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AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.
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Background/Aims@#Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. @*Methods@#Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. @*Results@#After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. @*Conclusions@#We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
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Objective@#To evaluate the safety and clinical outcomes of the Passeo-18 Lux drug-coated balloon (DCB) in endovascular revascularization procedures under real-world conditions in a Korean population with atherosclerotic disease of the infrainguinal arteries, including below-the-knee (BTK) arteries. @*Materials and Methods@#Eight institutions in the Republic of Korea participated in this prospective, multicenter, single-arm, post-market surveillance study. Two hundred patients with Rutherford class 2–5 peripheral arterial disease and infrainguinal lesions suitable for endovascular treatment were competitively enrolled. Data were collected at baseline, the time of intervention, discharge, and 1-, 6-, 12-, and 24-month follow-up visits. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months (except when limiting the time frame for procedure- or device-related mortality to within 30 days), and the primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CDTLR) within 12 months after the procedure. @*Results@#A total of 197 patients with 332 target lesions were analyzed. Two-thirds of the patients had diabetes mellitus, and 41.6% had chronic limb-threatening ischemia. The median target lesion length was 100 mm (interquartile range: 56–133 mm).Of the target lesions, 35.2% were occlusions, and 14.8% were located in the BTK arteries. Rate of freedom from MAE was 97.9% at 6 months, and the rate of freedom from CD-TLR was 95.0% and 92.2% at 12 and 24 months, respectively. Subgroup analysis of 43 patients and 49 target lesions involving the BTK arteries showed rate of freedom from MAE of 92.8% at 6 months and rates of freedom from CD-TLR of 88.8% and 84.4% at 12 and 24 months, respectively. @*Conclusion@#The results of the present study, including the BTK subgroup analysis, showed outcomes comparable to those of other DCB studies, confirming the safety and effectiveness of Passeo-18 Lux DCB in the Korean population.
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Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564 (with an average of 30,591) compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis
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Objective:To investigate the effects of low anterior resection syndrome (LARS) on psychological and physical function and quality of life in patients with rectal cancer.Methods:From May 2014 to May 2019, 200 patients were included. LARS scale score was adopted, and the clinical and pathological data were collected. Univariate analysis and multivariate Logistic regression analysis were performed. the European Organization for Research and Treatment of Cancer Quality of Life core questionnaire and psychological distress management screening tool survey were conducted to evaluate the quality of life and psychological state. The incidence of postoperative sexual dysfunction in male patients was analyzed.Results:The incidence of LARS was 43.0%. Multivariate analysis showed that body mass index ≥24 kg/m 2, anastomotic leakage, anastomotic distance ≤5 cm from anal margin, and preoperative radiotherapy were independent risk factors for LARS ( OR=2.123, 15.109, 7.302, 12.682, all P<0.05).The overall health level and the scores of physical function and emotional function in the functional dimension of patients in the severe LARS group were significantly lower than those in the no/mild LARS group ( t=5.788, 8.831, 8.745, all P<0.05). The scores of fatigue and diarrhea were significantly higher than those in the no/mild LARS group ( t=26.280, 49.476, all P<0.05). The psychological distress thermometer score and the scores of communication , emotional and physical problems in the severe LARS group were significantly higher than those in the no/mild LARS group ( t=4.246, 6.563, 5.913, 4.408, all P<0.05). Conclusion:LARS is a common complication after Dixon procedure for rectal cancer. Body mass index ≥24 kg/m 2, anastomotic leakage, anastomotic distance from anal margin ≤5 cm, and preoperative radiotherapy are independent risk factors for LARS.
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The necessity of transforming a CDC purification laboratory into an enhanced biosafety level 2(BSL-2)laboratory with polymerase chain reaction(PCR)detection function was introduced.The modification of the enhanced BSL-2 laboratory was described in terms of layout of ventilation system,air distribution,indoor pressure and gradient control.The enhanced BSL-2 laboratory after modification met the requirements for PCR detection,and references were provided for the transfor-mation of the same type of laboratories.[Chinese Medical Equipment Journal,2023,44(9):78-82]
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Objective @#To analyze the epidemiological characteristics and pathogen spectrum of hand，foot mouth disease (HFMD) in Anhui province from 2015 to 2022，and to provide scientific evidence for prevention and control measures of HFMD．@*Methods @# The surveillance data of hand，foot and mouth disease in Anhui province from 2015 to 2022 were analyzed by descriptive epidemiology. Real-time PCR was used to detect and classify HFMD samples. @*Results @#A total of 650 590 HFMD cases were reported in Anhui province from 2015 to 2022，including 1 406 se- vere cases and 17 deaths．The annual reported incidence was 131. 45 /100 000．The epidemic features of“low incidence in odd years and high incidence in even years”were presented from 2015 to 2019．The incidence showed a continuous decline from 2020 to 2022．The monthly distribution showed the characteristics of bimodal epidemic，and the main peak was not obvious in 2020．Hefei，Fuyang，Bozhou，Chuzhou and Suzhou ranked the top five cities in terms of cumulative incidence．The age of onset was mainly distributed in children aged 5 years and below，accounting for 89. 26% of the total cases．The male to female ratio was 1. 48 ∶ 1．A total of 28 657 laboratory-confirmed cases had been reported from 2015 to 2022．EV71 cases accounted for 10. 57% ，Cox A16 cases accounted for 24. 90% ，and other enterovirus cases accounted for 64. 53%．The dominant pathogens showed dynamic changes in different years．Since 2018，the proportion of EV71 decreased significantly，and the proportion of other enteroviruses gradually increased to become the dominant pathogens．Among other enteroviruses，Cox A6 strain was dominant (80. 48% ) ．@*Conclusion @# This study suggests that the prevention and control of HFMD in Anhui province should be paid more attention from April to July and from October to December．The focus areas are the cities in northern Anhui and Hefei where the floating population is large．The focus of prevention and control is on children aged 5 years and below．Other enteroviruses have become the dominant pathogens of hand-foot-mouth disease in Anhui province，Cox A6 strain is dominant.
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Objective:To compare the effect of middle meningeal artery embolization (MMAE) versus conventional therapy for chronic subdural hematoma (CSDH).Methods:Retrospective analysis of 38 patients with 48 CSDHs treated with MMAE from May 2019 to May 2021 was performed. Comparisons were made with a conventional treatment for 126 patients with 126 CSDHs from January 2016 to May 2021. The MMAE and conventional treatment patients were matched by the propensity score matching method, and a total of 25 pairs of patients (31 pairs of CSDHs) were successfully matched. The CSDH recurrence, rescue treatment, radiographic follow-up outcome, clinical improvement and complication between the two groups were compared by t test, χ 2 test or Fisher exact probability methods. Results:The rescue treatment rate in MMAE group was significantly lower than that in conventional treatment group [0 (0/31) vs 19.4% (6/31), P=0.024] and the complete resolution rate at 6 months follow-up in MMAE group was significantly higher than that in conventional treatment group [96.8 (30/31) vs 74.2% (23/31), P=0.026]. In terms of CSDH recurrence, there was a trend of lower recurrence in the MMAE group [3.2%(1/31) vs 22.6% (7/31), P=0.053]. The complete resolution rate at 3 months follow-up was 61.3% (19/31) in MMAE group and 45.2% (14/31) in conventional treatment, clinical improvement rate was 92.0% (23/25) in MMAE group and 88.0% (22/23) in conventional treatment, good outcome rate (mRS≤2) was 92.0% (23/25) in MMAE group and 84.0% (21/25) in conventional treatment, complication rate was 0(0/25) in MMAE group and 4.0% (1/25) in conventional treatment, and there were no significant differences in all above-mentioned parameters ( P>0.05). Conclusions:The MMAE may be considered as a safe and effective treatment for CSDH, and MMAE for CSDH is associated with lower trend of recurrence, lower rescue treatment rate and better radiographic follow-up outcome than conventional therapy.
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Objective: To understand the virulence gene and drug resistance profile of Shigella sonnei outbreak in Huainan city, and conduct pathogenic traceability analysis. Methods: Water samples and feces related to an infectious diarrhea outbreak in Huainan city in August 2020 were collected for multiple pathogen detection. Virulence gene, drug sensitivity, pulse-field gel electrophoresis and whole genome sequencing of Shigella isolates were analyzed respectively. Results: 38 strains of Shigella sonnei were detected in 56 samples of mucilage feces with a positive rate 67.86%, and all serotypes were Shigella sonnei Phase I. Three strains of Shigella sonnei were detected by fluorescence PCR in the Gram-negative (GN) bacterial enrichment solution of terminal water and well water. Virulence genes were ipaH positive (38), ipaH/ial (31) and ipaH/ial/sen positive (1), respectively. The drug resistance spectrum showed that 9 of 14 antibiotics were 100% resistant, and only imipenem, chloramphenicol, ceftazidime and ciprofloxacin were effective drugs. XbaⅠ restriction enzyme map type of 36 isolates was completely consistent, and the ST type analysis of 3 strains was ST152. Whole genome sequencing and analysis verified that the outbreak was caused by a single clonal group of strains, and revealed that the isolates of the outbreak were clustered into a large cluster with 3 Chinese strains and 1 Korean strain in the database, far away from the strains of other countries. Conclusion: The outbreak is caused by a single clone of Shigella sonnei, which are low virulence strains and have multiple drug resistance.
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Humanos , Brotes de Enfermedades , Disentería Bacilar/microbiología , Shigella , Shigella sonnei/genética , Agua/farmacologíaRESUMEN
Objective:To compare the effects of high progesterone induced ovulation (PPOs) and antagonist on the outcome of in vitro fertilization embryo transfer (IVF-ET) in patients with poor ovarian response (POR) .Methods:208 POR patients who underwent IVF-ET in our hospital were selected as the research objects, and were randomly divided into observation group and control group according to the random number table method, with 104 cases in each. The observation group were treated with PPOs regimen,while the control group were treated with antagonist regimen.The daily hormone levels of human chorionic gonadotropin (hCG) [follicle stimulating hormone (FSH) , luteinizing hormone (LH) , progesterone (P) , estradiol (E2) ], pregnancy outcome [total amount of gonadotropin (GN) , days of GN administration, number of oocytes retrieved, number of transferred embryos, cycle cancellation rate, oocyte maturation rate] and pregnancy outcomes were compared between the two groups (endometrial thickness on trigger day, number of transferred embryos, implantation rate, pregnancy rate, clinical pregnancy rate, abortion rate, live yield) .Results:The serum LH level in the observation group was significantly lower than that in the control group ( P<0.05) , and there was no difference in HCG hormone levels (FSH, P, E2) between the two groups after treatment ( P>0.05) . The total amount of Gn medication, Gn medication days, and oocyte maturation rate of the observation group after treatment were significantly higher than those of the control group, and the cycle cancellation rate was significantly lower than that of the control group ( P<0.05) ; The number of transferred embryos, embryo implantation rate, and live birth rate in the observation group after treatment were significantly higher than those in the control group, while the abortion rate was significantly lower than that in the control group ( P<0.05) ; There was no significant difference in the endometrial thickness and clinical pregnancy rate on trigger days between the two groups ( P>0.05) . Conclusions:Compared with the antagonist regimen, the PPOS regimen has a more obvious clinical effect in treatment of POR patients. It simplifies the process of ovulation stimulation and enhances the sensitivity of the ovaries to ovulation stimulation drugs. It is safe, convenient, economical and feasible, and is worthy of clinical promotion.
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Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells.K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.
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Objective:To investigate the role and mechanism of metformin in algesia of rats with type 2 diabetic neuropathic pain (DNP).Methods:Eighty sprague-dawley rats were randomly divided into normal control group ( n=15) and high-fat and high-glucose group ( n=65); normal diet and high-fat and high-sugar diet were given, respectively; before and 8 weeks after feeding, the body mass of rats and fasting blood glucose level were recorded, fasting insulin level was detected by ELISA, and insulin sensitivity index (ISI) was calculated. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) 8 weeks after feeding (baseline values) were measured in the high-fat and high-glucose group; after 12 h of fasting, intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) was performed; 3 d after fasting, blood glucose was measured; 14 d after STZ injection, body mass was recorded and MWT and TWL were measured again: when MWT and TWL were ≤85% baseline values, it was defined that DNP model was successfully established ( n=45); and the left were into the diabetic painless group ( n=15). The rats with successful DNP were randomly divided into DNP group, DNP+vehicle group and DNP+metformin group ( n=15); 14 d after STZ injection, rats in the DNP+metformin group were given intraperitoneal injection of metformin (200 mg/kg) once daily for 14 consecutive d; DNP group did not accept any treatment, and rats in DNP+vehicle group were intraperitoneally injected with same amount of normal saline. MWT and TWL of all rats were measured 14 d after STZ injection, and 3, 7, 14 and 21 d after metformin injection. The expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were detected by ELISA 7, 14 and 21 d after metformin injection. The fluorescence intensity of ionized calcium binding adaptor molecule-1 (Iba-1) in the spinal cord was detected by immunofluorescence staining, and the expression levels of Toll-like receptor 4 (TLR4), nuclear transcription factor (NF)-κB, phosphorylated (p)-NF-κB, adenylate activated protein kinase (AMPK), p-AMPK, and peroxisome proliferator activated receptor-γ coactivator (PGC)-1α in the spinal cord were detected by Western blotting 21 d after metformin injection. Results:(1) After 8 weeks of feeding, the body mass of rats in the high-fat and high-glucose group was significantly higher than that in the normal control group ( P<0.05); and the body mass of rats in the high-fat and high-glucose group was statistically lower than that in the normal control group 14 d after STZ injection ( P<0.05). Three d after STZ injection, the blood glucose level in high-fat and high-glucose group was significantly higher than that in normal control group ( P<0.05). After 8 weeks of feeding, the insulin level of high-fat and high-glucose group was statistically higher than that of normal control group, and the ISI in the high-fat and high-glucose group was significantly decreased as compared with that in the normal control group ( P<0.05). (2) As compared with those in the normal control group and diabetic painless group, MWT and TWL of DNP group and DNP+vehicle group were significantly decreased at each time point ( P<0.05). Three, 7, 14 and 21 d after metformin injection, MWT and TWL in DNP+metformin group were significantly increased as compared with those in DNP group and DNP+vehicle group ( P<0.05). (3) Seven, 14, and 21 d after metformin injection, the levels of IL-6, IL-1β and TNF-α in the spinal cord of rats in the DNP group and DNP+vehicle group were significantly increased as compared with those in the normal control group and diabetic painless group ( P<0.05); as compared with those in the DNP group and DNP+vehicle group, the levels of IL-6, IL-1β and TNF-α in the spinal cord of DNP+metformin group were significantly decreased ( P<0.05). (4) As compared with normal control group and diabetic painless group, the fluorescence intensity of Iba-1 and number of Iba-1 positive cells in the spinal cord tissues of DNP group and DNP+vehicle group were significantly increased ( P<0.05); while the fluorescence intensity of Iba-1 and number of Iba-1 positive cells in spinal cord tissues of DNP+metformin group were significantly decreased as compared with those in the DNP group and DNP+ vehicle group ( P<0.05). (5) As compared with those in the normal control group and diabetic painless group, the TLR4 and p-NF-κB protein expressions and p-NF-κB/NF-κB values in the spinal cord tissues of DNP group and DNP+vehicle group were significantly increased ( P<0.05); while those in the spinal cord tissues of DNP+metformin group were significantly decreased as compared with those in the DNP group and DNP+vehicle group ( P<0.05). As compared with those in the normal control group and diabetic painless group, the PGC-1α protein expression and p-AMPK/AMPK values in the spinal cord tissues of DNP group and DNP+vehicle group were significantly decreased ( P<0.05); while those in the spinal cord tissues of DNP+metformin group were significantly increased as compared with those in the DNP group and DNP+vehicle group ( P<0.05). Conclusion:Metformin, by activating AMPK/PGC-1α signaling pathway, may inhibit the TLR4/NF-κB expression, reduce the activation of microglia and the expressions of pro-inflammatory factors, and thus alleviate DNP.
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The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.
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Glucógeno Sintasa Quinasa 3 , Diana Mecanicista del Complejo 2 de la Rapamicina , Neoplasias/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Inhibidores de Proteínas Quinasas , Proteínas Proto-Oncogénicas c-akt , Serina-Treonina Quinasas TORRESUMEN
Objective:To compare drug-coated balloon (DCB) and standard angioplasty balloon (SAB) in the treatment of postoperative in-stent restenosis (ISR) in patients with arteriosclerosis obliterans (ASO) of the lower extremity.Methods:From Jan 2017 to Dec 2018, 43 ISR patients after percutaneous transluminal angioplasty for ASO of the lower extremity at our hospital were enrolled.Patients were divided into 2 groups with 18 patients treated by DCB and 25 by SAB. The patients were followed up for 6~12 months.Results:There was no significant difference in the incidence of complications between DCB group and SAB group ( P>0.05).Compared with that in SAB group, the plasma level of ET-1 in DCB group was lower while NO was higher at 6, 24 h and 2 weeks after surgery ( P<0.05), there was no significant difference in P-selectin ( P>0.05). The ABI values in both groups increased, and that in DCB group were higher than SAB group at 6 and 12 months after surgery ( P<0.05). The lumen loss in DCB group at 6 and 12 months after surgery was significantly lower ( P<0.05). At 6 and 12 months, the primary patency of target lesions in the DCB group was 100.00% and 88.89%, which was higher than the 72.00% and 52.00% in the SAB group ( P<0.05); the CD-TLR rate in the DCB group was 11.11%, which was lower than 48.00% in the SAB group ( P<0.05). Conclusion:DCB comes with lower postoperative ISR in ASO patients of the lower extremity.
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Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells.K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.
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Objective To investigate the clinicopathological features,immunohistochemical characteristics,diagnosis,treatment and prognosis of intrathyroid thymic carcinoma.Methods Clinical data of 7 patients with intrathyroid thymic carcinoma were retrospectively reviewed.Histological examination and immunohistochemical staining were performed on the surgically resected tumors.The infection of Epstein-Barr virus(EBV)was detected by EBER in situ hybridization.Results The 7 patients included 5 males and 2 females.The age ranged from 40 to 71 years,with a median of 54 years.The tumors were located in the thyroid gland,with the maximum diameter ranging from 2.2 cm to 6.0 cm and the average maximum diameter of(4.0±1.2)cm.All the patients underwent thyroid gland resection and local lymph node dissection.After operation,all the cases were treated with radiotherapy and five of them additionally received chemotherapy.Six patients were followed up for 10-163 months,all of whom were still alive,including 2 patients with recurrence in situ,1 patient with homolateral cervical lymph node metastasis and the rest with no recurrence or metastasis.CK-pan,P63,CD5 and CD117 were expressed in all the cases,while TTF-1,TG,CT and PAX8 were negative.One case of them expressed SYN and CgA.Ki-67 proliferation index ranged from 10% to 90%.EBER in situ hybridization showed negative results in all 7 cases.Conclusions Intrathyroid thymic carcinoma is a relatively low-grade malignant tumor.The combination of immunohistochemical CD5,CD117 and monoclonal PAX8 is helpful in the diagnosis and differential diagnosis of intrathyroid thymic carcinoma.EBV may not be involved in the development of intrathyroid thymic carcinoma.Thyroid gland resection plus central lymph node dissection is an important treatment measure for intrathyroid thymic carcinoma.For patients with regional lymph node metastasis and obvious peripheral tissue invasion,postoperative radiotherapy with/without chemotherapy can effectively delay the disease progression.
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Preescolar , Femenino , Humanos , Masculino , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Timoma , Neoplasias del Timo/terapiaRESUMEN
When this paper was first published the following ethical statement was omitted in error: This study was approved by the Ethics Committee of AAALAC (NO. 001488) and carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of Tianjin Institute of Pharmaceutical Research. The authors would like to apologise for any inconvenience caused. DOI of original article: https://doi.org/10.1016/j.chmed.2018.12.002
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BACKGROUND@# Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI.@*METHODS@# The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset <12 hours undergoing manual thrombus aspiration and Promus Element stent implantation. Patients were randomly assigned to control group (n=20) or post-dilatation group (n=21) in which a non-compliant balloon was inflated to >16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI.@*RESULTS@# There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P<0.0001), the primary study endpoint, with similar strut coverage (98.5% vs. 98.4%, P=0.63) and 1-year rate of major adverse cardiovascular events (MACE).@*CONCLUSION@# In STEMI patients, post-dilatation after stent implantation and thrombus aspiration improved strut apposition up to 7 months without affecting coronary blood flow or 1-year MACE rate. Larger and longer term studies are warranted to further assess safety (ClinicalTrials.gov identifi er: NCT02121223).
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To investigate the drug resistance pattern and drug resistance genotypes of Salmonella. spp isolated from fecal specimens and anal swabs of diarrhea cases in Anhui Province. The 149 strains of Salmonella.spp isolated from feces and anal swabs of diarrhea cases in Anhui Province from April to October 2017 were selected. The serotypes of Salmonella.spp were identified by slide agglutination. The susceptibility of all strains to 14 antibiotics were determined by micro-broth dilution method. Sixty of the cephalosporin-resistant antibiotics were selected. The β-lactamase encoding genes , , (1), (2), , , , and colistin resistance genes 1 and 2 were performed using the multi-PCR method. Of the 149 diarrhea cases, the median ((25), (75)) of the age was 5.0 (1.1, 38.5). The 92 of them were male and 54.4% were children. Of the 149 strains of Salmonella.spp, 105 strains had different degrees of resistance to 13 antibiotics other than imipenem. The resistance rate of ampicillin was 55.0% (82/149), which was the highest. 53.0% strains (79 strains) were multidrug resistant, main of which were Salmonella typhimurium and Salmonella enteritidis. A total of 53 resistance patterns were detected, and 10 strains were resistant to ampicillin-ampicillin/sulbactam-tetracycline-chloramphenicol-cefazolin-trimethoprim/sulfamethoxazole, which was the most common resistance pattern. Among the 60 cephalosporin resistant strains, 45 strains carried (1), 6 of which also carried (14) and 3 of which also carried (65). All the 32 strains carried only (1) show resistance to ampicillin and 31 of them show resistance to cefazolin. There were 2 strains showing negative results of gene detection. 1 was detected in a multidrug resistant strain. The resistance of Salmonella.spp to ampicillin shows a serious situation in this region, and there were a number of multidrug resistant strains. The (1) was the major drug resistance gene detected in this research. Detection of the 1 suggests the emergence of surveillance to colistin resistance of Salmonella.spp in this area.
RESUMEN
Objective@#To observe the effect of ulinastatin combined with glutamine on early hemodynamics in patients with severe burns.@*Methods@#Thirty-two patients with severe burns who met the inclusion criteria and hospitalized in the Affiliated Huaihai Hospital of Xuzhou Medical University from January 2016 to December 2018 were selected for conducting a prospective randomized controlled trial. According to the random number table, the patients were divided into conventional treatment group (4 males and 4 females), ulinastatin group (5 males and 3 females), glutamine group (5 males and 3 females), and ulinastatin+ glutamine group (4 males and 4 females), with ages of (36±8), (34±8), (35±9), and (38±13) years in turn. From post injury day 2, patients in the 4 groups were given nutritional support of equal nitrogen and equal calories, of which protein was 2.0 g/kg daily. In addition, patients in the ulinastatin group received intravenous injection of 100 kU ulinastatin every 8 hours for 7 consecutive days; 0.3 g/kg of protein given to patients in the glutamine group was provided by alanine glutamine for 7 consecutive days; patients in the ulinastatin+ glutamine group received corresponding treatments of both ulinastatin group and glutamine group. With the help of pulse contour cardiac output (PiCCO) monitoring technology, the cardiac index, stroke volume index (SVI), global end-diastolic volume index (GEDI), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI) of patients in each group were measured on treatment day (TD) 1, 3, and 7. Data were processed with Fisher′s exact probability method, one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni method.@*Results@#The cardiac index was low and the SVI value was lower than the normal value on TD 1 in patients of the 4 groups, without statistically significant differences between any two groups (P>0.05), and then they were all gradually increased. On TD 3 and 7, compared with those of the conventional treatment group, the cardiac index and SVI of patients in the other three groups were all increased, and the cardiac index and SVI of patients in the ulinastatin+ glutamine group were significantly increased (P<0.05 or P<0.01). On TD 1, the GEDI of patients in the conventional treatment group, ulinastatin group, glutamine group, and ulinastatin+ glutamine group were at normal low levels, which were (659±58), (661±79), (659±88), and (653±71) mL/m2 respectively, without statistically significant differences between any two groups (P>0.05), and then they all gradually increased. On TD 3 and 7, compared with (684±82) and (742±46) mL/m2 of the conventional treatment group, the GEDI of patients in the ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all elevated, which were (732±53) and (777±33), (725±58) and (783±49), (813±65) and (849±27) mL/m2 respectively, and the GEDI of patients in the ulinastatin+ glutamine group was significantly increased (P<0.05). The SVRI of patients in the four groups were all at high levels on TD 1, without statistically significant differences between any two groups (P>0.05), and then they all gradually decreased. On TD 3 and 7, compared with those of the conventional treatment group, the SVRI of patients in the other three groups were all increased, and the SVRI in the ulinastatin+ glutamine group was significantly increased (P<0.05). On TD 1, the EVLWI of patients in the conventional treatment group, ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all in the normal range, which were (6.6±0.6), (6.3±0.4), (6.5±0.4), and (6.6±0.6) mL/kg respectively, without statistically significant differences between any two groups (P>0.05), and then they all showed the increasing trend. On TD 3 and 7, compared with (7.1±0.9) and (7.9±0.5) mL/kg of the conventional treatment group, the EVLWI of patients in the ulinastatin group, glutamine group, and ulinastatin+ glutamine group were all decreased, which were (6.2±0.6) and (7.1±0.4), (6.3±1.0) and (7.2±0.9), (5.8±0.7) and (6.7±0.6) mL/kg respectively, and the EVLWI of patients in the ulinastatin+ glutamine group was significantly decreased (P<0.05). On TD 1, the PVPI of patients in the four groups were all in the normal range, without statistically significant differences between any two groups (P>0.05), and then they all gradually decreased. On TD 3 and 7, compared with those of the conventional treatment group, the PVPI of patients in the other three groups were all decreased, and the PVPI in the ulinastatin+ glutamine group was significantly decreased (P<0.05).@*Conclusions@#Ulinastatin combined with glutamine can increase the cardiac index, SVI, GEDI, and SVRI and reduce the EVLWI and PVPI in treating patients with severe burns, thereby increasing early cardiac output after injury, promoting tissue and organ perfusion, and reducing pulmonary edema, resulting in significant improvement in early hemodynamics of patients with severe burns.