Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

Objective:To compare the aortic remodeling of the Fabulous stent system and standard thoracic aortic endovascular repair (TEVAR) on distal aorta type B aortic dissection (TBAD). Methods:The prospective data collected between Dec 2017 and Oct 2019 from 134 patients with type B aortic dissection (TBAD) who underwent treatment with the "Fabulous" stent system, and retrospective data from 159 TBAD patients receiving standard TEVAR from corresponding multicenter. By using propensity score matching analysis, we compared the prognosis and aortic remodeling outcomes in patients undergoing Fabulous and standard TEVAR treatments during a 1-year postoperative follow-up.Results:In this study, 62 patients in Fabulous group and 62 patients in standard TEVAR were included.There were no significant statistical differences in baseline characteristics between the two groups. In terms of aortic remodeling in bare stent region, Fabulous group had better change trends of diameter of true lumen [10.6 (4.4, 14.5) mm vs. 4.7 (0.9, 10.7) mm, P=0.001] and false lumen [-24.2 (-30.5, -4.9) mm vs. 0.7 (-11.8, 2.3) mm, P<0.001] than those in the standard TEVAR group. The rate of complete false lumen thrombosis was also higher in the Fabulous group (62.9% vs. 37.1%, P=0.042). Conclusion:The Fabulous stent system, when compared to standard TEVAR surgery, demonstrates good aortic remodeling outcomes in the distal aorta.

Objective To investigate the efficacy and safety of subcutaneous immunotherapy(SCIT)using dust mites in children with allergic asthma.Methods In a prospective randomized controlled study,98 children with dust mite-induced allergic asthma were randomly divided into a control group(n=49)and an SCIT group(n=49).The control group received inhaled corticosteroid treatment,while the SCIT group additionally received a standardized three-year SCIT regimen.The two groups were compared based on peripheral blood eosinophil percentage,visual analogue score(VAS),total medication score,Asthma Control Test/Childhood Asthma Control Test scores,fractional exhaled nitric oxide(FeNO),and lung function before treatment,and at 6 months,1 year,2 years,and 3 years after treatment.Adverse reactions were recorded post-injection to evaluate the safety of SCIT.Results Compared with pre-treatment levels,the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils,VAS,total medication score,and FeNO,while lung function significantly improved,and asthma control levels were better 3 years after treatment(P<0.05).Compared with the control group,the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment(P<0.05).A total of 2 744 injections were administered,resulting in 157 cases(5.72%)of local adverse reactions and 4 cases(0.15%)of systemic adverse reactions,with no severe systemic adverse events.Conclusions SCIT is an effective and safe treatment for allergic asthma in children.

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*

Objective To investigate the role and mechanism of SR8278,a synthetic antagonist of nuclear receptor subfamily 1 group D member 1(NR1D1),in alleviating the structural and functional impairment of the extraorbital lacrimal glands induced by jet lag in mice.Methods Totally 36 healthy wild C57BL/6J mice aged 8-10 weeks were randomly divid-ed into 3 groups(normal group,jet-lag group,and jet-lag+SR8278 group)after adapting to a circadian rhythm chamber under the 12 h light/12 h dark(12 h/12 h LD)cycle for 2 weeks,with 12 mice in each group.Mice in the normal group were fed in a circadian rhythm chamber in a 12 h LD cycle,mice in the jet-lag group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule,and mice in the jet lag+SR8278 group were fed in a 12 h/12 h LD cycle with an 8-hour advanced LD schedule and received 25 mg·kg-1 SR8278.At the end of 5 days of intervention,locomotor activity,core body temperature and tear secretion of mice in each group were collected,and the weight of lacrimal gland tissues and size of lacrimal gland cells were measured.Immunohistochemical methods were used for histological evaluation of the extraor-bital lacrimal glands in mice.Lacrimal ribonucleic acid(RNA)was extracted for high-throughput RNA-sequencing analysis containing NR1D1,and the obtained transcriptomic data were used for KEGG and GO functional enrichment analysis.Re-sults Compared with the normal group,the jet-lag group had higher daytime activity,lower nighttime activity,higher daytime core body temperature,and lower nighttime core body temperature,with statistically significant differences(all P＜0.05).Compared with the jet-lag group,the jet-lag+SR8278 group had lower daytime activity,higher nighttime activi-ty,lower daytime core body temperature,and higher nighttime core body temperature,with statistically significant differ-ences(all P＜0.05).Compared with the normal group,the jet-lag group showed a decrease in lacrimal gland weight and tear secretion and an increase in size of lacrimal gland cells,with statistical significance(all P＜0.05);compared with the jet-lag group,the jet-lag+SR8278 group had an increase in lacrimal gland weight and tear secretion and a decrease in size of lacrimal gland cells,with statistical significance(all P＜0.05).Compared with the normal group,the jet-lag group showed a higher expression of NR1D1 in the lacrimal gland at night;compared with the jet-lag group,the jet-lag+SR8278 group showed a lower expression of NR1 D1 in the lacrimal gland at night(both P＜0.05).Bioinformatics analysis showed 947 significantly different genes in the jet-lag group and the jet-lag+SR8278 group,of which 43 are significantly upregulated genes,and 904 are significantly downregulated genes.The Notch signaling pathway has the most significant difference.Conclusion SR8278 effectively enhances the tear secretion function of jet-lagged mice by targeting NR1D1 inhibition.This process may be completed through the Notch signaling pathway.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Objective:To explore the effects of electroacupuncture in regulating the intestinal flora of high-fat diet (HFD)-fed mice from microbiota-derived extracellular vesicles. Methods:Obese mice with established nutritional obesity model were randomly divided into either the model group (n=10) or the electroacupuncture group (n=10). Acupuncture groups were chosen to pinprick points of Zhongwan, Guanyuan, Tianshu and Zusanli. Stool samples were collected from groups at the end of the intervention and extracellular vesicles (EVs) were isolated using ultracentrifugation. The morphology of EVs isolated from the stool was confirmed by transmission electron microscopy (TEM) and analysis of the associated intestinal flora by extracting microbial DNA from them for 16S rRNA sequencing. Results:The weight and Lee's index of obese mice decreased significantly after electroacupuncture intervention treatment (P<0.01). TEM images showed that EV extracted from stools were in the form of round or oval double-membraned vesicle-like structures. The 16S rRNA sequencing analysis showed that at the phylum level, the relative abundance of Proteobacteria in the model group was significantly higher than that of the normal group (P<0.05), while the relative abundance of Frimicutes and Bacteroidetes was significantly lower than that of the normal group(P<0.05). At the genus level, expressions of Psychrobacter and Planomicrobium in the model group were significantly higher than those in the normal group (P<0.01), while expressions of Solibacillus, Solibacillus, Proteus, Lactobacillus, Agrobacterium, Enterobacter, Brevundimonas, and Comamonas were significantly lower than those in the normal group (P<0.05). After electroacupuncture intervention, the intestinal microbial diversity of experimental mice increased, and the flora structure was closer to that of normal mice. Conclusion:Structural changes in the gut flora of nutritionally obese mice accompanied by changes in gut microbial-derived EVs profiles, and 16S rRNA sequencing analysis showed that microbial DNA in gut microbial-derived EVs reflected the composition of the gut microbiota, and that electroacupuncture for the treatment of obesity was not only related to the modulation of the gut flora, but was also closely related to gut microbial-derived EVs.

Objective To investigate whether Heshouwuyin can delay the aging of Leydig cells in rat testis through DNA methyltransferase 1(DNMT1).Methods Totally 40 male Wistar rats were randomly divided into 4 groups,with 10 rats in each group.Immunohistochemistry was used to detect the expression levels of DNMT1 in testis tissue of rats.Testosterone content in serum of rats in each group was detected by ELISA test.A rat Leydig cell aging model was established by free radical oxidative damage.DNMT1 was knocked down by lentivirus in Leydig cells,and the cell senescence status and the testosterone content and testosterone synthesis key enzyme 3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 family member 11A1(CYP11A1)content secreted by cells were detected by β-galactosidase(β-GAL)staining,immunofluorescenct staining and ELISA.Results Compared with the young control group(YCG),the expression of P16 protein and the positive rate of β-GAL in the testis tissue of rats in the natural aging group(NAG)increased significantly,and the expression of DNMT1 and serum testosterone levels decreased(P＜0.05).However,after Heshouwuyin intervention,the expression of P16 protein and the positive rate of β-GAL in the testis of aging rats were reduced,and DNMT1 expression and the serum testosterone levels increased(P＜0.05).The same trend was observed in Leydig cells.Knockdown of DNMT1 in Leydig cells,β-GAL positivity and P16 protein expression increased significantly,and testosterone secretion and testosterone synthesis key enzymes 3β-HSD,CYP11A1 content from Leydig cells decreased significantly,compared with the normal control group(NCG)(P＜0.05).When Heshouwuyin was added,the above phenomenon was improved.Conclusion Heshouwuyin can delay the aging of rat Leydig cells through DNMT1.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.
Adult ; Humans ; Databases, Factual ; Drugs, Chinese Herbal/therapeutic use* ; Dyspepsia/drug therapy* ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic