Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objective To investigate the protective effect of lovastatin on cardiomyocyte injury induced by hypoxia/reoxygenation and the regulation of protein kinase B(Akt)signal pathway.Methods Rat cardiomyocytes H9c2 were cultured in vitro,and divided into control group,model group,inhibitor group,combined group and experimental-L,-M,-H groups.Control group was cultured with normal medium,and the other 6 groups were treated with hypoxia/reoxygenation.Experimental-L,-M,-H groups were supplemented with 1,2 and 5 μmol·L-1 lovastatin,respectively;inhibitor group was supplemented with 1 μmol·L-1 LY294002;combined group was supplemented with 5 μmol·L-1 lovastatin and 1 pmol·L-1 LY294002.The cell viability was determined by thiazole blue assay,the apoptosis rate was determined by flow cytometry,and the expression level of phosphorylated Akt(p-Akt)was determined by Western blot.Results The cell viabilities of experimental-H,inhibitor,combined,model and control groups were(64.38±7.10)％,(21.64±1.32)％,(51.89±2.25)％,(47.18±6.66)％and(100.00±7.69)％;the cell apoptosis rates were(13.67±1.42)％,(38.52±2.42)％,(21.12±2.27)％,(20.42±3.33)％and(4.93±0.40)％;the relative protein expression levels of p-Akt were 0.54±0.04,0.04±0.01,0.25±0.03,0.20±0.01 and 0.45±0.02,respectively.The differences of above indicators were statistically significant between the experimental-H group and the model group,as well as between the combined group and the experimental-H and inhibitor groups(all P＜0.05).Conclusion Lovastatin can protect against hypoxia/reoxygenation cardiomyocyte injury by activating the Akt signaling pathway.

Objective To investigate the effects of saphenous nerve combined with posterior capsular block of knee joint on stress response,analgesic effect and joint function recovery of patients after total knee arthroplasty.Methods A total of 98 patients who received total knee arthroplasty in our hospital from January 2021 to January 2022 were selected and divided into the observation group(received saphenous nerve combined with posterior capsular block of knee joint)and the control group(received saphenous nerve block)by random number table,with 49 patients in each group.The visual analogue scale(VAS)score of resting and dynamic pain 6 hours,12 hours and 24 hours after surgery of patients in the two groups were compared.The range of knee joint motion before surgery,3 days,5 days and 7 days after surgery of patients in the two groups were compared.The stress indexes[cortisol(Cor),adrenocorticotropic hormone(ACTH)],and pain mediator indexs[calcitonin gene-related peptide(CGRP),beta-endorphins(β-EP),6-keto prostaglandin E1α(6-Keto-pGE1α),substance P(SP)]before surgery,4 hours,12 hours,24 hours,and 48 hours after surgery of patients in the two groups were compared.The occurrence of adverse reactions during treatment of patients in the two groups were recorded.Results There were statistically significant differences in the resting and dynamic VAS scores at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the range of knee joint motion at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the Cor and ACTH contents at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the contents of β-EP,SP,CGRP and 6-keto-PGE1α at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Saphenous nerve combined with posterior capsular block of knee joint for total knee arthroplasty can reduce patients' stress response,enhance postoperative analgesic effect,and improve the early motor function,with high safety.

AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

Aim To explore the effect of tanshinone II A (Tan II A) on reverse cholesterol transport in atherosclerosis model mice and RAW264. 7 cells and the underlying mechanism. Methods Thirty-two male LDLR -/- mice were randomly divided into four groups. These mice were fed with normal diet or high fat diet for 12 weeks. The control group and model group were given normal saline. Tan II A group and atorvastatin group were given Tan II A solution and atorvastatin solution for 12 weeks. RAW264. 7 cells were induced with oxidized low-density lipoprotein (ox-LDL) 100 mg • L-

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

OBJECTIVE: To explore clinical effects of the stageⅠrepair of full-thickness skin defect at dorsal skin of middle phalanx fingers using artificial dermis combing with digital artery perforator fascial flaps. METHODS: From January 2019 to May 2020, 21 patients(27 middle phalanx fingers)with full-thickness skin defect were repaired at stageⅠusing artificial dermis combing with digital artery perforator fascial flaps. All patients were emergency cases, and were accompanied by the exposure of bone tendon and the defects of periosteum and tendon membrane. Among patients, including 11 males and 10 females aged from 18 to 66 years old with an average age of (39.00±8.01) years old;9 index fingers, 10 middle fingers and 8 ring fingers;range of skin defect area ranged from (2.5 to 3.5) cm×(1.5 to 3.0) cm;range of exposed bone tendon area was (1.5 to 2.0) cm×(1.0 to 2.0) cm. The time from admission to hospital ranged from 1 to 6 h, operation time started from 3 to 8 h after injury. RESULTS: All patients were followed up from 6 to12 months with an average of (9.66±1.05) months. The wounds in 26 cases were completely healed at 4 to 6 weeks after operation. One finger has changed into wound infection with incompletely epithelialized dermis, and achieved wound healing at 8 weeks after dressing change. All fingers were plump with less scars. The healed wound surface was similar to the color and texture of the surrounding skin. These fingers have excellent wearability and flexibility. According to the upper limb function trial evaluation standard of Hand Surgery Society of Chinese Medical Association, the total score ranged from 72 to 100. 26 fingers got excellent result and 1 good. CONCLUSION StageⅠrepair of full-thickness skin defect at dorsal skin of middle phalanx fingers using artificial dermis combing with digital artery perforator fascial flaps is easy to operate with less trauma. It has made satisfactory recovery of appearance and function of fingers. It could provide an effective surgical method for clinical treatment of full-thickness skin loss of fingers with tendon and bone exposure.
Female ; Male ; Humans ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Aged ; Fingers ; Skin ; Perforator Flap ; Ulnar Artery ; Dermis

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype