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ObjectiveThe active ingredients， action targets， and signaling pathways of Cuscutae Semen to control premature ovarian failure were initially predicted by network pharmacology and molecular docking techniques， and an animal model of premature ovarian failure was constructed to explore the mechanism of Cuscutae Semen based on lipid and atherosclerosis signaling pathways. MethodThe effective components and corresponding targets of drugs were obtained from Traditional Chinese Medicines Systems Pharmacology Platform （TCMSP）， Swiss Target Prediction， Pharmmapper， and other databases. GeneCards database was used to collect disease-related targets. Venny2.1.0 online tool was used to screen out the intersection targets of drugs and diseases， and STRING database and Cytoscape v3.7.2 software were used to construct the network diagram of "drug-component-target" and protein-protein interaction （PPI）. The gene ontology （GO） and the Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of the intersection targets were performed by running the R language script. The molecular docking technology was utilized to dock drug components with targets and visualize some of the docking results. The mice were randomly divided into a blank group， a model group， a Cuscutae Semen group， and an estradiol valerate group， and the ovarian premature failure model was prepared by chronic stress. The blank group and the model group were gavaged with the same amount of normal saline， and the Cuscutae Semen group was given a Cuscutae Semen decoction of 2.6 g·kg-1·d-1. The estradiol valerate group was given an estradiol valerate solution of 0.13 mg·kg-1·d-1. After four weeks， samples were collected， and hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the ovary. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E2）， Muller's tube inhibitor/anti-Muller's tube hormone （AMH）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were determined by enzyme-linked immunosorbent assay （ELISA）. The expression levels of extracellular regulatory protein kinase （ERK）， nuclear transcription factor-κB p65 （NF-κB p65）， nuclear transcription factor-κB suppressor α （IκBα）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） were measured by Western blot. ResultA total of 171 targets of Cuscutae Semen for the prevention and treatment of premature ovarian failure were screened， mainly including tumor protein p53 （TP53）， protein kinase B1 （Akt1）， sarcoma （SRC）， tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， etc. KEGG pathway enrichment analysis predicts that Cuscutae Semen is mainly involved in lipid and atherosclerosis， TNF signaling pathway， and TP53 signaling pathway to control premature ovarian failure. The animal experiments show that compared with the premature ovarian failure model group， the Cuscutae Semen group can significantly upregulate AMH， E2， and HDL-C （P<0.05， P<0.01）， significantly downregulate LH， TC， and LDL-C （P<0.01）， greatly reduce IL-1β， IL-6， and TNF-α protein levels， as well as ERK， NF-κB p65， and their phosphorylation levels （P<0.01）. ConclusionCuscutae Semen can regulate hormone levels and improve ovarian function through a multi-component， multi-target， and multi-pathway approach， and the mechanism may be related to the regulation of lipid and atherosclerosis signaling pathways.
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Objective To evaluate the efficacy of vitamin C intravenous injection in the treatment of patients with sepsis.Methods PubMed,Embase,Scopus,Cochrane Library,and Clinical Trial databases were retrieved,with a retrieval period from database establishment to December 2022.English literatures on randomized controlled trial(RCT)of vitamin C intravenous injection for the treatment of sepsis or septic shock were collected.Meta-analysis was conducted using RevMan 5.3 software and Stata 15.0 software after literature screening,extraction,and evalua-tion of the bias risk included in the studies by two researchers independently.Results A total of 16 RCT studies involving 3 301 patients were included in the analysis.In terms of main outcomes,the 28-day mortality of patients in the vitamin C treatment group was slightly lower than that of the control group,but the difference was not statis-tically significant(RR=0.86,95％CI[0.72-1.03],P=0.10;I2=44％,P=0.10).In terms of secondary out-comes,vitamin C intravenous injection can reduce the duration of vasoactive drug usage time(MD=-23.44,95％CI[-30.53--16.35],P＜0.01;I2=0,P=0.97),but has no significant effect on the 90-day mortality,inten-sive care unit mortality,hospital mortality,duration of mechanical ventilation,difference in estimated sequential organ failure assessment score at 72 hour,length of stay in ICU,and total length of hospital stay of patients(P＞0.05).Conclusion Intravenous vitamin C injection can significantly reduce vasoactive drug usage time,but the available evidence is insufficient to support that intravenous vitamin C can improve the prognosis of patients with sepsis or septic shock.More high-quality,multicenter randomized controlled trial is needed to provide more substantial evidence about the efficacy of vitamin C in treating sepsis or septic shock.
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Objective:To investigate the effect of resveratrol on apoptosis of chondrocytes in rats with knee osteoarthritis(KOA)through autophagy mediated by silent information regulator 1(SIRT1)/adenylate activated protein kinase(AMPK)signaling pathway.Methods:Fifty healthy Wistar rats were randomly separated into control group,model group,resveratrol group,resveratrol+ SIRT1 inhibitor group,and autophagy activator group,with 10 rats per group.Except for the control group,the other rats were injected with Freund's complete adjuvant to establish the KOA rat model,resveratrol group,resveratrol+AMPK inhibitor group,and autophagy activator group were treated with 10 μmol/kg resveratrol,10 μmol/kg resveratrol+10 mg/kg EX527,2 mg/kg rapamycin,respectively.After 4 weeks,the grade of Lequesne MG knee joint of rats were observed;the levels of IL-6 and tumor necrosis factor-β(TNF-β)in rat knee joint fluid were measured;HE staining and TUNEL staining were used to observe the morphology and apoptosis of rat knee cartilage;transmission electron microscope was used to observe the autophagy in rat chondrocytes;Western blot was performed to determine the protein expressions of SIRT1,p-AMPK,AMPK,LC3 and Beclin-1.Results:Compared with control group,the local reaction,gait reaction,joint activity,and joint swelling of model group were increased;compared with model group,the local response,gait response(P<0.05),joint activity,and joint swelling in resveratrol group and autophagy activator group were reduced(P<0.05).Compared with control group,the cartilage tissue cells in model group were disordered and rough,with fibrotic degeneration,marginal humeral bulge,reduced organelles,and vacuolar degeneration,the number of autophagosomes was increased,the levels of IL-6 and TNF-β in knee joint fluid,chondrocyte apoptosis rate,Beclin-1 and LC3B/A were increased(P<0.05),the SIRT1 and p-AMPK/AMPK in cartilage tissue were decreased(P<0.05);compared with model group,resveratrol group and autophagy activator group showed improvement in the disordered arrangement of cartilage tissue cells and the marginal humeral bulge,the number of autophago-somes was increased,the levels of IL-6 and TNF-β in knee joint fluid,and the apoptosis rate of chondrocytes were decreased(P<0.05),the levels of SIRT1,p-AMPK/AMPK,Beclin-1 and LC3B/A in cartilage tissue were increased(P<0.05);SIRT1 inhibitor could reverse the protective effect of resveratrol group on rat chondrocytes.Conclusion:Resveratrol maybe autophagic KOA rat chon-drocyte apoptosis mediated by activating SIRT1/AMPK pathway,which can be reversed by SIRT1 inhibitor.
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Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.
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Gut microbiota participates in numerous physiological and metabolic processes in the human body,directly affecting human health.The imbalance of gut microbiota may lead to many diseases.This article reviews the types of gut microbiota,the impact of gut microbiota on different populations,and the relationship between gut microbiota abnormalities and diseases,in order to better explain the important role of gut microbiota in human health and diseases,and provide the theoretical basis for further understanding the relationship between gut microbiota and human health.
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Objective To investigate the expression of lymphoid enhancer binding factor 1(LEF1)in B cell chronic lymphoproliferative disorders(B-CLPD)and estimate its value in the differential diagnosis of the subtype of B-CLPD.Methods A retrospective study was conducted on 58 patients diagnosed with B-CLPD by using bone marrow biopsy samples or lymphnode biopsy samples from Hematology Department of The Second People′s Hospital of Wuhu from September 2018 to June 2023,as well as 20 bone marrow biopsy samples which were diagnosis as non-hematologic malignancy in the control group.Immunohistochemical method was used to detect the expression of LEF1 in 78 samples,and statistical analysis was conducted.Results In all 78 cases,16 of 20 chronic lymphocytic leukemia(CLL)patients were LEF1 positive,the positive rate was 80%;mantle cell lymphoma 1/12;Follicular lymphoma 1/5;marginal zone cell lymphoma 0/11;Lymphoplasmacyticlymphom 0/8;hairy cell leukemia 0/2;in Control group no patient was LEF1 positive(P = 0.000).The expression of LEF1 is correlated with CD200 and CLL score(P<0.05).In the LEF1 negative group with 4 CLL patients,2 were detected with +12 chromosomal abnormality,the detective rate was higher than that of the LEF1 positive group(P>0.05).Conclusion LEF1 was a sensitive and specific diagnosis marker in CLL and B-CLPD subtype.
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The construction of smart hospital is an important part of modern hospital management system,and it is also the key way to build the new system of high-quality hospital development.In terms of building smart hospitals,multi-campus hos-pitals face more difficulties and challenges than single campus hospitals,such as the lack of top-level design,the difficulty of in-tegrated management,the uneven development of hospitals and the widespread phenomenon of information islands.This study summarizes and analyzes the difficulties encountered in the construction and application of smart hospitals in multi-hospital areas.Guided by problems,it puts forward countermeasures and suggestions for the construction of refined and high-quality smart hospi-tals in multi-campus hospitals,including strengthening overall and forward-looking awareness,integrating management according to hospital conditions,characteristic development under demand guidance,establishing a data integration center for smart hospi-tals,scientific planning of talent reserve and discipline layout,etc.
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Objective:To analyze the current status of physical composition in medical workers and the evaluation effects of each indicator on nutritional status.Methods:It was a cross-sectional study. A total of 313 medical workers from one hospital in Beijing were recruited from May 21st to June 22nd in 2021 for body composition measurement. Variance analysis was used to compare the age and gender distribution differences in total body fat, fat-free body weight, body fat percentage, skeletal muscle, protein, water, mineral, and basal metabolic rate indicators among the medical workers. Protein content, body fat percentage, and body mass index (BMI) were used to evaluate the nutritional status of medical workers, and the evaluation effects were analyzed too.Results:Of the 313 medical workers included in this study, there were 221 females and 92 males. In females, total body fat, fat-free body weight, skeletal muscle mass, and basal metabolic rate were all positively correlated with age ( F=19.823, 6.745, 6.561, 6.707) (all P<0.001). There was no significant differences in body composition indicators among male participants of different age groups (all P>0.05). The total body fat in female medical workers was significantly higher than that in males (17.58 kg vs 17.08 kg). Total water, protein, minerals, fat-free body weight, skeletal muscle mass, and basal metabolic rate were all significantly lower in female medical workers when compared with those in males [30.40 kg vs 41.78 kg, 8.07 kg vs 11.26 kg, 2.96 kg vs 3.88 kg, 41.43 kg vs 56.92 kg, 22.37 kg vs 31.98 kg, 1 264.86 kcal (1 kcal=4.184 kJ) vs 1 599.39 kcal] (all P<0.05). Among the medical workers, 190 cases (60.7%) had normal protein levels, 103 cases (32.9%) had protein deficiencies, and 20 cases (6.3%) had protein levels exceeding the standard. Additionally, 110 cases (35.1%) had normal body fat ratios, 193 cases (61.6%) had excessive body fat ratios, and 10 cases (3.2%) had insufficient body fat ratios. Concerning body mass index (BMI), 198 cases (63.2%) had normal BMI. Among them, 145 cases (73.2%) had normal body fat ratios, 53 cases (26.7%) had excessive body fat ratios, 108 cases (54.5%) had normal protein levels, 89 cases (44.9%) had insufficient protein levels, and 1 case (0.5%) had excessive protein levels. Furthermore, 103 cases (32.9%) had excessive BMI, with 20 cases (19.4%) having normal body fat ratios indicating the muscle/bone strength type, and 83 cases (80.6%) having normal protein levels indicating the muscular type. Lastly, 12 cases (3.8%) had insufficient BMI, including 6 cases (50.0%) with normal body fat ratios. Conclusion:There are significant gender differences in body composition distribution among healthcare workers. In females, total body fat, lean body mass, skeletal muscle, and basal metabolic rate are all correlated with age. Evaluating individual nutrition status based solely on BMI would underestimate the obesity rate. Individuals with low or high protein/muscle content should not be assessed using BMI.
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As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.
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Objective:To explore the relationship between reduced folate carrier 1(RFC1) gene polymorphism a curative effect, plasma concentration and adverse reaction of methotrexate (MTX) in patients with rheumatoid arthritis (RA).Methods:A total of 268 RA patients with 82 males and 186 females, aged (52.47±10.29) years, who received MTX treatment in the First People's Hospital of Shangqiu, from Jan 20, 2018 to Jan 20, 2021 were collected by case-control study. The genotype of RFC1 G80A locus were detected. The plasma concentration of MTX were detected after initial administration for 48 hours. The curative effect and adverse reactions were observed and counted after treatment for 6 months. The differences of RFC1 G80A genotype among different groups were compared. Collinearity diagnosis and logistic regression were used to analyze the influencing factors of MTX efficacy and plasma concentration. The incidences of adverse reactions among patients with different genotype were compared by Chi-square test.Results:The distribution of RFC1 G80A genotype (GG/GA/AA) and gene frequency (G/A) showed statistically significant differences between the effective group and the ineffective group (χ 2=6.583, P=0.037; χ 2=6.249, P=0.012), and the effective rate of AA type [59.26% (32/54)] was higher than that of GG type [36.49% (27/74)] (χ 2=6.516, P=0.011). Logistic regression analysis showed that the OR (95% CI) value of MTX response rate in AA genotype patients versus GG genotype patients was 2.491(1.206-5.144). The 48 hour plasma drug concentration of AA type patients was 1.15 (0.75, 1.35) μmol/L. Compared with GG type [0.74 (0.61, 1.18) μmol/L] and GA type [0.84 (0.69, 0.99) μmol/L], the difference was statistically significant(χ 2=7.152, P=0.028). Logistic regression analysis showed that the probability of high 48 hour plasma drug concentration in patients with AA type was approximately 2.583 (1.238-5.390) times higher than that in patients with GG type. There was a statistically significant difference in the incidence of liver function injury among three different genotypes (GG/GA/AA) (χ 2=12.606, P=0.002). Conclusion:RFC1 G80A locus polymorphism can affect the MTX efficacy, blood drug concentration and liver function damage in RA patients. AA type patients have better efficacy and higher blood drug concentration compared to GG type patients, but the rate of liver function damage is also higher.
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Zuoguiwan， one of the classic formulas of traditional Chinese medicine （TCM）， has the effects of nourishing genuine Yin， supplementing essence， and replenishing marrow， and it is widely used in the clinical treatment of diseases caused by congenital essence deficiency. This article systematically reviewed the ancient books involving congenital deficiency and the modern research reports on the treatment of congenital deficiency with Zuoguiwan. From the formulation principle of Zuoguiwan and the TCM concept of congenital deficiency， this article discussed the theoretical basis of treating congenital deficiency with Zuoguiwan based on the modern research results. Ancient physicians have discovered that the deficiency of parents can lead to abnormal physical development and weakness of the offspring. ZHANG Jingyue divided congenital essence Qi into genuine Yin and primordial Yang and formulated Zuoguiwan based on the principle of Yin-Yang mutual assistance for supplementing congenital genuine Yin. Experimental studies have shown that Zuoguiwan can up-regulate the expression of connexin 43 （Cx43） protein and improve gap junction intercellular communication （GJIC） function to promote osteogenic differentiation and maturation of bone marrow mesenchymal stem cells and ameliorate abnormal bone development caused by congenital essence deficiency. Zuoguiwan can enhance the expression and activity of Reelin to ameliorate abnormal brain development. It can upregulate the expression of Cx43 protein to intervene in the phosphatidylinositol 3 kinase/protein kinase B （PI3K/Akt） pathway， thus repairing the reproductive functions. Zuiguiwan can promote the development and maturation of T cells and activate the Wnt/β-catenin signaling pathway in the thymus to improve immune functions. In addition， it can promote the expression of β-catenin and inhibit the expression of microtubule-associated proteins 1 light chain 3 （LC3） to attenuate skin dysfunctions. Moreover， Zuoguiwan can guide the differentiation of stem cells via the correlation between essence and vitality in TCM. Zuoguiwan has demonstrated significant therapeutic effects on some diseases in the pediatric， andrological， gynecological， geriatric， internal medicine， orthopedic and skin disease departments. On the basis of the results of experiments and clinical applications， this paper analyzes the specific connotation of congenital deficiency proposes that congenital deficiency should be subdivided into the four aspects of essence， Qi， Yin， and Yang. Congenital essence deficiency as the deficiency of genuine Yin can lead to deficiency of kidney essence in the offspring and dysfunction of kidney storing essence. Pharmacological studies have discovered that Cuscutae Semen， Lycii Fructus， and Achyranthis Bidentatae Radix in Zuoguiwan contain active components such as quercetin and kaempferol， which act on the targets such as recombinant prostaglandin endoperoxide synthase 2 （PTGS2）， interleukin-6 （IL-6）， mitogen-activated protein kinases （MAPK14）， tumor necrosis factor （TNF）， TP53， Vascular permeability factor A （VEGFA）， and albumin （ALB） to play a role in reproductive system development and hormone responses. Zuoguiwan has unique advantages over Liuwei Dihuangwan in nourishing congenital genuine Yin in the kidney and can achieve better therapeutic effects on the syndromes and diseases caused by congenital essence deficiency. This review is expected to enrich the knowledge about the efficacy and clinical application of Zuoguiwan， provide new perspectives and methods for the prevention and treatment of congenital deficiency and congenital essence deficiency， and give insights into the application of Zuoguiwan in modern healthcare， especially in the nurturing of offspring.
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ObjectiveTo investigate the effect of Zuoguiwan on the ovarian function in the rat model of cyclophosphamide-induced premature ovarian failure （POF） based on the changes of ferroptosis pathway. MethodForty SD rats were randomized into blank， model， and low- and high-dose （2， 8 g·kg-1， respectively） Zuoguiwan groups， with 10 rats in each group. The rats in the other groups except the normal group were intraperitoneally injected with CTX at a dose of 50 mg·kg-1 on the first day and 8 mg·kg-1 from the second day to the fifteenth day for the modeling of POF. After modeling， the rats were administrated with corresponding drugs or normal saline by gavage for four weeks. Hematoxylin-eosin staining was performed to observe the pathological changes in the ovarian tissue. The mitochondria of the ovarian tissue was observed by electron microscopy. The serum levels of follicle-stimulating hormone （FSH）， estradiol （E2）， luteinizing hormone （LH）， anti-Mullerian hormone （AMH）， malondialdehyde （MDA）， catalase （CAT）， superoxide dismutase （SOD）， and iron ion were measured by biochemical methods and enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， ferritin heavy chain （FTH1）， and acyl-CoA synthetase long chain family member 4 （ACSL4）. ResultCompared with the blank group， the model group showcased significantly increased atretic follicles， atrophied， fragmented， and vacuolated mitochondria， and reduced， loose， and disordered cristae in mitochondria. Compared with the model group， high-dose Zuoguiwan increased mature follicles， the volume of mitochondria in the ovary， alleviated the vacuolation， and improved the number and arrangement of mitochondrial cristae. Compared with the blank group， the modeling elevated the levels of iron， MDA， FSH， and LH， up-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， decreased the activities of SOD and CAT， lowered the levels of E2 and AMH， and down-regulated the expression of ACSL4 （P<0.05， P<0.01）. Compared with the model group， drug interventions lowered the levels of iron， MDA， FSH， and LH， down-regulated the expression of GPX4， SLC7A11， and FTH1 （P<0.05， P<0.01）， increased the activity of CAT， elevated the levels of E2 and AMH， and up-regulated the expression of ACSL4 （P<0.05， P<0.01）. ConclusionZuoguiwan may inhibit the occurrence of ferroptosis by regulating the SLC7A11/GPX4 axis， thereby improving the ovarian function of POF rats.
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ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress （PS） and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 （TLR4/NF-κB p65） signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups （n=8）： control， model， Zuoguiwan （18.9 mg·kg-1）， and vitamin E （1.44 mg·kg-1）. Except the control group， the other three groups were subjected to chronic unpredictable mild stress （CUMS） from day 11 of pregnancy， and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test， open field test， and serum corticosterone （CORT） level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， and anti-Mullerian hormone （AMH） in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence （IF） assay. The expression of TLR4， NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group， the model group showed reduced primordial follicles in the offspring on the day of birth （P<0.01） as well as disturbed estrous cycle， decreased ovary index and uterus index （P<0.01）， reduced corpus luteum， increased atretic follicles （P<0.01）， lowered serum levels of AMH and E2 （P<0.01）， elevated serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and up-regulated protein levels of TLR4， NF-κB p65， recombinant myeloid differentiation factor 88 （MyD88）， and phosphorylated NF-κB inhibitor （p-IκBα） （P<0.01） in the 75-day-old offspring rats. Compared with the model group， Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth （P<0.01）. Moreover， they resumed the estrous cycle， increased the ovary and uterine indices （P<0.05， P<0.01） and corpus luteum （P<0.01）， reduced atretic follicles （P<0.01）， elevated the serum levels of AMH and E2 （P<0.05， P<0.01）， lowered the serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and down-regulated the expression of TLR4， NF-κB p65， MyD88， and p-IκB-α （P<0.05， P<0.01） in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.
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ObjectiveTo explore the potential mechanism of Zuoguiwan in ameliorating polycystic ovary syndrome （PCOS） by network pharmacology and liquid chromatography-mass spectrometry （LC-MS）-based metabolomics. MethodThe active ingredients and potential targets of Zuoguiwan for treating PCOS were predicted by bioinformatics. SD rats were assigned into a control group and a modeling group. The rat model of PCOS was established by gavage with letrozole （1 mg·kg-1） combined with feeding with a high-fat diet. At the end of modeling， the modeled rats were assigned into model （normal saline）， metformin （300 mg·kg-1）， and Zuoguiwan （concentrate 1.62 g·kg-1） groups. The body weight and oestrous cycle of each rat were recorded， and the ovary was stained with hematoxylin and eosin for observation of ovarian morphology. Enzyme-linked immunosorbent assay was employed to determine the serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-mullerian hormone （AMH）， testosterone （T）， and estradiol （E2）， and the LH/FSH ratio was calculated. Serum metabolomics of rats was conducted by orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen the metabolite-enriched pathways. Furthermore， network pharmacology and association analysis were employed construct the compound-response-enzyme-gene network. ResultA total of 503 potential targets of Zuoguiwan and 5 843 targets of PCOS were screened out， with 271 common targets. The Gene Ontology enrichment analysis revealed that the common targets were involved in the response to lipopolysaccharide， etc.， and the Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment yielded 119 pathways. Animal experiments showed that compared with the control group， the model group presented increased body weight （P<0.01）， elevated LH and AMH levels （P<0.01）， increased LH/FSH ratio （P<0.01）， lowered E2 level （P<0.01）， and increased cystic follicles. Compared with the model group， Zuoguiwan and metformin decreased the body weight （P<0.01）， reduced atretic follicles and cystic follicles， increased mature follicles and corpus luteum， and thickened the granulosa layer. Moreover， Zuoguiwan lowered the T， FSH， LH， and AMH， and LH/FSH levels （P<0.01） and elevated the E2 level （P<0.01）. The principal component analysis and OPLS-DA in metabolomics showed that the differential metabolites between Zuoguiwan and model groups included 26 up-regulated metabolites in the Zuoguiwan group. There were 8 common pathways predicted by the KEGG enrichment analysis in network pharmacology and the metabolite enrichment in metabolomics. The results of topological analysis revealed the pathways of steroid hormone biosynthesis and glycerol-phospholipid metabolism， and the constructed compound-response-enzyme-gene network revealed that the key targets were protein kinase B1 （Akt1）， epithelial growth factor receptor （EGFR）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and mitogen-activated protein kinase 1 （MAPK1）. ConclusionZuoguiwan regulated the steroid hormone biosynthesis pathway to recover hormone levels， promote follicle production and development， and improve ovarian function， which may be the potential mechanism of this medicine in treating PCOS.
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ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.
摘要
OBJECTIVE To analyze the occurrence of adverse drug reactions （ADR） between bevacizumab biosimilars and original drugs， and to provide data support for rational use of drugs in clinical. METHODS ADR reports of bevacizumab biosimilars and original drugs reported by Jiangsu Cancer Hospital from January to December 2022 were retrospectively analyzed. RESULTS A total of 6 818 patients were treated with bevacizumab， and 136 ADR patients were reported. The incidence of ADR caused by bevacizumab biosimilars was higher than original drugs （2.18% vs. 0.71%， P＝0.004）. In ADR reports， the main treatment plan was bevacizumab combined with other tumor drugs （129 patients）； 118 patients were cured and improved； there were 108 general reports and 28 serious reports； the main system/organ involved in ADR was the cardiovascular system； there were no statistical significance in the incidence rates of hypertension/blood pressure increase， leukocyte/platelet decrease， diarrhea and fever caused by bevacizumab biosimilars and original drugs. CONCLUSIONS The incidence of ADR related to bevacizumab biosimilars is significantly higher than that of the original drugs， but there is no significant difference in the clinical manifestation of ADR. Clinicians can use bevacizumab biosimilars or original drugs based on the willingness of patients and their families.
摘要
Objective To investigate the expression levels of HBV pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in circulating serum of chronic hepatitis B (CHB) patients after withdrawal from nucleos(t)ide analogues (NUC), as well as the correlation of HBV pgRNA and HBcrAg levels in circulating blood in different periods of time with recurrence in CHB patients after drug withdrawal. Methods Among the patients who attended the outpatient service of Affiliated Hospital of North Sichuan Medical College from December 2019 to July 2022, a total of 108 CHB patients who received anti-HBV therapy for at least 5 years and met the criteria for drug withdrawal in 2017 EASL Guidelines were enrolled. According to the time of drug withdrawal, the patients were divided into 4-, 12-, and 24-week groups after drug withdrawal, and according to the presence or absence of recurrence, they were divided into recurrence group and non-recurrence group. Quantitative real-time PCR was used to measure the level of HBV pgRNA in circulating serum of CHB patients; ELISA was used to measure the expression level of HBcrAg in peripheral venous blood; quantitative real-time PCR was used to measure HBV DNA load with high accuracy. The t -test was used for comparison of continuous data between two groups. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Pearson correlation test was used to investigate the correlation between the indices in circulating blood. Results For the CHB patients after drug withdrawal, the recurrence rate was 17.1% at 4-12 weeks, cumulative recurrence rate reached 29.3% after 24 weeks of follow-up, the patients with positive HBV DNA alone accounted for 64.3% and 60.0%, respectively, those with positive HBeAg alone accounted for 28.5% and 20.0%, respectively, and those with positive HBV DNA and HBeAg accounted for 7.1% and 20.0%, respectively. The expression levels of HBV pgRNA, HBcrAg, and HBV DNA in circulating serum of CHB patients at 24 weeks after drug withdrawal were significantly higher than those at the time of drug withdrawal and at 4 weeks after drug withdrawal, and there was a significant difference between groups at different time points (all P 0.05). Conclusion The recurrence group had significantly higher expression levels of HBV pgRNA and HBcrAg than the non-recurrence group at the time of drug withdrawal, suggesting that the levels of HBV pgRNA and HBcrAg in the CHB patients of the non-recurrence group at the time of drug withdrawal may be used as the reference thresholds for safe drug withdrawal in CHB patients, and measurement of HBV pgRNA and HBcrAg may be one of the potential reference indicators for the selection of anti-HBV treatment endpoints in the future.
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Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
Subject(s)
Humans , Medicine, Chinese Traditional , Tissue Adhesions/prevention & control , Industrial Development , Drugs, Chinese Herbal/therapeutic use摘要
Persistent postural-perceptual dizziness（PPPD） is the most common chronic vestibular disease, the clinical manifestation is dizziness, unstable and non-rotational dizziness for three months or more. And the symptom is exacerbated by upright posture, active or passive movement, and complex visual stimuli. In addition, PPPD is a functional disease, so routine vestibular function tests and imaging tests are often negative. According to the diagnostic criteria established by the Barany Association, the diagnosis of PPPD often relies on history. This article provides a review of PPPD-related questionnaires.
Subject(s)
Humans , Dizziness/diagnosis , Vertigo/diagnosis , Vestibular Diseases/diagnosis , Surveys and Questionnaires摘要
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.