Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

AIM To study the chemical constituents from Ganoderma angustisporum J.H.Xing,B.K.Cui&Y.C.Dai and their α-glucosidase inhibitory activities.METHODS The ethyl acetate extract from G.angustisporum was isolated and purified by silica gel,ODS,TLC and HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.pNPG method was used to evaluate their α-glucosidase inhibitory activities.RESULTS Seven compounds were isolated and identified as N-acetyl-L-phenylalanine ethyl ester(1),N-acetyl-L-phenylalanine methyl ester(2),4-hydroxy-17R-methylincisterol(3),6,8-di-O-methylaverufin(4),aversin(5),methyl 2-(4-hydroxyphenyl)aceate(6),5-toluene-1,3-diol(7).Compounds 1-2,4-7 showed inhibitory activities of α-glucosidase with IC50 values being(33.80±0.47),(45.45±7.95),(48.80±5.86),(39.48±2.82),(41.47±6.68),(55.38±10.12)μmol/L,and compound 1 showed good inhibitory activity.CONCLUSION Compound 1 is a new natural product.Compounds 2-7 are isolated from genus Ganoderma for the first time.Compounds 1-2,4-7 have α-glucosidase inhibitory activities.

Ten compounds were isolated and purified from the dichloromethane extract of stems of Ephedra intermedia by various chromatographic methods. Based on the analysis of physicochemical properties and spectral data, the structures of the ten compounds were identified as 1-allyl-3,4-dimethoxy-benzene-5-O-β-D-glucopyranoside (1), lyoniresinol (2), secoisolariciresinol (3), 4,3′,4′-trihydroxy-3-methoxylignan-9,9′-diyldiacetate (4), dehydroconiferyl alcohol (5), isocubebin (6), balanophonin B (7), sesquipinsapol B (8), crataegifin A (9), 1-(2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl)ethan-1-one (10). Compound 1 is a new compound, named as 1-allyl-3,4-dimethhoxy-benzene-5-O-β-D-glucopyranosyl, compounds 2-10 are lignans and isolated from this plant for the first time. Compound 3, 4, 8 possess potentially anti-asthmatic activities.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To analyze the effects of probiotics combined with montmorillonite powder on intestinal mucosa and expressions of intestinal microorganism function-related genes in neonatal rats with rotavirus(RV)infection.Methods RV infection model was established by intragastric administration of SA11 strain rotavirus.Forty-eight suckling rats were randomly divided into normal group(0.9％NaCl),model group(0.9％NaCl),experimental group(0.06 g·mL-1 montmorillonite powder)and combined group(0.06 g·mL-1 montmorillonite powder+6.5 × 107 CFU·mL-1 Saccharomyces cerevisiae powder)with 12 rats in each group.The feces were collected for evaluation.The levels of serum tumor necrosis factor-a(TNF-a),interleukin-1 β(IL-1 β)and IL-17 were detected by enzyme-linked immunosorbent assay,the levels of aquaporin(AQP)in intestinal tissues was detected by real-time fluorescence quantitative polymerase chain reaction,and the counts of Bifidobacteria and Escherichia coli in feces were detected by bacterial 16srDNA fluorescence quantitative polymerase chain reaction.Results The feces scores in normal,model,experimental and combined groups were(1.01±0.10),(2.97±0.08),(2.84±0.03)and(2.77±0.03)points;TNF-α levels were(132.54±14.63),(185.66±19.64),(165.25±17.63)and(149.95±15.76)pg·mL-1;IL-1β levels were(172.32±18.68),(265.34±27.72),(202.34±21.34)and(186.24±19.46)pg·mL-1;IL-17 levels were(118.62±12.44),(173.24±18.25),(152.32±16.72)and(122.54±13.58)pg·mL-1;Bifidobacteria counts were(6.35±0.64),(4.31±0.44),(4.93±0.50)and(5.34±0.54)CFU·g-1;Escherichia coli counts were(6.14±0.62),(8.78±0.88),(8.46±0.85)and(8.12±0.83)CFU·g-1;mRNA levels of AQP2 were 1.02±0.05,0.72±0.07,0.89±0.08 and 1.21±0.12;mRNA expression levels of AQP4 were 1.04±0.07,0.42±0.05,0.78±0.08 and 1.19±0.12;mRNA expression levels ofAQP8 were 1.00±0.06,0.63±0.06,0.91±0.09 and 1.30±0.13,respectively.There were significant differences of above indexes between the model group with the normal,experimental and combined groups(all P＜0.05).Conclusion Montmorillonite powder combined with probiotics can improve fecal properties,reduce serum inflammatory factors and correct intestinal flora disorders in neonatal rats with RV infection,which may be related to improving the expressions of intestinal A QP2,AQP4 and AQP8.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Invasive fungal infections threaten the lives and health of humans, especially immunodeficient patients or hospitalized patients with serious underlying diseases, and impose a heavy economic burden on society. The emergence of drug-resistant fungi, the formation of biofilms, and the limits and side effects of existing antifungal drugs increase the difficulty of clinical treatment, and there is an urgent need for the development of novel antifungal drugs. Therefore, based on previous kinase chemical library antifungal activity screening studies, this paper further investigates the activity of anaplastic lymphoma kinase (ALK) inhibitor 3-[5-chloro-2-({2-methoxy-4-[4-(4-methylpiperazin-1-yl)hexahydropyridin-1-yl]phenyl}amino)pyrimidin-4-yl]-1H-indole (HG-14-10-04, HG) against various fungi and elucidates its mechanism of action. The in vitro antifungal activity of HG was evaluated by micro liquid-dilution method, time-killing curve, mycelium formation and biofilm formation assays. The results showed that HG exhibited inhibitory and even fungicidal effects against sensitive and resistant Candida albicans, Candida krusei, Cryptococcus neoformans, Candida tropicalis, Candida glabrata and Candida parapsilosis (MICs = 8-16 μg·mL^-1); HG significantly inhibited the mycelium and biofilm formation, and destroyed the mature biofilm; and it exhibited synergistic antifungal effects with amphotericin B. The antifungal mechanism of HG was investigated by flow cytometry and transmission electron microscopy, etc. Sequencing analysis showed a total of 1 041 differentially expressed genes, of which 666 were up-regulated and 375 were down-regulated. According to the GO functional classification results, the up-regulated genes were mainly involved in ribosome production, oxidation-reduction and other functions, while the down-regulated genes were mainly involved in the synthesis of carbohydrate, glycoproteins, glycolipids and their metabolism, GPI anchor synthesis, and cytoskeleton and other functions. In addition, HG could significantly increase the level of reactive oxygen species (ROS), induce the fungal necrosis, block the cell cycle at the G0/G1 phase, and change the ultrastructure of the fungi, especially the structure of the fungal cell wall. Therefore, the enhanced inhibitory and fungicidal activity of HG may be related to the elevation of ROS, alteration of cellular ultrastructure (especially cell wall structure) and cell cycle arrest at the G0/G1 phase. Further optimization of its structure will provide a basis for the discovery of novel antifungal drugs or lead compounds.

The study aims to investigate and compare the effects of probiotics and docosahexaenoic acid (DHA) with the Alzheimer's disease (AD) therapeutic drug donepezil on the learning cognition and brain damage related indexes in AD mice, and to provide experimental basis for its treatment of AD. All animal experiments were approved by the Ethics Committee of the Henan University of Chinese Medicine (ethics number DWLL2018080003). Fifty male C57BL/6J mice were randomly assigned to one of five groups: sham-operated, model, donepezil (10 mg·kg^-1), probiotic (2.7×10⁹ CFU·d^-1), and DHA (0.104 g·kg^-1). Except for the sham-operated group, the AD animal model was established by injecting Aβ_25-35 (200 μmol·L^-1) in the lateral ventricle, followed by gavage administration for 4 weeks. In all mouse groups, learning memory ability, neuronal morphology in the hippocampus, apoptosis of primary hippocampal cells, and immune cell levels were detected. The levels of Aβ_1-42, Aβ_1-40, p-Tau, AchE, Ach, oxidative stress, glial cell activation, and the inflammatory factors IL-1β, IL-10, and TNF-α in the brain tissue of mice were also detected. 16S rDNA sequencing was used to further investigate the effects of donepezil and probiotics on AD. Donepezil, probiotics and DHA improved cognitive deficits and enhanced learning memory in Aβ_25-35-induced mice by increasing locomotion time, locomotion distance, autonomic alternation rate, and shortening the time to reach the plateau; it significantly attenuated Aβ_25-35-induced brain injury and neuroinflammation in mice by decreasing Aβ_1-42, Aβ_1-40, p-Tau, AchE, IL-1β, TNF-α, and MDA and increasing the levels of Ach, IL-10, GSH-Px, and T-SOD in brain tissues, as well as decreasing the activation of glial cells, and had a modulatory effect on immune cells. 16S rDNA sequencing shows that both donepezil and probiotics restore flora homeostasis and that differential bacteria are strongly associated with cognition, AD pathology, and neuroinflammation. Combining all indicators, donepezil and probiotics were more effective than DHA. All in all, donepezil, probiotics and DHA ameliorate Aβ_25-35-induced cognitive dysfunction and brain damage in mice by modulating immune cells, reducing the number of apoptotic cells and glial cell activation in the brain, and decreasing the levels of oxidative stress and inflammatory factor expression, among which the effects of donepezil and probiotics were better than those of DHA, and the therapeutic effects of donepezil and probiotics on AD were closely related to the modulation of gut microbiome.