliative care through self-efficacy. It can improve the core competence of palliative care by taking active measures to enrich the past behavioral experience of end-of-life care and improve self-efficacy.
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Background Fine particulate matter (PM2.5) is a serious air pollutant associated with elevated levels of C-reactive protein (CRP), an inflammatory indicator. Objective To assess the potential impacts of long-term exposure to PM2.5 on CRP levels based on previous epidemiological studies. Methods PubMed, Embase, Web of Science, CNKI, and Wanfang databases were searched to screen the cohort studies published from January 1, 2000 to January 1, 2022 on the effects of long-term exposure to PM2.5 on CRP levels. "Fine Particulate Matter", "PM2.5", "Particulate Air Pollutants", "Ambient Particulate Matter", "CRP", "C-reactive Protein", and "High Sensitivity C-reactive Protein" in English or Chinese were the key words used in the search. The percentage change in CRP level per 10 μg·m−3 increase in PM2.5 concentration in each study was extracted, followed by meta-analysis, subgroup analysis, and sensitivity analysis. Results A total of 1241 articles were retrieved, and 7 articles were included. Random-effects models were used to merge the included data, and it was found that the percentage of CRP level increased by 10.41% (95%CI: 2.24%-18.57%, P<0.05), when PM2.5 concentration increased by 10 μg·m−3, І2=84.2%. The subgroup analysis conducted with grouping based on the annual mean concentration of PM2.5 long-term exposure showed that the intra-group heterogeneity was significantly reduced in the <15 μg·m−3 and the 15- μg·m−3 groups, and the subgroup forest analysis showed differences between the two groups. The results of sensitivity analysis showed that there was a high degree of heterogeneity among the 7 studies, and the 2 papers with the highest annual average PM2.5 concentration were the sources of heterogeneity. The Egger test and the funnel plot indicated that no obvious publication bias was found. Conclusion Long-term exposure to PM2.5 can raise levels of CRP in human body.
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AIM: To analyze the correlation of changes in non-contact intraocular pressure(IOPNCT)and the surgical parameters after femtosecond laser small incision lenticule extraction(SMILE)for high myopia.MOTHODS:A retrospective analysis, the clinical data of 98 patients(196 eyes)with high myopia were operated SMILE in the optometric center of Gansu Provincial Hospital from January 2018 to July 2019 were analyzed. The change of IOPNCT before and after operation was observed, and recorded the optical zone(OZ), lenticule thickness(LT), cap thickness(CT)and residual stromal thickness(RST)and the correlation with the change value of IOPNCT(△IOPNCT, △IOPNCT=IOPpreoperative-IOP postoperative at 6mo).RESULTS:After operation at 1d, 1wk, 1,3 and 6mo, the group of patients with IOPNCT(10.84±2.14,11.00±2.19,10.65±2.43,10.45±2.04,10.61±1.39mmHg)and the preoperative(16.79±1.65mmHg)comparison have a difference(P<0.001).The optical zone and lenticule thickness were positively correlated with △IOPNCT respectively(r=0.1537, 0.8161, all P<0.05). The cap thickness and residual stromal thickness were negatively correlated with △IOPNCT respectively(r=-0.8362, -0.3351, all P<0.0001). Introduce the above related factors into a multiple linear regression analysis model. The regression coefficients of variables are statistical significane. The regression equation was Y=16.189+0.227X1+0.032X2-0.083X3-0.007X4(Y=△IOPNCT, X1=OZ, X2=LT, X3=CT, X4=RST). The equation was statistically significant(F=195.704, P<0.001), and the regression model coefficient of determination R2=0.901.CONCLUSION:The intraocular pressure changes after SMILE with high myopic were correlated with optical zone, lenticule thickness, cap thickness and residual stromal thickness. The regression equation would provide reference to evaluation the real intraocular pressure after SMILE in clinic.
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Nuclear magnetic resonance spectroscopy is one of the main analytical techniques for detecting metabolomics, which has the advantages of simple operation, rapid detection and non-invasive feature. By monitoring the changes of metabolites in the body, it is helpful to deeply understand the mechanism of disease and play a role in the diagnosis and treatment of diseases, but its clinical application has not yet been popularized. In recent years, the application of metabolomics in tumors has increasingly become a research hotspot. Therefore, in order to provide a reference for the research and clinical application of tumor metabolomics, the nuclear magnetic resonance spectroscopy and tumor metabolomics were introduced in this paper, and the application progress of metabolomics analysis based on this technique in early tumor screening, clinical diagnosis and prognosis evaluation were reviewed in this paper.
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Objective:To evaluate the regular endoscopic therapy for esophageal and gastric variceal bleeding (EGVB) in patients with liver cirrhosis.Methods:A total of 305 patients of EGVB with liver cirrhosis who received endoscopic hemostasis in Nanjing Drum Tower Hospital between January 2015 and January 2018 were included in the retrospective cohort study. Patients were divided into the regular endoscopic treatment group ( n=145) and the irregular endoscopic treatment group ( n=160). The primary outcome measure was rebleeding rate, and the secondary outcome measures were follow-up time, rebleeding interval and rebleeding mortality. Results:There were no significant differences between the two groups in terms of gender composition, average age, etiology composition, the cause of disease under or out of control, liver reserve function, or administration of non-selective β-blockers ( P>0.05), and the baseline data were comparable. The rebleeding rate was 11.7% (17/145) in the regular endoscopic treatment group and 41.9% (67/160) in the irregular endoscopic treatment group ( χ2=38.74, P<0.001). The follow-up time, rebleeding intervals and mortalies of rebleeding in the regular endoscopic treatment group and the irregular endoscopic treatment group were 28.14±11.11 months and 21.10±12.37 months ( t=5.21, P<0.001), 12.0 (6.0, 23.0) months and 1.0 (1.0, 6.0) months ( U=164.00, P<0.001), and 1.4% (2/145) and 10.6% (17/160) ( χ2=11.13, P=0.001), respectively. Conclusion:Compared with irregular endoscopic treatment, regular endoscopic treatment of EGVB in patients with liver cirrhosis has more clinical significance, which can significantly reduce the rebleeding rate, prolong the rebleeding interval, and reduce the mortality of rebleeding.
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The "triple combination" review system provides an opportunity for the transformation of human use experience into new Chinese drugs. However, there are some methodological and technical limitations in the assessment of human experience. Hence, the efficacy and safety evaluation methods should be established in accordance with the characteristics of Chinese herbs. This study summarized some evidence-based methodology to promote the transformation of human use experience to new Chinese drugs, mainly including the individualized pragmatic randomized controlled trial(RCT), cluster RCT, single-case RCT, single arm RCT with objective performance criteria, and partially nested RCT. As the real world data can be used to support the transformation of human experience, attention should be paid to convenient and efficient collection of data, prudent selection of design types, and adoption of appropriate ana-lysis methods to deal with confounding bias, including multi-factor regression model and propensity score. The newly proposed mixed research method can also be utilized to assess the human use experience, which is suitable for mining the theory of traditional Chinese medicine(TCM) and expert experience from different aspects. Meanwhile, considering the study design requirements and TCM cha-racteristics, this study put forward the common problems and solutions in the development of new Chinese drugs based on human use experience, including how to select the feasible outcome indicators, how to collect prescription data in the case of herb and dosage adjustment, and how to evaluate the comprehensive effectiveness of TCM from the perspective of "combination of disease and syndrome".
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China , Drug Development , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional , Research DesignABSTRACT
Objective:Gasless laparoscopic surgery using lifting device was first introduced in 1993 mainly for general surgery and gynecology. Here we report its application in bifid rib treatment and explore the feasibility and safety of the surgery.Methods:From July 2008 to December 2019, according to the enrollment criteria, 278 patients of bifid ribs were treated at the Department of Thoracic Surgery, Beijing Children’s Hospital, Capital Medical University, including 183 males and 95 females, the mean age was(5.7±2.5) years old. There were 242 cases of single bifid rib and 36 cases of multiple bifid ribs. The bifid ribs were more common on the right side, as 184 cases had bifid ribs on right side, while only 68 cases on the left side and 26 cases on both sides. Patients’ clinical data were retrospectively summarized and analyzed, including the patients’ gender, age, location and type of bifid rib, perioperative outcome, and follow-up.Results:All the 278 patients successfully completed the operation. The abnormality was most frequently found in the fifth rib(incidence ranking: fifth > fourth > third > sixth). The mean operation time was(64.5±16.1)min, and the mean blood loss was(4.8±2.1)ml. No serious complications occurred during the surgery. Follow-up was done for 7 to 120 months, and no recurrent patients were observed.Conclusion:Gasless endoscopy with lifting device has been used as a safe and effective method to treat bifid ribs in our hospital. This surgery leads to less injury, smaller incision, and no scars on the front chest. Gasless endoscopic surgery with lifting device can be one of the options for correcting bifid ribs.
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Objective:To summarize the clinical features, diagnosis and treatment experience of esophageal hamartoma in children.Methods:From December 2013 to December 2019, 3 cases of esophageal hamartoma were admitted to our hospital, and a retrospective analysis was conducted.Results:There were 1 male and 2 females, with an average age of 6.4 years old. The clinical manifestations were vomiting in 2 cases and dysphagia with esophageal foreign body sensation in 1 case. Esophagography, chest contrast-enhanced CT, and esophagoscopy showed esophageal stenosis or esophageal mass effectg, and esophageal dilatation above the affected segment. The tumor was found in upper esophagus in 1 case and lower esophagus in 2 cases. Tumors were complete resection in all 3 cases and the patients were discharged smoothly. All the 3 cases were followed up after surgery for 10-74 months(average 37 months), and 1 case had gastroesophageal reflux. No stenosis or recurrence was found in all the cases, and all the patients could eat normal diet.Conclusion:The main manifestations of esophageal hamartoma in children are vomiting and choking. Complete surgical resection is the main treatment method, and the prognosis is good.
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Objective:To investigate the value of antithrombin Ⅲ (AT-Ⅲ) in evaluating patients with decompensated hepatitis B liver cirrhosis and complicated with esophagogastric variceal bleeding (EVB).Methods:From January 1, 2018 to December 31, 2021, clinical data of 193 hospitalized patients with hepatitis B liver cirrhosis diagnosed in the Second Hospital of Shanxi Medical University were retrospectively analyzed, which included coagulation indicator (AT-Ⅲ), liver function indicators (total bilirubin, etc.), abdominal ultrasound results (portal vein diameter, portal vein blood flow velocity), and the occurrence of esophagogastric varices. According to the presence or absence of main complications, 193 patients with hepatitis B liver cirrhosis were divided into compensated group (60 cases) and decompensated group (133 cases). According to the presence or absence of EVB, 133 patients of decompensated group were divided into non-bleeding subgroup (96 cases) and bleeding subgroup (37 cases). The above indicators were compared among compensated group, decompensated group and their subgroups. The independent related factors of decompensated hepatitis B liver cirrhosis and EVB were analyzed. The level of AT-Ⅲ of each group were compared, and the relationship between AT-Ⅲ and Child-Pugh score was analyzed. The diagnostic capability of AT-Ⅲ in decompensated hepatitis B liver cirrhosis and complicated with EVB were analyzed. Mann-Whitney U test, independent sample t test, chi-square test, multiple logistic regression analysis, Pearson correlation analysis and receiver operating characteristic curve (ROC) analysis were used for statistical analysis. Results:The total bilirubin level of the decompensated group was higher than that of the compensated group, the portal vein diameter was larger than that of the compensated group, and the portal vein blood flow velocity was lower than that of the compensated group (31.50 μmol/L (21.90 μmol/L, 48.80 μmol/L) vs. 19.40 μmol/L (15.00 μmol/L, 25.50 μmol/L); (14.31±3.53) mm vs. (12.57±3.83) mm; (13.39±3.49) cm/s vs. (15.08±4.28) cm/s), and the differences were statistically significant ( Z=-5.76, t=-2.78 and 2.40; P<0.001, =0.006 and 0.018). The incidence of esophagogastric varices of the compensated group and the decompensated group was compared (40.0%, 24/60 vs. 87.2%, 116/133), and the difference was statistically significant ( χ2=64.06, P<0.001). The diameter of portal vein of the bleeding subgroup was larger than that of the non-bleeding subgroup, and the portal vein blood flow velocity was lower than that of the non-bleeding subgroup ((15.54±4.23) mm vs. (13.87±3.16) mm; (12.05±3.12) cm/s vs. (13.85±3.51) cm/s), and the differences were statistically significant ( t=-2.15 and 2.23, P=0.034 and 0.028). The AT-Ⅲ levels gradually decreased in the non-bleeding subgroup and bleeding subgroup of the compensated group and decompensated group, which were (79.52±16.02)%, (63.91±19.96)% and (35.92±13.69)%, respectively, the difference was statistically significant ( F=5.71, P=0.018). The AT-Ⅲ level of the compensated group was higher than that of the non-bleeding subgroup and the bleeding subgroup of the decompensated group, and the AT-Ⅲ level of the non-bleeding subgroup of the decompensated group was higher than that of the bleeding subgroup, and the differences were statistically significant ( t=5.11, 13.74 and 7.84, all P<0.001). The results of multivariate logistic regression analysis showed that total bilirubin and AT-Ⅲ were independent related factors of decompensation of hepatitis B liver cirrhosis ( OR (95% confidence interval (95% CI) 1.060 (1.018 to 1.104) and 0.945 (0.922 to 0.970), P=0.005 and <0.001). AT-Ⅲ was an independent related factor of decompensation of hepatitis B liver cirrhosis and complicated with EVB ( OR(95% CI) 0.902 (0.856 to 0.950, P<0.001). AT-Ⅲ was negatively correlated with Child-Pugh score ( r=-0.559, P<0.001). ROC analysis showed that the cut-off values of AT-Ⅲ in the diagnosis of decompensated stage of hepatitis B liver cirrhosis and complicated with EVB were 62.5% and 61.5%, the sensitivity was 88.3% and 89.2%, the specificity was 70.7% and 61.5%, and the area under the curve (95% CI) was 0.815 (0.755 to 0.874, P<0.001) and 0.899 (0.828 to 0.971, P<0.001), respectively. Conclusion:AT-Ⅲ is an important indicator in evaluating the severity of disease progression in patients with hepatitis B liver cirrhosis, and it has a certain clinical value in evaluating the bleeding tendency of patients with decompensated hepatitis B liver cirrhosis and complicated with esophagogastric varices.
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Objective To review the Naegleria fowleri and primary amoebic meningoencephalitis caused by the naegleria fowleri， so as to strengthen the public awareness of the disease and its prevention. Methods We reviewed the literatures and reports， and summarized the following information： epidemic status， life cycle and characteristics， environmental distribution and infection routes， pathogenesis and clinical manifestations， diagnosis and treatment， prevention and control measures. Results Primary amoeba meningoencephalitis is a water-borne disease caused by the Naegleria fowleri， which enters human body through the nose and arrives at the central nervous system through olfactory nerve， leading to hemorrhagic and necrotic meningitis. Although the disease is rare， it has a fatality rate of 95%. Most of the patients reported were healthy children or young adults who had nasal contact with water contaminated with Naegleria fowleri a week before symptoms appeared. At present， its pathology can be divided into contact mechanism and non-contact mechanism. In contact mechanism， the Naegleria fowleri relies on the phagocytosis of food cup on its surface and the release of cytolytic molecules that directly destroy host cells. In non-contact mechanism， the Naegleria fowleri has toxic effects by secreting proteins. The clinical symptoms are episodic， with an average time of five days from illness to death. At beginning， the symptoms may include headache， vomiting， fever and other influenza-like symptoms， followed by central nervous system symptoms， such as stiff neck， drowsiness， anorexia， fear and so on. Intravenous or intrathecal injection of amphotericin B is considered to be the basic treatment of this disease， which can be combined with other adjunct therapies such as ventricular shunt and cooling to reduce encephaledema. Conclusion Primary amoebic meningoencephalitis is a rare but highly fatal disease. We should strengthen the public awareness of the disease and its prevention， especially to avoid nasal contact with contaminated water. We should also strengthen scientific research， improve the level of diagnosis， and develop effective drugs to prevent the disease before it happens.
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@#Au nanoplates (Au NPLs), a kind of novel two-dimensional metal materials with nanometer scale thickness, have attracted much attention due to their excellent properties; and have been widely used in the fields of tumor diagnosis and treatment in recent years.This article introduces the characteristics and preparation methods of Au nanoplates and summarizes their application in tumor diagnosis and treatment in recent years, in order to provide reference and ideas for the research and application of Au nanoplates in tumor.
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Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3+CD4+ cells, CD3+CD8+ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.
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Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.
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Objective:To investigate the clinical characteristics and prognosis of idiopathic inflammatory myopathy (IIM) patients with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:A total of 194 hospitalized IIM patients who were tested for myositis-specific autoantibodies (MSAs) in the Departments of Rheumatology and Immunology of Tianjin Medical University General Hospital from January 2015 to September 2020 were collected, including 29 cases with positive anti-MDA5 antibody and 165 cases with negative anti-MDA5 antibody. Their clinical data were analyzed retrospectively. T test was used for measurement data with normal distribution. Measurement data with non-normal distribution were tested by Mann-Whitney U rank sum test. χ2 test was used for counting data. Risk factors were analyzed by binary Logistic regression, survival analysis by Kaplan-Meier method and Cox regression analysis. Results:IIM patients with positive anti-MDA5 antibody had a high incidence of dermatomyositis specific skin rash, and the skin rash was the most common presenting symptom. In the positive anti-MDA5 antibody group, muscle symptoms were mild; and the patients were prone to have fever, arthritis, oral ulcer and weight loss. All patients were complicated with interstitial lung disease (ILD). In patients with negative anti-MDA5 antibody, white blood cell (WBC) count [7.59(5.61, 9.89)×10 9/L vs 4.07(3.17, 5.50×10 9/L, Z=-5.05, P<0.001], platelet (PLT) [249.00 (200.00, 302.00)×10 9/L vs 205.00 (178.00, 244.00)×10 9/L, Z=-2.59, P=0.010], lymphocyte (LY) [1.34(0.85, 1.94)×10 9/L vs 0.64(0.40, 0.83)×10 9/L, Z=-5.78, P<0.001), serum creatine kinase (CK) [558.00 (72.00, 2 959.00) U/L vs 64.00 (35.00, 149.50) U/L, Z=-3.97, P<0.001], creatine kinase isoenzymes (CK-MB) [38.00 (17.00, 127.00) U/L vs 16.00 (14.00, 25.00) U/L, Z=-3.84, P<0.001], myoglobin (MYO) [243.65 (60.50, 829.83) ng/ml vs 34.55(21.00, 104.23) ng/ml, Z=-3.98, P<0.001], troponin T (TnT) [0.09(0.03, 0.44) ng/ml vs 0.02(0.01, 0.04) ng/ml, Z=-4.17, P<0.001], albumin (ALB) [34.00(30.00, 38.00) g/L vs 31.00 (26.50, 36.00) g/L, Z=-2.68, P=0.007], cluster of differentiation 4 (CD4) + T cells [498.00(276.00, 752.00) cells/μl vs 259.50 (179.00, 498.25) cells/μl, Z=-2.79, P=0.005], partial pressure of carbon dioxide (PaCO 2) [39.00(36.13, 42.00) mmHg vs 35.35 (31.30, 38.88) mmHg, Z=-3.75, P<0.001], partial pressure of oxygen (PaO 2) [82.00(71.90, 90.20) mmHg vs 73.25(64.30, 84.05) mmHg, Z=-2.08, P=0.037], arterial oxygen saturation (SaO 2) [96.50% (95.05%, 97.30)% vs 95.80%(93.70%, 96.55%), Z=-2.11, P=0.035], diffusion capacity for carbon monoxide of the Lung (DLco) [(63±21) % vs (52±14)%, t=0.96, P=0.006] were significantly reduced, while UTP [260.50 (172.25, 401.25) g vs 331.00 (252.75, 666.25) g, Z=-2.18, P=0.029], alanine aminotransferase (ALT) [40.00 (21.00, 83.00) U/L vs 56.00(40.00, 107.50), Z=-2.27, P=0.023], glutamyltranspeptidas (GGT) [22.50(15.00, 42.00) U/L vs 57.00 (38.00, 101.50) U/L, Z=-4.98, P<0.001], D-Dimer [850.00 (485.00, 1 799.50) ng/ml vs 1 346.00 (896.50, 2 527.00) ng/ml, Z=-2.55, P=0.011], immunoglobulin (Ig)E [60.00 (25.60, 147.50) U/ml vs 173.00(68.25, 471.50) U/ml, Z=-3.06, P=0.002], C4[20.25(16.68, 25.03) mg/L vs 23.60(20.20, 28.35) mg/L, Z=-2.38, P=0.017], Fer [228.01 (115.40, 513.36) ng/ml vs 1 636.39 (851.80, 3 888.82) ng/ml, Z=-6.01, P<0.001], krebsvondenlungen-6 (KL-6) [365.00 (180.25, 1 018.75) U/ml vs 788.00 (406.00, 1 364.00) U/ml, Z=-2.10, P=0.035] were higher when compared to patients with positive anti-MDA5 antibody. In the anti-MDA5 antibody positive group, patients had high mortality rate [8.5%(14/165) vs 34.5%(10/29), χ2=13.07, P<0.001], and the use of intravenous immunoglobulin [32.7%(54/165) vs 65.5%(19/29), χ2=11.30, P=0.001] and steroid pulse therapy [4.8%(86/165) vs 27.6%(8/29), χ2=13.98, P<0.001] were more frequent. Patients in the positive anti-MDA5 antibody group were classified into two sub groups based on lung features: the rapidly progressive interstitial lung disease (RP-ILD) group (48.28%, 14/29) and the chronic interstitial lung disease (C-ILD) group (51.72%, 15/29). RP-ILD patients had significantly elder disease onset age, higher C-reaction protein (CRP), Fer, IgE levels and the positive rate of anti-Ro52 antibody, while ALT was lower. The difference was statistically significant. Regression analysis suggested that older onset age [ HR (95% CI)=1.154 (1.069, 1.246), P<0.001], male [ HR(95% CI)=6.383(1.038, 39.242), P=0.045], positive anti-MDA5 antibody [ HR(95% CI)=17.180 (2.900, 101.766), P=0.002], LY decrease [ HR (95% CI)=0.083 (0.008, 0.817), P=0.033], high serum Fer level [ HR (95% CI)=1.001(1.000, 1.001), P=0.016], increased D-Dimer [ HR(95% CI)=1.000(1.000, 1.001), P=0.004] and compicated with carcinoma [ HR (95% CI)=11.849 (1.978, 70.970), P=0.007] were independent risk factors for death in IIM patients. Binary logistic regression analysis suggested that late onset age [ OR(95% CI)=1.090 (1.005, 1.183), P=0.038], high Fer level [ OR (95% CI)=1.001 (1.000, 1.001), P=0.022] and decreased ALB [ OR (95% CI)=0.818 (0.696, 0.963), P=0.016] might be risk factors for RP-ILD in patients with positive anti-MDA5 antibody. Conclusion:In patients with positive anti-MDA5 antibody group, typical skin damage, mild muscle symptoms, high proportion of ILD and poor prognosis are chardcteristic when compared to patients without this autoantibody. It is necessary to monitor the disease activity closely and explore the treatment strategy.
ABSTRACT
Objective:To investigate the value of friend leukemia integration-1 (FLI1) and NKX2.2 in the diagnosis of pediatric extraskeletal Ewing′s sarcoma (E-EWS), and the differential diagnosis of other pediatric small round cell tumors.Methods:Clinical data of children with E-EWS and other small round cell tumors diagnosed in the Department of Pathology of Xi′an Children′s Hospital and Xijing Hospital, Air Forth Medical University from January 2014 to December 2020 were retrospectively analyzed.Expression levels of FLI1 and NKX2.2 were examined by immunohistochemical staining.Results:(1)A total of 27 cases of E-EWS and 145 cases of other small round cell tumors were included, including 40 cases of poorly differentiated and undifferentiated neuroblastoma, 34 cases of rhabdomyosarcoma, 30 cases of metanephric Wilms tumor, 25 cases of lymphoma, 10 cases of malignant rhabdomyosarcoma, 2 cases of myeloid sarcoma, 1 case of desmoplastic small round cell tumor, 1 case of BCOR-rearranged sarcoma, 1 case of CIC-rearranged sarcoma and 1 case of melanotic neuroectodermal tumor of infancy.(2)The sensitivity, specificity, positive and negative predictive value of FLI1 in E-EWS were 88.9%(24/27 cases), 5.5%(8/145 cases), 14.9%(24/161 cases) and 72.8% (8/11 cases), respectively, and those of NKX2.2 in E-EWS were 92.6%(25/27 cases), 97.9%(142/145 cases), 89.3% (25/28 cases) and 98.6%(142/144 cases), respectively.The sensitivity, specificity, positive and negative predictive value of combined FLI1 and NKX2.2 were 85.2%, 97.9%, 88.5%, and 97.3%, respectively.Conclusions:NKX2.2 is sensitive and specific for the differential diagnosis of E-EWS from other pediatric small round cell tumors, showing a high diagnostic utility.FLI1 has high sensitivity but poor specificity for diagnosing E-EWS.The combination of detecting FLI1, NKX2.2 and other antibodies and genetic analysis is recommended to prevent misdiagnosis.
ABSTRACT
OBJECTIVE@#To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis.@*METHODS@#Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO.@*RESULTS@#A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process.@*CONCLUSIONS@#CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.
Subject(s)
Fatty Acids , Hepatitis B virus/genetics , Hepatitis B, Chronic , Humans , Metabolomics , T-Lymphocytes , TongueABSTRACT
OBJECTIVE@#To explore the genotypes and prenatal diagnosis of thalassemia in couples of childbearing age in Quanzhou, Fujian Province.@*METHODS@#Blood routine and hemoglobin electrophoresis were performed for initial thalassemia screening in 76 328 couples in Quanzhou region from July 2017 to July 2020. The couples with positive initial screening results further underwent thalassemia gene test. Couples carrying homotypic thalassemia genes underwent prenatal diagnosis in the second trimester.@*RESULTS@#Among 76 328 couples of childbearing age, 1 809 couples of positive initial thalassemia screening were identified, with the positive rate about 2.37%. Further results of genetic detection of the 1 809 couples showed that 985 cases were diagnosed as α- thalassemia, of which --sea/αα was the most frequency, followed by -α3.7/αα and ααQS/αα; 296 cases were diagnosed as β-thalassemia, the most frequency mutations were 654M/N and 41-42M/N; 26 cases of compound α and β-thalassemia were detected. In addition, 3 rare cases of thalassemia were detected, including --THAI/αα, SEA-HPFH, and -α6.9/--sea. Among them, 108 couples were confirmed as homologous thalassemia, with the detection rate about 5.97%, including 96 couples of homologous α-thalassemia, 9 couples of homologous β-thalassemia, and 3 couples with one had compound α- and β-thalassemia. Among them, 17 couples with homologous α-thalassemia underwent prenatal diagnosis in the second trimester, of which 1 case of Hb Bart's Hydrops Syndrome, 3 cases of HbH disease, 9 cases of silent thalassemia or α-thalassemia minor, and 4 cases of healthy fetuses were detected. Fetal chromosome karyotype analysis showed that 16 cases were normal and 1 case diagnosed as Down syndrome.@*CONCLUSION@#Thalassemia screening in pre-marital and pre-pregnancy, and prenatal diagnosis can effectively reduce the birth of children with thalassemia intermediate and thalassemia major. It is necessary to perform chromosome karyotype analysis at the same time as prenatal diagnosis of thalassemia gene in order to avoid fetus with abnormal chromosome.