A Prediction Model for Clinical Outcomes of COVID-19 Hospitalized Patients: Construction and Accuracy Assessment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.

Immune checkpoint inhibitor induced colitis and arthritis: A case report.

RATIONALE: As a programmed cell death 1 (PD-1) inhibitor, camrelizumab is used in the treatment of a variety of malignancies. However, a variety of immune-mediated adverse reactions have been reported in a wide range of clinical applications, including immune-related colitis, arthritis, hepatitis, etc. PATIENT CONCERNS: This 56-year-old male patient experienced diarrhea, bloody stool, and knee pain after receiving camrelizumab for metastatic esophageal squamous cell carcinoma. Colonoscopy showed granular changes in the whole colonic mucosa and blurred or even disappeared vascular texture. Pathology showed chronic inflammation of the colonic mucosa. Magnetic resonance imaging of knee joint showed exudative inflammatory changes in bilateral knee joints. DIAGNOSIS: Immune checkpoint inhibitor-induced colitis and arthritis. INTERVENTIONS: Mesalazine oral (extended-release granules, 1000 mg/quarter in die daily). Dexamethasone sodium phosphate (once daily, 5mg in the evening) and compound cypress liquid (once daily, 100ml in the evening) were given by enema. Anti-inflammatory and analgesic treatment of bone pain plaster. OUTCOMES: The patient had diarrhea reduced to 3 times/day, no more bloody stools, and the knee pain was relieved. LESSONS: This article describes the cases of immune-related colitis and arthritis caused by camrelizumab, and recommends considering the risk of colitis and arthritis with camrelizumab monotherapy or combination therapy.

Antiepileptic drug-induced hypersensitivity syndrome with liver function abnormality and fever as the first manifestation: A case report.

RATIONALE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous drug reaction characterized by fever, lymphadenopathy, hematologic abnormalities, single or multiple organ involvement, and viral reactivation.[1] The most frequently reported offending drugs are aromatic antiepileptic agents, antibiotics, and allopurinol.[2] Though a relatively rare syndrome, DRESS can lead to severe multi-organ system dysfunction, and in some cases even death. DRESS is one of the severe drug eruptions in dermatological diseases, but it is difficult to diagnose for internist. In this paper, a typical drug hypersensitivity syndrome with abnormal liver function and fever as the first manifestations was reported. The objective of this study was to improve the understanding of rare drug hypersensitivity syndrome in digestion and other fields, and to avoid missed diagnosis and misdiagnosis. PATIENT CONCERNS: A 33-year-old Chinese female was initially diagnosed with acute hepatic insufficiency. Combined with the suspicious drug history, she developed DRESS with fever, target erythema, left lymph node enlargement, hematological abnormalities, and abnormal liver function. DIAGNOSES: Combined with the above characteristics, liver toxicity is the main manifestation, accompanied by fever, mainly moderate to high fever (above 38 °C) , sporadic rash, other organs (kidney, immune system) damage, and a marked increase in eosinophil granulocytic. Therefore the patient was diagnosed with definite case of DRESS syndrome based on clinical and laboratory findings. INTERVENTIONS: Hormones (methylprednisolone 60 mg/day for 12 days and 80 mg/day for 12 days) and immunoglobulins (intravenous immunoglobulin 10 g/day for 5 days and 20 g/day for 7 days) were given. OUTCOMES: The patient was discharged from the hospital after recovery. One month after discharge, she was re-admitted to the hospital because of elevated blood sugar and was diagnosed as diabetes. LESSONS: DRESS syndrome is a rare but life-threatening hypersensitivity reaction. The mortality will be very high if it's not diagnosed and treated timely. This paper presents a successful case of methylprednisolone plus intravenous immunoglobulin therapy, which provides a stronger evidence for the future diagnosis and treatment of the disease.

Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study.

INTRODUCTION: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. METHODS: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0-25%], moderate [26-50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. RESULTS: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m2] of 1.34 [95% CI: -2.56 to 5.23], 3.50 [95% CI: -0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10-3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52-5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. CONCLUSION: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

AIM2 deletion enhances blood-brain barrier integrity in experimental ischemic stroke.

AIMS: Ischemic stroke is a life-threatening disease with limited therapeutic strategies. Blood-brain barrier (BBB) disruption is a critical pathological process that contributes to poor outcomes in ischemic stroke. We previously showed that the microglial inhibition of the inflammasome sensor absent in melanoma 2 (AIM2) suppressed the inflammatory response and protected against ischemic stroke. However, whether AIM2 is involved in BBB disruption during cerebral ischemia is unknown. METHODS: Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice and brain microvascular endothelial cells (HBMECs), respectively. The infarct volume, neurological deficits, and BBB permeability were measured in mice after MCAO. Transendothelial electrical resistance (TEER) and neutrophil adhesion to the HBMEC monolayer were assessed after OGD/R treatment. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. RESULTS: AIM2 was shown to be expressed in brain endothelial cells and upregulated after ischemic stroke in the mouse brain. AIM2 deletion reduced the infarct volume, improved neurological and motor functions, and decreased BBB disruption. In vitro, OGD/R significantly increased the protein levels of AIM2 and ICAM-1 and decreased those of the tight junction (TJ) proteins ZO-1 and occludin. AIM2 knockdown effectively protected BBB integrity by promoting the expression of TJ proteins and decreasing ICAM-1 expression and neutrophil adhesion. Mechanistically, AIM2 knockdown reversed the OGD/R-induced increases in ICAM-1 expression and STAT3 phosphorylation in brain endothelial cells. Furthermore, treatment with the p-STAT3 inhibitor AG490 mitigated the effect of AIM2 on BBB breakdown. CONCLUSION: Our findings indicated that inhibiting AIM2 preserved the BBB integrity after ischemic stroke, at least partially by modulating STAT3 activation and that AIM2 may be a promising therapeutic target for cerebral ischemic stroke.

MicroRNA-146a inhibits autophagy to maintain the intracellular survival of Burkholderia pseudomallei by targeting LIPA.

Burkholderia pseudomallei is the etiological agent of melioidosis, which is an emerging infectious disease endemic to many tropical regions. Autophagy is an intrinsic cellular process that degrades cytoplasmic components and plays an important role in protecting the host against pathogens. Like many intracellular pathogens, B. pseudomallei can evade the autophagy-dependent cellular clearance. However, the underlying mechanism remains unclear. In this study, we applied a combination of multiple assays to monitor autophagy processes and found that B. pseudomallei induced an incomplete autophagic flux and eliminate autophagy clearance in macrophages by blocking autophagosome-lysosome fusion. Based on a high-throughput microarray screening, we found that LIPA (lysosomal acid LIPAse A) was downregulated during B. pseudomallei infection. MiR-146a was then identified to be specifically upregulated upon infection with B. pseudomallei and further regulated LIPA expression by interacting with 3'UTR of LIPA. Furthermore, overexpression of miR-146a contributed to the defect of autophagic flux caused by B. pseudomallei and was beneficial for the survival of B. pseudomallei in macrophages. Therefore, our findings suggest that miR-146a inhibits autophagy via posttranscriptional suppression of LIPA expression to maintain B. pseudomallei survival in macrophages.

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases.

AIM: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). METHODS: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m2, and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83-2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68-2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15-3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84-2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68-2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09-3.07) in the fully adjusted model. Then, hemoglobin levels were transformed to a binary variable for fitting the model according to the criteria for anemia of 110 g/L in the women and 120 g/L in men in China. The participants in the anemia group had an increased risk of developing outcomes compared with the nonanemia group in both genders (primary outcome: male: HR, 1.64; 95% CI, 1.01-2.68; female: HR, 1.68; 95% CI, 1.02-2.76; kidney failure: male: HR, 1.60; 95% CI, 0.97-2.64; female: HR, 1.58; 95% CI, 0.95-2.61) in the fully adjusted model. CONCLUSIONS: A low level of hemoglobin was nonlinearly associated with IgAN progression. The anemic IgAN patients presented a higher risk of developing poor outcomes compared with the nonanemic patients.

The HDAC3 inhibitor RGFP966 ameliorated ischemic brain damage by downregulating the AIM2 inflammasome.

Histone deacetylases 3 (HDAC3) modulates the acetylation state of histone and non-histone proteins and could be a powerful regulator of the inflammatory process in stroke. Inflammasome activation is a ubiquitous but poorly understood consequence of acute ischemic stroke. Here, we investigated the potential contributions of HDAC3 to inflammasome activation in primary cultured microglia and experimental stroke models. In this study, we documented that HDAC3 expression was increased in microglia of mouse experimental stroke model. Intraperitoneal injection of RGFP966 (a selective inhibitor of HDAC3) decreased infarct size and alleviated neurological deficits after the onset of middle cerebral artery occlusion (MCAO). In vitro data indicated that LPS stimulation evoked a time-dependent increase of HDAC3 and absent in melanoma 2 (AIM2) inflammasome in primary cultured microglia. Interestingly, AIM2 was subjected to spatiotemporal regulation by RGFP966. The ability of RGFP966 to inhibit the AIM2 inflammasome was confirmed in an experimental mouse model of stroke. As expected, AIM2 knockout mice also demonstrated significant resistance to ischemia injury compared with their wild-type littermates. RGFP966 failed to exhibit extra protective effects in AIM2-/- stroke mice. Furthermore, we found that RGFP966 enhanced STAT1 acetylation and subsequently attenuated STAT1 phosphorylation, which may at least partially contributed to the negative regulation of AIM2 by RGFP966. Together, we initially found that RGFP966 alleviated the inflammatory response and protected against ischemic stroke by regulating the AIM2 inflammasome.

Determination of freely dissolved polycyclic aromatic hydrocarbons in human serum using core-shell Fe3O4@polyacrylate magnetic microspheres by exclusive volume effect.

Freely dissolved concentration is an important parameter for evaluating the bioavailability of compounds. Negligible-depletion solid-phase microextraction (nd-SPME) has been widely used for the determination of freely dissolved compounds but suffered from long equilibrium time. Multifunctional mesoporous composite microspheres have large specific surface area and therefore extraction equilibrium could be reached in a short time. In this study, a novel method was developed for quick determination of freely dissolved polycyclic aromatic hydrocarbons (PAHs) in human serum using core-shell polyacrylate-ferriferous oxide magnetic microspheres (Fe3O4@PA). Mass transfer of PAHs from sample solution to Fe3O4@PA was greatly increased owing to unique properties including large surface area (58.5 m2 g-1), high pore volume (0.10 cm3 g-1) and thin coating layer (50 nm). Freely dissolved PAHs can be selectively extracted because of the mesoporous structure of PA coating layer with uniform pore size of 7.08 nm. However, bound forms of PAHs would not be able to access into pore channels due to size exclusion. In comparison with long equilibration time (139 h) by nd-SPME, equilibrium can be reached within 29 min (t90%) using Fe3O4@PA as novel sorbents. The sorption coefficients (log KBSA) of PAHs to bull serum albumin (BSA) ranged from 3.36 to 4.87, which are consistent with the values measured by nd-SPME (log KBSA = 3.64-5.12). Finally, the freely dissolved PAHs (Cfree) measured by the proposed method (0.69-1.92 µg L-1) have a good agreement with that by nd-SPME (0.56-2.11 µg L-1), indicating that it is feasible for rapid determination of free forms of compounds in real samples by Fe3O4@PA.

[Risk factors for hearing impairment induced by cytomegalovirus infection].

OBJECTIVE: To investigate the risk factors for hearing impairment induced by cytomegalovirus (CMV) infection in children. METHODS: One hundred and fifty-eight children diagnosed with CMV infection were enrolled as subjects. Based on the results of the brainstem auditory evoked potential (BAEP) test, patients were classified into normal hearing group (n=117; BAEP≤35) and abnormal hearing group (n=41; BAEP>35). A retrospective analysis was performed on the general information, routine blood indices, liver function, copy number of CMV-DNA in urine and breast milk. The receiver operating characteristic (ROC) curve was used to predict the copy number of CMV-DNA resulting in abnormal BAEP. The Spearman rank correlation analysis was used to test the correlations of the copy number of CMV-DNA in urine with the degree of hearing impairment and platelet count. RESULTS: The incidence rates of platelet abnormality and abnormal liver function and the copy number of CMV-DNA in urine were significantly higher in the abnormal hearing group than in the normal hearing group (P<0.01). According to the ROC curve, the copy number of CMV-DNA in urine had a sensitivity of 46.3% and a specificity of 93.2% in predicting hearing impairment when it reached 1.415×10(6) per mL. The results of correlation analysis showed that the degree of hearing impairment was positively correlated with the copy number of CMV-DNA (r=0.382, P<0.01); the platelet count was negatively correlated with the copy number of CMV-DNA in urine (r=-0.233, P=0.003). CONCLUSIONS: An increased copy number of CMV-DNA in urine might be a risk factor for hearing impairment induced by CMV infection. Children are likely to have hearing impairment when the copy number of CMV-DNA reaches 1.415×10(6) per mL. The monitoring of hearing should be strengthened in CMV-infected children with a decreased platelet count.

The association between CYP2C19 genotype and of in-stent restenosis among patients with vertebral artery stent treatment.

AIMS: Preventing stroke through endovascular treatment with vertebral artery stent remains a great challenge due to the occurrence of an in-stent restenosis. MATERIALS & METHODS: In this study, a retrospective analysis was conducted in 90 patients who had been treated with VAS between 2004 and 2011 in Nanjing Drum Tower Hospital. Patients were followed up at 3 months, 6 months,and 1 year after VAS treatment and annually thereafter. For each time point, neurological function tests, vessel ultrasound and computer tomography angiography were performed to preliminarily screen the vessel stenosis. Digital subtraction angiography was used to verify the narrow sign on CTA or ultrasound. Clinical features of each patient including clopidogrel metabolization genes (CYP2C19, CYP3A4, and P2Y12) were recorded with purpose to investigate the possible risk factors for the development of ISR. RESULTS: Single factor analysis dem-onstrated that hyperlipidemia (P < 0.05) and CYP2C19 (P < 0.01) loss-of-function geno-type increased the likelihood of ISR. A multiple logistic cox regression analysis also showed that stroke patients with hyperlipidemia (HR 3.719, 95% CI: 1.094-12.637, P = 0.035), and CYP2C19 loss-of-function genotype (HR 2.959, 95% CI: 1.325-6.610, P = 0.008) were more likely to suffer from ISR. Furthermore, CYP2C19 alleles were mainly divided into three groups: wt/wt (CYP2C19 *1/*1), wt/m (CYP2C19 *1/*2 and *1/*3), and m/m (CYP2C19 *2/*2,*2/*3 and*3/*3). Recurrent rate of ischemic stroke in m/m and wt/m groups was higher than the wt/wt group (OR: 0.141, 95% CI: 0.016-1.221, P = 0.042). CONCLUSION: The study leads to the conclusion that hyperlipidemia and CYP2C19 impotency are possible risk factors for the development of ISR in VAS-treated patients with ischemic. Moreover, VAS-treated patients with CYP2C19 impotency were susceptible to recurrent stroke during our 54-month follow-up.

CYP2C19 polymorphisms and antiplatelet effects of clopidogrel in acute ischemic stroke in China.

BACKGROUND AND PURPOSE: Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke. METHODS: A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated. RESULTS: The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance. CONCLUSIONS: CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.

Cervicocranial arterial dissection: an analysis of the clinical features, prognosis, and treatment efficacy.

Clinical features and therapeutic strategies of cervicocranial arterial dissection (CCAD) are still unclear. A retrospective review was conducted on 71 CCAD patients. Diagnosed by DSA and outcome evaluation was through mRS scores follow-up 12 months. All patients were allocated into three groups according to clinical situation: 1) subarachnoid hemorrhage (SAH), 2) ischemic symptoms and 3) mass effect. CCAD with anterior circulation arterial dissection (ACAD) had higher ischemia than that with posterior circulation arterial dissection (PCAD) (p=0.023). The non-aneurysmal dissection (NAD) patients were susceptible to ischemia (p=0.00) and patients with aneurismal dissection (AD) were more susceptible to SAH (p=0.001); The outcome of patients with SAH was significantly worse than patients with other manifestations (p=0.012). Following up one year, the outcome of CCAD involving posterior inferior cerebellar artery (PICA) was significantly worse than the other area (p=0.035). There was no statistically significant difference in mRS scores between endovascular treatment and conservative treatment (p=0.052) at one year follow-up. Patients suffering from SAH that received endovascular treatment experienced improved outcomes than patients with conservative treatment (p=0.033). The patients in the ACAD, NAD and extracranial CCAD groups were more likely to suffer from ischemia, while patients in the AD group were susceptible to SAH. CCAD with SAH or involving PICA had poor prognoses. The therapeutic efficacy of conservative treatment is nearly equal to endovascular treatment in CCAD patients follow up 12 months; however, endovascular treatment may decrease the risk of mortality for the patient with SAH.

Thrombolysis on ischemic stroke patients with decreased level of consciousness within 4.5 h.

BACKGROUND AND PURPOSE: Few reports concerned on recombinant tissue plasminogen activator (rt-PA) treatment in stroke patients with decreased consciousness. This study assesses the efficacy and safety of intravenous rt-PA administration within 4.5 h in stroke patients with decreased consciousness. METHODS: A total of 136 stroke patients with decreased consciousness, who received or not rt-PA intravenously within 4.5 h after stroke onset from Jiangsu province of China from 2009 to 2012, were reviewed retrospectively. Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), intracranial hemorrhage rate, and mortality were used to determine patient outcome when discharged. A 3-month outcome was calculated by modified Rankin Scale (mRS) with score 0 to 1 considered favorable outcome. RESULTS: Baseline characteristics of two groups were similar. When discharged, no significant differences were observed regarding NIHSS score (P = 0.994) or GCS score (P = 0.591) between groups. After 3 months, 22.8% patients in rt-PA group had favorable outcome as compared with 7.5% patients in control group (P = 0.014). Treatment with rt-PA did not significantly increase incidence of hemorrhage (P = 0.494) or mortality (P = 0.169). CONCLUSIONS: Intravenous rt-PA administration within 4.5 h after onset of symptoms benefited stroke patients with abnormal consciousness.

[Study of quantitative detection of circulating DNA in the plasma of patients with cervical lesion].

OBJECTIVE: To quantitatively detect circulating DNA levels in the plasma of patients withcervical lesion and to determine the value for diagnosis of cervical lesion and cervical cancer. METHODS: Preoperative blood samples were collected from 53 cases of low-grade lesions, 49 cases of high-grade lesions, 44 cases of cervical invasive cancer and 70 cases of healthy women. Plasma DNA was extracted by magnetic bead method (BILATEST DNA kit). The quantity of plasma DNA was determined by duplex real-time quantitative PCR. RESULTS: Median plasma DNA level of invasive cervical cancer patients was 61.59 mg/L (32.06-162.16 mg/L), which was significantly higher than that of healthy women [16.35 mg/L (11.98-22.71 mg/L), P<0.01]. Among invasive cervical cancer patients, median plasma DNA level of squamous carcinoma patients was slightly higher than that of adenocarcinoma (50.43 versus 47.31 mg/L, P>0.05). Median plasma DNA level of stage I patients was lower than that of stage II-III patients (46.02 versus 71.35 mg/L, P<0.05). CONCLUSION: Quantitatively detecting plasma circulating DNA may be with some application prospect in the diagnosis of cervical diseases.

Human umbilical mesenchymal stem cells enhance the expression of neurotrophic factors and protect ataxic mice.

Cerebellar ataxias, which comprise a wide spectrum of progressive disorders, are incurable at present. It has been reported that human umbilical mesenchymal stem cell (HU-MSC) transplantation has a protective effect on neurodegenerative diseases. In this study, we investigated the effect of HU-MSCs on ataxic mice induced by cytosine beta-D-arabinofuranoside (Ara-C). The ataxic mouse received an intravenous injection of 2×10(6) HU-MSCs once a week for three consecutive weeks. Neurological function was scored weekly by rotarod test and open field test. The mouse cerebellar volume and weight were also measured. The apoptotic cells, pathological alternations and distribution of HU-MSCs were determined by TUNEL assay and immunohistochemistry staining respectively. Double immunostaining was carried out to investigate the dynamics of HU-MSCs in the host animals. Neurotrophic factors in cerebellar tissue and serum were measured by Q-PCR and ELISA. Our results showed that HU-MSCs implantation significantly improved the motor skills of ataxic mice 8 weeks after application. HU-MSCs also alleviated cerebellar atrophy and decreased the number of apoptotic cells in the therapeutic group. Implanted HU-MSCs stayed in cerebellum for at least three months with no obvious differentiation. HU-MSC treated mice had enhanced expression of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in cerebellum extraction and blood serum. Double immunostaining revealed that a few MAB1287 positive cells co-localized with IGF-1 or VEGF express cells. Our results suggest that HU-MSC treatment is capable of alleviating the motor impairments and cerebellar atrophy in the ataxic mouse model, probably via promoting particular neurotrophic factors.

[Influence of mifepristone and lilopristone on proliferation and expression of nuclear factor-kappa B of ectopic stromal cells in vitro].

OBJECTIVE: To evaluate the effects of antiprogestins mifepristone and lilopristone on proliferation and expressions of nuclear factor-kappa B (NF-kappaB) of ectopic stromal cells in vitro. METHODS: The ectopic stromal cells of ovary were cultured in vitro. Methyl thiazolyl tetrazolium method was used to evaluate proliferative activity of ectopic stromal cells. Cells were divided into five groups according to drug concentration: control group, group I and group II of mifepristone and of lilopristone. The expressions of NF-kappaB P65 and NF-kappaB P65 mRNA of ectopic stromal cells were determined by immunocytochemistry and in situ hybridization of cell slice. RESULTS: Antiprogestins mifepristone and lilopristone were able to significantly suppress the proliferation of ectopic stromal cells in a time- and dose-dependent manner in vitro. The expressions of NF-kappaB P65 and NF-kappaB P65 mRNA of ectopic stromal cells in the control group were higher than that of group I and group II. Their expressions in mifepristone groups were higher than that of lilopristone groups. CONCLUSIONS: Antiprogestin mifepristone and lilopristone could significantly suppress the proliferation of ectopic stromal cells in a time- and dose-dependent manner in vitro. The action mechanisms may be associated with the suppression of expression of NF-kappaB P65 mRNA and NF-kappaB P65.