BACKGROUND: Ferroptosis-related genes play a crucial role in regulating intracellular iron homeostasis and lipid peroxidation, and they are involved in the regulation of tumor growth and drug resistance. The expression of ferroptosis-related genes in tumor tissues can be used to predict patients' future survival times, aiding doctors and patients in anticipating disease progression. Based on the sequencing data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) database, this study identified genes involved in the regulation of ferroptosis, constructed a prognostic model, and evaluated the predictive performance of the model. METHODS: A total of 1467 ferroptosis-related genes were obtained from the GeneCards database. Gene expression profiles and clinical data from 541 LUAD patients were collected from the TCGA database. The expression data of all ferroptosis-related genes were extracted, and differentially expressed genes were identified using R software. Survival analysis was performed on these genes to screen for those with prognostic value. Subsequently, a prognostic risk scoring model for ferroptosis-related genes was constructed using LASSO regression model. Each LUAD patient sample was scored, and the patients were divided into high-risk and low-risk groups based on the median score. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves were generated to assess model performance, followed by validation in an external dataset. Finally, univariate and multivariate Cox regression analyses were conducted to evaluate the independent prognostic value and clinical relevance of the model. RESULTS: Through survival analysis, 121 ferroptosis-related genes associated with prognosis were initially identified. Based on this, a LUAD prognostic risk scoring model was constructed using 12 ferroptosis-related genes (ALG3, C1QTNF6, CCT6A, GLS2, KRT6A, LDHA, NUPR1, OGFRP1, PCSK9, TRIM6, IGF2BP1 and MIR31HG). The results indicated that patients in the high-risk group had significantly shorter survival time than those in the low-risk group (P<0.001), and the model demonstrated good predictive performance in both the training set (1-yr AUC=0.721) and the external validation set (1-yr AUC=0.768). Risk scores were significantly associated with the prognosis of LUAD patients in both univariate and multivariate Cox regression analyses (P<0.001), suggesting that this score is an important prognostic factor for LUAD patients. CONCLUSIONS This study successfully established a LUAD risk scoring model composed of 12 ferroptosis-related genes. In the future, this model is expected to be used in conjunction with the tumor-node-metastasis (TNM) staging system for prognostic predictions in LUAD patients.
Humans ; Ferroptosis/genetics* ; Prognosis ; Adenocarcinoma of Lung/pathology* ; Lung Neoplasms/pathology* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; ROC Curve

The rapid development of perioperative intensive care in cardiac surgery has greatly improved the prognosis for patients undergoing major cardiovascular surgery.In the field of hemodynamics,besides traditional methods,such as a variety of arterial catheters and central venous catheter,thermodilution and echocardiography have gradually becoming routines in hemodynamic monitoring,but their clinical values require further investigation.At the same time,optimizing micro-circulation,in order to meet the demand of oxygen and metabolism,is the goal of hemodynamic resuscitation.The management of V-A extracorporeal membrane oxygenation(ECMO)in the perioperative period of cardiac surgery depends on persistent hemodynamic monitoring.Volume management,vasoactive drugs,inotropes and vasodilators are still keys in pharmacological management.In addition,many mechanical circulatory assist devices have brought more treatments and hope for end-stage heart failure and severe cardiopulmonary dysfunction.

Objective:To explore the changes of brain network functional connection in neonates with different degrees of hypoxic-ischemic encephalopathy(HIE), and to understand its influence on brain function.Methods:Clinical data of full-term HIE children hospitalized in Neonatology Department of Changzhou Children's Hospital from January 2017 to May 2020 were collected by convenient sampling method. A total of 44 cases were scanned by conventional and functional magnetic resonance image.Twenty-four of them met the inclusion criteria, including 11 mild patients (PT1 group) and 13 moderate and severe patients (PT2 group). The amplitude of low frequency fluctuation (ALFF) was used to compare the differences of ALFF values between PT1 group and PT2 group, and the differences of functional connectivity (FC) between PT1 group and PT2 group were compared by the method of brain network connectivity analysis.Results:In the edge analysis, compared with the PT1 group, the FC of the right supplementary motor area and the right precentral gyrus ( Z1=0.39, Z2 =-0.08), the right lingual gyrus and the right hippocampus ( Z1=0.61, Z2=0.20), the left calcarine cortex and the right amygdala ( Z1=0.30, Z2=-0.02), the right pallidus and the right posterior cingulate cortex ( Z1=0.33, Z2=0.05) were decreased in the PT2 group (all P<0.001, uncorrected). In ALFF analysis, there was no significant difference between PT1 group and PT2 group ( P>0.05, FDR adjusted). Conclusion:There are changes in functional connections in some brain regions in children with moderate and severe HIE.These functional connections are related to motor function, emotional processing, language development, cognitive function, learning and memory, etcetera.

Objective:To investigate the performance of ZNA(ZIP Nucleic Acid) probes and its application in the quantitative detection of Chlamydia trachomatis (CT)nucleic acid. Methods:Use CT positive plasmids to compare the PCR amplification curves of ZNA probes coupled with different ZIP numbers. Compare ZNA probes with other three sets of probes [namely, 29mer ordinary Taqman probes (long-DNA probe), 20mer ordinary Taqman probes (short-DNA probe) and MGB probes] for stability in PCR amplification curves and repeated freezing and thawing, and the difference in the detection rate of low-concentration plasmids. Use CT positive clinical samples to compare the difference in amplification curves between ZNA probes, long-DNA probe, short-DNA probe and MGB probes, and the detection rate of low-concentration samples.Results:(1) The Ct value and fluorescence value of the probes coupled with 5ZIP units are both better than those coupled with a smaller number of ZIPs. And the difference is biggest when compared with only coupled with 1 ZIP unit: Ct value increased by 1.34 (sensitivity increased by 2.37 times), and fluorescence value increased by 30%. (2) The amplification efficiency of the ZNA probe coupled with 5 ZIPs is 2.14-2.64 times that of the preferred ordinary Taqman probe and MGB probe, and the fluorescence value is 17%-90% higher. (3) The probe freeze-thaw stability results show that the ZNA probe has the best stability, and the lowest concentration of Ct value has the smallest deviation (CV% = 1.4), which is better than the other three sets of probes (CV%=1.7-3.7). (4) Using 35 CT positive clinical samples to compare the PCR amplification performance, compared with other three sets of probes, the amplification sensitivity of ZNA probes was increased by 1.60, 0.99 and 1.06 times respectively. And the results of the consistency analysis of the Ct value show that compared with short-DNA probe and MGB probes, ZNA probes have better detection performance for clinical samples. (5) Use low concentration plasmid template (200, 100, 50 and 10 copies/mL respectively) to compare the amplification sensitivity of the four sets of probes, the detection rate of ZNA probe is the best. Especially, at the lowest concentration 10 copies/mL, the detection rate of the other sets of probes is only 15%-20%, but the ZNA probe is still 30%. (6) In 20 clinical samples with different low concentrations (200, 150, 100, and 50 copies/mL), the detection rate of ZNA probes was the highest, which were 100%, 95%, 90%, and 70%, respectively.Conclusions:Through testing of the amplification efficiency, fluorescence value, freeze-thaw stability, the amplification performance of clinical samples and the detection sensitivity of low-concentration samples, ZNA probes coupled with 5 ZIPs show better performance than ordinary Taqman probes and MGB probes. As a new probe technology with flexible design and easy synthesis, ZNA probe can further improve detection sensitivity of low concentration samples in the field of gene expression.

Objective:To investigate the performance of ZNA(ZIP Nucleic Acid) probes and its application in the quantitative detection of Chlamydia trachomatis (CT)nucleic acid. Methods:Use CT positive plasmids to compare the PCR amplification curves of ZNA probes coupled with different ZIP numbers. Compare ZNA probes with other three sets of probes [namely, 29mer ordinary Taqman probes (long-DNA probe), 20mer ordinary Taqman probes (short-DNA probe) and MGB probes] for stability in PCR amplification curves and repeated freezing and thawing, and the difference in the detection rate of low-concentration plasmids. Use CT positive clinical samples to compare the difference in amplification curves between ZNA probes, long-DNA probe, short-DNA probe and MGB probes, and the detection rate of low-concentration samples.Results:(1) The Ct value and fluorescence value of the probes coupled with 5ZIP units are both better than those coupled with a smaller number of ZIPs. And the difference is biggest when compared with only coupled with 1 ZIP unit: Ct value increased by 1.34 (sensitivity increased by 2.37 times), and fluorescence value increased by 30%. (2) The amplification efficiency of the ZNA probe coupled with 5 ZIPs is 2.14-2.64 times that of the preferred ordinary Taqman probe and MGB probe, and the fluorescence value is 17%-90% higher. (3) The probe freeze-thaw stability results show that the ZNA probe has the best stability, and the lowest concentration of Ct value has the smallest deviation (CV% = 1.4), which is better than the other three sets of probes (CV%=1.7-3.7). (4) Using 35 CT positive clinical samples to compare the PCR amplification performance, compared with other three sets of probes, the amplification sensitivity of ZNA probes was increased by 1.60, 0.99 and 1.06 times respectively. And the results of the consistency analysis of the Ct value show that compared with short-DNA probe and MGB probes, ZNA probes have better detection performance for clinical samples. (5) Use low concentration plasmid template (200, 100, 50 and 10 copies/mL respectively) to compare the amplification sensitivity of the four sets of probes, the detection rate of ZNA probe is the best. Especially, at the lowest concentration 10 copies/mL, the detection rate of the other sets of probes is only 15%-20%, but the ZNA probe is still 30%. (6) In 20 clinical samples with different low concentrations (200, 150, 100, and 50 copies/mL), the detection rate of ZNA probes was the highest, which were 100%, 95%, 90%, and 70%, respectively.Conclusions:Through testing of the amplification efficiency, fluorescence value, freeze-thaw stability, the amplification performance of clinical samples and the detection sensitivity of low-concentration samples, ZNA probes coupled with 5 ZIPs show better performance than ordinary Taqman probes and MGB probes. As a new probe technology with flexible design and easy synthesis, ZNA probe can further improve detection sensitivity of low concentration samples in the field of gene expression.

Objective To investigate the efficacy of dexmedetomidine on sedation in post-cardiac surgery patients with NIV intolerance.The changes of respiratory function and hemodynamics of the patients as well as non-invasive ventilation (NIV) failure rate were also under evaluation.Methods Thirty-five post-cardiac surgery patients with NIV intolerance and hypoxemia were enrolled in this prospective study.All patients were sedated with dexmedetomidine.NIV was standardized according to the uniform protocol.The main outcome was NIV success (avoiding endotracheal intubation) or NIV failure (requiring endotracheal intubation or die).The cardiorespiratory parameters (BP,HtR and RR) and artery blood gas analysis were prospectively recorded before and after sedation.The respiratory function and hemodynamics changes in both groups (NIV success group and NIV failure group) were then evaluated.Factors independently associated with NIV failure were identified using a logistic regression model.Results Twenty out of 35 patients (57.14％) survived while 15 (42.86％) patients failed NIV.After 1 h and 4 h of NIV with dexmedetomidine sedation,respiratory rate in both groups were decreased compared with baseline,especially in NIV success group.The PaO2/FiO2 was also improved after 1h and 4h of NIV treatment compared with baseline.The improvement was more significantly in NIV success group.The heart rate was decreased compared with baseline with no differences between two groups.There were no significant changes on PaCO2 and mean arterial pressure (MAP) during the treatment.The respiratory and hemodynamics variables identified as predictors of NIV failure were included in a multivariate logistic regression.RR ＞ 23 time/min (OR =3.2,95％ CI:2.043 ～ 4.301,P ＜ 0.01) 1 h after NIV,RR ＞ 20 time/min (OR =2.1,95％ CI:1.659～3.231,P=0.025) 4 h after NIV,PaO2/FiO2 ＜178 mmHg (OR=2.4,95％CI:1.892 ～ 3.287,P ＜0.01) 1 h after NIV and PaO2/FiO2 ＜ 185 mmHg (OR =1.7,95％ CI:1.243 ～ 2.365,P =0.041) 4 h after NIV independendy predicted NIV failure.Conclusions Dexmedetomidine might be considered as an effective and safe sedative for post-cardiac surgery patients with NIV intolerance.Early identification of predictors of NIV failure may facilitate early intervention.

The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical arms of host innate immunity, which is a protein complex controlling maturation of IL-1β. To clarify whether T. schoenleinii is able to activate the inflammasome, we analyzed human monocytic cell line THP-1 for IL-1β production upon infection with T. schoenleinii strain isolated from Tinea favosa patients, and rapid IL-1β secretion from THP-1 cells was observed. Moreover, applying competitive inhibitors and gene specific silencing with shRNA, we found that T. schoenleinii induced IL-1β secretion, ASC pyroptosome formation as well as caspase-1 activation were all dependent on NLRP3. Cathepsin B activity, ROS production and K⁺ efflux were required for the inflammasome activation by T. schoenleinii. Our data thus reveal that the NLRP3 inflammasome plays an important role in host defense against T. schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection.
Animals ; Bone Marrow Cells ; cytology ; Carrier Proteins ; metabolism ; Caspase 1 ; metabolism ; Cell Line ; Dendritic Cells ; cytology ; metabolism ; microbiology ; Enzyme Activation ; Hot Temperature ; Humans ; Inflammasomes ; metabolism ; Interleukin-1beta ; biosynthesis ; metabolism ; Lysosomes ; metabolism ; Mice ; Monocytes ; cytology ; metabolism ; microbiology ; NLR Family, Pyrin Domain-Containing 3 Protein ; Potassium ; metabolism ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Trichophyton ; physiology

An analysis of the results of examination of diagnostics teaching in the middle of the semester of 2008 grade is made to discuss the pnoblems existing in teaching and learning so as to improve the teaching quality.

Objective To examine clinical features, neuroimaging presentation and treatment of intracranial fungal granulomas (ICFG) in order to improve the accuracy rates of diagnosis and cure. Methods Three pathologically proven cases with ICFG were retrospectively analyzed. Cases of ICFG reported in literature were also summarized. Results Among the 3 patients with ICFG, 1 patient had a history of head trauma and craniotomy and 1 had a history of type 2 diabetes mellitus and a long history of exposure to doves. In all 3 patients, the symptoms started with headache and vomiting, accompanied by low-grade fever, convulsion, and cranial nerve deficits. Intracranial mass lesion was revealed on brain computed tomography (CT) scan and (or) magnetic resonance imaging (MRI) with or without intravenous contrast. CT scan showed low-density lesions and granulations with ring and homogenous enhancement, indicating fungal abscesses. MRI in all 3 cases showed one or multiple circumscribed intracranial space-occupying lesion, with ring, heterogeneous contrast enhancement and perilesional edema. The treatments were initiated with craniotomy and surgical resection of granulations followed by intravenous injection of amphotericin B (AMB) combined with fluconazole. The daily administration of AMB was increased gradually from 0.25-1.50 mg/kg and the total dosage of 2-4 g should be achieved within 3 months. The combination therapy with fluconazole (400 mg/d ) was also given by intravenous injection. To increase penetration into cerebrospinal fluid, intrathecal injection of AMB had also been given at the maximum dosage of 1 mg every time, twice a week. Two patients were administered fluconazole (200 mg/d ) orally for 3, 6 months consecutively after completing the combination therapy of AMB with fluconazole, while the other patient refused continuous antifungal treatment 1 month postoperatively. All 3 patients were followed up for a period between 3, 24, 48 months. The 2 patients that completed full antifungal treatment were cured without recurrence. The other patient had improved transiently after operation but died after 3 months. Conclusions Because no distinct chnical and neuroimaging features are presented in ICFG, it is difficult to diagnose preoperatively. Indications for surgery include diagnosis, relief mass effect and increase efficiency of drug treatment. Use of appropriate and completed antifungal treatment decreases mortality. The treatment requires continued and long-term administration of antifungal medication to prevent relapses, whether granulomas are totally removed or not.

Objective To explore Sex differences of total homocysteine(tHcy) levels,and relationship between serum creatinine and homocysteine,and renal regulation to homocysteine in patients with cerebrovascular diseases within normal serum creatinine concentrations. Methods The levels of fasting serum tHcy?Scr?triglyceride(TG)?total cholesterol(TCHO)?high density lipoprotein cholesterol(HDL-C)?high density lipoprotein cholesterol(LDL-C)were determinedin groups of cerebral infarction(CI,278 males and 160 females),cerebral hemorrhage(CH,22 males and 16 females)and transient ischemic attacks(TIAs,27 males and 20 females).The situation that patients along with hypertension and diabetes mellitus were also investigated in three groups. Results Comparison in three groups:the tHcy concentrations were significantly higher in CI than in TIAs(P 0.05). Sex comparison(327 males,196 females,from CI,CH,TIAs):the tHcy concentration were significantly higher in males than females[P