1.Bugansan Regulates R-spondin1/Wnt3a-mediated Intestinal Injury to Ameliorate Digestion and Absorption Dysfunction in Rat Model of Aging Induced by D-galactose
Yixuan WANG ; Ran HUO ; Jin TIAN ; Fang FANG ; Na LIU ; Jiepeng WANG ; Chaoyi FANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):19-27
ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway, and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups: blank control, model, low-, medium-, and high-dose (7.03, 14.06, 28.12 g·kg-1, respectively) Bugansan, and vitamin E (suspension, 27 mg·kg-1), with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose (400 mg·kg-1), while the blank control group was injected with normal saline. Since the day of modeling, rats in intervention groups received corresponding agents by gavage, and those in blank control and model groups received an equal volume of normal saline (10 mL·kg-1). General biological features such as fur color, activity, body mass, water intake, and food intake were observed. Meanwhile, the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the serum were measured to assess aging. Grip strength and the content of total bile acids (TBA) and the activity of α-amylase (AMY) in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase (β-gal) in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 (GLP-1), vasoactive intestinal peptide (VIP), and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) and leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) in the duodenal tissue. Moreover, Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to quantify the mRNA levels of Ki67, Bmi1, and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally, the mRNA levels of R-spondin1, Wnt3a, β-catenin, and glycogen synthase kinase-3β (GSK-3β) and the protein levels of R-spondin1, Wnt3a, β-catenin, and phosphorylated GSK-3β (p-GSK-3β) in the duodenum were determined by Real-time PCR and Western blot, respectively, to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group, the model group showed decreases in body mass, water intake, food intake, grip strength, activities of SOD, GSH-Px, and AMY in the serum and content of GLP-1, VIP and D-xylose in the serum (P<0.05), increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum (P<0.05), reductions in villus length, villus width, crypt depth, and villi/crypt (V/C) value, down-regulated mRNA and protein levels of Ki67, Lgr5, Bmi1, R-spondin1, Wnt3a, β-catenin, and up-regulated level of GSK-3β, phosphorylation (p)-GSK-3β (P<0.05). Compared with the model group, Bugansan increased the body mass, water intake, food intake, grip strength, and activities of SOD, GSH-Px, and AMY and levels of GLP-1, VIP and D-xylose in the serum (P<0.05), while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum (P<0.05). Furthermore, Bugansan increased the villus length, villus width, crypt depth, and V/C value, up-regulated the mRNA and protein levels of Ki67, Lgr5, Bmi1, R-spondin1, Wnt3a, β-catenin, and down-regulated the level of GSK-3β and p-GSK-3β (P<0.05). ConclusionAging rats exhibit obvious impairments in digestion and absorption functions, accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions, ultimately contributing to the delay of aging.
2.Efficacy of ozone combined with low temperature plasma radiofrequency ablation in the treatment of cervical spondylotic radiculopathy
Yansong HUO ; Haiyan SUN ; Jinlei PANG ; Xiangfei GUO ; Yajing LIU ; Guangyuan RAN ; Mingwei HE
Basic & Clinical Medicine 2024;44(6):840-844
Objective To investigate the therapeutic effectiveness of ozone combined with low-temperature plasma coagulation therapy on patients with cervical spondylotic radiculopathy and its influence on inflammatory responses.Methods Ozone in combination with low-temperature plasma radio-frequency coagulation was applied to 75 patients with cervical spondylotic radiculopathy in Pain Medicine Department of Capital Medical University Affiliated Beijing Anzhen Hospital from May 2022 to May 2023.Pain scores were assessed using Visual Analog Scale(VAS)and Neck Disability Index(NDI)before and two weeks after treatment.Enzyme-linked immunosor-bent assay(ELISA)was used to analyze the level of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and interferon-gamma(IFN-γ)before and two weeks after treatment.Results After treatment with ozone plus low-temperature plasma radiofrequency,VAS and NDI scores showed a significant decrease[VAS:5.36(4,7)vs.1.32(1,2),P<0.000 1;NDI:32.72(24,70)vs.7.62(3.55,8.9),P<0.000 1].Two weeks after surgical intervention,there was an effective reduction in the level of IL-6,TNF-αand IFN-γ alleviating the inflammatory re-sponse[IL-6:4.33(2.51,5.04)vs.3.49(2.08,4.43),P<0.05;TNF-α:1.95(1.41,2.21)vs.1.61(1.02,2.03),P<0.05;IFN-γ:1.84(1.18,2.47)vs.1.55(0.76,2.09),P<0.05].Conclusions This Ozone combined with low-temperature plasma radiofrequency ablation is an effective technology for treatment of cer-vical spondylotic radiculopathy.
3.Analysis of clinical data of necrotizing fasciitis secondary to intestinal fistulas and screening the mortality risk factors
Chenyuyao ZHAO ; Yushen ZHANG ; Zhanjie YANG ; Mingqing WANG ; Wenjun XUE ; Ran HUO ; Ran ZHAO
Chinese Journal of Burns 2024;40(2):141-150
Objective:To analyze the clinical data and to screen the mortality risk factors of necrotizing fasciitis (NF) secondary to intestinal fistulas (NFsIF).Methods:This study was a retrospective observational study. The data of all NFsIF cases who met the inclusion criteria and were admitted into Shandong Provincial Hospital Affiliated to Shandong First Medical University (hereinafter referred to as our unit) from January 2000 to October 2023, and in PubMed, Web of Science, Scopus, China National Knowledge Infrastructure, and Chinese Medical Journal Network databases from its establishment to October 2023 were retrieved and screened. Based on clinical outcomes, the cases were divided into survival group (47 males and 24 females) and death group (16 males and 7 females), and the mortality rate was calculated. Clinical data of patients in the two groups including age, underlying diseases (most related to NF), symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement, and intestinal management and wound management measures were compared and analyzed to screen the risk factors of death in 94 patients with NFsIF.Results:A total of 94 valid cases were collected, including 90 patients reported in the literature and 4 patients admitted to our unit, with the mortality rate of patients being 24.5% (23/94). Univariate analysis showed that there were no statistically significant differences in age, underlying diseases, symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement between patients in the two groups ( P>0.05); there were statistically significant differences in intestinal treatment and wound treatment between the two groups (with χ2 values of 17.97 and 8.33, respectively, P<0.05). Multivariate logistic regression analysis showed that both intestinal treatment measures and wound treatments measures were independent risk factors for death in 94 NFsIF patients, among which first-stage colostomy+late-stage reconstruction and negative presssure therapy had higher protective effects (with odds ratios of 0.05 and 0.27, respectively, 95% confidence intervals of 0.01-0.33 and 0.08-0.88, respectively, P<0.05). Conclusions:The mortality risk of patients with NFsIF is high. Based on comprehensive treatments, active intestinal and wound treatment may be the key to avoid death, with first-stage colostomy+late-stage reconstruction and negative pressure therapy having higher protective effects.
4.Comparison of fetal imaging quality and maternal comfort level in different positions in a super large-bore magnet
Aonan WANG ; Jiajia XU ; Ran HUO ; Ying LIU ; Huishu YUAN
Journal of Practical Radiology 2023;39(12):2038-2041
Objective To compare the fetal imaging quality in different positions and the maternal comfort level in a super large-bore magnet,so as to estimate the application value of left lying position scanning in fetal brain MRI.Methods A total of 32 pregnant women in the third trimester who underwent fetal brain imaging in a super large-bore magnet(75cm)were collected.Each subject completed left lying position and supine position scanning and scored the comfort of the two.Radiologists scored the image subjectively,and objectively measured signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of fetal brain images.Results The comfort score of the left lying position(4.3±0.7)was higher than that of the supine position(3.4±0.7),and the difference was statistically significant(P<0.001).The subjective score showed that there was no significant difference between the left lying position and the supine position in terms of brain image quality(P>0.05),which could meet the needs of clinical diagnosis.The objective score showed that SNR of midbrain in left lying position was higher than in supine position(P<0.05).The CNR of left occipital lobe in left lying position was higher than in supine position(P<0.05).Conclusion In super large-bore magnet,left lying position scanning is a safe and pregnancy-friendly option that can not only improve maternal comfort level,but also improve fetal brain imaging.
5.Research advances of adipose stem cell matrix gel in promoting wound healing.
Nan XING ; Ran HUO ; Hai Tao WANG ; Jin Cun YANG ; Jiong CHEN ; Lei PENG ; Xiao Wen LIU
Chinese Journal of Burns 2023;39(1):81-84
In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.
Humans
;
Aged
;
Wound Healing/physiology*
;
Adipocytes
;
Adipose Tissue
;
Extracellular Matrix
;
Stem Cells
6.Meta-analysis on correlations between short-term exposures to 6 common air pollutants and incidence of ischemic stroke
Ran HUO ; Rongrong YE ; Fang ZHANG ; Zhengli DI
Journal of Environmental and Occupational Medicine 2023;40(2):184-189
Background Previous studies using meta-analysis to explore the relationship between air pollution exposure and ischemic stroke (IS) mostly focus on particulate matter-related themes, few include gaseous pollutants in the study, and subgroup analyses of factors such as different lag days, seasons, and genders are rarely been reported. Objective To quantitatively evaluate the relationships between short-term exposures to 6 common air pollutants, including fine particulate matter (PM2.5), inhalable particulate matter (PM10), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3), and the incidence of IS. Methods A systematic search was conducted to collect literature studying the 6 common air pollutants and IS published up to May 1, 2022 in 6 databases (China Journal Full-text Database, China Biology Medicine Disc, PubMed, Cochrane Library, Web of Science, and Embase). Literature quality evaluation was performed using the Newcastle-Ottawa Scale. Stata 16.0 software was used to conduct meta-analysis including heterogeneity test, combined effect size, meta-regression, subgroup analysis, sensitivity analysis, and publication bias test. Results A total of 33 articles were qualified for inclusion. The total number of samples included in the literature was 7195631. The meta-analysis results showed that short-term exposures to PM2.5 (OR=1.0082, 95%CI: 1.0049−1.0116), PM10 (OR=1.0017, 95%CI: 1.0008−1.0026), CO (OR=1.0328, 95%CI: 1.0231−1.0426), NO2 (OR=1.0150, 95%CI: 1.0079−1.0222), SO2 (OR=1.0158, 95%CI: 1.0078-1.0238), and O3 (OR=1.0017, 95%CI: 1.0003−1.0032) were associated with an increased risk of IS. PM10 and O3 increased the risk of IS in both lag0 and lag1, while PM2.5, CO, NO2, and SO2 all showed an associated increased risk of IS only in lag0. The results of sensitivity analysis showed stable results for all pollutants studied, and there was no publication bias in the literature on the association of the remaining five pollutants with IS incidence except for the PM2.5-related literature. Conclusion Short-term exposures to PM2.5, PM10, CO, NO2, SO2, and O3 may increase the incidence of IS, with this risk showing the most significant level on the day of IS onset.
7.Meaning, Efficacy and Mechanism of Huoxin Pills in Treating Coronary Heart Disease with Qi Deficiency and Blood Stasis Syndrome
Xiu-juan YANG ; Rui-xuan ZHU ; Ran XIE ; Lei YANG ; Jin-cheng CHEN ; Bao-xin XU ; Xiao-chun SHI ; Peng-qian WANG ; Hai-ru HUO ; Yu-qing TAN ; Lyu GAO ; Feng SUI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(9):205-213
Cardiovascular diseases, with high incidence and high mortality, belong to the category of "chest impediment and heart pain" in traditional Chinese medicine (TCM). Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills, one of the National Essential Drugs, is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease (Qi deficiency and blood stasis syndrome). This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi, activate blood, and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow, regulating immune functions, alleviating inflammation, detoxifying, and tranquilizing mind. Clinically, it is suitable for patients with angina pectoris caused by the lack of heart Yang, chest tightness, shortness of breath, palpitation, fear of cold for limbs and so on, especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports, this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets, location and links. Furthermore, we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research, aiming to provide data support and evidence for the clinical application of this medicine.
8.Comparison of initial periodontal therapy and its correlation with white blood cell level in periodontitis patients with or without diabetes mellitus.
Xin Ran XU ; Peng Cheng HUO ; Lu HE ; Huan Xin MENG ; Yun Xuan ZHU ; Dong Si Qi JIN
Journal of Peking University(Health Sciences) 2022;54(1):48-53
OBJECTIVE:
To compare the clinical efficacy of initial periodontal therapy in periodontitis patients with or without type 2 diabetes mellitus and its correlation with white blood cell counts.
METHODS:
In this study, 32 chronic periodontitis patients without systemic disease (CP group) and 27 chronic periodontitis patients with type 2 diabetes mellitus (CP+DM group) were enrolled. At admission, all the patients went through periodontal examination and fasting blood examination(baseline). Probing depth (PD), attachment loss (AL), bleeding index (BI), plaque index (PLI), white blood cells (WBC) counts and fasting blood glucose (FBG) were recorded respectively, while hemoglobin A1c (HbA1c) was recorded only in CP+DM group. After that, initial periodontal therapy was performed. All the tests were repeated 3 and 6 months after treatment. The changes of periodontal clinical indexes and WBC levels were compared between the two groups before and after treatment, and the correlation between WBC and periodontal clinical indexes and glucose metabolism indexes were analyzed by generalized linear mixed model.
RESULTS:
At baseline, the periodontal inflammation and destruction were similar in CP and CP+DM group, but the WBC level was significantly higher in CP+DM groups [(6.01±1.26)×109/L vs. (7.14±1.99)×109/L, P=0.01]. After 3 and 6 months of initial periodontal therapy, the mean PD, AL, BI, and PLI in CP+DM and CP groups were significantly lower than the baseline, and the PD in CP+DM group was further decreased by 6 months compared with 3 months [(3.33±0.62) mm vs. (3.61±0.60) mm, P < 0.05]. However, none of these periodontal indexes showed significant difference between the two groups by 3 or 6 months. In CP+DM group, HbA1c at 3 months and 6 months were significantly lower than the baseline [(7.09±0.79)% vs. (7.64±1.16)%, P < 0.05; (7.06±0.78)% vs. (7.64±1.16)%, P < 0.05], and FBG was significantly lower than the baseline by 6 months [(7.35±1.14) mmol/L vs. (8.40±1.43) mmol/L, P < 0.05]. The WBC level in CP group was significantly lower than the baseline level by 3 months [(5.35±1.37)×109/L vs. (6.01±1.26)×109/L, P < 0.05], while that in CP+DM group was significantly lower than the baseline level by 6 months [(6.00±1.37)×109/L vs. (7.14±1.99)×109/L, P < 0.05]. The analysis of genera-lized linear mixed model showed that WBC level was significantly positively correlated with PD and FBG (P < 0.05).
CONCLUSION
Initial periodontal therapy can effectively improve the periodontal clinical status of patients with or without type 2 diabetes mellitus, and have benefits on glycemic control in diabetic patients. However, the response of periodontal indexes and WBC level to initial therapy were relatively delayed in diabetic patients. WBC plays an important role in the correlation between diabetes mellitus and periodontitis.
Chronic Periodontitis/therapy*
;
Diabetes Mellitus, Type 2/complications*
;
Glycated Hemoglobin A/analysis*
;
Humans
;
Leukocytes/chemistry*
;
Periodontal Index
9.Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain.
Fu-Jun ZHAI ; Song-Ping HAN ; Tian-Jia SONG ; Ran HUO ; Xing-Yu LAN ; Rong ZHANG ; Ji-Sheng HAN
Neuroscience Bulletin 2022;38(4):403-416
Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.
Analgesics
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Animals
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Narcotic Antagonists/pharmacology*
;
Neuralgia/therapy*
;
Opioid Peptides
;
Rats
;
Receptors, Opioid/physiology*
;
Receptors, Opioid, kappa
;
Spinal Cord
;
Spinal Cord Stimulation
10.Effect of melatonin on embryo development after fertilization of in vitro matured oocytes in controlled ovarian hyperstimulation cycles
Qi Zhu ; Ding Ding ; Kaijuan Wang ; Ran Huo ; Xuesen Zhang ; Tingting Liu ; Yunxia Cao ; Zhiguo Zhang
Acta Universitatis Medicinalis Anhui 2022;57(4):616-621
Objective:
To explore the effects of melatonin(MT) on the fertilization of in vitro matured oocytes in controlled ovarian hyperstimulation(COH) cycles and the development of subsequent embryos.
Methods:
Imma-ture human oocytes from COH cycles were collected for in vitro maturation(IVM) culture and intracytoplasmic sperm injection( ICSI) insemination,and then the cleavage embryo and blastocyst culture medium supplemented with 0,10-11,10-9,10-7or 10-5mol/L MT were used in order to perform embryo culture in vitro,next the formed high-quality blastocysts were picked up and cryopreserved via vitrification,finally,array-CGH technology was used to detect aneuploidy of rewarmed high-quality blastocysts.
Results:
The blastocyst rate of 10-9mol/L group was significantly higher than that of 10-11,10-7,10-5and 0 mol/L groups( P<0. 05,P<0. 01,P<0. 000 1,P<0. 01),respectively; the high-quality blastocyst rate of 10-9mol/L group was higher than that of other groups,but there were only significant differences compared with 10-5mol/L and 0 mol/L groups( P<0. 01,P<0. 05); the incidence of aneuploidy in MT group( 17. 6%) was lower than that in non-MT group( 33. 3%),but no significant difference was found.
Conclusion
The addition of MT to human embryo culture medium can promote the in vitro development of embryo,which is related to concentration,and 10-9mol/L is the optimal concentration.


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