ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

ObjectiveTo observe the effect of modified Shibaotang on serum sex hormone levels in patients with male late-onset hypogonadism of kidney essence deficiency syndrome complicated with diabetes mellitus. MethodsA total of 60 patients with male late-onset hypogonadism of kidney essence deficiency syndrome complicated with diabetes mellitus，who met the inclusion criteria and were admitted to Yinchuan Hospital of Traditional Chinese Medicine from October 2022 to October 2023，were selected and randomly divided into an observation group and a control group，with 30 patients in each group. Both groups continued their original treatments，including blood glucose lowering and blood lipid regulation. The observation group was treated with modified Shibaotang，while the control group was treated with testosterone undecanoate capsules. The treatment lasted for 12 weeks. The changes in traditional Chinese medicine （TCM）syndrome scores，partial androgen deficiency in aging males （PADAM）symptom scores，glucose metabolism indexes ［fasting plasma glucose （FPG），2-hour postprandial glucose （2 h PG），glycosylated hemoglobin （HbA1c）］，and serum sex hormone indexes ［sex hormone-binding globulin （SHBG），free testosterone （FT），total testosterone （TT），prolactin （PRL），luteinizing hormone （LH），follicle stimulating hormone （FSH），estrogen （E₂）］ were compared between the two groups before and after treatment. Safety was also evaluated. Results（1）Clinical efficacy comparison：After treatment，the clinical efficacy in both groups was similar，and there was no statistically significant difference between the two groups. （2）TCM syndrome score and PADAM symptom score comparison：After treatment，both groups showed a significant reduction in TCM syndrome scores and PADAM symptom scores （P<0.01），and the observation group showed a significantly greater reduction compared to the control group （P<0.05）. （3）Glucose metabolism indexes comparison：After treatment，the levels of FPG，2 h PG，and HbA1c were significantly reduced in both groups （P<0.01），and there was no statistically significant difference between the two groups regarding FPG，2 h PG，and HbA1c levels after treatment. （4）Serum sex hormone indexes comparison：After treatment，the levels of FT，TT，PRL，LH，and FSH were significantly increased in both groups （P<0.01），while E₂ levels were significantly decreased （P<0.01）. There was no statistically significant difference between the two groups in the levels of FT，TT，PRL，LH，FSH，and E₂ after treatment. There was also no significant difference in SHBG levels within or between the groups before and after treatment. During the clinical observation，neither group exhibited any obvious adverse reactions. ConclusionModified Shibaotang can significantly improve the clinical symptoms of male late-onset hypogonadism of kidney essence deficiency syndrome complicated with diabetes mellitus，reduce blood glucose，and increase sex hormone levels. The mechanism may involve the inhibition of aromatase transformation in adipocytes，promotion of GnRH production，and regulation of the hypothalamic-pituitary-gonadal axis function.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

BACKGROUND: The urban-rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions. METHODS: We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7-18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups. RESULTS: The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33-12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10-11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72-33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33-6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82-27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43-8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985-2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025. CONCLUSIONS The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban-rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.
Humans ; Child ; Adolescent ; Female ; Male ; Rural Population/statistics & numerical data* ; Overweight/epidemiology* ; Prevalence ; China/epidemiology* ; Pediatric Obesity/epidemiology* ; Obesity/epidemiology* ; Urban Population

BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models