Risk of HBV reactivation in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors in the antiviral era.

BACKGROUND: Although routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade-based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals. METHODS: We included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr. RESULTS: HBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010-21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246-10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946-148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581-0.831, P = 0.006). CONCLUSION: HBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.

Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders.

BACKGROUND: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND). METHODS: This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival. RESULTS: Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. INTERPRETATION: In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.

Longitudinal Disability, Cognitive Impairment, and Mood Symptoms in Patients With Anti-NMDA Receptor Encephalitis.

BACKGROUND AND OBJECTIVES: Longitudinal outcomes in anti-NMDA receptor encephalitis (anti-NMDARe) are still not fully understood and may not be adequately captured with the modified Rankin Scale (mRS), often the sole reported outcome. We aim to characterize longitudinal outcomes in anti-NMDARe using multiple outcome measures. METHODS: This single-center, retrospective, observational study examined outcome measures (mRS and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]) in adults with NMDA receptor-IgG in CSF at short- and long-term follow-ups using linear and logistic regression modeling. Patients with evaluations for cognitive impairment (Montreal Cognitive Assessment/Mini-Mental State Examination), depression (Patient Health Questionnaire-9), and anxiety (General Anxiety Disorder-7) >6 months from symptom onset were correlated with final CASE scores. RESULTS: Thirty-eight patients (76% female, median disease onset age = 28 years, range = 1-75 years) were included. The majority received first-line immunosuppressants (97%) at a median of 3.9 weeks (interquartile range [IQR] = 2.1-9.7) from symptom onset and 68% received second-line therapies. At baseline, median/mean mRS and CASE were 4 (IQR = 3-5) and 12.9 (SD = 7.2), respectively. At short-term follow-up (median = 10 weeks, IQR = 6-17), factors associated with higher CASE and mRS included dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission (p < 0.05). At long-term follow-up (median = 70 weeks, IQR = 51-174), median/mean mRS and CASE were 2 (IQR = 1-3) and 4.4 (SD = 4.2), respectively. Only weakness at symptom onset predicted higher mRS scores (odds ratio = 5.6, 95% confidence interval 1.02-30.9, p = 0.047). Despite both mRS and CASE improving from baseline (p < 0.001), only 9 patients (31%) returned to their premorbid function. Among patients with cognitive and mood evaluations >6 months from onset, moderate-severe cognitive impairment (42%), depression (28%), and anxiety (30%) were frequent. Cognitive and depression measures were associated with final CASE subscores (including memory, language, weakness, and psychiatric). DISCUSSION: Multiple clinical factors influenced short-term outcomes, but only onset weakness influenced long-term mRS, highlighting that mRS is predominantly affected by global motor function. Although mRS and CASE improved over time for most patients, these outcome measures did not capture the full extent of long-term functional impairment in terms of mood, cognition, and the ability to return to premorbid function. This emphasizes the need for increased utilization of more nuanced cognitive and mood outcome measures.

Development and validation of a universal esophageal patient-reported outcome measure: The Cleveland Clinic Esophageal Questionnaire (CEQ).

OBJECTIVE: Currently, there is no validated patient-reported outcome measure (PROM) applicable to all esophageal diseases. Our objective was to create a psychometrically robust, validated universal esophageal PROM that can also objectively assess patients' quality of life (QoL). METHODS: The pilot PROM constructed based on expert opinions, literature review, and previous unpublished institutional research had 27 items covering 8 domains. It was completed by 30 patients in the outpatient clinic followed by a structured debriefing interview, which allowed for refining the PROM. The final PROM: Cleveland Clinic Esophageal Questionnaire (CEQ) included 34 items across 6 domains (Dysphagia, Eating, Pain, Reflux & Regurgitation, Dyspepsia, Dumping), each accompanied by a corresponding QoL component. Further psychometric assessment of the PROM was conducted by evaluating (1) acceptability, (2) construct validity, (3) reliability, and (4) responsiveness. RESULTS: Five hundred forty-six unique patients (median 63.7 years [54.3-71.7], 53% male [287], 86% White) completed CEQ at >90% completion within 5 minutes. Construct validity was demonstrated by differentiating scores across esophageal cancer (n = 146), achalasia (n = 170), hiatal hernia (n = 160), and other diagnoses (n = 70). Internal reliability (Cronbach alpha 0.83-0.89), and test-retest reliability (intraclass correlation coefficients 0.63-0.85) were strong. Responsiveness was demonstrated through CEQ domains improving for 53 patients who underwent surgery for achalasia or hiatal hernia (Cohen d 0.86-2.59). CONCLUSIONS: We have constructed a psychometrically robust, universal esophageal PROM that allows concise, consistent, objective quantification of symptoms and their effect on the patient. The CEQ is valuable in prognostication and tracking of longitudinal outcomes in both benign and malignant esophageal diseases.

Antibacterial Activity and Mechanism of Polygonatum sibiricum Extract Against Bacillus cereus and Its Application in Pasteurized Milk.

The purpose of this study was to reveal the antibacterial activity and mechanism of Polygonatum sibiricum extract (PSE) against Bacillus cereus and further analyze the application of PSE in pasteurized milk (PM). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values and growth curve analysis were used to evaluate the antibacterial activity of PSE against B. cereus. The changes in contents of intracellular adenosine 5'-triphosphate (ATP) and reactive oxygen species (ROS), activities of ß-galactosidase, adenosine triphosphatase (ATPase) and alkaline phosphatase (AKP), cell membrane potential, protein and nucleic acid leakage, and cell morphology were used to reveal the antibacterial mechanism. The effects of PSE on viable count and sensory evaluation of PM during storage were analyzed. The results showed that the MIC and MBC values of PSE against B. cereus were 2 and 4 mg/mL, respectively. Growth curve analysis showed that PSE with a concentration of 2 MIC could completely inhibit the growth of B. cereus. After treatments with PSE, the levels of intracellular ATP and ROS, and activities of ß-galactosidase, ATPase and AKP of B. cereus were significantly reduced (p < 0.05). Cell membrane was depolarized, amounts of protein and nucleic acid leakage were significantly increased (p < 0.05), and cell morphology was destroyed. Furthermore, PSE significantly reduced the viable count of B. cereus in PM and improved the sensory quality of PM during storage (p < 0.05). Together, our findings suggested that PSE had the desired effect as a natural preservative applied in PM.

Development and Validation of a Novel Prognosis Model Based on a Panel of Three Immunogenic Cell Death-Related Genes for Non-Cirrhotic Hepatocellular Carcinoma.

Purpose: The accurate prediction of non-cirrhotic hepatocellular carcinoma (NCHCC) risk facilitates improved surveillance strategy and decreases cancer-related mortality. This study aimed to explore the correlation between immunogenic cell death (ICD) and NCHCC prognosis using The Cancer Genome Atlas (TCGA) datasets, and the potential prognostic value of ICD-related genes in NCHCC. Methods: Clinical and transcriptomic data of patients with NCHCC patients were retrieved from TCGA database. Weighted gene co-expression network analysis was performed to obtain the NCHCC phenotype-related module genes. Consensus clustering analysis was performed to classify the patients into two clusters based on intersection genes among differentially expressed genes (DEGs) between cancer and adjacent tissues, NCHCC phenotype-related genes, and ICD-related genes. NCHCC-derived tissue microarray was used to evaluate the correlation of the expression levels of key genes with NCHCC prognosis using immunohistochemical staining. Results: Cox regression analyses were performed to construct a prognostic risk score model comprising three genes (TMC7, GRAMD1C, and GNPDA1) based on DEGs between two clusters. The model stratified patients with NCHCC into two risk groups. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. Univariable and multivariable Cox regression analyses revealed that these signature genes are independent predictors of OS. Functional analysis revealed differential immune status between the two risk groups. Next, a nomogram was constructed, which demonstrated the potent distinguishing ability of the developed model based on receiver operating characteristic curves. In vitro functional validation revealed that the migration and invasion abilities of HepG2 and Huh7 cells were upregulated upon GRAMD1C knockdown but downregulated upon TMC7 knockdown. Conclusion: This study developed a prognostic model comprising three genes, which can aid in predicting the survival of patients with NCHCC and guide the selection of drugs and molecular markers for NCHCC.

GRg1 inhibits the TLR4/NF-kB signaling pathway by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR.

BACKGROUND: Diabetic retinopathy (DR) is a common diabetic neurodegenerative disease that affects vision in severe cases. Current therapeutic drugs are ineffective for some patients with severe side effects, and ginsenoside-Rg1 (GRg1) has been shown to protect against DR and may serve as a new potential drug for DR. This study aimed to confirm the protective effect of GRg1 against DR and its molecular mechanism. METHODS: Human retinal microvascular endothelial cells (hRMECs) and rats were used to construct DR models in vitro and in vivo. Cell proliferation was detected by BrdU assays, the cell cycle was detected by flow cytometry, and TNF-α, IL-6 and IL-1ß levels were detected by ELISA. qRT‒PCR, Western blotting and immunohistochemistry were used to detect the expression of related genes and proteins, and angiogenesis assays were used to assess angiogenesis. RIP and RNA pull down assays were used to determine the relationship between miR-216a-5p and TLR4; retinal structure and changes were observed by HE staining and retinal digestive spread assays. RESULTS: GRg1 effectively inhibited HG-induced hRMEC proliferation, cell cycle progression and angiogenesis and reduced the levels of intracellular inflammatory cytokines and growth factors. HG downregulated the expression of miR-216a-5p and upregulated the expression of TLR4/NF-kB signaling pathway-related proteins. Importantly, GRg1 inhibited TLR4/NF-kB signaling pathway activation by upregulating miR-216a-5p, thereby inhibiting HG-induced cell proliferation, cell cycle progression, angiogenesis, and the production of inflammatory cytokines and growth factors. In addition, animal experiments confirmed the results of the cell experiments. CONCLUSIONS: GRg1 inhibits TLR4/NF-kB signaling by upregulating miR-216a-5p to reduce growth factors and inflammatory cytokines in DR, providing a potential therapeutic strategy for DR.

Efficacy of combined conjoint fascial sheath and levator muscle composite flap suspension for congenital severe ptosis.

BACKGROUND: Conjoint fascial sheath (CFS) suspension has been gradually recognized and accepted for the treatment of congenital severe blepharoptosis in recent years. To address the problem of postoperative upper eyelid position regression of only CFS suspension, we designed and implemented a CFS combined Levator muscle (CFS+LM) complex flap. This research aims to analyze the surgical efficacy of CFS+LM and FMF suspension surgery. METHODS: Patients diagnosed with congenital severe ptosis with levator muscle function ≦4 mm were enrolled. According to the surgical method, the patients were divided into the CFS+LM and FMF groups. To compare and statistically analyze the postoperative effect between CFS+LM and FMF suspension. RESULTS: Data from 182 patients (220 eyes) were collected in this study, including 89 patients (103 eyes) in the CFS+LM group and 93 patients (117 eyes) in the FMF group. The full correction rate, patient satisfaction, postoperative upper eyelid excursion and lagophthalmos in the CFS+LM group were significantly better than those in the FMF group. The eyelid retraction rate was significantly higher in the FMF group than in the CFS+LM group. The complication rate in the CFS+LM group was significantly lower than that in the FMF group. CONCLUSION: CFS+LM suspension had better outcomes than FMF. Considering that the CFS tissue could be weak in patients under 5 years old and have poor muscle elasticity in patients with levator muscle function ≤1 mm, FMF suspension is firstly recommended. For patients over 5 years old with severe ptosis, CFS+LM suspension is recommended.

The expression of interleukin-1ß in patients with chronic hepatitis B treated with pegylated-interferon-alpha combined with tenofovir disoproxil fumarate and monotherapy.

BACKGROUND: Anti-hepatitis B virus (HBV) treatment uses tenofovir disoproxil fumarate (TDF) along with Pegylated-interferon-alpha (Peg-IFN-α), which is more effective than TDF/Peg-IFN-α monotherapy. We have previously shown that interleukin-1beta (IL-1ß) is related to the effectiveness of IFN-α treatment in chronic hepatitis B (CHB) patients. The aim was to investigate the expression of IL-1ß in CHB patients treated with Peg-IFN-α combination with TDF and TDF/Peg-IFN-α monotherapy. METHODS: Huh7 cells infected with HBV were stimulated by Peg-IFN-α and/or Tenofovir (TFV) for 24h. A single-center cohort study of prospective recruitment of CHB patients: untreated CHB (Group A), TDF combined with Peg-IFN-α therapy (Group B), Peg-IFN-α monotherapy (Group C), TDF monotherapy (Group D). Normal donors served as controls. The clinical datas and blood of patients were collected at 0, 12, and 24 weeks. According to the early response criteria, Group B and C were divided into two subgroups: the early response group (ERG) and the non-early response group (NERG). Stimulation of HBV-infected hepatoma cells with IL-1ß to validate the antiviral activity of IL-1ß. To test the blood sample, cell culture supernatant, and cell lysates and to assess the expression of IL-1ß and HBV replication levels in various treatment protocols, Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used. SPSS 26.0 and GraphPad Prism 8.0.2 software were used for statistical analysis. P values < 0.05 was considered to be statistically significant. RESULTS: In vitro experiments, Peg-IFN-α plus TFV treatment group expressed higher IL-1ß and inhibited HBV more effectively than monotherapy. Finally, 162 cases were enrolled for observation (Group A (n = 45), Group B (n = 46), Group C (n = 39), and Group D (n = 32)), and normal donors (n = 20) were enrolled for control. The early virological response rates of Group B, C, and D were 58.7%, 51.3%, and 31.2%. At 24 weeks, IL-1ß in Group B(P = 0.007) and C(P = 0.034) showed higher than at 0 week. In Group B, the IL-1ß showed an upward trend at 12w and 24w in the ERG. IL-1ß significantly reduced HBV replication levels in hepatoma cells. CONCLUSION: The increased expression of IL-1ß may enhance the efficacy of TDF combined with Peg-IFN-α therapy in achieving an early response for CHB patients.

The Application of Multiple Magnetic Resonance Scanning Techniques in Evaluating the Stability of Intracranial Aneurysms.

Purpose: To evaluate the stability of unruptured intracranial aneurysm (UIA) with high-resolution magnetic resonance imaging of the vessel wall (HR-VWI). Materials and Methods: A total of 92 UIA patients were enrolled. After MRA, HR-VWI imaging, the reconstruction of volume rendering (VR) and maximum intensity projection (MIP) were performed to observe the location and size of aneurysms, AR value (ratio of aneurysm height to aneurysmal diameter), SR value (ratio of maximum tumor depth to proximal parent artery diameter), and signal intensity were measured. Results: There were 7 aneurysms with UIA located in the anterior cerebral artery, 31 aneurysms with UIA in the middle cerebral artery, 1 aneurysm with UIA in the posterior cerebral artery, 18 aneurysms with UIA in the anterior communication, 5 aneurysms with UIA in the posterior communication, 34 aneurysms with UIA in the intracranial segment of the internal carotid artery and 3 aneurysms with UIA in the vertebral artery. Among them, 8 patients had more than two multiple aneurysms. The lesion size was 2-38mm (6.3 ± 5.09). There are 46 aneurysms with wall enhancement: the maximum SR value was 7.03 and the minimum 1.2, and the maximum AR value was 7.5 and the minimum 1.0. Fifty-five aneurysms showed no enhancement of the tumor wall. The maximum SR value was 4.55 and the minimum 0.58, and the maximum AR value was 4.0 and the minimum 0.6, respectively. Patients were divided into a stable group and an unstable group according to the aneurysm wall. The enhancement rate, SR value, and AR value in the stable aneurysm group were significantly lower than those in the unstable aneurysm group (P < 0.05). Conclusion: MRA and HR-VWI can objectively reflect the stability of aneurysms by judging the morphology, SR value, and signal enhancement of UIA, and can provide a certain basis for diagnosis and treatment, which has become routine examination.

How do the older adults in nursing homes live with dignity? A protocol for a meta-synthesis of qualitative research.

INTRODUCTION: As the population continuous to age and family sizes decrease, residing in nursing homes has emerged as a crucial option for older adults' care. Ensuring a dignified life for older adults in nursing homes is critical for enhancing their overall quality of life. The primary objective of this study is to synthesise the evidence of qualitative research on the feelings and experiences of dignity among older adults living in nursing homes. This will enable a better understanding of the factors influencing the perception of dignity and its preservation, ultimately assisting older adults in achieving a more comfortable and fulfilling experience in nursing homes. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses will guide this meta-synthesis. We conducted an initial search on 1 June 2022, for studies published between the inception of each database and 2022, using the population exposure-outcome nomenclature. We searched the Embase, Web of Science, CINAHL, Cochrane Library and PubMed databases for relevant studies. For data synthesis, we will employ the Ritchie and Spencer framework, and the Supporting the Use of Research Evidence Framework will be used for data analysis. To minimise the risk of bias, we will critically appraise the selected studies using the Qualitative Assessment and Review Instrument. ETHICS AND DISSEMINATION: This review does not involve human participants and, therefore, does not necessitate ethical approval. We plan to disseminate the protocol and findings through relevant channels, including publication in pertinent journals, presentations at conferences and symposia, and engagement with local and international health stakeholders. PROSPERO REGISTRATION NUMBER: CRD42022343983. CONCLUSION: This study aims to offer comprehensive evidence to guide nursing staff in providing dignity-focused interventions for older adult residents in nursing homes.

Construction of a lncRNA-mediated ceRNA network and a genomic-clinicopathologic nomogram to predict survival for breast cancer patients.

Breast cancer (BC) is the most common cancer among women and a leading cause of cancer-related deaths worldwide. The diagnosis of early patients and the prognosis of advanced patients have not improved over the past several decades. The purpose of the present study was to identify the lncRNA-related genes based on ceRNA network and construct a credible model for prognosis in BC. Based on The Cancer Genome Atlas (TCGA) database, prognosis-related differently expressed genes (DEGs) and a lncRNA-associated ceRNA regulatory network were obtained in BC. The patients were randomly divided into a training group and a testing group. A ceRNA-related prognostic model as well as a nomogram was constructed for further study. A total of 844 DElncRNAs, 206 DEmiRNAs and 3295 DEmRNAs were extracted in BC, and 12 RNAs (HOTAIR, AC055854.1, ST8SIA6-AS1, AC105999.2, hsa-miR-1258, hsa-miR-7705, hsa-miR-3662, hsa-miR-4501, CCNB1, UHRF1, SPC24 and SHCBP1) among them were recognized for the construction of a prognostic risk model. Patients were then assigned to high-risk and low-risk groups according to the risk score. The Kaplan-Meier (K-M) analysis demonstrated that the high-risk group was closely associated with poor prognosis. The predictive nomogram combined with clinical features showed performance in clinical practice. In a nutshell, our ceRNA-related gene model and the nomogram graph are accurate and reliable tools for predicting prognostic outcomes of BC patients, and may make great contributions to modern precise medicine.

Ginsenoside Rg1 Inhibits High Glucose-Induced Proliferation, Migration, and Angiogenesis in Retinal Endothelial Cells by Regulating the lncRNA SNHG7/miR-2116-5p/SIRT3 Axis.

Background: Diabetic retinopathy (DR), including retinal angiogenesis and endothelial cell proliferation and migration, is a serious complication in diabetic patients. It has been reported that ginsenoside Rg1 can prevent retinal damage. However, the mechanism by which Rg1 prevents retinal damage is unknown. Therefore, the aim of the present study was to investigate the mechanism by which Rg1 inhibits high glucose-induced complications through the regulation of the lncRNA SNHG7/miR-2116-5p/SIRT3 axis. Methods: Under high glucose (HG) conditions, human retinal endothelial cells (HRECs) were cultured to simulate a DR environment, and Rg1 was added after 48 h. Negative control (NC), miR-2116-5p mimic, si-SNHG7, pc-DNA SIRT3, and miR-2116-5p inhibitor were transfected into HRECs, and CCK-8 assay was used to detect the cell viability. Angiogenesis and transwell assays were used to evaluate angiogenesis and cell migration, respectively. qRT-PCR and Western blot were used to detect the expression of related genes and proteins. Luciferase reporter assays and bioinformatics were used to analyze the target binding sites of miR-2116-5p to lncRNA SNHG7 and SIRT3. Results: The proliferation, migration and angiogenesis of HRECs were induced by HG. As expected, HG upregulated miR-2116-5p and VEGF expression but downregulated lncRNA SNHG7 and SIRT3 expression. Importantly, Rg1 inhibited HG-induced HREC proliferation, migration, and angiogenesis by upregulating the lncRNA SNHG7, and miR-2116-5p had a target regulatory relationship with both lncRNA SNHG7 and SIRT3. Conclusion: Rg1 inhibits HG-induced proliferation, migration, angiogenesis, and VEGF expression in retinal endothelial cells through the lncRNA SNG7/miR-2116-5p/SIRT3 axis. This finding provides theoretical evidence for the clinical application of Rg1 in DR.

Modified conjoint fascial sheath suspension for the correction of severe congenital blepharoptosis in pediatric patients at different ages.

Objective: To evaluate the surgical outcomes of modified combined fascia sheath (CFS) and levator muscle (LM) complex suspension for the correction of severe congenital blepharoptosis in pediatric patients. Methods: Pediatric patients with severe congenital blepharoptosis were enrolled form July 2017 to July 2021. All patients were divided into two groups according to their age (group A ≤ 7 years; group B > 7 years) and received CFS + LM suspension surgery. Main surgical outcome indexes include margin reflex distance 1 (MRD1) and MRD1 regression. Postoperative complications such as lagophthalmos (LAG), conjunctival prolapse, exposure keratopathy and trichiasis were documented. Results: Fifty patients (60 eyes) were enrolled, including 17 patients (18 eyes) in group A and 33 patients (42 eyes) in group B. The MRD1 in group A was 3.06 ± 0.64 mm at 6 months after the operation, and the MRD1 in group B was 2.64 ± 0.69 mm 6 months postoperatively which is significantly lower than that of group A (P = 0. 044). At the last visit, however, the MRD1 in group A was 3.00 ± 0.69 mm and the MRD1 in group B was 2.64 ± 0.70 mm. There was no significant difference in MRD1 between two groups in long term (P = 0.255). Additionally, there were a variety of degrees of MRD1 regression, especially in the first month after the operation in both groups (both P < 0.001). Moreover, there were 9 cases of postoperative complications in group A and 13 cases in group B. The overall occurrence of postoperative complications in group A was significantly lower than that in groups B (χ 2 = 4.413, P = 0.036). Conclusions: CFS + LM suspension, a modified CFS-based surgery, is an effective treatment for severe congenital blepharoptosis in pediatric patients. Moreover, CFS + LM suspension demonstrate excellent long-term outcomes, including good movement of the eyelid, satisfied eyelid closure and fewer postoperative complications.

Norkurarinone and isoxanthohumol inhibit high glucose and hypoxia-induced angiogenesis via improving oxidative stress and regulating autophagy in human retinal microvascular endothelial cells.

Diabetic retinopathy (DR) is one of the most serious complications of diabetic microangiopathy. Recent studies have shown its close association with high glucose-induced oxidative stress and autophagy disorder. Previous studies showed that various compounds of flavonoids of Sophora flavescens Aiton extracted using ethyl acetate (SFE) could cross the blood-retinal barrier, exerting favorable effects on retinal tissue disorders and angiogenesis in rats with DR. However, the mechanism and the specific material basis for SFE are still unclear. Here, we established the in vitro DR model of human retinal microvascular endothelial cell (HRMECs) induced by high glucose and hypoxia (HGY), screened out the potential pharmacodynamic components of SFE viz. norkurarinone (NKR) and isoxanthohumol (IXM), and proved that they could improve the pathological features of angiogenesis. Further, we explored the mechanism of action of NKR and IXM, investigating their effects on cellular oxidative stress and autophagy levels under HGY conditions. Finally, the role of the PI3K/AKT/mTOR signaling pathway in the regulation of cell autophagy by NKR and IXM was evaluated. Collectively, NKR and IXM could improve cellular oxidative stress state and activate PI3K/AKT/mTOR signaling pathway to regulate autophagy dysregulation, thus playing a significant role in protecting HRMECs from HGY-caused angiogenesis.

Combination of 18F-Fluorodeoxyglucose PET/CT Radiomics and Clinical Features for Predicting Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma.

OBJECTIVE: To identify epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma based on 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and clinical features and to distinguish EGFR exon 19 deletion (19 del) and exon 21 L858R missense (21 L858R) mutations using FDG PET/CT radiomics. MATERIALS AND METHODS: We retrospectively analyzed 179 patients with lung adenocarcinoma. They were randomly assigned to training (n = 125) and testing (n = 54) cohorts in a 7:3 ratio. A total of 2632 radiomics features were extracted from the tumor region of interest from the PET (1316) and CT (1316) images. Six PET/CT radiomics features that remained after the feature selection step were used to calculate the radiomics model score (rad-score). Subsequently, a combined clinical and radiomics model was constructed based on sex, smoking history, tumor diameter, and rad-score. The performance of the combined model in identifying EGFR mutations was assessed using a receiver operating characteristic (ROC) curve. Furthermore, in a subsample of 99 patients, a PET/CT radiomics model for distinguishing 19 del and 21 L858R EGFR mutational subtypes was established, and its performance was evaluated. RESULTS: The area under the ROC curve (AUROC) and accuracy of the combined clinical and PET/CT radiomics models were 0.882 and 81.6%, respectively, in the training cohort and 0.837 and 74.1%, respectively, in the testing cohort. The AUROC and accuracy of the radiomics model for distinguishing between 19 del and 21 L858R EGFR mutational subtypes were 0.708 and 66.7%, respectively, in the training cohort and 0.652 and 56.7%, respectively, in the testing cohort. CONCLUSION: The combined clinical and PET/CT radiomics model could identify the EGFR mutational status in lung adenocarcinoma with moderate accuracy. However, distinguishing between EGFR 19 del and 21 L858R mutational subtypes was more challenging using PET/CT radiomics.

Young male with syphilitic cerebral arteritis presents with signs of acute progressive stroke: A case report.

INTRODUCTION: Neurosyphilis is a chronic infection of the central nervous system that is commonly found in adult with long latency periods. Neurosyphilis-attributed deaths in young patients have grown exponentially in the past decade, yet there have been few studies on the early stages of neurosyphilis. PATIENT CONCERNS: A young male patient with syphilitic cerebral arteritis was evaluated in our clinic for the clinical signs of progressive ischemic stroke. DIAGNOSIS: The progression of syphilitic cerebral arteritis was observed through computed tomography imaging, magnetic resonance imaging, magnetic resonance angiogram, and transcranial color Doppler. The pathological changes and clinical outcomes were reviewed. In this specific case, the development of syphilitic cerebral arteritis was dynamic, continuous, and rapid. The pathogenesis was related to Heubner arteritis, in which the formation of a mural thrombus (MT) causes the severe obstruction of blood flow without complete occlusion, leading to an increased risk of infarction. In this patient, formation of the MT resulted in the infarction of the smaller vessels and narrowing of the larger vessels. The partial dislodgment of the MT from the arterial wall of the larger vessels occluded the smaller vessels, leading to infarction. INTERVENTIONS: Standard pharmacotherapy for the treatment of the cerebral infarction and a single course of penicillin were applied. OUTCOMES: Muscle strength was recovered. The Glasgow Coma Scale score was 15, whereas the NIH Stroke Scale score was 0. The increase in blood flow of the right MCA was accompanied by severe stenosis with compensation of the anterior communicating artery. In addition, moderate to severe stenosis of the right vertebral artery and the basilar artery was suspected. There was a possibility that the right posterior communicating artery was recruited for compensation. CONCLUSION: Progressive stroke was the initial symptom of the neurosyphilis. Disease progression is rapid and difficult to control with a single course of penicillin.

Mouse Models for Cancer Immunotherapy Research.

Immunotherapy has revolutionized cancer therapy, largely attributed to the success of immune-checkpoint blockade. However, there are subsets of patients across multiple cancers who have not shown robust responses to these agents. A major impediment to progress in the field is the availability of faithful mouse models that recapitulate the complexity of human malignancy and immune contexture within the tumor microenvironment. These models are urgently needed across all malignancies to interrogate and predict antitumor immune responses and therapeutic efficacy in clinical trials. Herein, we seek to review pros and cons of different cancer mouse models, and how they can be used as platforms to predict efficacy and resistance to cancer immunotherapies.Significance: Although immunotherapy has shown substantial benefit in the treatment of a variety of malignancies, a key hurdle toward the advancement of these therapies is the availability of immunocompetent preclinical mouse models that recapitulate human disease. Here, we review the evolution of preclinical mouse models and their utility as coclinical platforms for mechanistic interrogation of cancer immunotherapies. Cancer Discov; 8(11); 1358-65. ©2018 AACR.

Research of falls risk of taking central nervous system drugs in oncology inpatients.

This study aimed to analyze the medication use and related falls risk of central nervous system(CNS) drugs in oncology inpatients, explore the association between CNS drugs and falls. In this study, we enrolled inpatients, hospitalized in the oncology department of the Teaching Hospital of Chengdu University of Traditional Chinese Medicine, from March 2013 to October 2015. All inpatients were divided into two groups: taking-CNS drugs group (treatment group) and non CNS drugs group (control group). The falls risk between two groups were being compared and analyzed. Results showed that a total of 768 inpatients were enrolled in this study; 401 of them were males and 367 were females; the average age was 47.9±5.8 year-old. Of them, 129 were taking CNS drugs, while 639 were not. In the treatment group, the number of fall patients was 39, at an incidence rate of 30.23%; of the 39 fall patients, 3 suffered fractures, and 1 suffered an intracranialhemorrhage; while in the control group, the incidence of falls totaled at 45, at an incidence rate of 7.04%; 4 of the patients suffered fractures. The difference of incidence rate between two groups had statistical significance (P＜ 0.01). The incidence rate of falls in the treatment group was 4.29 times that in the control group. By the further analysis of CNS drugs, results implied that hypnotics, sedatives, selective serotonin reuptake inhibitors (no patient taking tricyclic antidepressants in this study), opioids, antiepileptics and antipsychotics had relationship with falls (OR>1). Our finding indicates that oncology inpatients have a higher risk of falls resulting from taking CNS drugs. Therefore, it is necessary to build up a systemic mechanism of nursing safety management on preventing falls of oncology inpatients, to improve nursing quality, and reduce the risk of falls.

Comparison of image quality and application values on different field-of-view diffusion-weighted imaging of breast cancer.

BACKGROUND: Single-shot echo planar imaging (SS-EPI) diffusion-weighted magnetic resonance imaging (DW-MRI) is the most-widely sequence in breast MRI. MRI artifacts and magnetic susceptibility are sometimes severe when this sequence is utilized at 3T. PURPOSE: To compare the imaging quality, ADC values between SS-EPI DWI sequence and two reduced field-of-view (rFOV) DWI sequences of breast cancer. MATERIAL AND METHODS: Twelve cases with breast cancer were scanned using SS-EPI DWI (FOV, 360 × 360 mm), rFOV DWI1 (FOV, 360 × 180 mm), and rFOV DWI2 (FOV, 280 × 140 mm), respectively. Image quality (scores 1 to 5) and ADC values of breast imaging were compared among three groups by different DWI sequences. SNR were compared between rFOV DWI1 and rFOV DWI2. RESULTS: The imaging quality score of 12 cases was 5.00 in rFOV DWI1, 3.60 in SS-EPI DWI, and 3.75 in rFOV DWI2. The mean ADC value of 12 cases was 1.211 × 10(-3 )mm(2)/s in SS-EPI DWI, 1.107 × 10(-3 )mm(2)/s in rFOV DWI1, and 1.038 × 10(-3 )mm(2)/s in rFOV DWI2. SNR of rFOV DWI1 images was much higher than that of rFOV DWI2. CONCLUSION: rFOV DWI1 is the optimal DWI sequence in our study. Comparing with SS EPI DWI, suitable rFOV DWI has an obvious advantage, which can present higher image resolution and less distortion. It may be helpful in the diagnosis of breast cancer.