Life and disease status of patients with Parkinson's disease during and after zero-COVID in China: an online survey.

BACKGROUND: Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. METHODS: This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. RESULTS: A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%). CONCLUSIONS: The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation.

The relationship between diabetes-related cognitive dysfunction and leukoaraiosis.

Cognitive dysfunction is a degenerative disease of the central nervous system, which often associates with ageing brain as well as neurodegenerative diseases. A growing body of evidence suggests that patients with diabetes mellitus (DM) have a significantly higher risk of cognitive impairment. In recent years, studies have found that patients with diabetes-related cognitive dysfunction have an increased burden of leukoaraiosis (LA), and larger white matter hyperintensity (WMH) volume. With the recent advancement of technologies, multimodal imaging is widely exploited for the precise evaluation of central nervous system diseases. Emerging studies suggest that LA pathology can be used as a predictive signal of white matter lesions in patients with diabetes-related cognitive dysfunction, providing support for early identification and diagnosis of disease. This article reviews the findings, epidemiological characteristics, pathogenesis, imaging features, prevention and treatment of LA pathophysiology in patients with diabetes-related cognitive dysfunction.

[Expression and function of Cx32 and Cx43 junctions in medically intractable temporal lobe epilepsy in human].

OBJECTIVE: To study the expression of Cx32 and Cx43 in medically intractable temporal lobe epilepsy in human and investigate the pathogenic relationship between gap junctions and seizures. METHODS: The expression of Cx32 and Cx43 was detected by Western blot and immunohistochemistry in 14 consecutive samples of hippocampus from epileptic patients undergoing an amygdalohippocampectomy for the treatment of intractable seizures. During postmortem dissection, 8 samples of hippocampus in nonepileptic patients dying of other diseases were taken as control group. RESULTS: The expression of Cx32 and Cx43 was at a low level in the control group [Cx32: count of positive cell (9.4 +/- 1.1), ratios of gray scale (0.2 +/- 0.1); Cx43: count of positive cell (9.2 +/- 4.7), ratios of gray scale (0.5 +/- 0.2)], but Cx43 and Cx32 appeared to be expressed at a higher level in epileptic patients compared with that of the control group by immunohistochemistry [Cx32: count of positive cell (14.6 +/- 3.4), Cx43: count of positive cell (16.5 +/- 3.1)] (P < 0.01), and their expression significantly increased by Western blot [Cx32: ratios of gray scale (1.5 +/- 0.2), Cx43: ratios of gray scale (1.4 +/- 0.3)] (P < 0.01). Over-expression of Cx32 and Cx43 was found in 14 consecutive samples of hippocampus from epileptic patients. CONCLUSION: Gap junctions play an important role in the occurrence and progression of intractable seizures.

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer's Disease Risk.

To determine the role of A disintegrin and metalloproteinase 10 (ADAM10) in genetic susceptibility to Alzheimer's disease (AD) in a representative Chinese sample, we genotyped 362 AD patients and 370 healthy controls for the rs514049A/C and rs653765C/T polymorphisms in the ADAM10 promoter using the SNaPshot technique. We also examined the potential impact of these polymorphisms on the plasma level of soluble receptor for advanced glycation end products (sRAGE), a decoy receptor whose reduction has been associated with a higher risk of AD. Additionally, a meta-analysis was performed using the present study and the largest GWAS from the International Genomics of Alzheimer's Project (IGAP). No significant differences were found in the distributions of genotypes or alleles between AD patients and control subjects. However, age-at-onset stratification analysis revealed that there were significant differences in the genotypes (P = 0.015) and alleles (P = 0.006) of the rs653765 SNP. Furthermore, patients with the rs653765 CC genotype showed a lower ADAM10 level and a faster cognitive deterioration than those in patients with the CT/TT genotype in late-onset AD (LOAD), and the rs653765 CC polymorphism was able to regulate the production of the ADAM10 substrate sRAGE. In contrast, the rs514049 polymorphism was not statistically associated with AD. In the meta-analysis, we observed that both rs514049 (A allele vs. C allele, P = 0.002) and rs653765 (C allele vs. T allele, P = 0.004) were associated with AD risk. The present study indicated that the rs653765 polymorphism might be associated with the risk and development of LOAD; in particular, the risk genotype, CC, may decrease the expression of ADAM10, influencing the plasma levels of sRAGE, and thus may be correlated with the clinical progression of AD.

Modulating Three-Dimensional Microenvironment with Hyaluronan of Different Molecular Weights Alters Breast Cancer Cell Invasion Behavior.

Hyaluronan (HA), a polymer with various molecular weights (MW) found in tumor microenvironments, is associated with malignant progression of breast cancer. Reducing the amount of high-MW HA in the microenvironment by hyaluronidase is a promising approach for breast cancer treatment. However, whether the generation of HA fragments negatively affects breast cancer cells remains to be determined. Furthermore, HA forms three-dimensional (3D) networks by cross-linking with other extracellular molecules to function. Therefore, a model mimicking the cross-linked HA network is required to determine the effect of HA fragments on breast cancer cells. To clarify the differential roles of low (HA35) versus high (HA117) MW HA on cancer cell phenotype, a 3D culture system was set up by covalently cross-linking HA with alginate and investigating the behavior of 4T-1 and SKBR3 breast cancer cells alongside a two-dimensional (2D) control. The results show the invasion and migration abilities of 4T-1 and SKBR3 cells are significantly enhanced by the presence of HA35 but inhibited by HA117 in both 2D monolayers and 3D spheroids. The differential effects of HA35 and HA117 on cancer cell epithelial-mesenchymal transition (EMT) phenotype were further confirmed in terms of differential regulation of E-cadherin and vimentin as important EMT markers at both the cellular and mRNA levels. Additional experiments show the CD44-Twist signaling pathway might be involved in the differential effects of HA35 and HA117. These results have important implications with respect to understanding the role of HA in breast cancer development and for the design of therapeutic approaches based on the eradication of HA with hyaluronidase.

[Thinking on acupuncture depth].

With acupuncture depth as a perspective, some related issues are discussed in this paper. Firstly, the possible reasons of divergence on needling depth are explained. Secondly, by literature retrieval, the advantages and disadvantages of the clinical efficacy of deep needling and shallow needling are explored, and the essential value of shallow needling is emphasized in promoting acupuncture. Thirdly, due to the placebo acupuncture that led to the controversy of the curative effect of acupuncture, it is crucial to establish a method of modern system of scientific research which should be suitable for the development of acupuncture. Finally, the "cun" in acupuncture is inappropriate to transform into millimeter, and the standardization of acupuncture should focus on the improvement of curative efficacy. From the acupuncture depth, it is clear that there are plenty of problems in acupuncture, which could not only limit the development of acupuncture, but also affect the future of acupuncture.

Association between Polymorphisms of the AKT1 Gene Promoter and Risk of the Alzheimer's Disease in a Chinese Han Population with Type 2 Diabetes.

AIMS: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with type 2 diabetes (T2D) where the v-akt murine thymoma viral oncogene homolog 1 (AKT1) plays an important role in the protein synthesis pathways and cell apoptosis processes. Evidence has been shown that AKT1 protein may be related to AD risk among patients with T2D. The aim of this study was to analyze the potential association between single nucleotide polymorphisms of AKT1 promoter and the risk of AD among patients with T2D. METHODS: The association between AKT1 polymorphisms and AD risk in patients with T2D was assessed among 574 consecutive unrelated subjects including 112 AD patients with T2D, 231 patients with AD, and 231 healthy controls in a case-control study. The cognitive function of all subjects was assessed using MMSE. Six single nucleotide polymorphisms with minor allele frequency >0.2 (rs2498786, rs74090038, rs2494750, rs2494751, rs5811155, and rs2494752) in AKT1 promoter were analyzed by polymerase chain reaction (PCR), and the concentration of AKT1 protein in serum was tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, there was statistically significant difference in AKT1 rs2498786 polymorphism. The CC frequency of AKT1 rs2498786 polymorphism in AD with T2D group and AD control group was significantly higher than that in healthy control group (PAD+T2D vs. health < 0.0001, PAD vs. health < 0.0001). However, the difference was not found between AD with T2D group and AD control group. Compared with healthy control group, the plasma levels of AKT1 protein in AD with T2D group (PAD+T2D vs. health < 0.0001) and AD control group (PAD vs. health = 0.0003) decreased significantly. Among genotypes of AKT1 rs2498786 polymorphism, the AKT1 protein level in GG genotype was significantly higher than that in GC genotype (PGG vs. GC < 0.0001) and CC genotype (PGG vs. CC < 0.0001). CONCLUSION: The study suggests that AKT1 rs2498786 polymorphism in insulin signaling pathway may be associated with AD risk and different genotypes may affects levels of protein expression. However, the polymorphism is not shown to be exclusive in AD patients with T2D.

Polymorphism -116C/G of human X-box-binding protein 1 promoter is associated with risk of Alzheimer's disease.

AIM: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with endoplasmic reticulum (ER) stress response. In the response, the regulator factor human X-box-binding protein 1 (XBP1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid-beta (Aß) and tau, and play an important role in the survival of neurons. The aim in the study was to analyze the potential association between the -116C/G polymorphism of XBP1 and the risk of AD. METHODS: The association between -116C/G polymorphism of XBP1 promoter and possible risk of AD was assessed among 276 patients with AD and 254 matched healthy individuals in a case-control study. RESULTS: Overall, there was a significantly statistical difference in genotype (P = 0.0354) and allele frequencies (P = 0.0150, OR = 1.3642, 95% CI = 1.0618-1.7528) between the AD subjects and control subjects, showing that the -116C/G polymorphism of XBP1 might lead to increased susceptibility for AD in a Chinese Han population. In addition, the -116CG and -116GG genotypes were significantly associated with increased AD risk in female (P = 0.0217) and in subjects with APOE є4 (-) (P = 0.0070) in stratified analyses, and the -116CC genotype was significantly associated with fast cognitive deterioration in the AD patients (P = 0.0270). CONCLUSION: The study supports a role for the -116C/G polymorphism of XBP1 gene in the pathogenesis of AD, and further studies with a larger sample size and detailed data should be performed in other populations.