ObjectiveAs the central hub of the classical visual pathway, the primary visual cortex not only encodes and processes visual information but also establishes dense neural circuit connections with higher-order cognitive brain regions. Numerous studies have shown that 40 Hz flicker stimulation can induce γ oscillations in the brain and significantly improve learning and cognitive impairments in patients with neurodegenerative diseases. Moreover, flickering light phenomena naturally occur in daily environments. Given that the primary visual cortex serves as the brain’s first cortical hub for receiving visual input, it is essential to comprehensively understand how non-invasive light flicker stimulation modulates its information processing mechanisms. This study systematically investigates the effects of non-invasive light flicker stimulation at different frequencies on the functional properties of neurons in the primary visual cortex of adult mice, aiming to uncover how such stimulation modulates this region and, consequently, affects overall brain function. MethodsThree groups of adult mice (approximately 12 weeks old) were exposed to light flicker stimulation at frequencies of 20 Hz, 40 Hz, and 60 Hz, respectively, for a duration of two months. A control group was exposed to the same light intensity without flickering. Following the stimulation period, in vivo multi-channel electrophysiological recordings were conducted. During these recordings, anesthetized mice were presented with various types of moving sinusoidal light gratings to assess the effects of different flicker frequencies on the functional properties of neurons in the primary visual cortex. ResultsThe experimental results demonstrate that two months of light flicker stimulation at 20 Hz, 40 Hz, and 60 Hz enhances the orientation tuning capabilities of neurons in the primary visual cortex. Specifically, 40 Hz and 60 Hz stimulation improved contrast sensitivity, whereas 20 Hz had no significant effect. Further analysis revealed that all three frequencies reduced neuronal response variability (as measured by the Fano factor), increased the signal-to-noise ratio, and decreased noise correlation (r_sc) between neurons. ConclusionNon-invasive light flicker stimulation enhances orientation tuning (e.g., orientation bias index) and contrast sensitivity (e.g., contrast threshold and C₅₀) in neurons of the primary visual cortex. This enhancement is likely due to improved information processing efficiency, characterized by reduced neuronal variability and increased signal-to-noise ratio. These findings suggest that the primary visual cortex can achieve precise and efficient information encoding in complex lighting environments by selectively adapting to different flicker frequencies and optimizing receptive field properties. This study provides new experimental evidence on how various types of light flicker influence visual perception and offers insights into the mechanisms through which specific frequencies enhance brain function.

Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the α-shape analysis to determine the habitat of L. rotata. We then carried out the climate-niche factor analysis (CNFA) to assess the vulnerability of L. rotata to climate change based on five climate variables (i.e., mean diurnal range, temperature seasonality, mean temperature of warmest quarter, precipitation of driest month and precipitation of warmest quarter) in the context of two shared socioeconomic pathways (i.e., SSP126 and SSP585) and three global climate models (CMCC-ESM2: Centro Euro-Mediterraneo sui Cambiamenti Climatici-Earth System Model version 2; HadGEM3-GC31-LL: Hadley Global Environment Model version 3-Global Coupled configuration 3.1; IPSL-CM6A-LR: Institut Pierre Simon Laplace-Climate Model version 6) during two different periods (2041-2060 and 2081-2100). The vulnerability of L. rotata to climate change was calculated by integrating the sensitivity and exposure indices of L. rotata to five climate variables. The results showed that L. rotata had the highest vulnerability to the precipitation of warmest quarter. Its vulnerability within its habitat range generally showed a spatial pattern of high value in the southern region and low in the northern region, high in the western region and low in the eastern region. In general, the vulnerability of L. rotata under the SSP585 scenario was higher than that under the SSP126 scenario. The climate data of different global climate models have some influence on the results, while the resulted uncertainty can be reduced by data integration methods. As a result of climate change, the pressure on the survival of L. rotata in the future will be intensified in the low-altitude areas such as the Yarlung Zangbo River, Yigongzangbu River, Zayu River, and Jiaomuzu River, etc., while the highly weathered scree flats or stony alpine meadows in the high-altitude zones, such as the eastern Tanggula Mountain Range, the northern part of Hengduan Mountain Range, and the western part of the Qinling Mountains, may become its refuge. It is necessary to focus on and strengthen the protection and management of L. rotata resources in these vulnerble and critical areas.

Objective To explore the current application of high-throughput drug sensitivity(HDS)testing in children with relapsed and refractory acute leukemia(RR-AL)and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted,followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing,including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia.The detection rate of highly sensitive chemotherapy drugs/regimens was 53%(9/17),while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100%(17/17).Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens,the MOACD regimen(mitoxantrone+vincristine+cytarabine+cyclophosphamide+dexamethasone)accounted for 100%,with the highest inhibition rate for single-agent mitoxantrone(94%,16/17),and the highest inhibition rate for targeted therapy being bortezomib(94%,16/17).Nine patients adjusted their chemotherapy based on HDS testing results,with 4 undergoing hematopoietic stem cell transplantation.Four patients achieved disease-free survival,while 5 died.Eight patients received empirical chemotherapy,with 2 undergoing hematopoietic stem cell transplantation;4 achieved disease-free survival,while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL,improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Objective To explore the incidence of long CO VID symptoms in patients infected with Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods According to the inclusion and exclu-sion criteria of literatures,relevant studies without language restrictions published up to 2024 were retrieved from both Chinese and English databases.The Chinese databases were China National Knowledge Infrastructure(CNKI),Wanfang Database,and VIP databases,and the foreign databases were PubMed,Embase,and Web of Science.Three-step screening was used to select literatures,and Stata 17.0 software was used for analysis.Results The incidence of at least one sequelae in patients infected with Omicron variant was 29.62％.The most common symptoms included fatigue(19.10％),joint or muscle pain(11.06％),memory loss(9.71％),brain fog(8.80％),cough(8.42％),headache(7.26％),and sore throat(6.68％).Subgroup analysis results showed that with the extension of follow-up(3 months vs 6 months),the incidence of smell or taste changes was significantly re-duced(7.22％vs 0.78％).The higher the proportion of women(＜50％vs 50％-65％vs＞65％),the higher the incidence of joint or muscle pain(1.09％vs 4.62％vs 19.53％);the greater the median age(≥45 years vs＜45 years),the higher the incidence of chest pain or chest distress(0.90％vs 3.86％),all with statistically significant differences(all P＜0.05).Conclusion Incidence of long COVID in Omicron-infected patients is high and can cause various symptoms.Follow-up time,median age and gender proportion have significant impacts on the incidence of some symptoms.

Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

[ Abstract] Objective To explore the role pathway and pattern of the Kruppel-like factor 4 (KLF4) and its mRNA interaction with microRNA (miRNAs) and circular RNA (circRNAs) at 0 hour and the 120 th hour in the rat liver regeneration. Methods The rat 2 / 3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNA (ceRNA) were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3. 2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and the 120th hour PH, the ratio value of KLF4 mRNA showed 1. 00±0. 16 and 3. 14±0. 27, miR-881-3p displays 18. 30±1. 44 and 0. 47±0. 02, circRNA_20298 indicated 0. 32±0. 10 and 4. 24±0. 22, circRNA_14826 showed 0. 42±0. 13 and 0. 61±0. 08. At the same time, the four kinds of cell apoptosis-related genes adrenoceptor beta 2 (ADRB2), dimethylarginine dimethylaminohydrolase 2 (DDAH2), annexin A5 (ANXA5), ect, which were promoted in expression by KLF4, were down-regulated at 0 hour after PH, but the cell apoptosis-related genes synuclein gamma (SNCG), glutathione-disulfide reductase (GSR), FYVE, RhoGEF and PH domain containing 4 (FGD4), ect, which were inhibited in expression by KLF4, were up-regulated at 0 hour after PH. On the other hand, the cell apoptosis-related genes ANXA5 and thymosin beta 10 (TMSB10), which are promoted in expression by KLF4, were up-regulated at the 120th hour after PH, but the cell apoptosis-related genes chloride intracellular channel 4 (CLIC4) and ataxin 3 (ATXN3), ect, which were inhibited in expression by KLF4, were down-regulated at the 120th hour after PH. Conclusion The correlation in expression and role of the miRNAs, which are inhibited by circRNAs, KLF4, its mRNA is inhibited by miRNAs, and the cell apoptosis-related genes, which are regulated by KLF4, are helpful for the hepatocyte to be in active state 0 hour after PH and to be in apoptotic state 120-hour after PH.

OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (β-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum β-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), β-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the β-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum β-EP level and the increase of pain threshold so that analgesia is obtained.
Female ; Humans ; Ankle ; beta-Endorphin ; Wrist ; Acupuncture Therapy ; Abdominal Pain ; Acupuncture Points

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

Six new prenylated flavonoid glycosides, including four new furan-flavonoid glycosides wushepimedoside A-D (1-4) and two new prenyl flavonoid derivatives wushepimedoside E-F (5-6), and one know analog epimedkoreside B (7) were isolated from biotransformation products of the aerial parts of Epimedium wushanense. Their structures were elucidated according to comprehensive analysis of HR-MS and NMR spectroscopic data, and the absolute configurations were assigned using experimental and calculated electronic circular dichroism (ECD) data. The regulatory activity of compounds 1-7 on the production of testosterone in primary rat Leydig cells were investigated, and 4 and 5 exhibited testosterone production-promoting activities. Molecular docking analysis suggested that bioactive compounds 4 and 5 showed the stable binding with 3β-HSD and 4 also had good affinity with Cyp17A1, which suggested that these compounds may regulate testosterone production through stimulating the expression of the above two key proteins.
Animals ; Epimedium/chemistry* ; Flavonoids/chemistry* ; Furans ; Glycosides/chemistry* ; Hydrolysis ; Male ; Molecular Docking Simulation ; Molecular Structure ; Rats ; Testosterone ; beta-Glucosidase/metabolism*