ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg^-1）， medium-dose TFA （TFA-M， 54 mg·kg^-1）， high-dose TFA （TFA-H， 108 mg·kg^-1）， and losartan potassium （LST， 4.5 mg·kg^-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl₄）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl₄ was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E₂ （PGE₂）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE₂ levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE₂ levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B₄， leukotriene D₄， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.

In the central nervous system (CNS), the myelin sheath, a specialized membrane structure that wraps around axons, is formed by oligodendrocytes through a highly coordinated spatiotemporal developmental program. The process begins with the directed differentiation of neural precursor cells into oligodendrocyte precursor cells (OPCs), followed by their migration, proliferation, differentiation, and maturation, ultimately leading to the formation of a multi-segmental myelin sheath structure. Recent single-cell sequencing research has revealed that this process involves the temporal regulation of over 200 key genes, with a regulatory network composed of transcription factors such as Sox10 and Olig2 playing a central role. The primary function of the myelin sheath is to accelerate nerve signal transmission and protect nerve fibers from damage. Its insulating properties not only increase nerve conduction speed by 50-100 times but also ensure the long-term functional integrity of the nervous system by maintaining axonal metabolic homeostasis and providing mechanical protection. The pathological effects of myelin sheath injury exhibit a cascade amplification pattern: acute demyelination leads to action potential conduction block, while chronic lesions may cause axonal damage and neuronal death in severe or long-term cases, ultimately resulting in irreversible neurological dysfunction with neurodegenerative characteristics. Multiple sclerosis (MS) is a neurodegenerative disease characterized by chronic inflammatory demyelination of the CNS. Clinically, the distribution of lesions in MS exhibits spatial heterogeneity, which is closely related to differences in the regenerative capacity of oligodendrocytes within the local microenvironment. Emerging evidence suggests that astrocytes form a dynamic “neural-immune-metabolic interface” and play a multidimensional regulatory role in myelin development and regeneration by forming heterogeneous populations composed of different subtypes. During embryonic development, astrocytes induce the targeted differentiation of OPCs in the ventricular region through the Wnt/β-catenin pathway. In the mature stage, they secrete platelet-derived growth factor AA (PDGF-AA) to establish a chemical gradient that guides the precise migration of OPCs along axonal bundles. Notably, astrocytes also provide crucial metabolic support by supplying energy substrates for high-energy myelin formation through the lactate shuttle mechanism. In addition, astrocytes play a dual role in myelin regulation. During the acute injury phase, reactive astrocytes establish a triple defense system within 72 h: upregulating glial fibrillary acidic protein (GFAP) to form scars that isolate lesions, activating the JAK-STAT3 regeneration pathway in oligodendrocytes via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.

Locomotion, a fundamental motor function encompassing various forms such as swimming, walking, running, and flying, is essential for animal survival and adaptation. The mesencephalic locomotor region (MLR), located at the midbrain-hindbrain junction, is a conserved brain area critical for controlling locomotion. This review highlights recent advances in understanding the MLR’s structure and function across species, from lampreys to mammals and birds, with a particular focus on insights gained from optogenetic studies in mammals. The goal is to uncover universal strategies for MLR-mediated locomotor control. Electrical stimulation of the MLR in species such as lampreys, salamanders, cats, and mice initiates locomotion and modulates speed and patterns. For example, in lampreys, MLR stimulation induces swimming, with increased intensity or frequency enhancing propulsive force. Similarly, in salamanders, graded stimulation transitions locomotor outputs from walking to swimming. Histochemical studies reveal that effective MLR stimulation sites colocalize with cholinergic neurons, suggesting a conserved neurochemical basis for locomotion control. In mammals, the MLR comprises two key nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). Both nuclei contain glutamatergic and GABAergic neurons, with the PPN additionally housing cholinergic neurons. Optogenetic studies in mice by selectively activating glutamatergic neurons have demonstrated that the CnF and PPN play distinct roles in motor control: the CnF drives rapid escape behaviors, while the PPN regulates slower, exploratory movements. This functional specialization within the MLR allows animals to adapt their locomotion patterns and speed in response to environmental demands and behavioral objectives. Similar to findings in lampreys, the CnF and PPN in mice transmit motor commands to spinal effector circuits by modulating the activity of brainstem reticular formation neurons. However, they achieve this through distinct reticulospinal pathways, enabling the generation of specific behaviors. Further insights from monosynaptic rabies viral tracing reveal that the CnF and PPN integrate inputs from diverse brain regions to produce context-appropriate behaviors. For instance, glutamatergic neurons in the PPN receive signals from other midbrain structures, the basal ganglia, and medullary nuclei, whereas glutamatergic neurons in the CnF rarely receive inputs from the basal ganglia but instead are strongly influenced by the periaqueductal grey and inferior colliculus within the midbrain. These differential connectivity patterns underscore the specialized roles of the CnF and PPN in motor control, highlighting their unique contributions to coordinating locomotion. Birds exhibit exceptional flight capabilities, yet the avian MLR remains poorly understood. Comparative studies suggest that the pedunculopontine tegmental nucleus (PPTg) in birds is homologous to the mammalian PPN, which contains cholinergic neurons, while the intercollicular nucleus (ICo) or nucleus isthmi pars magnocellularis (ImC) may correspond to the CnF. These findings provide important clues for identifying the avian MLR and elucidating its role in flight control. However, functional validation through targeted experiments is urgently needed to confirm these hypotheses. Optogenetics and other advanced techniques in mice have greatly advanced MLR research, enabling precise manipulation of specific neuronal populations. Future studies should extend these methods to other species, particularly birds, to explore unique locomotor adaptations. Comparative analyses of MLR structure and function across species will deepen our understanding of the conserved and evolved features of motor control, revealing fundamental principles of locomotion regulation throughout evolution. By integrating findings from diverse species, we can uncover how the MLR has been adapted to meet the locomotor demands of different environments, from aquatic to aerial habitats.

Objective To understand and grasp the status quo of resistance of Culex pipiens pallens to four commonly used insecticides in Hefei City, and to provide a scientific basis for the chemical control of mosquito larvae. Methods From June to July 2023, Cx. pipiens pallens larvae were collected from 9 counties (cities and districts) in Hefei City. The LC50 of late third-instar to early fourth-instar larvae of Cx. pipiens pallens to commonly used insecticides was determined by larval immersion method (sensitive baseline method). Results Cx.pipiens pallens larvae in Hefei City exhibited different degrees of resistance to four insecticides: permethrin, beta-cypermethrin, temephos, and propoxur. The relative resistance coefficients to permethrin and beta-cypermethrin were 26.96 and 21.17, respectively, indicating the moderate resistance level. The relative resistance coefficients to propoxur were 6.70, indicating a low resistance level. The relative resistance coefficient to temephos was 2.43, indicating a sensitivity level. Culex pipiens pallens against pyrethroids such as 0.25% permethrin, 0.025% deltamethrin and 0.025% cypermethrin in 1 h knockout rate and 24 h mortality rates were 3.25% (4/123) and 46.34% (57/123), 3.60% (5/139) and 35.97% (50/139), 3.85% (6/156) and 40.38% (63/156), respectively. For 5% malathion and 0.1% propoxur, the 1 h knockdown rate and 24 h mortality rate were 97.69% (127/130) and 99.23% (129/130), 94.48% (137/145) and 100.00% (145/145), respectively. It showed resistance to 0.25% permethrin, 0.025% deltamethrin and 0.025% cypermethrin, and sensitivity to 5% malathion and 0.1% propoxur. Conclusions Culex pipiens pallens in Hefei City have developed varying degrees of resistance to parathyroid and carbamate insecticides. In the control of mosquito vectors, it is essential to strengthen the scientific and rational use of chemical control in combination with environmental and physical control measures to form an integrated control strategy. This approach will improve the control efficiency while delaying the occurrence and development of insecticide resistance.

Objective To explore the relationship between osteoporosis and carotid atherosclerosis in patients with coronary heart disease aged≥60 years and analyze prevention suggestions. Methods The clinical data of 380 patients with coronary heart disease aged≥60 years who underwent various examinations in the hospital between April 2024 and April 2025 were retrospectively analyzed. According to the bone mineral density (BMD) classification criteria, the patients were divided into osteoporosis group and non-osteoporosis group. The differences in general data and carotid atherosclerosis-related indicators were compared between osteoporosis group and non-osteoporosis group. Pearson method was used to analyze the correlation between carotid atherosclerosis indicators and clinical indicators in patients with coronary heart disease aged≥60 years. According to the IMT detection thickness in patients with coronary heart disease and osteoporosis aged≥60 years were divided into IMT thickening group and IMT non-thickening group and between plaque group and non-plaque group, and the differences in BMD and bone metabolism indicators were compared. Binary logistics analysis was adopted to analyze the risk factors of IMT thickening and carotid plaque formation in patients with coronary heart disease≥60 years old. Results Age and duration of osteoporosis group TC、LDL-C、CTX、 Carotid artery IMT and carotid atherosclerosis degree were higher than those in the non osteoporosis group, the difference was statistically significant (P<0.05). BMI, OPG, OCN, 25 (OH) D, BMD, carotid artery elasticity coefficient were lower than those in the non osteoporosis group, the difference was statistically significant (P<0.05). Carotid IMT, carotid atherosclerosis degree, and carotid elasticity coefficient were significantly correlated with age, course of disease, TC, LDL-C, CTX, BMI, OPG, OCN, BMD, and 25 (OH) D of coronary heart disease patients ≥60 years old (P<0.05). OPG, OCN, BMD and 25(OH)D in IMT thickening group and plaque group were lower compared to IMT non-thickening group and non-plaque group (P<0.05) while CTX was significantly higher than that in IMT non-thickening group and non-plaque group (P<0.05). Binary logistics regression analysis showed that OPG, OCN, BMD, 25(OH)D and CTX were associated with IMT thickening in patients with coronary heart disease and osteoporosis aged≥60 years (P<0.05). OPG, OCN and BMD were associated with carotid plaque formation in patients with coronary heart disease complicated with osteoporosis aged≥60 years (P<0.05). Conclusion There is a significant correlation between osteoporosis and arteriosclerosis in patients with coronary heart disease aged≥60 years. As the bone mass decreases, the manifestations of arteriosclerosis become become more and more obvious, which needs attention and prevention.

Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P＜0.01),and a significant de-crease in DAI scores(P＜0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P＜0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P＜0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P＜0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P＜0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P＜0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P＜0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P＜0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.

The receptors of Newcastle disease virus(NDV)are sialic acid receptors that mainly in-clude neu5ac-α-2,3gal-β-1,4Glc(SAα2,3Gal)and neu5ac-2-s-α-2,6Gal10Me(SAα2,6Gal).The distribution and abundance of the two receptors in host cells have important effects on virus sus-ceptibility and intracellular proliferation.In order to further explore the effects of sialic acid recep-tors on susceptibility and proliferation characteristics of NDV different strains,the expression lev-els of SAα2,3Gal and SAα2,6Gal receptors on BHK-21 cell membrane were adjusted by overex-pression and RNAi assays,and the TCID50 values were determined after different BHK-21 cells were inoculated with NDV strains Ⅰ and LaSota.The results suggested that NDV strain LaSota preferentially binds to SAα2,6Gal and strain Ⅰ selectively binds to SAα2,3Gal receptor.Further-more,the viral titers of NDV strains LaSota and Ⅰ in cell culture were positively correlated with the expression levels of SAα2,6Gal and SAα2,3Gal receptors on host cell membrane respectively.In conclusion,our studies provide an understanding of the relationship between infectivity of NDV different strains and receptor types of host cell,and provide a method to increase viral titer of NDV for cell-based vaccine production.

In 2015,the International Ascites Club proposed a new definition of hepatorenal syndrome-acute kidney injury based on the progression of hepatorenal syndrome,and studies are still being conducted to explore the exact pathogenesis of hepatorenal syndrome-acute kidney injury.Intestinal barrier plays an important bridging role in liver-kidney connection,and intestinal flora disturbance,bacterial translocation,and endotoxins entering the blood cause damage to the kidneys by releasing proinflammatory cytokines and activating immune-related cells.The entrance of bile acid into the circulation system also directly or indirectly lead to the development and progression of hepatorenal syndrome-acute kidney injury.This article reviews the crosstalk mechanism of hepatorenal syndrome-acute kidney injury from the perspective of the intestinal barrier and further clarifies the key role of the liver-gut-kidney axis in the pathogenesis of this disease,in order to provide new treatment ideas.

Objective To observe the clinical efficacy and safety of dexmedetomidine injection combined with esketamine injection in the treatment of patients with oral squamous cell carcinoma radical resection.Methods Patients with oral squamous cell carcinoma radical resection were randomly divided into treatment and control groups.The treatment group will receive intravenous administration of 0.6 μg·kg-1 dexmedetomidine 10 minutes before anesthesia induction.Subsequently,anesthesia induction will be performed with intravenous administration of 0.5 mg·kg-1 esketamine.Anesthesia maintenance will be achieved with intravenous infusion of 0.25 mg·kg-1·h-1 esketamine and 0.3 μg·kg-1·h-1 dexmedetomidine used an infusion pump.The control group will receive intravenous administration of an equivalent volume of 0.9％NaCl 10 minutes before anesthesia induction.Anesthesia induction will then be performed with intravenous administration of 2.5-5.0 μg·kg-1 fentanyl.Anesthesia maintenance will involve intravenous infusion of 0.10-0.25 μg·kg-1·min-1 remifentanil used an infusion pump.The anesthesia effectiveness,analgesic effectiveness,hemodynamics and safety were compared between the two groups.Results Treatment group were enrolled 62 cases,1 case dropped out,and 61 cases were finally included in the statistical analysis.Control group were enrolled 61 cases,1 case dropped out,and 60 cases were finally included in the statistical analysis.The recovery room stay time of treatment and control groups was(25.97±4.52)and(18.39±3.64)min,the extubation time was(16.75±4.84)and(10.16±3.18)min,and the differences were statistically significant(all P＜0.05).After operation 24 h,visual analogue scores of treatment and control groups were(0.85±0.17)and(1.39±0.25)points,adrenocorticotropin levels were(60.07±7.13)and(72.64±9.81)pg·mL-1,cortisol levels were(481.20±49.15)and(539.94±57.77)nmol·L-1,and the differences were statistically significant(all P＜0.05).The mean arterial pressure at 30 min after anesthesia induction(T1)and at the end of surgery(T2)in treatment group were(82.34±4.98)and(86.57±4.18)mmHg,while those in control group were(77.25±7.16)and(76.02±6.29)mmHg;the heart rates of T1 and T2 in treatment groups were(64.08±4.19)and(66.45±4.83)time·min-1,while those in control group were(68.44±6.02)and(72.08±7.27)time·min-1;and the differences were statistically significant(all P＜0.05).The adverse drug reactions in two groups were nausea,vomiting,bradycardia and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 8.20％and 15.00％,without significant difference(P＞0.05).Conclusion Dexmedetomidine injection combined with esketamine injection has a definitive analgesia efficacy in the treatment of patients with oral squamous cell carcinoma radical resection,which can significantly reduce stress responses,maintain hemodynamic stability,without increasing the incidence of adverse drug reactions.

Objective:This study aims to investigate the predictive performance of serum levels of white blood cell count(WBC),D-dimer(D-D)and N-terminal pro-brain natriuretic peptide(NT-proBNP)for major adverse cardiovascular events(MACE)in elderly patients with acute ST-segment elevation myocardial infarction(ASTE-MI).Methods:A total of 70 elderly patients with ASTEMI treated in Bozhou People's Hospital between April 2020 and May 2023 were prospectively selected as observation group.Incidence of MACE during 1-year follow-up were recorded,another 50 patients with unstable angina pectoris treated in our hospital simultaneously were selected as control group.Serum levels of WBC,D-D and NT-proBNP were compared among above groups.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum WBC,D-D and NT-proBNP for MACE in elderly patients with ASTEMI.A nomogram was established,and calibration curve and deci-sion curve analysis(DCA)were used to evaluate the performance of model.Results:A total of 40 cases(59.70％)experienced MACE during one-year follow-up.Compared to those in control group,patients in observation group had significant higher serum WBC[(11.43±1.98)×109/Lvs.(6.30±1.99)× 109/L],D-D[(0.91±0.20)mg/L vs.(0.47±0.18)mg/L]andNT-proBNP[(192.31±63.19)pg/ml vs.(114.05±22.79)pg/ml](P＜0.001 all).Compared to participants without MACE,those with MACE had significantly higher serum WBC[(13.33±1.90)× 109/L vs.(10.27±0.98)× 109/L],D-D[(1.11±0.25)mg/L vs.(0.87±0.21)mg/L]and NT-proBNP[(238.73±50.22)pg/ml vs.(150.70±39.16)pg/ml](P＜0.001 all).ROC analysis showed that the ar-ea under the curve(AUC)of the combined detection of serum WBC(AUC=0.791,95％CI 0.677～0.879),D-D(AUC=0.767,95％CI 0.650～0.859)and NT-proBNP(AUC=0.733,95％CI 0.614～0.832)was 0.916(95％CI 0.825～0.969),which was significantly higher than those of single detections(Z=2.386,4.953,3.190,P=0.017,0.004,＜0.001).The total score of the nomogram model constructed based on the levels of WBC,D-D and NT-proBNP ranged from 70 to 126 points.The predicted incidence was basically consistent with the actual in-cidence.For the internal verification of the model,the AUC of ROC curve of the training set and the validation set was 0.863 and 0.926 respectively.The DCA curve was located above the critical curve,indicating that the model had a net benefit and good clinical effectiveness.Conclusion:Serum WBC,D-D and NT-proBNP significantly el-evated in elderly patients with ASTEMI.The combined detection of serum WBC,D-D and NT-proBNP levels has good predictive value for MACE in these patients.