Prevalence, predictors, and outcomes of acute respiratory distress syndrome in severe stroke.

OBJECTIVES: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. METHODS: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored. RESULTS: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005-1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979-0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989-0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days. CONCLUSIONS: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied.

The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage.

Background: Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia. Methods: Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis. Results: A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147). Conclusions: Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission.

Clinical features of actinomycosis: A 20-year experience of a single institute in Southern China.

BACKGROUND: Actinomycosis is a rare indolent infectious disease with nonspecific clinical presentations that delay diagnosis. Although actinomycosis is thought to be more prevalent in developing countries, data from developing countries are scarce. This study aimed to profile actinomycosis in developing countries and identify how it differed from profiles of developed countries. METHODS: Patients fulfilling the inclusion criteria for actinomycosis from Nanfang Hospital in southern China between January 1999 and December 2018 were retrospectively analyzed. We described clinical characteristics, diagnostic procedures, differential diagnosis, and management of actinomycosis of clinical significance. RESULTS: Thirty­one patients were included in this study. The disease was diagnosed predominately in the orocervicofacial (n = 14), cardiothoracic (n = 11), abdominopelvic (n = 5), and soft tissue (n = 1) regions. Diagnosis was obtained by either histopathology (n = 29, 94%) or microbiology (n = 2, 6%). Only one-third of patients presented with general symptoms, such as fever and weight loss. Ten were lost during follow-up, and the median duration of antibiotic use was 93.5 days (interquartile range 28-300), whereas the median follow-up time was 34 months (interquartile range 9-132). Ten patients receiving complete resection of the lesion were cured without postoperative use of antibiotics. Only one patient relapsed during the follow-up period. CONCLUSIONS: Actinomycosis is a rare disease even in developing countries, and both misdiagnosis and missed diagnosis are common. Diagnosis was often delayed and was obtained postoperatively from histopathology in developing countries. Hence, clinicians should be aware of this disease in patients with high risk factors. In the future, specific molecular methods may help to improve early diagnosis and treatment.

Accuracy of brush cytology in biliopancreatic strictures: a single-center cohort study.

OBJECTIVE: False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis. METHODS: The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient's clinical course. RESULTS: Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results. CONCLUSIONS: Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

Macrovascular Endothelial Cells Enhance the Motility of Liver Cancer Cells by Up-regulation of MMP-3, Activation of Integrin/FAK Signaling Pathway and Induction of Non-classical Epithelial-mesenchymal Transition.

Background: Liver cancer with portal vein tumor thrombus (PVTT) indicates a serious prognosis. The molecular mechanism of PVTT formation is not totally clarified, the invasion of blood vessels by liver cancer cells is the key step and portal vein endothelial cells plays critical role. Methods: Conditioned medium (CM) of human umbilical vein endothelial cells (HUVEC) were used to culture liver cancer cells and prostate cancer cells for cell motility and viability analysis for the purpose of simulating the role of macrovascular endothelial cells in the development of liver cancer. Results: HUVEC-CM caused long spindle-shaped changes in liver cancer cells; the invasion and migration ability of Bel-7402 and MHCC-LM3 (cultured in HUVEC-CM) increased significantly. Integrins/FAK (focal adhesion kinase) signaling pathway was activated and MMP-3 was up-regulated. However, classical epithelial-mesenchymal transition (EMT) did not involve. HUVEC-CM caused a decrease of cell population in G1- and S-phase of Bel-7402, it also caused an accumulation of cell population in G1 phase and a decrease of cell population in S-phase of MHCC-LM3, MHCC-97L and DU-145. HUVEC-CM promotes apoptosis of Bel-7402 and MHCC-97L and the nude mouse tumorigenic experiment did not find that the HUVEC-CM increase the tumorigenic ability of liver cancer cells. Conclusion: HUVEC may provide an easy-to-adhere roadbed for liver cancer cells invasion of blood vessels by altering extracellular matrix (ECM), activating integrins/FAK pathway and inducing non-classical EMT. The effect of HUVEC-CM on cell viability was cancer cell type dependent. It is a meaningful glance at the mechsanism of PVTT.

The role of cancer-associated fibroblast MRC-5 in pancreatic cancer.

Background: Our previous study showed that cancer-associated fibroblast MRC-5 promoted hepatocellular carcinoma progression by enhancing migration and invasion capability. However, few studies have explored the role of MRC-5 in pancreatic cancer (PC). In this study, we examined the exact role and associated mechanisms of MRC-5. Methods: The conditioned media for MRC-5 was used to culture PC cell lines SW1990 and PANC-1. Cell proliferation was compared based on colony formation assays of PC cells in normal media and of PC cells cultured with conditioned media of MRC-5. Cell migration and invasion were assayed by transwell chambers. The expression of EMT-related proteins and apoptosis-related proteins was evaluated using Western blot. And confocal microscopy was used to further detect the expression of EMT-related proteins. qRT-PCR was used to confirm the expression changes of related genes at the mRNA level. We also used flow cytometry to examine the cell cycle, apoptotic rate, and expression of CD3, CD4, CD14, CD25, CD45, CD61, CD90, TLR1, and TLR4. Results: MRC-5 repressed the colony formation ability of PC cells and significantly inhibited cell migration and invasion potential. MRC-5 induced S-phase cell cycle arrest but did not augment the apoptotic effects in PC cells. We hypothesized that the weakened malignant biological behavior of PC cells was correlated with MRC-5-induced altered expression of the cancer stem cell marker CD90; the immune-related cell surface molecules CD14, CD25, TLR4, and TLR1; and cell polarity complexes Par, Scribble, and Crumbs. Conclusion: MRC-5 limits the malignant activities of PC cells by suppressing cancer stem cell expansion, remolding epithelial polarity, and blocking the protumoral cascade reaction coupled to TLR4, TLR1, CD14, and CD25.

[Association of genetic polymorphism of 14 STR loci on chromosome 2 with Kashin-Beck disease].

OBJECTIVE: To analyze the differences of genetic polymorphism of 14 STR loci on chromosome 2 between KBD patients and controls living in and outside of KBD catchment areas. METHODS: Blood samples anticoagulated with EDTA were collected from 135 unrelated individuals of Han population in Shaanxi Province, which included 45 samples from KBD patients, 45 from normal residents living in the KBD catchment areas, and 45 from normal residents outside of the KBD catchment areas. The DNA was extracted from the blood samples for PCR amplification of relevant fragments. The amplified products were analyzed using the ABI 3730 Genetic Analyzer. RESULTS: The allele numbers for 14 STR loci (D2S286, D2S165, D2S160, D2S2211, D2S367, D2S125, D2S206, D2S117, D2S142, D2S2333, D2S126, D2S325, D2S364, D2S337) in the KBD patients were 8, 11, 7, 7, 9, 10, 11, 11, 8, 10, 11, 10, 6 and 9, respectively. Different allele numbers for 14 STR loci were found in the normal residents in the KBD catchment areas (7, 10, 6, 7, 7, 8, 10, 10, 8, 8, 11, 8, 7 and 7) and those outside of the KBD catchment areas (8, 11, 7, 7, 10, 9, 11, 11, 7, 9, 11, 7, 8 and 7). There were significant differences in the allele frequencies in the D2S165 and D2S2333 locus between the KBD patients and the normal residents living in and outside of the KBD catchment areas (P > 0.05). Significant difference in the allele frequencies in the D2S160 loci was found between the KBD patients and the normal residents living in the KBD catchment areas (P = 0.046). Significant difference in the allele frequencies in the D2S364 loci was found among the three groups of participants (P = 0.046). CONCLUSION: The allele distribution patterns of the D2S165 and D2S2333 locus in KBD patients are different from normal people.

Inhibition of mouse embryonic carcinoma cell growth by lidamycin through down-regulation of embryonic stem cell-like genes Oct4, Sox2 and Myc.

Lidamycin (LDM, also known as C-1027) as an anti-cancer agent inhibits growth in a variety of cancer cells by inducing apoptosis and cell cycle arrest. In this study we demonstrated that inhibition of mouse embryonic carcinoma (EC) cell growth using LDM at low concentrations can be attributed to a loss of the cell's self-renewal capability but not to apoptosis or cell death, which can be correlated to the down-regulation of embryonic stem (ES) cell-like genes Oct4, Sox2 and c-Myc. MTT assays showed that LDM inhibited the growth of mouse P19 EC cells in a time- and dose-dependent manner. The EC cells exposed to a low dose (0.01 nM) of LDM lost their capability to generate colonies, as evidenced by the colony forming assay. Flow cytometer analyses demonstrated that LDM induced G1 arrest in exposed EC cells without apoptosis. Real-time qPCR, Western blotting and immunocytochemistry revealed that Oct4, Sox2 and c-Myc were down-regulated in LDM-exposed EC cells, but not adriamycin (ADM)-exposed cells. Furthermore, a combination of the low dose of LDM and ADM significantly reduced the proliferation of the cancer cells than single-agent treatment. This suggested that synergy of ADM and LDM improved chemotherapy. Taking together, our results indicate that LDM can reduce the capability for self-renewal that mouse EC cells possess through the repression of ES cell-like genes, thereby inhibiting carcinoma cell growth. This data also suggests that LDM might have potential for application in CSC-based therapy and be a useful tool for studying ES cell pluripotency and differentiation.

[Familial aggregation and sibling heritability in Kashin-Beck disease].

OBJECTIVE: To explore the family aggregation and the role of hereditary factors in the pathogenesis of Kashin-Beck disease (KBD). METHODS: With a stratified sampling method, the general population of 14 villages of Linyou County were studied, from whom 225 KBD probands were selected using systematic sampling at the rate of (1/2). A total of 304 siblings of the probands were ascertained, and in these sibling pairs, the segregation ratio, heritability in different age groups and weighted mean heritability of the siblings were estimated using the methods of Li-Mantel-Grart and Falconer. RESULTS: The KBD distribution scope in the KBD families exceeded the scope of binomial distribution (P<0.001), suggesting obvious family aggregation. The prevalence rate in the siblings of the KBD pedigree was 19.41% (59/304), significantly higher than that in the 14 KBD villages [10.90% (1180/10823), chi2=21.62, P<0.001]. The segregation ratio and heritability in the siblings of the KBD pedigrees were 0.061 and 28.61%, respectively. CONCLUSION: As a polygenetic inheritance disease, KBD exhibits obvious familial aggregation, and genetic susceptibility accounts for (1/4) of the risk factors for KBD.

[Genetic polymorphism analysis of 8 short tandem repeat loci on chromosome 2 in Chinese Han population in Shaanxi Province].

OBJECTIVE: To analyze the genetic polymorphism of 8 short tandem repeat (STR) loci on human chromosome 2 in Chinese Han population in Shaanxi Province. METHODS: Blood samples anticoagulated with EDTA were collected from 176 unrelated Chinese Han individuals in Shaanxi Province. The DNA was extracted for PCR amplification of the relevant fragments, and the amplified products were analyzed using the ABI 3730 Genetic Analyzer. RESULTS: On human chromosome 2, the loci D2S112, D2S162, D2S2330, D2S2216, D2S347, D2S259, D2S319 and D2S168 had 7, 11, 9, 8, 9, 9, 8 and 13 alleles, respectively, with 15, 33, 23, 18, 13, 12, 25 and 33 genotypes for the corresponding alleles. The genotype distribution of all the 8 loci met Hardy-Weinberg equilibrium. The heterozygosities for the 8 STR loci were 0.6985, 0.8274, 0.8042, 0.6816, 0.6541, 0.5213, 0.8432 and 0.8091, with polymorphic information content of 0.6911, 0.8199, 0.7891, 0.6809, 0.6388, 0.5187, 0.8372 and 0.8049, respectively. CONCLUSION: The 8 loci on chromosome 2 have high heterozygosity and polymorphic information content in Chinese Han population, suggesting their value as useful genetic markers.

[Expression of nestin and neurogenin 3 in the human fetal pancreas].

OBJECTIVE: To examine the expression of nestin and neurogenin 3 (Ngn3), the markers of pancreatic stem cells, in the human fetal pancreas. METHODS: The human fetal pancreas tissue of 12 and 14 weeks were examined for the expression of nestin and Ngn3 using the techniques of immunofluorescence dye and RT-PCR. RESULTS: Both nestin and Ngn3 expressed widely in 12 and 14 weeks before in human fetal pancreatic tissue. In these positive cells there was no co-expressing insulin or glucagon. There were nestin and Ngn3 co-expressing cells in ducts but not in the islets. The results of RT-PCR also indicated the expression of nestin and Ngn3. CONCLUSIONS: There was no expression of the markers of mature endocrine cells in the nestin and Ngn3 positive cells, and they were the marks of no-differentiation cells in the human fetal pancreatic tissue.