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Objectives: Recent studies have suggested that neuroinflammation may play a role in the progression of spinal muscular atrophy (SMA), and this may influence the efficacy of antisense oligonucleotide treatment. This study explored the biomarkers associated with SMA and the efficacy of nusinersen therapy., Methods: Fifteen patients with SMA were enrolled and their motor function (World Health Organization motor milestone, Hammersmith Functional Motor Scale Expanded (HFMSE), and Revised Upper Limb Module [RULM] scores, and 6-minute walking test) was evaluated before, during (63 days), and after (6 months) nusinersen treatment. The concentrations of monocyte chemoactive protein 1 (MCP1), tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-10 in the cerebrospinal fluid were measured at the indicated time points, and their correlations with motor function were analysed., Results: A significant increase in MCP1 was observed after 6 month's treatment compared with that before treatment, while TNF-α gradually decreased over the course of treatment. IL-10 levels were negatively correlated with HFMSE scores before treatment, and reductions in IL-10 levels were correlated with improvements in RULM scores., Conclusions: This study suggests that neuroinflammation may be associated with the severity of SMA and with the therapeutic effects of nusinersen, which could have clinical implications in the treatment of SMA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Polybrominated diphenyl ethers (PBDEs) are widespread and persistent environmental contaminants, but their association with nodular goiter (NG) remains unknown. The present case-control study of 179 NG cases and 358 matched normal controls aimed to investigate the association between PBDEs and risk of NG. The plasma concentrations of 8 PBDEs congeners (BDE-28, -47, -99, -100, -153, -154, -183, and -209) were determined by gas chromatograph-mass spectrometer. Conditional logistic regression model was used to evaluate the odds ratio (OR) and 95% confidence interval (CI) for the association between each PBDEs congener and NG. Bayesian kernel machine regression (BKMR) was used to evaluate the association between overall levels of 8 PBDEs mixture and NG. The results of logistic model suggested that increased risk of NG was associated with elevated concentrations of all PBDEs congeners, except for BDE-209. In BKMR model, the risk of NG increased with the increase in overall exposure level of 8 PBDEs mixture. Compared to when all PBDEs mixture were at their median value, the risk of exposure-response function for NG increased by 0.34 units when all PBDEs were at their 75th percentile. In women, the results showed similar trends after additional adjustment for age at menarche and menopausal status. These findings provide novel epidemiological evidence for the prevention of NG. However, larger prospective studies are required to address the associations between PBDEs exposure and NG risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-β-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC 50 values of 0.43 ± 0.03, 0.46 ± 0.02, 0.50 ± 0.03 and 0.51 ± 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest/no competing financial interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: It is unclear whether weight change after middle adulthood influences the risk of thyroid cancer. The aim of this study was to investigate associations between the risk of papillary thyroid cancer (PTC) and body mass index (BMI) and weight change after middle adulthood (age 35)., Methods: A matched case-control study based on three hospitals included 516 pairs of cases newly diagnosed with PTC and controls. Current height and weight after defecation in the morning were measured by trained nurses. During measurement, all subjects were requested to wear lightweight clothing and no shoes. Weight at age 35 was self-reported. BMI and weight change were modeled as continuous and categorical variables. Conditional and unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95%CI) for the association between BMI and weight change after middle adulthood and PTC., Results: After adjustment for covariates, measured BMI at the time of current diagnosis was positively associated with PTC (OR 1.16, 95%CI 1.10-1.21). According to WHO BMI guidelines for Asia-Pacific populations, the OR (95%CI) for PTC risk in obesity was 2.99 (1.92-4.67) compared to normal weight (p-trend <0.001). Moreover, PTC was positively associated with BMI at age 35; the OR (95%CI) for PTC risk per unit increase in BMI was 1.06 (1.02-1.11). Compared to stable weight (changed <0.5 kg/year), weight gain ≥1.0 kg/year after middle adulthood was positively associated with PTC (OR 2.57, 95%CI 1.39-4.76, p-trend <0.001). Compared to maintaining non-overweight status, the PTC risk was significantly increased in those individuals who gained weight and became overweight after middle adulthood (OR 3.82, 95%CI 2.50-5.85)., Conclusion: This study showed that high BMI and obesity were positively associated with increased risk of PTC, and weight gain after middle adulthood also could elevate the PTC risk., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state., Methods: To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB ., Results: HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes., Conclusion: The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Intravenous zanamivir (IVZ) is a neuraminidase (NA) inhibitor (NAI) under investigation for the treatment of subjects hospitalised with influenza. The study included 130 symptomatic, hospitalised adults with influenza. Subjects received IVZ for 5-10 days. Viruses were cultured and analysed for susceptibility to zanamivir. Mean IC 50 s (n = 50) (±SD) for influenza A/H1N1pdm09, A/H3N2 and influenza B were 0.20 ± 0.06, 0.26 ± 0.07 and 1.61 ± 0.35 nM, respectively, and are comparable to data observed for sensitive isolates. A total of 185 NA and 180 haemagglutinin (HA) sequences were obtained from 123 subjects; the majority did not contain resistance substitutions. Four influenza A/H1N1pdm09 viruses from four subjects harboured NA resistance substitutions: three, Y155H, D199G and S247N, were present at Day 1 before IVZ exposure and the fourth, E119D/E, was detected at Post Treatment +5 Days but was not present at 5 other timepoints. Five subjects harboured virus with treatment-emergent NA substitutions not associated with resistance; N63D, V83A, W190C, M269K (A/H1N1pdm09) and R210K (A/H3N2). Viruses from fifteen subjects harboured HA resistance substitutions, (A/H1N1pdm09) one emerged during treatment: S162N (Day 5). Five viruses harboured treatment-emergent HA substitutions (A/H1N1pdm09) not associated with resistance: E81K, V108L, S164D, D168N and S185N. 10/92 subjects with A/H1N1pdm09 harboured a D222 HA substitution, which has been associated with increased virulence. The emergent substitutions are not associated with resistance but may have arisen due to selection pressure during IVZ treatment or by chance. In this study, there was evidence for resistance selection in a post treatment sample but the resistant variant did not persist in later visit samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Lead (Pb) levels, delta-aminolevulinic acid dehydratase (ALAD) activities, zinc protoporphyrin (ZPP) levels in blood, and urinary delta-aminolevulinic acid (ALA) and coproporphyrin (CP) concentrations were measured for 318 environmental Pb exposed children recruited from an area of southeast China. The mean of blood lead (PbB) levels was 75.0μg/L among all subjects. Benchmark dose (BMD) method was conducted to present a lower PbB BMD (lower bound of BMD) of 32.4μg/L (22.7) based on ALAD activity than those based on the other three haematological indices, corresponding to a benchmark response of 1%. Childhood intelligence degrees were not associated significantly with ALAD activities or ALA levels. It was concluded that blood ALAD activity is a sensitive indicator of early haematological damage due to low-level Pb exposures for children., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Our research on adverse effects of lead exposures on physical and neurobehavioral health of children aged 6-12years in 4 villages, labeled as K, M, L, and X, in rural China, was reported in this article. Lead in blood (PbB), urine (PbU), hairs (PbH), and nails (PbN) were measured by graphite furnace atomic absorption spectrometry. Abbreviated Symptom Questionnaire of Conner's instruments and Revised Raven's Standard Progressive Matrices were applied to evaluate childhood attention deficit/hyperactivity disorders (ADHD) and intelligences. Geometric means (SD) of PbB, PbU, PbH and PbN concentrations were 71.2 microg/L (1.56), 11.7 microg/g (1.75), 12.5 microg/g (2.82), and 25.3 microg/g (2.79), respectively. 54 (17.0%) children had PbB levels of > or =100 microg/L. Boys, 6-10 years old, and living in village K were 2.11, 2.48, and 9.16 times, respectively, more likely to be poisoned by lead than girls, aged 11-12 years, and residing in X. 18 (5.7%) and 37 (11.7%) subjects had ADHD and mental retardations, respectively. Inverse relationships between intelligences and natural log transformed PbU and PbH levels were observed with respective odds ratios (95%CI) of 1.79 (1.00-3.22) and 1.46 (1.06-2.03) or 1.28 (1.04-1.58) and 1.73 (1.18-2.52) by binary or ordinal logistic regression modeling. ADHD prevalence was different by gender and age of subjects. PbU, PbH, and PbN related to PbB positively with respective correlation coefficients of 0.530, 0.477, and 0.181. Receiver operating characteristic (ROC) curves of the three measurements revealed areas under curves (AUCs) being 0.829, 0.758, and 0.687, respectively. In conclusion, children had moderate levels of lead exposures in this rural area. Intelligence declines were associated with internal lead levels among children. ROC analysis suggests PbU an internal lead indicator close to PbB.