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.

Blood-brain barrier damage and new onset refractory status epilepticus: An exploratory study using dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: This study was undertaken to characterize the blood-brain barrier (BBB) dysfunction in patients with new onset refractory status epilepticus (NORSE) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: This study included three groups of adult participants: patients with NORSE, encephalitis patients without status epilepticus (SE), and healthy subjects. These participants were retrospectively included from a prospective DCE-MRI database of neurocritically ill patients and healthy subjects. The BBB permeability (Ktrans) in the hippocampus, basal ganglia, thalamus, claustrum, periventricular white matter, and cerebellum were measured and compared between these three groups. RESULTS: A total of seven patients with NORSE, 14 encephalitis patients without SE, and nine healthy subjects were included in this study. Among seven patients with NORSE, only one had a definite etiology (autoimmune encephalitis), and the rest were cryptogenic. Etiology of encephalitis patients without SE included viral (n = 2), bacterial (n = 8), tuberculous (n = 1), cryptococcal (n = 1), and cryptic (n = 2) encephalitis. Of these 14 encephalitis patients without SE, three patients had seizures. Compared to healthy controls, NORSE patients had significantly increased Ktrans values in the hippocampus (.73 vs. .02 × 10-3 /min, p = .001) and basal ganglia (.61 vs. .003 × 10-3 /min, p = .007) and a trend in the thalamus (.24 vs. .08 × 10-3 /min, p = .017). Compared to encephalitis patients without SE, NORSE patients had significantly increased Ktrans values in the thalamus (.24 vs. .01 × 10-3 /min, p = .002) and basal ganglia (.61 vs. .004 × 10-3 /min, p = .013). SIGNIFICANCE: This exploratory study demonstrates that BBBs of NORSE patients were impaired diffusely, and BBB dysfunction in the basal ganglia and thalamus plays an important role in the pathophysiology of NORSE.

Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV: A cross-sectional study.

We aimed to analyze the efficacy and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV (PLWH). A total of 143 PLWH and 50 healthy individuals were included in this study. A commercially available magnetic chemiluminescence enzyme immunoassay kit was used to detect serum IgG and IgM antibodies against SARS-CoV-2. Serum levels of SARS-CoV-2-specific IgG were significantly higher in the control group than in the PLWH group (p = 0.001). Overall, 76% of individuals in the control group were detected with seropositivity IgG against SARS-CoV-2 compared to 58% in the PLWH group (p = 0.024). In PLWH with IgG seropositivity, CD4+ T-cell counts before antiretroviral therapy (ART) was higher (p = 0.015). Multivariable analysis indicated that CD4+ T cells at IgG detection (odds ratio [OR] = 1.004, p = 0.006) and time after vaccination (OR = 0.977, p = 0.014) were independently associated with seropositivity IgG against SARS-CoV-2 in PLWH. Neutralizing antibody (nAb) titers in PLWH against wild-type SARS-CoV-2 were similar to those in the control group (p = 0.160). The proportion of seropositive nAbs against wild-type SARS-CoV-2 was also similar (95% in the control group vs. 97% in the PLWH group, p = 0.665). Similar results were obtained when nAb was detected against the delta variants with similar titers (p = 0.355) and a similar proportion of seropositive nAbs were observed (p = 0.588). All the side effects observed in our study were mild and self-limiting. The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in Chinese PLWH.

Geniposide attenuates early brain injury by inhibiting oxidative stress and neurocyte apoptosis after subarachnoid hemorrhage in rats.

BACKGROUND: Oxidative stress and neurocyte apoptosis are crucial pathophysiological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Geniposide (GNP) has been reported to exert neuroprotective effects by reducing oxidative injury and neurocyte apoptosis. However, the effect of GNP has not been clarified in EBI after SAH. The study was performed to evaluate the neuroprotective effects and mechanisms of GNP in EBI after SAH. METHODS AND RESULTS: A total of 60 male Wistar rats were randomly divided into five groups. The prechiasmatic cistern SAH model was used in this study. SAH grade was evaluated using a grading system. Neurological function was evaluated using the Garcia scores. Brain edema was measured by the wet-dry method. Blood-brain barrier (BBB) permeability was measured by the extravasation of Evans Blue (EB). The neurocyte apoptosis was observed using TUNEL assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), glutathione S-transferase (GST) and quinone oxidoreductase-1 (NQO-1) were performed. The results showed that GNP reduced brain edema, attenuated BBB permeability, inhibited neurocyte apoptosis and improved neurological function. Moreover, GNP also decreased the levels of ROS and MDA, elevated Nrf2 expression in the temporal cortex and up-regulated the expression of NQO-1, HO-1 and GST after SAH. CONCLUSIONS: GNP could ameliorate oxidative stress and neurocyte apoptosis to exert neuroprotective effects by Nrf2 pathway.

Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration: A single-center analysis.

Background: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has become an important modality for identification of intra-abdominal masses. This study analyzed the accuracy of EUS-FNAB in a single medical center and explored factors related to positive diagnosis. Materials and methods: In total, 77 patients with EUS-FNAB were retrospectively reviewed from July 2016 to February 2020. "Atypical (tends to be neoplasm/malignancy)," "suspicious (first consider neoplasm/malignancy)," and "malignant" were defined as positive cytology. The final diagnoses were based on histopathologic examination. The positive rate of EUS-FNAB for the diagnosis of neoplasm and its associations with age, sex, target puncture mass size, liver function, tumor markers, albumin, hypertension, and diabetes were examined. Results: Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in all patients were 77.9% (60/77), 76.1% (54/71), 100%, 100%, and 26.1% (6/23), respectively. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNAB cytologic diagnoses in the pancreas were 80.0% (48/60), 79.3% (46/58), 100%, 100%, and 14.3% (2/14), respectively. The results of EUS-FNAB in pancreatic masses showed that the level of CA19-9 was higher in the true positive group than in the false-negative group (p<0.05). There were no factors associated with the true positive cytologic diagnoses (p>0.05). Conclusions: Our single-medical center study showed that EUS-FNAB is an accurate diagnostic procedure for the evaluation of intra-abdominal masses. Further follow-up is required to explore factors associated with the true positive cytology.

MRC-5 fibroblast-conditioned medium influences multiple pathways regulating invasion, migration, proliferation, and apoptosis in hepatocellular carcinoma.

BACKGROUND: Carcinoma associated fibroblasts (CAFs), an important component of tumor microenvironment, are capable of enhancing tumor cells invasion and migration through initiation of epithelial-mesenchymal transition (EMT). MRC-5 fibroblasts are one of the CAFs expressing alpha-smooth muscle actin. It is ascertained that medium conditioned by MRC-5 fibroblasts stimulate motility and invasion of breast cancer cells. However, its role in hepatocellular carcinoma (HCC) is less clear. The aim of our study was to investigate the effect of MRC-5-CM on HCC and explore the underlying mechanisms. METHODS AND RESULTS: Using a combination of techniques, the role of MRC-5-CM in HCC was evaluated. We determined that MRC-5-CM induced the non-classical EMT in Bel-7402 and MHCC-LM3 cell lines. Initiation of the non-classical EMT was mainly via quintessential redistribution of α-, ß- and γ-catenin, P120 catenin, E-cadherin, and N-cadherin, rather than up-regulation of typical EMT-related transcription factors (i.e., Snail, Twist1, ZEB-1 and ZEB2). We also found that MRC-5-CM potentiated both the migration and invasion of Bel-7402 and MHCC-LM3 cells in mesenchymal movement mode through activation of the α6, ß3, ß4, ß7 integrin/FAK pathway and upregulation of MMP2. The flow cytometric analysis showed that MRC-5-CM induced G1 phase arrest in Bel-7402 cells with a concomitant reduction of S phase cells. In contrast, MRC-5-CM induced S phase arrest in MHCC-LM3 cells with a concomitant reduction of cells in the G2/M phase. MRC-5-CM also inhibited apoptosis in Bel-7402 cells while inducing apoptosis in MHCC-LM3 cells. CONCLUSION: Collectively, MRC-5-CM promoted HCC cell motility and invasiveness through initiation of the non-classical EMT, including redistribution of α-, ß- and γ-catenin, P120 catenin, E-cadherin, and N-cadherin, activation of the integrin/FAK pathway, and upregulation of MMP2. Hence, MRC-5-CM exerted distinct roles in Bel-7402 and MHCC-LM3 cell viability by regulating cyclins, cyclin dependent kinases (CDKs), CDK inhibitors (CKIs), Bcl-2 family proteins and other unknown mechanosensors.

Prevalence, early predictors, and outcomes of sepsis in neurocritical illnesses: A prospective cohort study.

BACKGROUND: Patients with neurocritically illness are an under-recognized population at high risk of sepsis. We aimed to investigate the prevalence, early predictors, and outcomes of sepsis in neuro-ICU. METHODS: Daily and accumulative incidences of sepsis in neuro-ICU were explored. Demographics, medical history, baseline disease severity scores, and baseline biomarkers regarding inflammation, immunology, organ function, and nutritional status were collected and analyzed as potential predictors of sepsis. Logistic regression analyses were used to determine the independent predictors, and a nomogram was used to estimate the individual probability of sepsis in neuro-ICU. RESULTS: 153 patients were included in this study. Fifty-nine (38.6%) patients developed sepsis, and 21 (14%) patients developed septic shock. More than 86% of the septic cases occurred within the first week. Sequential organ failure assessment score ((relative risk) RR 1.334, P = .026), history of diabetes (RR 2.346, P = .049), and transferrin (RR 0.128, P = .042) on admission are independent predictors of sepsis. Septic patients had significantly higher mortality (P = .011), higher medical cost (P = .028), and a lower rate of functional independence (P = .010), compared to patients without sepsis. CONCLUSIONS: Sepsis afflicted more than one-third of neurocritically-ill patients and occurred mostly in the first week of admission. History of diabetes, serum transferrin, and sequential organ failure assessment score on admission were early predictors. Sepsis led to significantly worse outcomes and higher medical costs.

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.

A Novel Prognostic Score Including the CD4/CD8 for AIDS-Related Lymphoma.

Background: A simple and clinically applicable prognostic scoring system for AIDS-related lymphoma (ARL) in the era of combination antiretroviral therapy (cART) is needed to better stratify patients' risks and to assist in the decision-making of therapeutic strategies. Methods: We conducted a retrospective multicenter cohort study in 138 primary ARL patients over an 8-year period from 2013 to 2020. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were performed to identify the association between patient-, lymphoma-, and HIV-specific variables with progression-free survival (PFS) and overall survival (OS). The incremental prognostic value of novel inflammatory biomarkers in the International Prognostic Index (IPI) was evaluated by comparing the receiver operating characteristic (ROC) curves, the concordance index (C-index), and the integrated Brier score (IBS). Results: The median age was 49.14 ± 14.20 (range 18-79) years, 81.9% were men, and the median follow-up was 44.94 (95% CI = 37.05-52.84) months. The 3-year OS and PFS were 39.4% (95% CI = 16.3-21.2) and 38.7% (95% CI = 14.5-19.7), respectively. We found that age, extranodal sites, bulky mass, CD4 T-cell counts, CD4/CD8 ratio, and hypoalbuminemia were associated with OS (all P < 0.05) at both univariate and multivariate analyses. Of the new inflammatory markers, only the CD4/CD8 ratio was an independent prognostic parameter of OS and PFS. A lower CD4/CD8 ratio was strongly associated with adverse clinical factors, including older age, advanced Ann Arbor stage, more extranodal sites, elevated erythrocyte sedimentation rate, prior history of HIV, higher red cell distribution width ratio, hypoproteinemia, and emaciation. When the CD4/CD8 ratio was added to the IPI, the composite HIV-IPI score showed significantly better discrimination than IPI alone [AUC (95% CI): HIV-IPI, 0.83 (0.77-0.89) vs. IPI, 0.72 (0.70-0.85)]. The HIV-IPI model provided good predictive performance [C-index (95% CI): HIV-IPI, 0.82 (0.81-0.83) vs. IPI, 0.75 (0.73-0.77), P < 0.001] and a satisfactory calibration function. Conclusions: The CD4/CD8 ratio, an inexpensive and readily available marker, is a powerful independent prognostic parameter in patients with ARL. Furthermore, when the CD4/CD8 ratio is used in combination with IPI, it increases prognostic ability. The useful prediction of expected outcomes in ARL can inform treatment decisions.

Hypoalbuminemia predicts inferior outcome in patients with AIDS-related lymphoma.

BACKGROUND: The prognostic value of serum albumin in acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) remains covered. METHODS: We retrospectively analyzed de novo ARL patients from 2013 to 2019 across three centers. Factors correlated with progression-free survival (PFS) and overall survival (OS) were evaluated in Kaplan-Meier, univariate and multivariate Cox proportional hazard models. RESULTS: A total of 86 ARL patients were enrolled with a median follow-up of 34 months. In the cohort, the OS and 2-year PFS rates were 37.5% and 35.4%, respectively. In multivariate models, older age (PFS, hazard ratios [HR] = 1.035, p = 0.037; OS, HR = 1.034, p = 0.041) and hypoalbuminemia (OS, HR = 0.910, p = 0.038) predicted inferior survival. ARL patients with hypoalbuminemia showed worse OS and 2-year PFS (p = 0.028 and p = 0.01, respectively), which was associated with poor Eastern Cooperative Oncology Group performance status (ECOG PS) and higher International Prognosis Index (IPI) score. CONCLUSION: In conclusion, serum albumin at diagnosis is an independent prognostic factor for overall survival in AIDS-related lymphoma.

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.

[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.

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.

Reversible leukoencephalopathy caused by 2 rodenticides bromadiolone and fluoroacetamide: A case report and literature review.

RATIONALE: With the easy access, rodenticide poisoning has been a public health problem in many countries. Characteristics of central nervous system (CNS) lesions induced by rodenticides are scarcely reported. PATIENT CONCERNS: We presented a case of a 40-year-old man with seizure and consciousness disorder, coagulation dysfunction, and symmetric lesions in white matter and corpus callosum. DIAGNOSIS: He was diagnosed with rodenticide poisoning due to bromadiolone and fluoroacetamide. INTERVENTIONS: He was treated with vitamin K, hemoperfusion, acetamide, and calcium gluconate. OUTCOMES: His leukoencephalopathy was reversed rapidly with the improvement of clinical symptoms. LESSONS: This report presented the impact of rodenticide poisoning on CNS and the dynamic changes of brain lesions, and highlighted the importance of timely targeted treatments.

Umbilical cord blood stem cells transplantation in a patient with severe progressive supranuclear palsy: a case report.

BACKGROUND: Progressive supranuclear palsy is a neurodegenerative condition that worsens over time. Given the lack of targeted treatments, patients with severe progressive supranuclear palsy have very low life expectancy. CASE PRESENTATION: We present a case of a 61-year-old Chinese man with severe progressive supranuclear palsy and treated with umbilical cord blood stem cells transplantation. After the umbilical cord blood stem cells therapy, his neurologic symptoms stopped deteriorating, his muscle rigidity was mildly improved, and he remains alive for more than 8 years. CONCLUSIONS: Umbilical cord blood stem cells transplantation may be an alternative therapy for patients with severe progressive supranuclear palsy.

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.

Refractory Status Epilepticus Responsive to Electroacupuncture at Shuigou Acupoint: A Case Report.

Refractory status epilepticus (RSE) is a critical and intractable neurological emergency. Around 55% of RSE episodes still persist despite high dose of continuous infusion of anesthetics. It's a clinical urgency and challenge to search for novel alternative treatments to control RSE as soon as possible. Here, we reported a case of RSE in a 67-year-old woman with varicella-zoster virus encephalitis. She had persistent non-convulsive SE despite the continuous infusion of midazolam. On the basis of fundamental treatments, she was given electroacupuncture at Shuigou acupoint for 10 min. An immediate EEG suppression was seen after the electroacupuncture treatment and lasted for 9 min, and lasting epileptic discharges (> 10 s) and clinical seizures were not observed any more. Midazolam was withdrawn gradually 24 h later. This case report may bring an alternative treatment for RSE.

Notch signaling mitigates chemotherapy toxicity by accelerating hematopoietic stem cells proliferation via c-Myc.

The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. Here, we showed that disruption of Notch signaling aggravated chemotherapy-induced myelosuppression in inducible genetic mice. Conversely, Notch activation correlated positively with clinical HSC engraftment. We used endothelial-targeted chimeric Notch ligand Delta-like 1 (D1R) to activate Notch signaling in hematopoietic stem/progenitor cells through micro-environmental cellular contact. Recombinant protein D1R contributed to the recovery of the HSC pool and sustained HSC vitality in response to various chemotherapeutic agents in vivo. Mechanistically, D1R treatment promoted HSC proliferation transiently, prevented HSC exhaustion, correlated with activation of the downstream phosphoinositide 3-kinase (PI3K)/extracellular-signal-regulated kinase (ERK)/BCL2 associated agonist of cell death (BAD) signaling axis during regeneration, and partially mediated upregulation of c-Myc in HSCs. These data reveal an unrecognized role for Notch signaling in promoting HSC repopulation after myelosuppressive chemotherapy and offer a new therapeutic approach to mitigate chemotherapy-induced injury.

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.

Hepatocyte growth factor promotes proliferation and migration in immortalized progenitor cells.

Hepatocyte growth factor (HGF) and its receptor c-Met are widely expressed in the developing and adult brain. However, little is known about the role of HGF during the development of the human dopaminergic neuronal system. We have established telomerase-immortalized dopaminergic progenitor cells isolated from the fetal striatum that express markers for neural progenitor cells and tyrosine hydroxylase. We show that the cells were able to differentiate into dopaminergic neurons and release dopamine. Exogenous HGF-induced proliferation was inhibited by U0126, whereas migration was completely blocked by LY294002. Study demonstrates that HGF regulates the proliferation and migration of dopaminergic progenitor cells. Modulating dopaminergic progenitor cells in the striatum may prove to be a new approach for treating Parkinson's disease.