ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

OBJECTIVE To explore clinical characteristics and risk factors of drug-induced hypofibrinogenemia， providing a reference for rational clinical drug use. METHODS Retrospective case analyses literature on drug-induced hypofibrinogenemia were collected from domestic and international databases from their inception to December 31， 2024. The patients’ gender， age， fibrinogen （FIB） levels before and after treatment， drug types， the incidence of drug-induced hypofibrinogenemia， time of occurrence， bleeding rates， clinical manifestations， risk factors， and protective factors were all analyzed. RESULTS A total of 40 retrospective case analysis studies were included， involving 17 313 patients. Patient age ranged from 0.83 to 78.40 years， with males accounting for 16.90%-81.00%. The involved drugs comprised 5 categories and 13 specific agents， including tigecycline， snake venom hemocoagulase， tocilizumab， and alteplase， etc. The incidence of drug-induced hypofibrinogenemia ranged from 0 to 100%， occurring between 2 hours and 9 months after drug administration， and FIB levels rebounded in most patients after drug discontinuation. The bleeding rate varied from 0% to 91.30%， including epistaxis， airway bleeding， gastrointestinal bleeding， and cerebral hemorrhage. Risk factors included high drug dosage， prolonged treatment duration， abdominal infection， advanced age， and low baseline FIB levels. Protective factors were only mentioned in studies on tigecycline， including skin and soft tissue infections and high baseline FIB levels. CONCLUSIONS Drug-induced hypofibrinogenemia is commonly associated with tigecycline， hemocoagulase， and tocilizumab. Its clinical features vary depending on the drug， and risk factors include high drug dosage， prolonged treatment， low baseline FIB levels， and advanced age. For high-risk medications， individualized medication management and monitoring of FIB levels are recommended.

Objective To investigate the prevalence of common diseases among primary and secondary school students in Yichang City from 2019 to 2022, and to provide a scientific basis for formulating effective intervention measures in the future. Methods By random cluster sampling , 7 schools in urban areas and 5 schools in suburban counties were selected to screen common diseases such as myopia, dental caries, obesity and abnormal spinal curvature. Descriptive epidemiological methods were employed for statistical analysis. Results A total of 17 023 primary and secondary school students were screened from 2019 to 2022. The overall detection rate of common diseases from high to low was myopia (54.12%), caries (36.75%), overweight (15.17%), obesity (11.88%), malnutrition (5.80%), and abnormal spinal curvature (3.49%). The detection rates of myopia and abnormal curvature of the spine showed an increasing trend with years and school stages, while the detection rates of malnutrition and dental caries showed a decreasing trend with years and school stages. The detection rates of overweight and obesity showed no trend difference with years, and the detection rates of obesity showed a decreasing trend with school stages. The rates of myopia, overweight and obesity were higher in urban areas than those in suburban counties, and the rate of dental caries was higher in suburban counties than that in urban areas. The prevalence of overweight, obesity, and malnutrition in boys was higher than that in girls. The prevalence of myopia and dental caries in girls was higher than that in boys. The above differences were statistically significant (all P<0.05). Conclusion Myopia, dental caries, obesity, and abnormal curvature of the spine are the current focus of the prevention and treatment of common diseases in students. There are great differences between different regions, school stages, and genders. The ^“tripartite linkage^” of schools, families, and communities should be achieved with the joint efforts of the education and health departments to actively take targeted intervention measures to reduce the prevalence.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

ObjectiveBased on the ultrastructure of enteric nervous system （ENS）-platelet-derived growth factor receptor α positive （PDGFRα⁺） cell - smooth muscle cell （SMC） network， the effect and mechanism of Shuwei Decoction （舒胃汤） for rats with functional dyspepsia （FD） of liver-depression and spleen-deficiency syndrome were explored. MethodsFifty SD rats were divided into blank group， model group， low-， medium- and high-dose Shuwei Decoction groups randomly， with 10 rats in each group. The blank group was not set up， and the other 4 groups were set up with the modified composite cause （chronic restraint stress + tail irritation + excessive fatigue + diet disorder） for 21 days， resulting in FD model rats with liver-depression and spleen-deficiency syndrome. After successful modelling， rats in the low-， medium- and high-dose groups were given 3.78， 7.56 and 15.12 g/（kg·d） of Shuwei Decoction by gavage， respectively， while rats in the blank group and the model group were given 10 ml/（kg·d） of saline by gavage； all of them were given gavage once a day for 14 days. Body mass increase were collected before and after gavage， and compared after the experiment； the elevated cross maze experiment was conducted to observe the percentage of staying time and the percentage of times entering the open arm of rats； the gastric emptying rate and small intestinal propulsion rate were measured by black semi-solid paste； HE staining was used to observe histopathology of the gastric antrum； the Western Blotting and RT-qPCR were used to detect the expression levels of PDGFRα， small conductance calcium activated potassium （SK3）， and purinergic G protein-coupled receptor P2Y1 （P2Y1 R）， and mRNA expression in gastric antrum； immunofluorescence double staining was used to detect the co-localization of PDGFRα with receptor tyrosine kinase （C-kit）， protein gene product 9.5 （PGP9.5）， Sk3， and smooth muscle cells （SMCs） in gastric sinusoidal tissues； and transmission electron microscopy was used to observe the ultrastructure of the ENS-PDGFRα⁺ cell-SMC network. ResultsHE staining results showed that the mucosal folds of gastric tissue were clear in all groups， no organic lesions such as bleeding， ulceration and swelling were observed， and the arrangement of gastric glands in the lamina propria of gastric sinusoidal tissues in model group and low-dose Shuwei Decoction group was disordered. The arrangement of gastric glands in lamina propria in medium- and high-dose Shuwei Decoction groups was more orderly， and the lesion degree was less than that in model group and low-dose Shuwei Decoction group. Compared with the blank group， the growth value of body mass， the percentage of open arm retention time， the percentage of times entering the open arm， the small intestine propulsion rate， and the gastric empty rate of rats in the model group significantly decreased after gavage； the expressions of PDGFRα， Sk3， P2Y1 protein and mRNA in gastric sinusoidal tissues decreased； the co-localization expression of PDGFRα with C-kit， Sk3， SMC and PGP9.5 significantly decreased （P＜0.05 or P＜0.01）； the ultrastructure of ENS-PDGFRα⁺ cell-SMC network was damaged without gap junction. Compared with model group and low-dose Shuwei Decoction group， the growth value of body mass， the percentage of open arm retention time， the percentage of times entering the open arm， the small intestine propulsion rate， and the gastric empting rate of rats in medium- and high-dose Shuwei Decoction groups increased after gavage； the expressions of PDGFRα， Sk3， P2Y1 protein and mRNA in gastric sinusoidal tissues increased； the co-localization expression of PDGFRα with C-kit， Sk3， SMC and PGP9.5 significantly increased （P＜0.05 or P＜0.01）； the ultrastructure of ENS-PDGFRα⁺ cell-SMC network was intact. Compared with medium-dose Shuwei Decoction group， the protein expressions of PDGFRα， Sk3 and P2Y1， the mRNA expressions of PDGFRα and Sk3， and the co-localization expressions of PDGFRα and C-kit， Sk3， SMC， and PGP9.5 in high-dose Shuwei Decoction group increased （P＜0.05 or P＜0.01）. ConclusionShuwei Decoction can improve the pathological lesion of the gastric antrum in the FD model rats with liver-depression and spleen-deficiency syndrome and increase the gastric emptying rate as well as the small intestinal propusion rate. The mechanism of Shuwei Decoction on FD rats with liver-depression and spleen-deficiency syndrome is related to the protection of the ultrastructural integrity of ENS-PDGFRα⁺ cell-SMC network.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Objective To investigate the effects and mechanisms of peimine(PME)on chronic obstructive pulmonary disease(COPD)in mice.Methods The mice were randomly divided into 4 groups(20 mice in each group),control group,PME group,chronic obstructive pulmonary disease group and treatment group.Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke.The effects of PME on COPD model mice was analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on COPD model mice were analyzed by HE staining,transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue.The effects of PME on inflammatory factor tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting.The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium(DHE)staining and Western blotting.The effects of PME on nuclear factor kappa-B(NF-κB)pathway and nuclear factor erythroid 2-related factor 2(Nrf2)pathway were analyzed by protein immunoblotting.Results Compared with the COPD group,PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice,and the wet/dry weight ratio of lung tissue was significantly reduced.Compared with the control group,the levels of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced.In addition,compared with the control group,the protein expression of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice significantly increased,and the level of TNF-α,IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced.Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2)protein in COPD group was significantly lower than that in control group,while PME treatment could improve the level of superoxide dismutase protein.The analysis of MDA content in lung tissue showed that compared with the COPD group,the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment.Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα)and the transfer of NF-κB p65 to the cell nucleus,and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1)in the lung tissue of mice treated with PME significantly increased.Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.