Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

Objective:To extract the early result of postoperative echocardiographic evaluation in patients underwent left ventricular assist device (LVAD) implantation, and to assess the efficacy of surgical treatment for end-staged heart failure.Methods:Between June 2019 and May 2023, the patients underwent left ventricular assist device implantation were enrolled in this study. Demographic baseline characteristics and perioperative echocardiographic parameters were collected and analyzed.Results:A total of 28 patients were included in the study. After LVAD implantation, the heart sizes of the patients obviously reduced and the left heart contractibility function improved. The right ventricular contractibility remained stable. The proportion of the patients with moderate to severe mitral regurgitation was significantly reduced, but patients with mild to moderate aortic insufficiency increased. No serious complications such as death, pericardial tamponade and thrombosis events were observed during the follow-up period.Conclusion:LVAD implantation improved the left cardiac function, while the right cardiac function remained stable. However, it should be paid attention that the aortic valve function was impaired after the surgery. Generally, the early results of LVAD implantation for the treatment of end-stage heart failure were satisfactory.

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/chemistry* ; Rehmannia/chemistry* ; Flavonoids/analysis*

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

Illumina Xten was employed for shallow sequencing of Panax ginseng(ginseng) samples, MISA for screening of SSR loci, and Primer 3 for primer design. Polymorphic primers were screened from 180 primers. From the successfully amplified polymorphic primers, 15 primers which featured clear peak shape, good polymorphism, and ease of statistics were selected and used to evaluate the genetic diversity and germplasm resources of 36 ginseng accessions with different fruit colors from Jilin province. The results showed that red-fruit ginseng population had high genetic diversity with the average number of alleles(N_a) of 1.031 and haploid genetic diversity(h) of 0.172. The neighbor-joining cluster analysis demonstrated that the germplasms of red-fruit and yellow-fruit ginseng populations were obviously intermixed, and pick-fruit ginseng germplasms clustered into a single clade. The results of STRUCTURE analysis showed high proportion of single genotype in pick-fruit ginseng germplasm and abundant genotypes in red-fruit and yellow-fruit ginseng germplasms with obvious germplasm mixing. AMOVA revealed that genetic variation occurred mainly within populations(62.00%, P<0.001), and rarely among populations(39%, P<0.001), but homogenization was obvious among different populations. In summary, pink-fruit ginseng population may contain rare genotypes, which is the basis for breeding of high-quality high-yield, and multi-resistance varieties, genetic improvement of varieties, and sustainable development and utilization of ginseng germplasm resources.
Fruit/genetics* ; Genetic Variation ; Microsatellite Repeats ; Panax/genetics* ; Plant Breeding

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

BACKGROUND: The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population. METHODS: A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR <60 mL·min -1 ·1.73 m -2 . RESULTS: After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, β -2.53, 95% confidence interval -3.89, -1.17, Ptrend < 0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference <90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no). CONCLUSIONS Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.
Humans ; Male ; Middle Aged ; China/epidemiology* ; Kidney/metabolism* ; Prospective Studies ; Sex Hormone-Binding Globulin/physiology* ; Testosterone ; Tomography, Emission-Computed, Single-Photon ; Glomerular Filtration Rate

OBJECTIVE: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. METHODS: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. RESULTS: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. CONCLUSION The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.
Middle Aged ; Male ; Humans ; Creatinine ; Cross-Sectional Studies ; Asian People ; Glomerular Filtration Rate ; China

Objective: Cytoreductive surgery followed by adjuvant chemotherapy is a standard frontline treatment for epithelial ovarian cancer (EOC). We aimed to develop an ovarian cancer risk score (OVRS) based on the expression of 10 ovarian-cancer-related genes to predict the chemoresistance, and outcomes of EOC patients. Methods: We designed a case-control study with total 149 EOC women including 75 chemosensitives and 74 chemoresistants. Gene expression was measured using the quantitative real-time polymerase chain reaction. We tested for correlation between the OVRS and chemosensitivity or chemoresistance, disease-free survival (DFS), and overall survival (OS), and validated the OVRS by analyzing patients from the TCGA database. Results: The chemosensitive group had lower OVRS than the chemoresistant group (5 vs.15, p≤0.001, Mann-Whitney U test). Patients with disease relapse (13 vs. 5, p<0.001, MannWhitney U test) or disease-related death (13.5 vs. 6, p<0.001) had higher OVRS than those without. OVRS ≥10 (hazard ratio=3.29; 95% confidence interval=1.94–5.58; p<0.001) was the only predictor for chemoresistance in multivariate analysis. The median DFS (5 months vs. 24 months) and OS (39 months vs. >60 months) of patients with OVRS ≥10 were significantly shorter than those of patients with OVRS <9). The high OVRS group also had significantly shorter median OS than the low OVRS group in 255 patients in the TCGA database (39 vs. 49 months, p=0.046). Conclusions Specific genes panel can be clinically applied in predicting the chemoresistance and outcome, and decision-making of epithelial ovarian cancer.