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OBJECTIVE@#To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI.@*METHODS@#The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay.@*RESULTS@#The patient was found to carry homozygous missense c.677C>T (p.Ser226Leu) mutation of the WNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46,XX).@*CONCLUSION@#A patient-specific WNT1 gene mutation (WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.
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Humans , Induced Pluripotent Stem Cells/pathology , Osteogenesis Imperfecta/genetics , Mutation , Cell Differentiation/genetics , Cell LineABSTRACT
Objective:To analyze the application effect of standardized exercise program based on motivation and volitional model in home-based cardiac rehabilitation of patients with acute myocardial infarction.Methods:The method of non-simultaneous control trial was used. Using convenient sampling method, 60 patients with acute myocardial infarction treated in the Department of Cardiovascular Medicine of Huaibei People's Hospital Affiliated to Bengbu Medical College from December 2021 to April 2023 were selected as subjects. The patients were divided into two groups according to the order of admission: 30 patients admitted from December 2021 to June 2022 as the control group, and 30 patients from July 2022 to April 2023 as the observation group. The control group received routine nursing methods,on the basis of routine nursing, the observation group was intervened with the standardized exercise program based on the theoretical model of motivation and will. The differences of 6-minute walking distance, Duke Activity Status Index Score, Exercise Self-efficacy Score, compliance level of cardiac rehabilitation exercise prescription between the two groups were compared.Results:There were 23 males and 7 females in the control group with age of (58.27 ± 10.86) years old, and 24 males and 6 females in the observation group with age of (57.07 ± 10.91) years old. After 3 months of intervention, 6-minute walking distance, Duke Activity Status Index Score and Exercise Self-efficacy Score in the observation group were (565.53 ± 66.90) m, (29.80 ± 9.76) and (41.87 ± 11.76) points respectively, significantly higher than those in the control group (488.00 ± 91.94) m, (21.63 ± 7.21) and (29.80 ± 8.48) points, the differences were statistically significant ( t=3.73, 3.69, 4.56, all P<0.01). The rates of good, average, and poor compliance with cardiac rehabilitation exercise in the observation group were 56.7% (17/30), 36.7% (11/30), and 6.7% (2/30), respectively, while in the control group were 23.3% (7/30), 46.7% (14/30), and 30.0% (9/30), respectively. The difference between the two groups was statistically significant ( χ2=8.98, P<0.05). Conclusions:The application of standardized exercise program in home-based cardiac rehabilitation of patients with acute myocardial infarction can improve patients ′ exercise endurance, improve exercise self-efficacy, enhance the effect of home-based cardiac rehabilitation, and further reduce cardiovascular risk factors.
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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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With the rapid development of the biopharmaceutical industry in China, the laboratory animal sector has entered a stage of rapid growth, and the construction of facility operation systems has become increasingly automated and intelligent. Compared to traditional laboratory animal facilities, new facilities require a more specialized technical team for the maintenance of air supply and exhaust systems, air conditioning, automated control, and the entire barrier system. The Lingang Laboratory’s animal facilities accommodate both large and small animals for feeding and experimental purposes. The facility management team has summarized daily maintenance experiences and explored various operational and maintenance modes based on the characteristics of laboratory operation. After analyzing the advantages and disadvantages of three common modes, this paper provides new ideas for the management of these laboratory animal facilities, and offers guidance for peers in choosing the most appropriate professional maintenance mode.
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At present, in vitro artificial liver support system has achieved a good therapeutic effect in the diseases such as liver failure due to various causes, non-function state before and after liver transplantation, and severe cholestasis. Non-bioartificial liver (NBAL) is widely used in clinical practice through various combinations of modes, mainly the plasma exchange mode for improving coagulation factors and albumin combined with other modes for enhancing the elimination of toxic substances in the body. Bioartificial liver (BAL), based on the design concept of the synthesis and transformation of hepatocytes, has achieved rapid development in recent years. Patients with liver failure can almost obtain the normal physiological function of human liver after NBAL detoxification and BAL synthesis and transformation of active substances in the body. NBAL mode combined with BAL with a stable therapeutic effect according to the conditions of the patient is the direction of in vitro support treatment for patients with severe liver disease in the future.
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Objective @#To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer (FET) cycles in patients with polycystic ovary syndrome (PCOS) . @*Methods @#A retrospective analysis was conducted on patients ’data from 882 FET cycles . According to the pregnancy outcome , the patients were divided into non-implantation group (Group A) , abortion group ( Group B1) and live birth group ( Group B2) . Clinical data and laboratory parameters were compared among the three groups , and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET. Patients were also divided into four groups (C1-C4) based on the number of high-quality embryos obtained (0 - 3 , 4 - 6 , 7 - 10 , ≥11) , and their clinical data and laboratory parameters were compared .@*Results @#The clinical pregnancy rate , live birth rate , and miscarriage rate in the 882 treatment cycles were 71 . 09% (627/882) , 61 . 68% (544/882) , and 13 . 24% (83/627) ,respectively. Single-factor analysis showed significant differences in body mass index (BMI) , infertility type , human chorionic gonadotropin (hCG) day estradiol ( E2 ) level , number of retrieved oocytes , and number of high-quality embryos among Groups A , B1 , and B2 (P < 0. 05) . Further multiple Logistic regression analysis revealed that BMI(OR = 1 . 046 , 95% CI:1 . 001 - 1 . 093 , P = 0. 044) and a history of previous pregnancy(OR = 1 . 417 , 95% CI:1 . 030 - 1 . 950 , P = 0. 032) were independent risk factors for successful FET in PCOS patients , while an increased number of high-quality embryos was an independent protective factor for successful pregnancy. Based on the results of Group B2 , compared to Group A , OR = 0. 920 , 95% CI:0. 880 - 0. 962 , P = 0. 000;compared to Group B1 , OR = 0. 923 , 95% CI:0. 862 - 0. 988 , P = 0. 022 . Compared with the other three groups( C1-C3) , the total amount of gonadotropin (Gn) in the C4 group was the lowest and the number of oocytes obtained was the highest (P < 0. 05) . Multiple comparisons showed that Group C4 had lower BMI , follicle-stimulating hormone (FSH) , very low-density lipoprotein ( vLDL) levels , a higher luteinizing hormone and follicle-stimulating hormone ( LH/FSH) ratio compared to Group C1 (P < 0. 05) . Group C4 had lower fasting insulin (FINS) and homeostasis model assessment of insulin resistance ( HOMA-IR) levels compared to Group C3 , and higher high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) levels compared to Groups C2 and C3 (P < 0. 05) . @*Conclusion@#BMI , the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles . Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles .
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Pseudoexfoliative glaucoma(PEXG)is an eye disease that seriously endangers vision. It is more invasive than primary open-angle glaucoma(POAG), with more serious damage to the optic nerve, worse prognosis and higher resistance to treatment. Early diagnosis of PEXG can help to treat the disease in time and delay the progress of the disease, so it is important to determine appropriate biomarkers. In recent years, more and more people have begun to study the biomarkers of PEXG, hoping to understand the pathogenesis of the disease, find out the potential early diagnosis and treatment targets of PEXG, and provide some help to the disease through the research of genomics, transcriptomics, proteomics, metabolomics and lipomics markers. This article will review the progress of biomarkers of PEXG in recent years, some biomarkers may provide new ideas for early diagnosis of PEXG in the future.
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Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ2 test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ2=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ2=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m2(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.
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Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.
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Rare diseases refer to a group of single diseases with low incidence rates, complex pathogeneses, severe disease conditions, and rapid progression. Most rare diseases have a genetic background and may occur in childhood. Paying attention to the rare genetic diseases in children and performing early diagnosis and treatment can effectively delay the course of disease and improve the quality of life of children. Many rare diseases can be diagnosed with the help of various experimental techniques, but the diagnosis of rare diseases is still not widely understood. This article summarizes the laboratory diagnostic techniques currently used for rare genetic diseases in children, so as to provide clues for the diagnosis and treatment of such diseases and help to enhance the theoretical understanding and precise medical treatment of rare genetic diseases in children.
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Child , Humans , Rare Diseases/therapy , Quality of LifeABSTRACT
In direct contact with the external environment, the ocular surface is susceptible to multiple antigens and pathogens.Ocular microbial communities are involved in the regulation of immune tolerance, metabolism, and epithelial barrier function.The microbial composition of the human eye plays an important role in both health maintenance and disease development.It is increasingly evident that certain diseases are caused by imbalances in the microbiota.The human microbiome is complex and primarily consists of bacteria.The human microbiome has initially been studied in five major body regions, namely, gastrointestinal tract, nasal cavity, skin, urogenital tract, and oral mucosa.The relationship between the ocular surface bacterial community and disease has become one of the hot research topics with the development of high-throughput 16SrRNA sequencing and metagenomic shotgun sequencing in the past few years.Ocular surface microbiomes differ in different regions, and they also exhibit vertical distribution characteristics.In addition, several factors, such as age, gender, environment, and geography, may affect the composition of the ocular surface bacterial community.Repeated use of topical antibiotics could lead to increased antibiotic resistance of the ocular surface bacterial community.Ocular surface diseases such as different types of dry eye, keratitis and blepharitis are related to the changes in the ocular surface bacterial community.This article reviewed the composition, distribution, and influencing factors of the ocular surface bacterial community and its relationship with dry eye, keratitis, and blepharitis, providing new insights into the mechanisms of ocular surface disease and guidance for treatment.
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Human papillomavirus (HPV) is an epitheliotropic virus. High-risk HPV infections lead to precancerous lesions which may progress to cancer in the cervix, vagina and vulva, while low-risk HPV infections cause benign lesions such as genital warts and recurrent respiratory papillomas. HPV infection remains one of the major public health problems threatening human health. To date, six prophylactic preventive HPV vaccines have been licensed, and the effectiveness of HPV vaccination has gradually appeared in some countries with earlier vaccination. HPV vaccination has been proved to be effective in protecting against diseases related to HPV infection, which leads to significant reductions in the incidence of vaccine-type HPV-related infection, high cervical lesions, anogenital warts, recurrent respiratory papillomatosis and other relevant diseases. The herd protection effect of the vaccines is outstanding. Meanwhile, a bivalent HPV vaccine has been demonstrated for the cross-protection against HPV infections of non-vaccine types (HPV31/33/45) in real-world vaccination practice.
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Objective:To explore the clinical characteristics of neurological syndrome associated with anti-glutamic acid decarboxylase (GAD) antibodies (Abs).Methods:Six patients with neurological syndrome associated with anti-GAD-Abs admitted to Department of Neurology, Henan Provincial People's Hospital from January 2019 to October 2022 were chosen. The clinical manifestations, imaging and laboratory results, therapeutic schedules, and follow-up prognoses of these patients were collected and summarized.Results:Three females and 3 males were included, with onset age of (54.3±17.7) years. Three patients had stiff-person syndrome (SPS), 1 had limbic encephalitis+generalized epilepsy, 1 had extralimbic encephalitis+occipital epilepsy, and 1 had cerebellar ataxia who was diagnosed with paraneoplastic syndrome associated with small cell lung cancer. Four patients had elevated level of thyroid peroxidase antibodies, and 1 patient was positive for overlapping anti-gamma aminobutyric acid B receptor antibodies and Amphiphysin antibodies. Two patients with SPS had failed lumbar puncture; 1 had slightly increased white blood cells and proteins in cerebrospinal fluid (CSF); the remaining 3 patients were basically normal. Specific oligoclonal bands in CSF were observed in 2 patients. Brain MRI showed abnormal signals in the bilateral occipital lobes in 1 patient, and no specific inflammatory lesions in other patients. All patients accepted corticosteroids and intravenous immunoglobulin/plasma exchange therapies; except for the one with paraneoplastic syndrome associated with small cell lung cancer, the remaining 5 patients had improved modified Rankin scale (mRs) scores at discharge and received long-term immunotherapy. Two patients with SPS had gradually aggravated symptoms, and mRs scores reached 5 at the last follow-up (one for 3 years and the other one for 2 years).Conclusions:The clinical manifestations of patients with neurological syndrome associated with anti-GAD-Abs include SPS, limbic encephalitis, extralimbic encephalitis, epilepsy and cerebellar ataxia; some of these patients have paraneoplastic syndromes. Immunotherapies are effective except for these patients with paraneoplastic syndromes. Some patients with SPS tend to have a chronic course and a poor prognosis.
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Objective@#To investigate the difference of clinical characteristics of recurrent spontaneous abortion (RSA) in patients with losses after spontaneous gestation and after in vitro fertilization and embryo transfer ( IVFET) .@*Methods @#237 patients diagnosed with RSA were divided into spontaneous gestation group ( n = 185) and IVF group (n = 52) according to their previous modes of fertilization.The clinical characteristics of the two groups were analyzed. @*Results@#Compared with the spontaneous gestation group,the age of the first pregnancy and the age at the time of RSA in the IVF group were statistically greater than those in the natural pregnancy group ( P < 0. 05 ) .The number of biochemical pregnancies in IVF group was statistically higher than that in spontaneous gestation group,and the number of spontaneous abortions in IVF group was statistically lower than that in spontaneous gestation group (P<0. 001) .The proportion of patients with irregular menstruation in IVF group was statistically higher than that in spontaneous gestation group ( P < 0. 05 ) . The serum activated partial prothrombin time (APTT) ,R , K,high density lipoprotein cholesterol (HDL-C) ,thyrotropin (TSH) and homocysteine ( HCY) in IVF group were statistically lower than those in spontaneous gestation group,and the Angel,Ma,low density lipoprotein cholesterol (LDL-C) and body mass index (BMI) in IVF group were statistically higher than those in spontaneous gestation group (P<0. 05) .In the comparison of etiological composition between the two groups,the proportion of anatomical factors in IVF group was statistically higher than that in spontaneous gestation group (P < 0. 05) .@*Conclusion@#The abortion risk factors in RSA patients after IVF-ET is more serious than that in RSA patients after natural pregnancy.It is suggested to further improve and implement the pre-pregnancy examination and education of infertile patients during IVF-ET treatment,so as to reduce the risk of RSA and obtain a better pregnancy outcome.
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BackgroundMental illness during pregnancy has become a major public health problem in China over the recent years, and depression is the most common psychological symptom during pregnancy. Current research efforts are directed towards the therapy on prenatal depression, whereas the construction of prediction model for prenatal depression risk has been little studied. ObjectiveTo construct a simple model for predicting the risk of prenatal depression, thus providing a valuable reference for the prevention of maternal depression during pregnancy. MethodsA total of 803 pregnant women attending three hospitals in Nanchong city were consecutively recruited from May 2021 to February 2022. A self-administered questionnaire was developed for the assessment of social demographic variables, obstetrical and general medical indexes and psychological status of all participants, and Self-rating Depression Scale (SDS) was utilized to screen for the presence of maternal depression. Subjects were randomly assigned into modelling group (n=635) and validation group (n=168) at the ratio of 8∶2 under simple random sampling with replacement. The candidate risk factors of maternal depression during pregnancy were screened using binary Logistic regression analysis, and the predictive model was constructed. Then the performance of the predictive model was validated using receiver operating characteristics (ROC) curve. Results① Lack of companionship (β=-0.692, OR=0.501, 95% CI: 0.289~0.868), low mood during the last menstrual period (β=-1.510, OR=0.221, 95% CI: 0.074~0.656), emotional stress during the last menstrual period (β=-1.082, OR=0.339, 95% CI: 0.135~0.853), unsatisfactory relationship between mother-in-law and daughter-in-law (β=-1.228, OR=0.293, 95% CI: 0.141~0.609), and indifferent generally relationship between mother-in-law and daughter-in-law (β=-0.831, OR=0.436, 95% CI: 0.260~0.730) were risk factors for prenatal depression in pregnant women (P<0.05 or 0.01). ② Model for predicting the prenatal depression risk yielded an area under curve (AUC) of 0.698 (95% CI: 0.646~0.749), the maximum Youden index was 0.357 in modelling group with the sensitivity and specificity was 0.606 and 0.751, and an AUC of 0.672 (95% CI: 0.576~0.767) and maximum Youden index of 0.263 in validation group with the sensitivity and specificity of 0.556 and 0.707. ConclusionThe simple model constructed in this study has good discriminant validity in predicting of the risk of prenatal depression. [Funded by Nanchong Social Science Research Project of the 14th Five-Year Plan (number, NC21B165)]
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Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations | Δ G FEP - Δ G EXP | < 2 kcal/mol) than those ΔG MM-PBSA or ΔG MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.
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Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.
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According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.
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Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Glycyrrhizic Acid/analysis , Paeonia , Quality Control , ThiocyanatesABSTRACT
Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.
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@# Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.