Efficacy of neuroendoscopy-assisted surgery in the treatment of chronic subdural hematoma: a meta-analysis.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgery. It is the result of chronic intracranial hemorrhage that converges between the dura mater and arachnoid three weeks after externally injuring the head. Chronic subdural hematomas are a common complication in neurosurgery. With the gradual increase in the amount of hematoma, the surrounding brain tissue is pushed and compressed, resulting in corresponding clinical symptoms and signs. It is reported that the overall incidence rate of CSDH is 1.72 to 20.6 per 100,000 people every year, and the incidence rate of the elderly is particularly high. METHODS: The computer retrieves eight databases to obtain controlled trials at home and abroad on the effects of neuroendoscopy-assisted surgery in patients with chronic subdural hematoma. After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software. RESULTS: Twenty studies were ultimately included in this meta-analysis. Seventeen studies reported the Recurrence rate of the test group and the control group, which was significantly lower (OR 0.27; 95% Cl 0.18, 0.38; P < 0.01) than the control group, Recovery rate (OR 1.18; 95% Cl 1.01, 1.38; P = 0.03), Total effective rate (OR 1.11; 95% Cl 1.04, 1.17; P < 0.01), Operative time (SMD 15.78; 95% Cl 9.69, 21.86; P < 0.01), Hospital stay (SMD - 1.66; 95% Cl - 2.17, - 1.14; P < 0.01) and Complications (OR 0.48; 95% Cl 0.30, 0.78; P < 0.01). CONCLUSION: The results of this study suggest that neuroendoscopy-assisted surgery may be effective in patients with chronic subdural hematoma, as evidenced by recurrence rate, recovery rate, total effective rate, operative time, hospital stay, complications, and the above conclusions need to be verified by more high-quality studies.

An observational study of the marketing practice of e-cigarette specialty stores in two large cities in China: Is there potential to normalize the use of e-cigarettes?

INTRODUCTION: Supervision measures in China have designated offline retail as the only legal channel for the sale and advertising of e-cigarettes. Specialty stores, exclusively selling vaping devices and e-liquids, are professionally designed to showcase company images and provide the best examples of e-cigarette marketing strategies. The goal was to analyze the retail marketing practice of e-cigarette specialty stores and provide a scientific reference for future e-cigarette point-of-sale regulation. METHODS: On-site observations were conducted in specialty stores among the popular business districts of Chengdu and Shanghai, China, from January to May 2021. 'Dianping', known as 'Chinese Yelp', was used to identify 8 business districts in Shanghai and 5 in Chengdu as observation sites. Two trained observers visited each store in the identified business districts. The data were collected with a checklist, which consisted of 5 sections with 37 items, including basic information, marketing practice, age restriction and health warnings. RESULTS: In total, 161 e-cigarette specialty stores, including 82 specialty stores in Shanghai and 79 in Chengdu, were identified. Of these stores, 156 were single-brand retailers and 5 were multi-brand retailers. Each store displayed e-cigarette products, which were visible from outside the store. The most common e-cigarette products were rechargeable kits and nicotine-containing e-liquids, which were available at all specialty stores. Frequent forms of promotion were free e-liquid samples (100%) and slogans (57.8%). Signage stating prohibition of minor use and purchase was presented at 141 (87.6%) specialty stores. Relatively few specialty stores (31.7%) displayed health warnings. CONCLUSIONS: E-cigarette specialty stores featured highly visible product displays, varied product selections, abundant marketing materials, free trial services, absent entry restrictions for minors, and a lack of health warnings. Policymakers should move to reduce youth exposure to e-cigarette products and marketing in the retail environment by strengthening regulations on product display and marketing.

Paper-based multicolor sensor for on-site quantitative detection of organophosphate pesticides based on acetylcholinesterase-mediated paper-based Au3+-etching of gold nanobipyramids and CIELab color space.

On-site quantitative detection of organophosphorus pesticides (OPs) is crucial for safeguarding food and public safety. This study presents a novel acetylcholinesterase (AChE)-mediated paper-based Au3+-etching of gold nanobipyramids (AuNBPs) system. The system employs a long-term storable AuNBPs-deposited nylon membrane embedded within a portable and temperature-controlled paper-based analytical device. This system, coupled with a colorimeter-based quantitative method, enables the development of a practical paper-based multicolor sensor (PMS) for on-site quantitative detection of three common OPs (paraoxon, dichlorvos, and trichlorfon). In the absence of OPs, AChE hydrolyzes acetylthiocholine to thiocholine, which reduces Au3+ to Au+. The presence of OPs inhibits AChE activity, thereby preserving Au3+ to etch AuNBPs on nylon membranes, accompanied by multicolor changes. These color changes can be simply quantified by measuring the a∗ parameter of the CIELab color space using a portable colorimeter. Under optimal conditions, the PMS displayed eight OPs-corresponding color changes with a minimum detectable concentration of 1.0-10 µg/L (visual observation) and limits of detection of 0.8-7.2 µg/L (colorimeter) and 0.2-3.4 µg/L (UV-vis spectrometry). The PMS successfully determined the OPs in vegetable and rice samples with recoveries of 89.0-109 % and RSDs (n = 5) of <6 %. These results were consistent with those obtained using the HPLC-MS method. The PMS demonstrates excellent portability, AuNBPs stability, detection sensitivity, and reproducibility, making it a promising tool for the on-site quantitative detection of OPs residues in food. Furthermore, the paper-based etching system coupled with the colorimeter-based quantitative method provides a valuable reference to develop practical PMSs for various targets in diverse fields.

Establishment of predictive models and determinants of preoperative gastric retention in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Study on influencing factors of gastric retention before endoscopic retrograde cholangiopancreatography (ERCP) background: With the wide application of ERCP, the risk of preoperative gastric retention affects the smooth progress of the operation. The study found that female, biliary and pancreatic malignant tumor, digestive tract obstruction and other factors are closely related to gastric retention, so the establishment of predictive model is very important to reduce the risk of operation. AIM: To analyze the factors influencing preoperative gastric retention in ERCP and establish a predictive model. METHODS: A retrospective analysis was conducted on 190 patients admitted to our hospital for ERCP preparation between January 2020 and February 2024. Patient baseline clinical data were collected using an electronic medical record system. Patients were randomly matched in a 1:4 ratio with data from 190 patients during the same period to establish a validation group (n = 38) and a modeling group (n = 152). Patients in the modeling group were divided into the gastric retention group (n = 52) and non-gastric retention group (n = 100) based on whether gastric retention occurred preoperatively. General data of patients in the validation group and modeling group were compared. Univariate and multivariate logistic regression analyses were performed to identify factors influencing preoperative gastric retention in ERCP patients. A predictive model for preoperative gastric retention in ERCP patients was constructed, and calibration curves were used for validation. The receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive value of the model. RESULTS: We found no statistically significant difference in general data between the validation group and modeling group (P > 0.05). The comparison of age, body mass index, hypertension, and diabetes between the two groups showed no statistically significant difference (P > 0.05). However, we noted statistically significant differences in gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction between the two groups (P < 0.05). Multivariate logistic regression analysis showed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were independent factors influencing preoperative gastric retention in ERCP patients (P < 0.05). The results of logistic regression analysis revealed that gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction were included in the predictive model for preoperative gastric retention in ERCP patients. The calibration curves in the training set and validation set showed a slope close to 1, indicating good consistency between the predicted risk and actual risk. The ROC analysis results showed that the area under the curve (AUC) of the predictive model for preoperative gastric retention in ERCP patients in the training set was 0.901 with a standard error of 0.023 (95%CI: 0.8264-0.9567), and the optimal cutoff value was 0.71, with a sensitivity of 87.5 and specificity of 84.2. In the validation set, the AUC of the predictive model was 0.842 with a standard error of 0.013 (95%CI: 0.8061-0.9216), and the optimal cutoff value was 0.56, with a sensitivity of 56.2 and specificity of 100.0. CONCLUSION: Gender, primary disease, jaundice, opioid use, and gastrointestinal obstruction are factors influencing preoperative gastric retention in ERCP patients. A predictive model established based on these factors has high predictive value.

L48H37, a curcumin analog, suppresses matrix metalloproteinase-9 expression and activity to hamper nasopharyngeal cancer cell migration.

OBJECTIVE: Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism. METHODS: Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors. RESULTS: In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells. CONCLUSIONS: Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.

Inducing a Synergistic Effect on Ptδ+/Electron-Rich Sites via a Platinization Strategy: Generating Hyper-High Current Density in Hydrogen Evolution Reaction.

Herein, we propose a platinization strategy for the preparation of Pt/X catalysts with low Pt content on substrates possessing electron-rich sites (Pt/X: X = Co3O4, NiO, CeO2, Covalent Organic Framework (COF), etc.). In examples with inorganic and organic substrates, respectively, Pt/Co3O4 possesses remarkable catalytic ability toward HER, achieving a current density at an overpotential of 500 mV that is 3.22 times higher than that of commercial Pt/C. It was also confirmed by using operando Raman spectroscopy that the enhancement of catalytic activity was achieved after platinization of the COF, with a reduction of overpotential from 231 to 23 mV at 10 mA cm-2. Density functional theory (DFT) reveals that the improved catalytic activity of Pt/Co3O4 and Pt/COF originated from the re-modulation of Ptδ+ on the electronic structure and the synergistic effect of the interfacial Ptδ+/electron-rich sites. This work provides a rapid synthesis strategy for the synthesis of low-content Pt catalysts for electrocatalytic hydrogen production.

Isoliquiritigenin diminishes invasiveness of human nasopharyngeal carcinoma cells associating with inhibition of MMP-2 expression and STAT3 signalling.

Nasopharyngeal carcinoma (NPC) is prevalent in Asia and exhibits highly metastatic characteristics, leading to uncontrolled disease progression. Isoliquiritigenin (ISL) have attracted attention due to their diverse biological and pharmacological properties, including anticancer activities. However, the impact of ISL on the invasive and migratory ability of NPC remains poorly understood. Hence, this study aimed to investigate the in vitro anti-metastatic effects of ISL on NPC cells and elucidate the underlying signalling pathways. Human NPC cell NPC-39 and NPC-BM were utilized as cell models. Migratory and invasive capabilities were evaluated through wound healing and invasion assays, respectively. Gelatin zymography was employed to demonstrate matrix metalloproteinase-2 (MMP-2) activity, while western blotting was conducted to analyse protein expression levels and explore signalling cascades. Overexpression of signal transducer and activator of transcription 3 (STAT3) was carried out by transduction of STAT3-expressing vector. Our findings revealed that ISL effectively suppressed the migration and invasion of NPC cells. Gelatin zymography and Western blotting assays demonstrated that ISL treatment led to a reduction in MMP-2 enzyme activity and protein expression. Investigation of signalling cascades revealed that ISL treatment resulted in the inhibition of STAT3 phosphorylation. Moreover, overexpression of STAT3 restored the migratory ability of NPC cells in the presence of ISL. Collectively, these findings indicate that ISL inhibits the migration and invasion of NPC cells associating with MMP-2 downregulation through suppressing STAT3 activation. This suggests that ISL has an anti-metastatic effect on NPC cells and has potential therapeutic benefit for NPC treatment.

Diagnostic and Therapeutic Roles of Extracellular Vesicles and Their Enwrapped ncRNAs in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory disease whose precise pathogenesis remains mysterious. The involvement of epigenetic regulation in the pathogenesis of RA is one of the most anticipated findings, among which non-coding RNAs (ncRNAs) hold great application promise as diagnostic and therapeutic biomarkers for RA. Extracellular vesicles (EVs) are a heterogeneous group of nano-sized, membrane-enclosed vesicles that mediate intercellular communication and substance exchange, especially the transfer of ncRNAs from donor cells, thereby regulating the functional activities and biological processes of recipient cells. In light of the significant correlation between EVs, ncRNAs, and RA, we first documented expression levels of EVs and their-encapsulated ncRNAs in RA individuals, and methodically discussed their-implicated signaling pathways and phenotypic changes. The last but not least, we paied special attention to the therapeutic benefits of gene therapy reagents specifically imitating or silencing candidate ncRNAs with exosomes as carriers on RA animal models, and briefly highlighted their clinical application advantage and foreground. In conclusion, the present review may be conducive to a deeper comprehension of the diagnostic and therapeutic roles of EVs-enwrapped ncRNAs in RA, with special emphasis on exosomal ncRNAs, which may offer hints for the monitoring and treatment of RA.

Susceptibility to e-cigarette among high school students: a study based on the ecological model of health behavior.

Introduction: Youth e-cigarette (EC) use has rapidly increased in the last few years. It is crucial to identify the susceptible youth and prevent them from EC uptake. This study was conducted to investigate factors that affect youth susceptibility to EC use. Methods: This study employed a cross-sectional survey design, utilizing multi-center stratified cluster sampling method to select two junior high schools and two senior high schools in Shanghai, Guangzhou, and Chengdu. One-third of classes of each grade in the selected schools were involved in this survey. After obtaining the informed consent of parents, an anonymous and self-administered questionnaire was distributed to students. Questionnaire was designed based on the Ecological Models of Health Behavior. Associations between EC susceptibility and covariates were identified using multivariate logistic regression. Results: Among 2,270 students who had never vaped, 38.0% were susceptible to ECs. Logistic regression analysis identified factors on different levels affecting the susceptibility. Individual factors included senior high school students (OR = 1.34, 95% CI: 1.08-1.65), sensation seeker (OR = 1.11, 95%CI: 1.08-1.14), poor academic performance (OR = 1.24, 95% CI: 1.01-1.54), ever cigarette user (OR = 2.27, 95% CI: 1.29-4.01), unaware of the second-hand smoke from vaping (OR = 1.56, 95% CI: 1.25-1.96), agreeable with "I do not want to hang around vapers" (OR = 0.79, 95% CI: 0.64-0.97), agreeable with "ECs are more fashionable than cigarette" (OR = 2.50, 95% CI: 1.72-3.62) and favorable attitudes toward vaping (OR = 5.09, 95% CI: 3.78-6.85) were significantly associated with susceptibility to ECs. At interpersonal level, students who believe they would not be punished by parents for vaping increased susceptibility (OR = 1.27, 95% CI:1.01-1.59). At community level, exposure of EC advertising (OR = 1.81, 95% CI:1.46-2.25), exposure to hazard information (OR = 0.76, 95% CI: 0.59-0.97) and seeing vaping in daily life (OR = 2.11, 95% CI: 1.62-2.74), were statistically significantly associated with youth susceptibility to ECs. Conclusion: EC susceptibility was observed in a substantial proportion of adolescents who had never vaped, influenced by factors on different levels. This research underscores the urgent need for comprehensive intervention strategies to prevent the youth susceptibility to ECs.

Batch and Continuous-Flow Electrochemical Geminal Difluorination of Indeno[1,2-c]furans.

An electrochemical gem-difluorination of indeno[1,2-c]furans using commercially available and easy-to-use triethylamine trihydrofluoride as both the electrolyte and fluorinating agent was developed. Remarkably, different reaction pathways of indeno[1,2-c]furans, i.e., paired electrolysis and net oxidation, are operative in a batch reactor and a continuous-flow microreactor to afford the corresponding gem-difluorinated indanones and indenones, respectively.

Sugemalimab combined with chemotherapy for the treatment of advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis.

Background: This study aims to systematically analyze the cost-effectiveness of the combination therapy comprising sugemalimab and chemotherapy in the management of advanced ESCC from the Chinese healthcare system perspective. Methods: An advanced ESCC patient simulation partitioned survival approach model was developed to mimic the disease progression of patients undergoing treatment with sugemalimab in combination with chemotherapy versus chemotherapy alone. To ensure accuracy and precision, clinical data, treatment costs, and utility values were collected from comprehensive clinical trials and reliable economic databases. The cost-effectiveness analysis was conducted by assessing the incremental cost-effectiveness ratio in relation to the established willingness-to-pay threshold. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model. Results: The cumulative expenditure for the group of patients administered with sugemalimab amounted to US$ 41734.87, whereas the placebo group was associated with a total cost of US$ 22926.25. By evaluating the ICER, which quantifies the additional cost incurred per QALY gained, a value of US$ 61066.96 per QALY was determined. It is imperative to note that this ICER value surpasses the predetermined threshold for WTP in China, set at US$ 39,855.79 per QALY. Sensitivity analyses demonstrated that the results were sensitive to the cost of sugemalimab, progression-free survival, and utility values. These fluctuations did not result in a reversal of the study findings. Conclusion: The combination of sugemalimab with chemotherapy for the treatment of ESCC in China is currently not considered a cost-effective therapeutic approach. However, it is suggested that additional reductions in price may facilitate the potential for achieving cost-effectiveness.

Clinical and pathological analyses of 14 cases of angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.

Recurrent Occupational Hantavirus Infections Linked to Feeder Rodent Breeding Farm, Taiwan, 2022.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

Stable peptide-assembled nanozyme mimicking dual antifungal actions.

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical ß-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

A comparative study of hypothalamic involvement in patients with myelin oligodendrocyte glycoprotein antibody-associated disease, neuromyelitis optica spectrum disorder, and multiple sclerosis.

BACKGROUND AND PURPOSE: We aimed to characterize hypothalamic involvement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare it with neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). METHODS: A retrospective study was performed to identify hypothalamic lesions in patients diagnosed with MOGAD, NMOSD, or MS from January 2013 to May 2020. The demographic, clinical, and radiological features were recorded. Hypothalamic dysfunction and prognosis were assessed through physical examination, biochemical testing, sleep monitoring, and magnetic resonance imaging. RESULTS: Hypothalamic lesions were observed in seven of 96 patients (7.3%) with MOGAD, 34 of 536 (6.3%) with NMOSD, and 16 of 356 (4.5%) with MS (p = 0.407). The time from disease onset to development of hypothalamic lesions was shortest in MOGAD (12 months). The frequency of bilateral hypothalamic lesions was the lowest in MOGAD (p = 0.008). The rate of hypothalamic dysfunction in MOGAD was 28.6%, which was lower than that in NMOSD (70.6%) but greater than that in MS patients (18.8%; p = 0.095 and p = 0.349, respectively). Hypothalamic dysfunction in MOGAD manifests as hypothalamic-pituitary-adrenal axis dysfunction and hypersomnia. The proportion of complete regression of hypothalamic lesions in MOGAD (100%) was much greater than that in NMOSD (41.7%) and MS patients (18.2%; p = 0.007 and p = 0.001, respectively). An improvement in hypothalamic dysfunction was observed in all MOGAD patients after immunotherapy. CONCLUSIONS: MOGAD patients have a relatively high incidence of asymptomatic hypothalamic lesions. The overall prognosis of patients with hypothalamic involvement is good in MOGAD, as the lesions completely resolve, and dysfunction improves after immunotherapy.

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

BACKGROUND: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS: In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS: Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS: Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

Diabetes and further risk of cancer: a nationwide population-based study.

BACKGROUND: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood. METHODS: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period. RESULTS: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001). CONCLUSIONS: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.

Design, synthesis and molecular modeling of novel D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives as anti-inflammatory agents by inhibition of COX-2/iNOS production and down-regulation of NF-κB/MAPKs in LPS-induced RAW264.7 macrophage cells.

It has been reported that 4,5-dihydropyrazole and thiazole derivatives have many biological functions, especially in the aspect of anti-inflammation. According to the strategy of pharmacophore combination, we introduced thiazolinone and dihydropyrazole moiety into steroid skeleton to design and synthesize a novel series of D-ring substituted steroidal 4,5-dihydropyrazole thiazolinone derivatives, and assessed their in vitro anti-inflammatory profiles against Lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. The anti-inflammatory activities assay demonstrated that compound 12e was considered as the most effective anti-inflammatory drug, which suppressed the expression of pro-inflammatory mediators including nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), it also dose-dependently inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 macrophage cells. Furthermore, the results of the Western blot analysis showed a correlation between the inhibition of the Nuclear factor-kappa B (NF-κB) and Mitogen-activated protein kinases (MAPKs) signaling pathways and the suppressive effects of compound 12e on pro-inflammatory cytokines. Molecular docking studies of compound 12e into the COX-2 protein receptor (PDB ID: 5IKQ) active site was performed to rationalize their COX-2 inhibitory potency. The results were found to be in line with the biological findings as they exerted more favorable interactions compared to that of dexamethasone (DXM), explaining their remarkable COX-2 inhibitory activity. The findings revealed that these candidates could be identified as potent anti-inflammatory agents, compound 12e could be a promising drug for the treatment of inflammatory diseases.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.