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3.
Clin Lab ; 66(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32390376

RESUMO

BACKGROUND: Serum prealbumin (PAB) is an effective tool to evaluate patients with malnutrition. In recent years, studies have shown that PAB is statistically reduced during the course of disease infection. The pneumonia severity index (PSI) scoring system is one of the most widely used scoring tools to evaluate the condition and prognosis of community acquired pneumonia (CAP) patients. However, few studies have reported on PSI combined with blood indicators to predict the prognosis of pneumonia. The aim of this study was to investigate the prognostic value of PAB combined with PSI in patients with CAP. METHODS: We retrospectively analyzed the data of 400 patients who met the inclusion criteria. Death and survival were selected as prognostic indicators of pneumonia. On the first day after admission, venous blood samples were taken to test PAB and PSI scores. Subject operating characteristic curve (ROC) was used to evaluate PSI, PAB, and PSI combined with PAB to predict 30-day mortality of CAP patients. RESULTS: The 30-day mortality rate of CAP patients was 10.5% (42/400). PAB and PSI score were independent risk factors for 30-day mortality in CAP patients. The sensitivity, specificity, positive predictive value, and negative predictive value of PAB predicting the death of CAP patients were 86.3%, 79%, 50.74%, and 95.83%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSI predicting the death of CAP patients were 74.80%, 63%, 33.71%, and 90.99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the combined index predicting the death of CAP patients were 95.20%, 77.80%, 51.70% and 98.41%, respectively. CONCLUSIONS: Serum prealbumin is a relatively simple acquired index and an independent risk factor for death in CAP patients. Serum prealbumin improves the sensitivity of pneumonia severity index in predicting 30-day mortality of CAP patients.

4.
Zhonghua Bing Li Xue Za Zhi ; 49(5): 441-447, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32392927

RESUMO

Objective: To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features. Methods: Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed. Results: Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age (P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions: Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

5.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(5): 337-342, 2020 May 09.
Artigo em Chinês | MEDLINE | ID: mdl-32392977

RESUMO

Objective: To study the bacterial microleakage at the interface between dental implant and abutment in rats. Methods: Under aseptic conditions, suspension of 0.25 µl of Porphyromonas gingivalis (Pg) (10(9) CFU/ml) was added into the customized implant. After the abutment was connected, the suspension was cultured in an Ep (eppendorf) tube containing 1 ml brain heart infusion (BHI) culture medium. After 7 days and 14 days, the liquid in the Ep tube was taken and inoculated, and the growth of bacteria was observed. Six male SD rats with 12 implants were divided into experimental group (4 implants), negative control group (4 implants) and blank control group (4 implants). All 6 rats had two implants implanted in their bilateral upper jaws. During the second operation, suspension of 0.25 µl Pg (10(9) CFU/ml) was added to the inner part of the implant of the experimental group, culture solution of 0.25 µl was added to the control group and nothing was added to the blank control group. The amount of Pg and total bacteria in each group were evaluated by quantitative real-time PCR (qPCR). The inflammatory cell infiltrate in the peri-implant mucosa was evaluated histomorphometrically. Results: The in vitro model directly verified the presence of bacterial microleakage at implant-abutment interface (IAI), and the animal model confirmed the existence of microleakage through the infiltrate of inflammatory cells near the micro-gap in the experimental group indirectly. In vitro experiments found that Pg had penetrated from the implant within a week by observation and culture. In animal study, the presence of 10(2)-10(4) Pg was detected in the experimental group and it was not detected in the negative control group and the blank control group. At the same time, under the light microscope, in the experimental group, there were inflammatory cells aggregation in the connective tissue around the micro-gap and the density of inflammatory cells gradually decreased from the micro-gap to coronal and the apical of the connective tissue, while there were only scattered inflammatory cells in the connective tissue around the blank control group and the negative control group. In the experimental group, inflammatory cells density in area of 0.25-0.50 mm, 0-0.25 mm coronal to the micro-gap and 0-0.25 mm, 0.25-0.50 mm apical to the mico-gap was respectively, 976 (655), 1 673 (1 245), 2 267 (819) and 895 (162) cells/mm(2),which was significantly more than the blank control group in the corresponding position [respectively 201 (180), 321 (351), 309 (236) and 218 (272) cells/mm(2)] (P<0.05). Conclusions: Pg in the dental implants of rats can be found in the microleakage through implant-abutment interface, and cause the soft tissue inflammation around the implant, and the inflammation has certain distribution characteristics.

6.
Br J Surg ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449154

RESUMO

BACKGROUND: Various minimally invasive approaches have been described for infected necrotizing pancreatitis. This article describes a modified minimal-access retroperitoneal pancreatic necrosectomy (MARPN) procedure assisted by gas insufflation. METHODS: This retrospective, observational study documented patients who had undergone a step-up MARPN between 1 January 2010 and 31 December 2016. A minimum follow-up of 1 year was required for inclusion. The step-up approach involved percutaneous catheter drainage followed by the modified MARPN and necrosectomy. If more than one access site was needed it was categorized as complex MARPN. RESULTS: Of 212 patients with infected necrotizing pancreatitis, 164 (77·4 per cent) underwent a step-up approach. The median number of percutaneous catheter drains and MARPN procedures was 3 (range 1-7) and 1 (1-6) respectively. Ninety patients (54·9 per cent) underwent complex MARPN. For residual necrosis after MARPN, three patients (1·8 per cent) underwent sinus tract gastroscopy, and 11 (6·7 per cent) had sinography combined with a tube change. However, operations in 13 patients (7·9 per cent) required conversion to open surgery. Postoperative complications developed in 103 patients (62·8 per cent). The mortality rate was 6·1 per cent (10 deaths). CONCLUSION: A step-up approach using a modified MARPN for infected necrotizing pancreatitis is a reasonable option.

7.
Eur Rev Med Pharmacol Sci ; 24(8): 4451-4460, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32373983

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effect of Casitas b-lineage lymphoma b (Cblb) on the regulation of T follicular helper (Tfh) in the development of lupus nephritis. MATERIALS AND METHODS: The Tfh (CD4+CXCR5+PD-1+) cells in peripheral blood were analyzed by flow cytometry. Forty mice were divided into 4 groups (10/group), WT, lpr, Cblb-/- and lpr.Cblb-/-. Urine protein, serum creatinine, blood urea nitrogen (BUN), dsDNA, and antinuclear antibody (ANA) titer of mice were monitored once every four weeks. Peripheral blood mononuclear cells (PBMCs) from mice were collected to assess circulating Tfh. The expressions of Cblb in Tfh cells were regulated by transfecting siRNA and overexpression plasmid approach in vitro. RESULTS: The patients with lupus nephritis (LN) had abnormal renal clinical manifestations compared with healthy volunteers. The peripheral Tfh cells were increased and the expression of Cblb were downregulated in patients with LN (p<0.05). Both lpr mice and lpr.Cblb-/- mice had LN symptoms. LN symptoms were more serious in lpr.Cblb-/- mice compared with that in lpr mice (p<0.05). The number of Tfh cells in peripheral blood from lpr.Cblb-/- mice was significantly higher than that from lpr mice (p<0.05). Overexpression of Cblb in Tfh cells led to reduction of IgG expression, while the knockdown of Cblb in Tfh cells was accompanied by increased expression of immunoglobulin (IgG) (p<0.05). CONCLUSIONS: Cblb showed a negative regulatory effect on Tfh. The deletion of Cblb may be a key factor in progression of renal injury.

8.
Anaesthesist ; 69(6): 432-435, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32377797

RESUMO

Crouzon syndrome (CS) is a rare autosomal dominant inherited disorder caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. The disease is characterized by premature fusion of the coronal and sagittal sutures of the skull, resulting in clinical manifestations of midfacial hypoplasia, shallow orbit, maxillary dysplasia, and occasional upper respiratory obstruction. This article presents the case of a child aged 2 years and 7 months with CS scheduled for bilateral tonsillectomy and adenoidectomy. The patient had a difficult procedure of extubation and was reintubated and the tracheal intubation was removed 2 days after surgery. The CS is a rare condition with physical characteristics that can result in difficult airway manipulation. It is important for anesthesiologists to recognize and avoid potential airway complications in the management of such patients through detailed preoperative evaluation and careful observation after surgery to reduce perioperative risks.

10.
Eur Rev Med Pharmacol Sci ; 24(7): 3586-3591, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32329833

RESUMO

OBJECTIVE: To uncover the prognostic potentials of long non-coding RNA (lncRNA) UCA1 and miR-18a in hepatocellular cancer (HCC). PATIENTS AND METHODS: Expression levels of UCA1 and microRNA-18a (miR-18a) in HCC tissues and adjacent normal ones harvested from 55 HCC patients were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Clinical data of HCC patients were recorded, including pathological grading, tumor staging, intrahepatic metastasis, serum level of α-fetoprotein (AFP), tumor size, tumor number, recurrence, etc. Based on the median levels of UCA1 and miR-18a, enrolled HCC patients were classified into high-level and low-level group. Potential correlation between expression levels of UCA1 and miR-18a with survival of HCC patients was analyzed. The 5-year follow-up data of HCC patients were collected for analyzing factors that may influence prognosis in HCC patients by the Cox regression model. RESULTS: UCA1 was upregulated and miR-18a was downregulated in HCC tissues. HCC patients with stage III-IV, tumor size ≥5 cm or multiple tumors expressed high level of UCA1. Besides, HCC patients with stage I-II, non-intrahepatic metastasis or primarily diagnosed expressed a relatively low level of miR-18a. High-level UCA1 and low-level miR-18a predicted worse prognosis in HCC patients. Cox regression analysis revealed that tumor node metastasis (TNM) staging, intrahepatic metastases, postoperative recurrences, and UCA1 were risk factors for HCC, while miR-18a was the protective factor. CONCLUSIONS: LncRNA UCA1 is upregulated and miR-18a is downregulated in HCC tissues. High-level UCA1 and low-level miR-18a are closely linked to poor prognosis in HCC.

11.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(2): 254-260, 2020 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-32306007

RESUMO

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION: Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.


Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Neoplasias da Mama , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , China , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Receptor ErbB-2 , Estudos Retrospectivos , Trastuzumab , Resultado do Tratamento
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(2): 261-268, 2020 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-32306008

RESUMO

OBJECTIVE: To assess the impact of enteral nutrition support on response and toxicity of the first-line chemotherapy in those patients with advanced or metastatic esophageal cancer. METHODS: We collected the clinical data of 118 patients with unresectable advanced or metastatic esophageal cancer who received the first-line chemotherapy in our center from July 2014 to December 2016. All these 118 esophageal cancer patients were then divided into two groups: the nutrition group (received enteral nutrition support in addition to chemotherapy) and the control group (received chemotherapy only). Differences were analyzed before and after chemotherapy in each of the nutritional indicators including Karnofsky performance status (KPS), weight, body mass index (BMI), hemoglobin (Hb), number of lymphocytes (Lymph), total protein (TP), albumin (Alb), triglycerides (TG), total cholesterol (TC) in both groups. And differences of the efficacy and toxicities of the first-line chemotherapy between the two groups were also analyzed. RESULTS: (1) Weight, BMI and Hb were all significantly decreased after chemotherapy in the control group (P<0.001), while there was no significant change of weight and BMI in the nutrition group, just with Hb decrease only. However, there was no significant change of all the other nutrition indicators after chemotherapy in both groups. (2) Compared with the control group, the nutrition group had significantly lower incidence of grade 3 to 4 hematologic toxicities after chemotherapy (15.4% vs. 42.1%, P=0.004). In addition, the incidence of grade 3 to 4 nonhematologic toxicities after chemotherapy was also lower in the nutrition group but without statistical significance (0 vs. 9.2%, P=0.123). Logistic regression model was then used for multivariate analysis to identify the factors that affected the toxicity of chemotherapy in these patients, and the results showed that nutrition therapy was an independent influencing factor of grade 3 or higher hematological toxicity after chemotherapy in the patients with esophageal cancer (P=0.008, RR=6.048, 95%CI: 1.589-23.027). (3) The response rate of chemotherapy between the control group and the nutrition group had not significant difference. CONCLUSION: Enteral nutrition support in addition to chemotherapy could improve nutrition status and reduce toxicity of chemotherapy in advanced or metastatic esophageal cancer patients.


Assuntos
Nutrição Enteral , Neoplasias Esofágicas , Índice de Massa Corporal , Peso Corporal , Humanos , Metástase Neoplásica , Estado Nutricional
13.
Clin Lab ; 66(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32255298

RESUMO

BACKGROUND: Pulmonary sequestration is an uncommon pulmonary disorder. We presented an adult case with recurrent pulmonary infection firstly misdiagnosed as pneumonia, which proved as pulmonary sequestration by enhanced CT scan and CT angiography. METHODS: Appropriate laboratory tests, chest CT scan, bronchoscopy, and CT angiography were performed for diagnosis. RESULTS: The white blood cells detected by routine blood test were 11.8 x 109/L, the plain chest CT scan showed the volume of the lower lobe of the left lung decreased and the density increased. Enhanced CT and maximum intensity projection (MIP) algorithms were used for three-dimensional (3D) reconstruction of the images: no abnormally enhanced shadows were seen in the reduced lower lobe of the left lung, and tortuous vascular shadows were seen in the mediastinum. Bronchoscopy showed a narrowing of the opening in the dorsal segment of the lower lobe of the left lung. Thoracic aortography revealed an abnormal arterial supply to the lower left lung, the pathological results of thoracoscopic resection of the lower left lung were pulmonary sequestration. CONCLUSIONS: Pulmonary consolidation may be more than a simple pulmonary infection. Physicians should consider the possibility of pulmonary sequestration in patients with recurrent or refractory pneumonia. Enhanced CT findings of abnormal blood vessel supply are helpful for pulmonary sequestration diagnosis, and CT angiography is the gold standard for diagnosis.

14.
J Dairy Sci ; 103(7): 6612-6626, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32307158

RESUMO

Adrenal responsiveness was tested in nonpregnant, lactating Holstein dairy cows fed diets supplemented with OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ), an immune modulator, and in nonsupplemented control (CON) cows following bolus infusions of a combination of corticotropin-releasing hormone (CRH; 0.3 µg/kg of BW) and arginine vasopressin (VP; 1.0 µg/kg of BW) or ACTH (0.1 IU/kg of BW) in 2 environments: thermoneutral [TN; temperature-humidity index (THI) <60] for 24 h/d and heat stress (HS; THI >68 for 17 h/d). Cows (506) were initially fed OG (n = 254) or CON (n = 252) diets for 44 d before selection of a subgroup of cows (n = 12; 6 OG, 6 CON) for the study. The 2 subgroups were balanced for parity, milk yield, and days in milk. All cows were transported to and housed in 2 environmentally controlled rooms at the University of Arizona Agricultural Research Complex (Tucson). Cows were given 3 d to acclimate to the rooms and then underwent 12 d of TN conditions and then 8 d of HS conditions for a total of 24 d on experiment. Cows were infused with CRH-VP on d 9 of TN and on d 1 of HS and with ACTH on d 10 of TN and on d 2 of HS. Hormone infusions took place at 1000 h (0 h) on each infusion day. Blood samples, taken in 30-min intervals, were first collected at 0800 h (-2 h) and were drawn until 1800 h (8 h). Before infusion, serum progesterone was elevated in OG cows compared with CON cows. Infusion of releasing factors (CRH-VP or ACTH) caused increases in serum cortisol and progesterone, but cortisol release was greater in CON cows than in OG cows during HS, whereas progesterone did not differ between the 2 treatments. Serum ACTH increased following infusion of releasing factors, but this increase was greater following CRH-VP infusion than ACTH infusion. Serum bovine corticosteroid-binding globulin also increased following infusion of releasing factors in both treatment groups, but this increase was greater during HS in cows fed OG. The free cortisol index (FCI) increased following CRH-VP and ACTH and was higher in HS than in TN for both OG and CON cows. However, the FCI response was blunted in OG cows compared with CON cows during HS. Heat stress enhanced the adrenal response to releasing factors. Additionally, the adrenal cortisol and FCI response to releasing factors was reduced during acute heat stress in cows fed OG. Collectively, these data suggest that OG supplementation reduced the adrenal responsiveness to factors regulating cortisol secretion during acute HS.

15.
Clin Lab ; 66(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32162862

RESUMO

BACKGROUND: The score of Dyspnea, Eosinopenia, Consolidation, Acidemia and Atrial Fibrillation (DECAF) can be used to predict the in-hospital mortality of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). It is worth noting that the DECAF score is the first scoring standard combining biomarkers and clinical variables. The application of biomarkers is helpful for improving the accuracy of the scoring system. In recent years, more and more reports and studies paid attentions to procalcitonin (PCT) in respiratory infectious diseases and its clinical value has attracted increasing attention. The study aimed at investigating the effectiveness of the DECAF score combined with PCT in predicting admission of AECOPD patients to intensive care unit (ICU). METHODS: We conducted a retrospective study. We analyzed data from 171 non-immune individuals over the age of 40 in this study. All patients received blood routine measurement and DECAF score calculation on admission. The primary outcome used to assess the probability of an AECOPD patient was who would get a bed in general ward or ICU. Receiver operating characteristic curves (ROC) are used to assess the sensitivity and specificity of PCT, WBC, creatinine, and DECAF scores in predicting the risk of admissions to the ICU of COPD patients. We combined PCT, WBC, and creatinine with DECAF scores, observing the sensitivity and specificity of the different combinations in predicting COPD patients with regard to who should be admitted to ICU. RESULTS: After analyzing the data from 171 patients, we found that the probability of entering the ICU was 21.05% (36/171). The area under curve (AUC) of PCT, WBC, creatinine, and DECAF score in individually predicting the probability of entering the ICU of AECOPD patients were 0.71 (95% CI 0.61 - 0.81), 0.64 (95% CI 0.52 - 0.75), 0.74 (95% CI 0.63 - 0.84), and 0.88 (95% CI 0.81 - 0.94), respectively, with statistically significant differences (p = 0.00). The sensitivities of PCT, WBC, creatinine and DECAF scores were 0.61, 0.61, 0.56, and 0.91, respectively. The specificities of PCT, WBC, creatinine, and DECAF scores were 0.76, 0.67, 0.88 and 0.74, respectively. The AUC of Combination 1 (PCT&DECAF scores), Combination 2 (WBC&DECAF scores), and Combination 3 (creatinine&DECAF scores) for predicting AECOPD patients entering the ICU was 0.92 (95% CI 0.86 - 0.97), 0.89 (95% CI 0.84 - 0.94), and 0.91 (95% CI 0.85 - 0.96), respectively, with statistically significant differences (p = 0.00); the sensitivities were 0.92, 0.86, and 0.94, respectively, and the specificities were 0.97, 0.78, and 0.74, respectively. CONCLUSIONS: Procalcitonin improves the accuracy and sensitivity of the DECAF score in predicting the probability of AECOPD patients entering the ICU, and PCT was superior to other indexes to improve the sensitivity and specificity of the DECAF score.

16.
Cell Death Dis ; 11(3): 196, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193368

RESUMO

T cells play a critical role in controlling viral infection; however, the mechanisms regulating their responses remain incompletely understood. Here, we investigated the role of topoisomerase IIA (Top2α, an enzyme that is essential in resolving entangled DNA strands during replication) in telomeric DNA damage and T cell dysfunction during viral infection. We demonstrated that T cells derived from patients with chronic viral (HBV, HCV, and HIV) infection had lower Top2α protein levels and enzymatic activity, along with an accumulation of the Top2α cleavage complex (Top2cc) in genomic DNA. In addition, T cells from virally infected subjects with lower Top2α levels were vulnerable to Top2α inhibitor-induced cell apoptosis, indicating an important role for Top2α in preventing DNA topological disruption and cell death. Using Top2α inhibitor (ICRF193 or Etoposide)-treated primary T cells as a model, we demonstrated that disrupting the DNA topology promoted DNA damage and T cell apoptosis via Top2cc accumulation that is associated with protein-DNA breaks (PDB) at genomic DNA. Disruption of the DNA topology was likely due to diminished expression of tyrosyl-DNA phosphodiesterase 2 (TDP2), which was inhibited in T cells in vitro by Top2α inhibitor and in vivo by chronic viral infection. These results suggest that immune-evasive viruses (HBV, HCV, and HIV) can disrupt T cell DNA topology as a mechanism of dysregulating host immunity and establishing chronic infection. Thus, restoring the DNA topologic machinery may serve as a novel strategy to protect T cells from unwanted DNA damage and to maintain immune competence.

17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(3): 323-326, 2020 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-32187940

RESUMO

To conduct outbreak identification and transmission factor analysis of typhoid epidemic occurred in Xinqiao town, Jiangyin city from June to September 2016. A total of 14 strains of Salmonella typhi isolated from confirmed cases were collected, and 65 external environment samples and 13 food samples related to the outbreak were taken. Real-time PCR was used to detect specific gene of Salmonella typhi in the samples. Conventional method was used to isolate strains. The strains isolated from both the samples and patients in the epidemic were subjected to antimicrobial susceptibility testing and PFGE molecular characteristics. Salmonella typhi strain was isolated from one external sample (well water of a deli processing plant). The results of drug susceptibility showed that 15 strains were resistant to nalidixic acid. A total of 15 strains of Salmonella typhi were divided into 2 molecular patterns by pulsed field gel electrophoresis. The fingerprints of PFGE from the 13 patients and the environmental isolate were completely consistent, and there was one band difference from the other patient isolate. Combined with the epidemiological investigation and laboratory test results, it was determined that the outbreak was caused by genetic clone of the same Salmonella typhi. Food processing plant should be one of the key links.


Assuntos
DNA Bacteriano/genética , Surtos de Doenças , Epidemias , Salmonella enterica/genética , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Antibacterianos/uso terapêutico , China/epidemiologia , Resistência Microbiana a Medicamentos , Eletroforese em Gel de Campo Pulsado , Humanos , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase em Tempo Real , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação , Salmonella typhi/classificação , Salmonella typhi/efeitos dos fármacos , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/tratamento farmacológico , Febre Tifoide/microbiologia
18.
Neoplasma ; 67(3): 692-699, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32202907

RESUMO

Conditionally reprogrammed cell (CRC) technology is an effective method for culturing primary malignant cells and non-malignant epithelial cells in vitro. This can be useful for precision medicine applications, such as drug sensitivity assays. However, this approach is commonly hindered by the non-specific growth of non-malignant epithelial cells in CRC cultures and the lack of effective biomarkers/assays to distinguish them from primary tumor cells. In this study, we developed a DNA methylation-based, real-time PCR assay to investigate SHOX2 and PTGER4 gene promoters as sensitive markers for human lung cancer. We first found that in formalin-fixed, paraffin-embedded (FFPE) malignant lung samples, 90% (28/31) had increased SHOX2 and/or PTGER4 promoter methylation as compared with their adjacent non-malignant samples. We then applied this assay to fresh surgical tumors and found increased SHOX2 and/or PTGER4 promoter methylation in 80% (20/25) of tumor samples as compared with their corresponding adjacent non-malignant tissues. Increased methylation of SHOX2 or PTGER4 promoter regions was also detected in 52% (13/25) of CRC cultures. The presence of malignant cells was confirmed by growth in soft agar cultures, a hallmark of malignant transformation, as well by EGFR mutation analysis. These results demonstrate that SHOX2 and PTGER4 promoter methylation levels can be used to detect malignant lung epithelial cells in CRC cultures.

19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(4): 480-484, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32129581

RESUMO

Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Modelos Estatísticos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Betacoronavirus , China/epidemiologia , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/transmissão , Medição de Risco
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(2): 207-212, 2020 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-32164131

RESUMO

Objective: To detect the spatial clustering and high risk areas of pulmonary tuberculosis (PTB) in Sichuan province in 2018 and, to compare the effects of application on both SaTScan 9.4.1 software and FleXScan 3.1.2 software to detect the PTB spatial clusters. Methods: Geographic information database was established by using the incidence data of PTB and demographic data reported in the 'China disease prevention of infectious disease reporting information management system' in Sichuan province in 2018. Spatial clustering analysis was conducted using the Poisson model in software SaTScan 9.4.1 and FleXScan 3.1.2 to detect the high risk areas of PTB by software ArcGIS 10.5. Differences of clusters locations and scopes in the two scanning methods were compared. Results: The reported incidence rate of PTB was 57.34/100 000 (47 601 cases) in Sichuan province in 2018, presenting an obvious clustering distribution. SaTScan and FleXScan scanned 8 and 10 clusters showed statistically significant differences (P<0.05), with log-likelihood ratio (LLR) as 24.62-2 416.05 and 1.48-2 618.96, respectively. Results from scanning of the two methods showed that the most likely clusters appeared in the Daliangshan and Xiaoliangshan of Liangshan Yi ethnic aggregation areas. The other clustering areas would include some minority areas in the western Sichuan plateau, detected by both two methods differences in the shape and scope of the clustering were detected by both methods. The clustering scopes detected by SaTScan covered some counties, in which the actual incidence was not high. FleXScan could distinguish the clusters and detect more irregular shaped clusters. Conclusions: Obvious spatial clusters of PTB distribution were found in Sichuan in 2018. Areas of Daliangshan, Xiaoliangshan and the minority areas in Western Sichuan plateau appeared at high risk, suggesting these were the key areas for prevention and control. FleXScan seemed more conducive in accurately distinguishing the "cold spot" areas in the highly aggregated areas, and more suitable for the application of spatial clustering detection for TB, in Sichuan province.


Assuntos
Software , Tuberculose Pulmonar/epidemiologia , China/epidemiologia , Análise por Conglomerados , Humanos , Incidência , Reprodutibilidade dos Testes , Análise Espacial
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