Neuropeptide Y (NPY) is a neurotransmitter or neuromodulator that mainly exists in the nervous system. It plays a neuroprotective role in organisms and widely participates in the regulation of ...various physiological processes
. Studies in both humans and animal models have been revealed that NPY levels are altered in some neurodegenerative and neuroimmune disorders. NPY plays various roles in these diseases, such as exerting a neuroprotective effect, increasing trophic support, decreasing excitotoxicity, regulating calcium homeostasis, and attenuating neuroinflammation. In this review, we will focus on the roles of NPY in the pathological mechanisms of neurodegenerative and neuroimmune diseases, highlighting NPY as a potential therapeutic target in these diseases.
EGF receptor (EGFR) inhibition is efficacious in cancer therapy, but initially sensitive tumors often develop resistance. In this study, we investigated the potential to overcome acquired resistance ...to EGFR inhibitors with MEHD7945A, a monoclonal antibody that dually targets EGFR and HER3 (ErbB3). In cancer cells resistant to cetuximab and erlotinib, we found that MEHD7945A, but not single target EGFR inhibitors, could inhibit tumor growth and cell-cycle progression in parallel with EGFR/HER3 signaling pathway modulation. MEHD7945A was more effective than a combination of cetuximab and anti-HER3 antibody at inhibiting both EGFR/HER3 signaling and tumor growth. In human tumor xenograft models, we confirmed the greater antitumor potency of MEHD7945A than cetuximab or erlotinib. MEHD7945A retained potent activity in tumors refractory to EGFR inhibitor alone. Furthermore, MEHD7945A also limited cross-resistance to radiation in EGFR inhibitor-resistant cells by modulating cell-cycle progression and repair processes that control apoptotic cell death. Taken together, our findings confirm an important role of compensatory HER3 signaling in the development of acquired resistance to EGFR inhibitors and offer preclinical proof-of-concept that MEHD7945A can effectively overcome EGFR inhibitor resistance.
Nulliparity is considered to be a risk factor of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). With the new two-child policy launched in 2016, more Chinese women ...have delivered their 2nd baby. Yet few studies have assessed the impact of parity on adverse birth outcomes in China. This study aimed to examine the association between parity and risks of PTB, LBW and SGA in a Chinese population. The combined effects of maternal age and parity on adverse birth outcomes were also assessed.
This retrospective study included all non-malformed live births born during January 1, 2014 and December 31, 2018 in Chengdu, China. A total of 746,410 eligible live singletons with complete information were included in the analysis. Parity was classified into nulliparity (i.e. has never delivered a newborn before) and multiparity (i.e. has delivered at least one newborn before). Log-binomial regression analyses were applied to evaluate the association between parity and PTB, LBW and SGA. We further divided maternal age into different groups (< 25 years, 25-29 years, 30-34 years and ≥ 35 years) to assess the combined effects of maternal age and parity on adverse birth outcomes.
Multiparity was associated with reduced risks of PTB (aRR = 0.91, 95% CI: 0.89-0.93), LBW (aRR = 0.74, 95% CI: 0.72-0.77) and SGA (aRR = 0.67, 95% CI: 0.66-0.69) compared with nulliparity. In each age group, we observed that multiparity was associated with lower risks of adverse birth outcomes. Compared to nulliparous women aged between 25 and 29 years, women aged ≥35 years had greater risks of PTB and LBW, regardless of their parity status. In contrast, multiparous women aged ≥35 years (aRR = 0.73, 95% CI: 0.70-0.77) and those aged < 25 years (aRR = 0.88, 95% CI: 0.84-0.93) were at lower risk of SGA compared with nulliparous women aged between 25 and 29 years.
Multiparity was associated with lower risks of all adverse birth outcomes. Special attention should be paid to nulliparous mothers and those with advanced age during antenatal care, in order to reduce the risks of adverse birth outcomes.
Both excessive screen time and early screen exposure have been linked to children's health outcomes, but few studies considered these two exposures simultaneously. The aim of this study was to ...explore the independent and interactive associations of excessive screen time and early screen exposure with health-related quality of life (HRQOL) and behavioral problems among Chinese children attending preschools.
A cross-sectional study of 4985 children aged between 3 and 6 years was conducted in Chengdu, China. Each parent has finished an online questionnaire regarding their children's screen use, HRQOL, and behavioral problems. Children with screen time over 1 h/day were considered as having excessive screen time. Early screen exposure was defined if the children had started using screen-based media before the age of 2 years. HRQOL was assessed by the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0), while behavioral problems were confirmed with the 48-item Conners' Parent Rating Scale (CPRS-48).
Of the 4985 children (2593 boys and 2392 girls) included, the mean age was 4.6 (SD: 1.0) years. After adjustment for confounders and early screen exposure, excessive screen time was significantly associated with worse HRQOL scores in all dimensions and summary scales, as well as each type of behavioral problems (all p values < 0.05). We also found that compared to children with later initiation of screen exposure, those with screen use before the age of 2 years had significantly lower emotional functioning score (β: - 2.13, 95%CI: - 3.17, - 1.09) and psychosocial health summary score (β: - 0.82, 95%CI: - 1.54, - 0.10) of HRQOL, as well as higher risks of conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, and hyperactivity index, which were independent of excessive screen use. Furthermore, there were significant interactive effects of excessive screen time and early screen exposure on emotional functioning domain of HRQOL scores and conduct problems.
Excessive screen time and early screen exposure are two independent and interactive factors to children's HRQOL and behavioral problems. Our findings support current guidelines to limit screen exposure in children. Appropriate screen use may represent an important intervention target to improve children's HRQOL and reduce their behavioral problems.
MicroRNAs (miRNAs) handle immune response to pathogens by adjusting the function of target genes in plants. However, the experimentally documented miRNA/target modules implicated in the interplay ...between rice and
pv.
(
) are still in the early stages. Herein, the expression of osa-miR1432 was induced in resistant genotype IRBB5, but not susceptible genotype IR24, under
strain PXO86 attack. Overexpressed osa-miR1432 heightened rice disease resistance to
, indicated by enhancive enrichment of defense marker genes, raised reactive oxygen species (ROS) levels, repressed bacterial growth and shortened leaf lesion length, whilst the disruptive accumulation of osa-miR1432 accelerated rice susceptibility to
infection. Noticeably,
(
) was experimentally confirmed as a target gene of osa-miR1432, and the overexpressing
transgenic plants exhibited compromised resistance to
infestation. Our results indicate that osa-miR1432 and
were differently responsive to
invasion at the transcriptional level and fine-tune rice resistance to
infection, which may be referable in resistance gene discovery and valuable in the pursuit of improving
resistance in rice breeding.
Cervical cancer poses a significant health challenge in developing countries, emphasizing the need for appropriate screening strategies to accelerate the elimination of this disease. This study ...summarized the results of a large-scale community-based cervical cancer screening program conducted in Chengdu, China, to understand the prevalence of HPV infection and cervical lesions in the population, and to compare the real-world effectiveness of two different screening methods implemented in the program. From January 2021 to December 2022, a total of 363,376 women aged 35-64 years in Chengdu received free screenings. Among these participants, 70.1% received cytology screening and 29.9% received HPV testing combined with 16/18 genotyping and cytology triage. Ultimately, 824 cases of high-grade lesions and cervical cancer were detected, with a total detection rate of cervical cancer and precancerous lesions of 226.8 per 100,000. The follow-up rate of patients with high-grade lesions and above was 98.9%, and the treatment rate was 86.6%. The overall high-risk HPV infection rate was 11.7%, with the HPV 16/18 infection rate of 1.4%. The rate of abnormal cytology results was 2.8%. The attendance rates for colposcopy and histopathology were 71.6% and 86.1%, respectively. By calculating the age-standardized rates to eliminate the different age composition between the two group, the HPV-based screening strategy had a higher rate of primary screening abnormalities (3.4% vs. 2.8%, P<0.001), higher attendance rates of colposcopy (76.5% vs. 68.9%, P<0.001) and histopathological diagnosis (94.1% vs. 78.0%, P<0.001), higher percentage of abnormal colposcopy results (76.0% vs. 44.0%, P<0.001), and higher detection rate of cervical precancerous lesions and cancer (393.1 per 100,000 vs. 156.4 per 100,000, P<0.001) compared to cytology screening. Our study indicates that the combination of HPV testing with 16/18 genotyping and cytology triage has demonstrated superior performance in cervical cancer screening compared to cytology alone in large-scale population.
Background After China ended its 'dynamic zero-COVID policy' on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide ...prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected. Methods All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection. Results A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07-1.88 and clinical practitioners (aOR: 10.32, 95% CI: 6.57-16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age greater than or equal to 60 years (aOR: 0.30, 95% CI: 0.19-0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23-0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22-0.97 for within 1-3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms. Conclusion Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China's deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak. Keywords: COVID-19, China, Incidence, Omicron, Associated factors, Symptoms
The inflammatory immune response (IIR) is a physiological or excessive systemic response, induced by inflammatory immune cells according to changes in the internal and external environments. An ...excessive IIR is the pathological basis for the generation and development of neurological diseases. Ginkgolides are one of the important medicinal ingredients in
Ginkgo biloba
. Many studies have verified that ginkgolides have anti-platelet-activating, anti-apoptotic, anti-oxidative, neurotrophic, and neuroimmunomodulatory effects. Inflammatory immunomodulation is mediated by inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. They also inhibit the platelet-activating factor (PAF)-mediated signal transduction to attenuate the inflammatory response. Herein, we reviewed the studies on the roles of ginkgolides in inflammatory immunomodulation and suggested its potential role in novel treatments for neurological diseases.
Greater trochanteric pain syndrome (GTPS) possesses a harmful influence on quality of life. Numerous conservative management modalities with varying success have been proposed for patients with GTPS. ...However, it is not clear which treatment is more effective for reducing pain. The purpose of this Bayesian analysis was to assess the current evidence for the effectiveness of conservative treatments on improving Visual Analog Scale (VAS) pain scoring of GTPS and to determine the most effective treatment protocol.
A comprehensive study search was performed from inception until July 18, 2022, via the electronic databases PubMed, the Cochrane Library, and Web of Science for potential research. The risk of bias assessment for the included studies was independently performed based on the Cochrane Collaboration Risk of Bias Tool. Bayesian analysis was conducted by using ADDIS software (v1.16.5). The DerSimonian-Laird random effects model was used to perform the traditional pairwise meta-analysis.
Eight full-text articles with a total of 596 patients with GTPS were included in the analysis. In comparing ultrasound-guided platelet-rich plasma application (PRP-U) to ultrasound-guided corticosteroid injection (CSI-U), patients who received PRP therapy experienced reduced pain as the VAS decreased significantly (MD, -5.21; 95% CI, -6.24 to -3.64). VAS score in group of extracorporeal shockwave treatment (ESWT) was significant improved than that in exercise (EX) group (MD, -3.17; 95% CI, -4.13 to -2.15). There were no statistically significantly different VAS scores between the CSI-U group and the CSI under landmark (CSI-B) group. The treatment efficacy rankings of the different treatments on improving VAS scores showed that the most likely efficacious treatment was PRP-U (99%) followed by ESWT (81%), CIS-U (58%), usual care (48%), CIS-B (54%), and EX (84%).
Bayesian analysis revealed that PRP injection and ESWT are relatively safe and effective in the treatment of GTPS. More multicenter high-quality randomized clinical trials with large sample sizes are still needed in the future to provide further evidence.
Abstract Alzheimer´s disease (AD) is common age-associated dementia with neurodegeneration. The pathogenesis of AD is complex and still remains unclear. The inflammation, amyloid β (Aβ) and ...neurofibrillary tangles as well misfolded tau protein in brain may contribute to the occurrence and development of AD. Compared with tau protein, Aβ is less toxic. So far all efforts made in the treatments of AD with targeting these pathogenic factors were unsuccessful over past decades. Recently many studies demonstrated that changes of intestinal environment and gut microbiota via gut-brain axis pathway can cause neurological disorders, such as AD, which may be involved in the pathogenesis of AD. Thus, the remodeling the gut microbiota by various ways to maintain their balance might be a novel therapeutic strategy for AD. In the review, we analyze the characteristics of gut microbiota and its dysbiosis in AD and its animal models, and investigate the possibility of targeting the gut microbiota in treatment of the patients with AD in the future.
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