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Objective:To explore the value of serum procalcitonin (PCT), amylase (AMY), albumin (ALB) and lactate dehydrogenase (LDH) in the clinical diagnosis and evaluation of severe acute pancreatitis (SAP).Methods:A total of 70 patients with acute pancreatitis treated in Yancheng First People′s Hospital from January 1, 2020 to December 31, 2022 were enrolled as pancreatitis group. According to disease severity, they were divided into mild group (22 cases) and severe group (48 cases). A total of 70 controls during the same period were enrolled as control group. The general data of all the objects were collected at enrollment. The levels of plasma PCT, AMY, ALB and LDH were detected. The diagnostic value of the above indexes for SAP and their evaluation value for disease severity were analyzed by receiver operating characteristic (ROC) curves.Results:The levels of serum PCT, AMY and LDH in the pancreatitis group were significantly higher than those in the control group: (3.14 ± 0.67) μg/L vs. (0.82 ± 0.21) μg/L, (602.53 ± 199.47) U/L vs. (99.97 ± 30.85) U/L, (767.24 ± 198.73) U/L vs. (423.61 ± 59.19) U/L, P<0.05; while ALB was significantly lower than that in the control group: (33.47 ± 6.98) g/L vs. (45.79 ± 6.12) g/L, P<0.05. ROC curves analysis showed that area under the curve (AUC) values of PCT, AMY, LDH, ALB and combined detection in the diagnosis of acute pancreatitis were 0.783, 0.792, 0.697, 0.732 and 0.915, respectively. The levels of serum PCT and LDH in the mild group were significantly lower than those in the severe group: (2.76 ± 0.44) μg/L vs. (3.59 ± 0.61) μg/L, (507.06 ± 131.67) U/L vs. (848.95 ± 207.79) U/L, P<0.05; while ALB was significantly higher than that in the severe group: (35.39 ± 4.73) g/L vs. (32.64 ± 5.09) g/L, P<0.05. ROC curves analysis showed that the AUC values of PCT, LDH, ALB and combined detection for evaluating disease severity were 0.668, 0.749, 0.741 and 0.959, respectively. The evaluation value of combined detection was significantly higher than that of single index ( P<0.05). Conclusions:The levels of serum PCT, AMY and LDH are abnormally increased, while ALB level is abnormally decreased in patients with acute pancreatitis, and which all can be applied for clinical diagnosis. PCT, LDH and ALB can be applied for disease evaluation.
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Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
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ObjectiveTo investigate the potential active ingredients and targets of Baihu Jia Renshentang(BHJRST) for the treatment of obesity combined with type 2 diabetes mellitus(T2DM) by network pharmacology and in vivo experiments. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to analyze and identify the material basis of BHJRST. Subsequently, potential targets for the action of the active ingredients were queried in databases such as ChEMBL, Therapeutic Target Database(TTD), YaTCM, DisGeNET and Traditional Chinese Medicine on Immuno-Oncology(TCMIO), and the shared targets were identified by taking the intersection of these targets with disease targets. The shared targets were imported into the STRING database to construct a protein-protein interaction(PPI) network, the hub genes were identified by cytoHubba plug-in, and molecular docking was used to validate the binding energy of the hub genes to the bioactive ingredients in BHJRST. Meanwhile, the shared targets were imported into the DAVID platform for gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The predicted results were subsequently verified by animal experiments. Eighteen 8-week-old male skeletal muscle insulin-like growth factor-1 receptor dysfunction(MKR) mice were induced by a high-fat diet for 12 weeks in order to prepare a mouse model of obesity combined with T2DM. The mice were randomly divided into the model group, metformin group(0.2 g·kg-1) and BHJRST group(27 g·kg-1 in raw material), and another 6 male FVB mice of the same age as the normal group. The mice in each group were were given the corresponding drugs by gavage, and the normal and model groups were given the same amount of distilled water by gavage, 1 time/d for 6 consecutive weeks. At the end of administration, the body mass, Lee's index, fasting blood glucose(FBG), oral glucose tolerance test(OGTT) of mice in each group were examined, and the pathological morphology of the white adipose tissue of the epididymis was observed, and the expression of the mRNA of the hub genes in the white adipose tissue of the epididymis was detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). ResultA total of 200 bioactive components of BHJRST were identified, of which 64 bioactive components were reverse-matched to 384 targets, and a total of 308 targets were associated with obesity combined with T2DM. Hub genes included mitogen-activated protein kinase 1(MAPK1), signal transducer and activator of transcription 3(STAT3), MAPK3, interleukin(IL)-2, Janus kinase 1(JAK1), nuclear transcription factor-κB p65(RELA), estrogen receptor 1(ESR1), transcription factor AP-1(JUN), MAPK14 and lymphocyte-specific protein tyrosine kinase(LCK). GO functional annotation showed that it was mainly enriched in cytoplasm, cell membrane and nucleus, and was closely related to important biological processes such as peptide serine phosphorylation, protein phosphorylation and inflammation. In KEGG enrichment analysis, metabolic pathway, lipid and atherosclerosis, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) and MAPK signal pathways were significantly enriched. The molecular docking results showed that the hub genes had a stable binding relationship with 10 bioactive components, including quercetin, isoliquiritigenin, and morin, in BHJRST. The results of animal experiments showed that BHJRST could significantly reduce body mass, Lee's index and FBG levels(P<0.01) in mice with obesity combined with T2DM, improve the pathological changes of white adipose tissue, and down-regulate the the mRNA expression of the hub genes in white adipose tissue of the epididymis(P<0.01). ConclusionIn this study, 10 potentially active components such as quercetin, isoliquiritigenin, and morin in BHJRST are identified through network pharmacology and animal experiments, and it is possible to treat obesity combined with T2DM by regulating lipid and atherosclerosis, phosphatidylinositol PI3K/Akt and MAPK signal pathways, which provides important clues and theoretical basis for the study of its mechanism and clinical application.
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ObjectiveTo study the mechanism of astragaloside Ⅳ (AS Ⅳ) on db/db mice with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups: model group, metformin group, and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg-1 by gavage, and the metformin group was given 0.067 g·kg-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration, fasting blood glucose (FBG) was detected, and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology, and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK, p-AMPK, sterol regulatory element-binding protein-1 (SREBP-1), and fatty acid synthetase (FAS) in liver tissue were detected by Western blot. ResultCompared with the blank group, the levels of body mass, liver weight coefficient, fasting blood glucose, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased (P<0.05, P<0.01). The pathology of liver tissue showed significant improvement in lipid accumulation, and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α (VEGFA), galactoagglutinin 3 (LGALS3), serine/threonine kinase B2 (Akt2), RHO-associated coiled-coil protein kinase 1 (ROCK1), serine/threonine kinase B1 (Akt1), signaling and transcriptional activator protein (STAT3), and messtimal epidermal transformation factor (MET) were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes (KEGG) enrichment showed that the AMP-dependent protein kinase (AMPK) signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group, the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated, while those of SREBP-1 and FAS proteins were significantly up-regulated (P<0.01). Compared with the model group, the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated, while those of SREBP-1 and FAS proteins were significantly down-regulated (P<0.05, P<0.01). ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway, thereby improving lipid metabolism.
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OBJECTIVE To systematically reevaluate (umbrella review) the systematic review/meta-analysis of Tripterygium glycosides (TG) in the treatment of diabetic kidney disease (DKD), in order to provide a higher quality evidence-based reference for TG in the treatment of DKD. METHODS The systematic reviews/meta-analysis of TG in the treatment of DKD were searched from CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library and Embase. The PRISMA 2020 statement, the AMSTAR 2 scale and the GRADE tool were used to evaluate the quality of the report, the quality of the methodology, and the quality of the evidence, respectively. The quantitative results of the included systematic review/meta-analysis were analyzed comprehensively. RESULTS A total of 18 systematic reviews/meta-analyses were included. PRISMA 2020 stated that 3 reports were complete, 13 reports had partial information defects, and 2 reports had serious information defects. The results of the AMSTAR 2 scale evaluation showed that 4 literature had low methodological quality, and 14 literature had very low methodological quality. GRADE tool evaluation results showed that there were 106 outcome indicators, including 34 intermediate-quality evidence accounted for 32.1%, 51 poor-quality evidence accounted for 48.1%, 21 very poor-quality evidence accounted for 19.8%, and there was no high- quality evidence. Comprehensive analysis of quantitative results of various outcome indicators showed that TG had definite improvement effects on the total effective rate of DKD, 24-hour urinary protein quantity and serum albumin, and the adverse drug reactions were different in every study. CONCLUSIONS The efficacy of TG in the treatment of DKD is relatively accurate, safety still needs to be paid attention to, and future studies with larger sample size need to be verified.
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Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
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Humanos , Óxido Nítrico , Ácido Úrico , Hiperuricemia , Disponibilidade Biológica , CitocinasRESUMO
OBJECTIVE@#To explore method and clinical effect of microsurgical thinned anterolateral thigh perforator flap to repair soft tissue defects of foot and ankle.@*METHODS@#From March 2017 to January 2022, totally 20 patients with soft tissue defects of ankle joint were treated with micro-thinning anterolateral perforator flap for free transplantation, included 13 males and 7 females, aged from 22 to 58 years old with an average of (36.45±12.36) years old. The size of flap ranged from 8.0 cm×5.0 cm to 20.0 cm×12.0 cm. Before operation, perforating vessels on the anterolateral thigh region were detected and marked with a portable Doppler detector. For the defect width less than 8 cm, 11 patients were repaired with a single flap. For the defect width more than 8 cm, the wound could not be sutured directly, and the lobulated flap technique was used in 9 patients, the width was converted to length, and the donor site was closed directly. Under the microscope, all flaps were thinened in a stepwise manner from the center of the pedicle to the periphery. After operation, survival of the flap, the shape, texture, sensory function recovery were observes, and recovery of foot function was evaluated by Maryland foot function evaluation standard.@*RESULTS@#All 20 patients with microsurgical thinned anterolateral thigh perforator flaps were survived. Venous crisis occurred in 1 patient due to subcutaneous hematoma, after removal of the hematoma, the crisis was relieved and the flap survived successfully. The wounds in the donor and recipient sites healed well, and only linear scars left in the donor sites. Twenty patients were followed up for 3 to 26 months after operation, good shape of flaps without bloated, and good texture. The two-point discrimination of free flaps ranged from 9.0 to 16.0 mm, and the protective sensation was restored. The ankle flexion and extension function recovered well and patients could walk normally. According to Maryland foot function evaluation standard, 8 patients got excellent result, 10 patients good and 2 middle.@*CONCLUSION@#Microsurgical thinned anterolateral thigh perforator flap is an ideal method to repair soft tissue defects in functional area of foot and ankle, with good appearance and texture of the flap, no need for re-plastic surgery, reduced hospitalization costs, and less donor site damage.
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Feminino , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Tornozelo/cirurgia , Coxa da Perna/cirurgia , Articulação do Tornozelo , Retalho Perfurante , HematomaRESUMO
This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.
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Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fígado , Lipoproteínas LDL/metabolismo , Transdução de Sinais , Dieta Hiperlipídica/efeitos adversos , RNA Mensageiro/metabolismoRESUMO
The theory of Zang Xiang is the core of the theory of traditional Chinese medicine,and its content mostly comes from the comparison of images.Among them,the liver Zang of"main drainage"and"main blood storage"involves many systems such as nerve,digestion,circulation,hematopoiesis,reproduction and so on.It is difficult to find the corresponding anatomical organs or tissues in western medicine.The author analyzes and believes that the collection of the functional system of the liver system of traditional Chinese medicine,compares the physiological function and pathological changes of the liver system with the histamine receptor distributed in multiple systems of the whole body,as well as the main symptoms and adverse reactions of the drugs regulating the histamine receptor,and believes that the functional system composed of histamine receptors may carry the important functions of the liver system of traditional Chinese medicine.
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ObjectiveTo explore the effects of Baihu Jia Renshen Tang (BHRS) on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway in the liver of MKR diabetic model mice. MethodThirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks,followed by intraperitoneal injection of streptozotocin(STZ)for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose (FBG) of ≥11.1 mmol·L-1. After modeling,the mice were randomly divided into a model group,a BHRS group (12.09 g·kg-1·d-1),and a metformin group (0.065 g·kg-1·d-1),with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration,the mice were sacrificed,followed by the oral glucose tolerance test (OGTT) and FBG detection. Serum very low-density lipoprotein(VLDL)content was determined by semi-quantitative enzyme-linked immunosorbent assay (ELISA). Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin(HE)staining. Western blot was used to detect the protein expression of PI3K,Akt,phosphorylated(p)-PI3K,p-Akt,forkhead box protein O1 (FoxO1),insulin receptor(InsR),and insulin receptor substrate-2(IRS-2) in liver tissues of mice. Real-time polymerase chain reaction(Real-time PCR) was used to detect the mRNA expression of PI3K,Akt,FoxO1,InsR,and IRS-2 in liver tissues of mice. ResultCompared with the control group,the model group showed poor general conditions,abnormal glucose tolerance (P<0.05),increased FBG (P<0.01),abnormal blood lipid metabolism,increased serum total cholesterol (TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and VLDL (P<0.05),decreased level of high-density lipoprotein cholesterol(HDL-C)(P<0.05),fatty degeneration and obvious pathological changes of liver cells,reduced protein expression of PI3K,Akt,p-PI3K/PI3K,p-Akt/Akt,IRS-2,and InsR in liver tissues(P<0.05),increased protein expression of FoxO1(P<0.05),decreased mRNA expression of PI3K,Akt,IRS-2,and InsR in liver tissues (P<0.05),and increased FoxO1 mRNA expression(P<0.05). Compared with the model group,the BHRS group showed improved general conditions and glucose and lipid metabolism (P<0.05),improved pathological state of liver cells,increased protein expression of PI3K,Akt,p-PI3K/PI3K,p-Akt/Akt,IRS-2,and InsR in liver tissues(P<0.05),decreased protein expression of FoxO1(P<0.05),increased mRNA expression of PI3K,Akt,IRS-2,and InsR in liver tissues (P<0.05),and reduced FoxO1 mRNA expression(P<0.05). ConclusionBHRS can effectively reduce blood glucose,regulate blood lipid metabolism,and improve the pathological state of the liver in MKR diabetic mice,and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.
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ObjectiveTo summarize the modeling elements, evaluation indicators, characteristics, and drawbacks of the animal models of diabetic nephropathy, and thus provide guidance for the standardized modeling and rational application of these models. MethodThe articles about the animal experiments of diabetic nephropathy published in the last decade were retrieved from China National Knowledge Infrastructure, Wanfang Data, and PubMed. The data of animal species, sex, modeling techniques, modeling criteria, and evaluation indicators were analyzed in Excel. ResultA total of 287 publications were included in this study. Male SD rats were mainly used for the modeling of diabetic nephropathy. The animal models of type 1 diabetes were mainly established by intraperitoneal injection of streptozotocin (STZ) at 60-69 mg·kg-1 once or 50 mg·kg-1 for 5 continuous days, and those of type 2 diabetes by intraperitoneal injection of STZ at 30-39 mg·kg-1 once or 30 mg·kg-1 for 2 continuous days combined with 4 weeks of high-fat and high-sugar diet. Blood glucose and 24-hour urine protein were mainly used to determine whether the modeling was successful. The evaluation indicators of the animal models mainly included basic indicators, glucose and lipid metabolism indicators, and renal function indicators. ConclusionAnimal models are commonly used in the research on diabetic nephropathy, while there is no unified standards for the preparation or evaluation of the animal models. Moreover, Chinese medicine is rarely considered in the modeling. Through literature review and data analysis, this paper summarizes the modeling elements and standards, key evaluation indicators, characteristics, and shortcomings, aiming to build the animal models of diabetic nephropathy with a high success rate and with the characteristics in line with the clinical pathogenesis and syndromes.
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ObjectiveTo investigate the effect of Jingui Shenqiwan on diabetic osteoporosis (DOP) in mice by regulating the advanced glycation end products (AGEs)/receptor activator of nuclear factor-κB ligand (RANKL)/nuclear factor-κB (NF-κB) signaling pathway based on the theory of "kidneys governing bones". MethodForty 6-week-old male and female skeletal-muscle-specific, dominant negative insulin-like growth factor-1 receptor (MKR) mice were selected and fed on a high-fat diet for eight weeks to establish the DOP model. The model mice were randomly divided into a model group, low- and high-dose Jingui Shenqiwan group (1.3, 2.6 g·kg-1), and an alendronate sodium group (0.01 g·kg-1), with 10 mice in each group. Additionally, 10 FVB/N mice of the same age were assigned to the normal group. The corresponding drugs were administered orally to each group once a day for four weeks. After the administration period, fasting blood glucose (FBG) measurement and oral glucose tolerance test (OGTT) were conducted. Kidney function and kidney index were measured. Renal tissue pathological changes were observed through hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry was performed to assess the protein expression levels of AGEs, phosphorylated NF-κB (p-NF-κB), and RANKL in renal tissues. Western blot analysis was conducted to measure the expression of proteins related to the AGEs/RANKL/NF-κB signaling pathway, osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) proteins in femoral bone tissues. ResultCompared with the normal group, mice in the model group exhibited significantly increased FBG (P<0.01), trabecular bone degeneration, abnormal bone morphological parameters, significantly increased area under the curve (AUC) of OGTT (P<0.01), enlarged kidney volume, significantly increased kidney function indicators and kidney index (P<0.01), disrupted renal glomeruli and renal tubule structures, significantly increased expression of AGEs, RANKL, and p-NF-κB/NF-κB in renal tissues (P<0.05), and significantly decreased expression of OPG and RUNX2 in femoral bone tissues (P<0.01). Compared with the model group, mice in the Jingui Shenqiwan groups showed a significant decrease in OGTT AUC (P<0.01). Histopathological analysis revealed alleviated structural lesions in renal glomeruli and renal tubules. Furthermore, the expression of AGEs, RANKL, and p-NF-κB/NF-κB in renal tissues was significantly reduced (P<0.05, P<0.01), and the expression of RUNX2 and OPG in femoral bone tissues was significantly increased (P<0.05, P<0.01). ConclusionJingui Shenqiwan can improve kidney function and downregulate the AGEs/RANKL/NF-κB signaling pathway to inhibit inflammatory reactions, thereby alleviating the symptoms of DOP in mice, demonstrating a therapeutic effect on DOP from the perspective of the kidney.
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ObjectiveTo investigate the mechanism of Zuogui Jiangtang Qinggan prescription (ZJQP) in improving glucose and lipid metabolism in loss of skeletalmuscle-specific insulin-like growth factor-1 receptor function (MKR) mice with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). MethodNAFLD was induced by high-fat diet feeding for 8 weeks in MKR mice, which were randomly divided into model group, metformin group (0.067 g·kg-1), and ZJQP high and low-dose groups(14.8, 7.4 g·kg-1). Ten FVB mice of the same age were used as the normal group. After 8 weeks of drug treatment, the oral glucose tolerance test (OGTT) was performed, the serum was taken to detect triacylglycerol (TG) and total cholesterol (TC), and the wet weight of the mouse liver was weighed. Haematoxylin-eosin (HE) staining and oil red O staining were performed to assess histopathology of liver. The mRNA expression and protein expression of Fork head box protein O1 (FoxO1), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and apolipoprotein C3 (ApoC-Ⅲ) in liver tissues were detected by real-time fluorescent quantitative PCR (Real-time PCR) and Western blot, respectively. ResultAs compared with the normal group, the levels of fasting blood glucose, liver index, serum TG, TC, and OGTT of mice in the model group increased significantly (P<0.01). As compared with model group, the fasting blood glucose and liver index of the mice in the metformin group and the ZJQP group decreased significantly (P<0.01), the serum levels of TG and TC in the high-dose ZJQP group decreased significantly (P<0.05,P<0.01), and the OGTT of mice in the metformin group and the high-dose ZJQP group improved (P<0.05). In histopathology, as compared with the normal group, mice in the model group showed decreased lipid droplets and vacuoles in hepatocytes, and their volumes became larger. Compared with the model group, the ZJQP group and metformin group showed that the lipid droplets in liver tissues were reduced, the vacuoles in liver cells were reduced, and the volume was smaller. At the molecular level, as compared with the normal group, the mRNA and protein levels of FoxO1, PEPCK, G6Pase, and ApoC-Ⅲ in liver tissues of mice in the model group were significantly up-regulated (P<0.01). As compared with the model group, the mRNA and protein levels of FoxO1, PEPCK, G6Pase, and ApoC-Ⅲ in the ZJQP group was significantly decreased (P<0.01). ConclusionZJQP can improve the glucose and lipid metabolism of T2DM with NAFLD and repair the pathological damage of liver, which may be through regulating the expression of FoxO1, PEPCK, G6Pase, ApoC-Ⅲ-related proteins in liver tissues to achieve the effects of regulating lipid, lowering glucose, and delaying hepatic steatosis.
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This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.
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Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Microbioma Gastrointestinal , RNA Ribossômico 16S , Diabetes Mellitus Tipo 2/metabolismo , Ocludina/farmacologia , Claudina-1/metabolismo , Mucosa Intestinal , Fígado , Triglicerídeos/metabolismo , Dieta Hiperlipídica , Homeostase , Camundongos Endogâmicos C57BLRESUMO
Objective: To investigate the clinical outcome and preventive effect of polyetheretherketone(PEEK) rod hybrid surgery on proximal junction failure(PJF) after long-segment fusion of adult spinal deformity. Methods: A retrospective study was conducted to analyze patients with degenerative scoliosis/kyphosis who underwent long-segment decompression and fusion surgery at Department of Orthopedics, Peking University First Hospital from January 2017 to December 2021. A total of 75 patients were included in the study, including 14 males and 61 females, aged (67.2±6.8)years (range:55 to 84 years). According to the operation method chosen by the patients, the patients were divided into PEEK rod hybrid group (20 cases) and traditional titanium rod group (55 cases). The general information of the patients was collected, and the coronal and sagittal parameters of the spine were measured before operation, at 1 month after operation, and at the last follow-up. The clinical effect of surgery was judged by the visual analogue scale (VAS) and Oswestry disability index (ODI). Whether proximal junctional kyphosis (PJK) and PJF occurred during the follow-up and the time of occurrence were recorded. Comparisons between groups were performed using independent sample t test, Mann-Whitney U test, χ2 test and Fisher's exact probability method. The data before and after surgery in the same group were compared using the paired sample t test and the Wilcoxon test. Results: There were no significant differences in age, gender, body mass index, bone mineral density, distal instrumented vertebrae, surgical segments, osteotomy method, operation time, and intraoperative bleeding between the two groups (all P>0.05). The follow-up time of the PEEK rod group was shorter(M(IQR)16.5(4.8) vs. 25.0(12.0),Z=-4.230,P<0.01). There were no significant differences in coronal, sagittal parameters, VAS and ODI between the two groups before operation (all P>0.05). Postoperative coronal Cobb angle, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, sagittal vertical axis (SVA), VAS and ODI were significantly improved in both groups(all P<0.05). At the last follow-up, the SVA of the PEEK rod hybrid group was(3.74±2.40)cm, which was significantly lower than that of the titanium rod group (6.28±4.06)cm (t'=-3.318, P=0.002). At the last follow-up, the ODI of the PEEK rod hybrid group was 30.7±6.1, significantly better than the titanium rod group 39.3±17.2(t=-3.203, P=0.046). PJK occurred in 2 patients (10.0%) in the PEEK rod hybrid group, and no PJF phenomenon was observed. In the titanium rod group, 18 patients (32.7%) developed PJK, and 11 patients (20.0%) developed PJF. There was a statistically significant difference in the incidence of PJF between the PEEK rod hybrid group and the titanium rod group (P=0.031). Conclusions: PEEK rod hybrid surgery can achieve good clinical results in the treatment of adult spinal deformities. Compared with traditional titanium rod surgery, it can significantly reduce the incidence of postoperative PJF and improve the clinical function of patients.
Assuntos
Masculino , Feminino , Animais , Humanos , Adulto , Estudos Retrospectivos , Titânio , Cifose/etiologia , Sacro , Osteotomia/efeitos adversos , Fusão Vertebral/métodos , Vértebras Lombares , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologiaRESUMO
Objective:To explore the law of Chinese medicine patent compound prescription in treating diabetic retinopathy (DR).Methods:The patents of TCM compound for the treatment of DR Published in the patent database of China National Knowledge Resource Database (CNKI) from the establishment of the database to September 1, 2022 were searched and screened. The Ancient and Modern Medical Record Cloud Platform V2.0 was used to analyze the frequency of medication, nature, taste, and meridian distribution, and the rules of compatibility of medication were mined and analyzed based on association rules and cluster analysis.Results:A total of 113 compound patents were included, involving 201 kinds of Chinese materia medica. The top five drugs in frequency of use were Rehmanniae Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix, Ganoderma and Astragali Radix. Their properties were mostly cold and warm, and their tastes were sweet and bitter. The top three meridians were liver meridian, lung meridian and kidney meridian. Six pairs of commonly used drugs were obtained, and four kinds of medicines were obtained by clustering analysis. Complex network analysis showed that core TCM combination was Rehmanniae Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix, Ganoderma, Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Lycii Fructus, Prinsepiae Nux, and Cuscutae Semen.Conclusions:TCM compound patents for the treatment of DR are mainly used to treat cold and liver meridian, and the medication is mainly used to replenish qi and nourish yin, clear heat and cool blood, promote blood circulation and remove blood stasis, and tonify liver and kidney. The drug pairs are mainly used to supplement qi and nourish yin, clear heat and detoxify, invigorate qi and nourish blood, and invigorate qi and stop bleeding. The modified Danggui Buxue Decoction and Siwu Decoction are often used in treatment, and wind drugs are added as appropriate to soothe liver and improve eyesight, which can provide reference for clinic.
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Objective:To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes.Methods:Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios ( RRs) and their 95% confidence intervals ( CIs) between baseline RC level and incident DR. Results:The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR ( RR=1.40, 95% CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times ( RR=5.59, 95% CI 1.51-20.73). Conclusion:The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.
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Type 2 diabetes mellitus (T2DM) can be categorized into “xiao ke (消渴)” in traditional Chinese medicine (TCM). The theory of “yin restricts fire” originates from Inner Canon of Yellow Emperor (《黄帝内经》) which states that “yin essence restricts chief fire”, and the crucial pathogenesis and treatment of xiao ke coincide with this theory. ZHANG Zhongjing,s three prescriptions of Jizizhuang (egg yolk) are Baihe Jizizi Decoction (百合鸡子汤), Huanglian Ejiao Decoction (黄连阿胶汤) and Painong Powder (排脓散), which are scattered in different chapters of Treatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》). By analyzing and summarizing the mechanism and characteristics of the three prescriptions, it is found that the three prescriptions are in line with the characteristics of “yin restricts fire” and the pathogenesis of T2DM. These three prescriptions are composed of Jizizhuang and different medicinals. Baihe Jizizi Decoction is composed of Jizizhuang and Baihe (Bulbus Lilii), and can be used to treat T2DM and mental diseases. Huanglian Ejiao Decoction is composed of Jizihuang, Ejiao (Colla Corii Asini), Shaoyao (Radix Paeoniae Alba seu Rubra), Huanglian (Rhizoma Coptidis) and Huangqin (Radix Scutellariae), which could be used to treat T2DM and cardiorenal system diseases. Painong Powder is composed of Jizizhuang, Shaoyao, Jiegeng (Radix Platycodonis) and Zhishi (Fructus Aurantii Immaturus), which can be used to treat T2DM and carbuncle. Therefore, based on the theory of “yin restricts fire” and “many different diseases can be treated in the same wa”, this paper propose that the three Jizihuang prescriptions could be used in T2DM, which could provide ideas for clinical treatment.
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ObjectiveTo explore the effect and underlying mechanism of alcohol extract of Phyllanthi Fructus on silicosis mice induced by silicon dioxide (SiO2). MethodThirty-six male Kunming mice of SPF grade were randomly divided into a blank group,a model group,high-, medium, and low-dose Phyllanthi Fructus groups (800, 400, 200 mg·kg-1),and a tetrandrine group (0.039 mg·kg-1),with six mice in each group. The silicosis model was induced by static SiO2 exposure in mice except for those in the blank group. After 28 days of administration by gavage,the lung tissues were collected and the organ coefficient was calculated. Hematoxylin-eosin(HE)staining and Masson staining were used to detect the morphology of lung tissues. The content of hydroxyproline (HYP),superoxide dismutase (SOD),malondialdehyde (MDA), and catalase (CAT) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Western blot and Real-time polymerase chain reaction(Real-time PCR) were used to detect the protein and mRNA expression of nuclear factor E2-related factor 2 (Nrf2),heme oxygenase-1 (HO-1),NAD(P)H:quinone oxidoreductase 1 (NQO1),and Kelch-like ECH-associated protein 1 (Keap1), respectively. ResultCompared with the blank group,the model group showed seriously damaged morphological structure of lung tissues with inflammatory cell infiltration and fibrous tissue proliferation, reduced serum content of SOD and CAT(P<0.01),increased content of HYP and MDA(P<0.01), down-regulated protein and mRNA expression of Nrf2,HO-1, and NQO1(P<0.01),and up-regulated protein and mRNA expression of Keap1 (P<0.05,P<0.01). Compared with the model group,the high- and medium-dose Phyllanthi Fructus groups showed significantly restored morphological structure of lung tissues with reduced collagen deposition, increased serum content of SOD and CAT(P<0.05,P<0.01),decreased content of HYP and MDA(P<0.01), up-regulated protein and mRNA expression of Nrf2,HO-1, and NQO1 (P<0.05,P<0.01),and down-regulated protein and mRNA expression of Keap1(P<0.05,P<0.01). ConclusionThe alcohol extract of Phyllanthi Fructus can inhibit pulmonary fibrosis in silicosis mice,and the underlying mechanism may be related to the regulation of the Nrf2/antioxidant response element (ARE) signaling pathway.
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The continuous pandemic coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is a serious threat to human life and health because of high infectious pathogenicity, and it also has posed a new challenge to the current medical model. Many literatures have shown that these changes range from the more common ocular surface diseases such as inflammation of the cornea, conjunctiva, and sclera, to the relatively rare paracentral acute middle maculopathy and acute macular neuroretinopathy. For patients with ocular symptoms as the first or accompanying symptoms of SARS-CoV-2 infection, how to identify the correlation between ocular manifestations and SARS-CoV-2 infection is undoubtedly a serious challenge for ophthalmologists. In this review, the ocular pathology caused by both SARS-CoV-2 infection and vaccination was discussed, covering pathological changes in the ocular surface, uvea, retina and macula, and cranial nerves.