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1.
Article in Chinese | WPRIM | ID: wpr-929075

ABSTRACT

OBJECTIVE@#To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection.@*METHODS@#DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments.@*RESULTS@#The average length of FDOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX.@*CONCLUSION@#As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.


Subject(s)
Animals , Breast Neoplasms/drug therapy , Cell Line, Tumor , Delayed-Action Preparations/therapeutic use , Doxorubicin/therapeutic use , Female , Heterografts , Humans , Hydrogels/therapeutic use , Mice , Mice, Inbred BALB C , Phosphates
2.
Article in Chinese | WPRIM | ID: wpr-929073

ABSTRACT

Objective Circular RNAs (circRNAs) are non-coding RNAs (ncRNA) circularized without a 3' polyadenylation [poly-(A)] tail or a 5' cap, resulting in a covalently closed loop structure. circRNAs were first discovered in RNA viruses in the 1970s, but only a small number of circRNAs were discovered at that time due to limitations in traditional polyadenylated transcriptome analyses. With the development of specific biochemical and computational methods, recent studies have shown the presence of abundant circRNAs in eukaryotic transcriptomes. circRNAs play vital roles in many physiological and pathological processes, such as acting as miRNA sponges, binding to RNA-binding proteins (RBPs), acting as transcriptional regulatory factors, and even serving as translation templates. Current evidence has shown that circRNAs can be potentially used as excellent biomarkers for diagnosis, therapeutic effect evaluation, and prognostic assessment of a variety of diseases, and they may also provide effective therapeutic targets due to their stability and tissue and development-stage specificity. This review focuses on the properties of circRNAs and their immune relationship to disease, and explores the role of circRNAs in immune-related diseases and the directions of future research.


Subject(s)
Biomarkers , MicroRNAs/genetics , RNA, Circular , Transcriptome
3.
Article in Chinese | WPRIM | ID: wpr-928644

ABSTRACT

OBJECTIVES@#To study the application of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity.@*METHODS@#Random sampling combined with convenience sampling was used to obtain research samples, and then the samples were divided into an obesity group (23 cases), an overweight group (21 cases), and a normal group (24 cases). Three-dimensional speckle-tracking imaging was used to measure the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of the left ventricle. An automatic arteriosclerosis tester was used to measure ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). These parameters were compared among the three groups. The correlation of three-dimensional speckle-tracking parameters with ABI and baPWV was evaluated.@*RESULTS@#There were no significant differences in GLS, GRS, and GCS between the obesity and normal groups (P>0.05). The overweight group had a significantly higher GLS than the normal group [(-24±7) vs (-19±12), P<0.05]. The obesity and overweight groups had a significantly lower ABI than the normal group [(1.00±0.09)/(1.09±0.13) vs (2.25±0.13), P<0.05). The obesity group had a significantly higher baPWV than the normal group [(978±109) vs (905±22), P<0.05]. In the children with obesity, GLS was positively correlated with baPWV (r=0.516, P<0.05) , but not correlated with ABI (P>0.05), and GCS and GRS had no significant correlation with ABI or baPWV (P>0.05).@*CONCLUSIONS@#There are varying degrees of changes in left ventricular systolic function and peripheral arterial elasticity in children with simple obesity, and there is a certain correlation between them.


Subject(s)
Ankle Brachial Index , Child , Echocardiography, Three-Dimensional/methods , Elasticity , Humans , Obesity , Overweight , Prospective Studies , Pulse Wave Analysis
4.
Article in Chinese | WPRIM | ID: wpr-928032

ABSTRACT

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.


Subject(s)
China , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Prescriptions , Public Health
5.
Article in Chinese | WPRIM | ID: wpr-928001

ABSTRACT

The development of traditional Chinese medicine(TCM) has always been highly valued and supported since 1949. However, Chinese medicine industry still faces great challenges in view of the current status of the industry and registration and approval of new products in recent years. Related policies also directly influence the development of the industry. The latest version of the Provisions for Drug Registration and Requirement on Registration Classification and Application Information of Traditional Chinese Medicines have been put into practice since 2020. Registration classification is the core content of the Chinese medicine registration management system, as it is closely related to the research, development, and registration of Chinese medicine and the innovative development of the industry. This article aims to systematically review the historical evolution of the category of Chinese medicine registration and analyze the current status and problems, which is expected to provide a reference for the formulation of supporting documents according to related laws and regulations.


Subject(s)
Drug Industry , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Policy
6.
Article in English | WPRIM | ID: wpr-927631

ABSTRACT

OBJECTIVE@#This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.@*METHODS@#A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.@*RESULTS@#After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.@*CONCLUSIONS@#In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.


Subject(s)
Adult , Cytochrome P-450 Enzyme System/genetics , Female , Genotype , Heart Defects, Congenital/genetics , Humans , Infant, Newborn , Polymorphism, Genetic , Pregnancy , Pregnancy Complications/drug therapy
7.
Article in Chinese | WPRIM | ID: wpr-927387

ABSTRACT

This device is an auxiliary device with reasonable design for placebo acupuncture research, so as to make double-blind placebo acupuncture control possible. This new auxiliary acupuncture device includes an acupuncture device and a placebo acupuncture device with exactly the same appearance. Both of them are composed of a hemispherical base and a telescopic tube. Through the rotation of the telescopic tube in the notch of the base, the insertion angle of needles can be adjusted from 15 degrees to 165 degrees. The operation of twisting and lifting and inserting can be carried out through the horizontal rotation and vertical sliding of the telescopic tube. A silicone needle pad is arranged in the base, which can simulate the blocking feeling of skin and muscle during needle insertion. The bottom of the base is attached with hydrogel, which has good fixity. The auxiliary device is applicable to multiple parts of the human body and can effectively reduce the risk of unblinding.


Subject(s)
Acupuncture Therapy/instrumentation , Biomedical Research/methods , Double-Blind Method , Humans , Needles , Skin
8.
Article in Chinese | WPRIM | ID: wpr-927346

ABSTRACT

OBJECTIVE@#To observe the effect of Tiaoshen Qianyang acupuncture on morning blood pressure, sleep quality and post-stroke nerve function recovery in patients with stroke-related sleep disorders (SSD) complicated with hypertension.@*METHODS@#A total of 120 patients were randomized into an observation group (60 cases) and a control group (60 cases, 1 case dropped off). Both groups were treated with Xingnao Kaiqiao acupuncture (Neiguan [PC 6], Shuigou [GV 26], Sanyinjiao [SP 6], Jiquan [HT 1], Chize [LU 5] and Weizhong [BL 40]). In addition, Tiaoshen Qianyang acupuncture was applied in the observation group, deep needling at Baihui (GV 20) and Sishencong (EX-HN 1) for 5 h. Once a day, 5 times a week, 30 times in total. The morning blood pressure was measured during treatment in the two groups, the Pittsburgh sleep quality index (PSQI) and National Institute of Health stroke scale (NIHSS) scores before and after treatment were observed in the two groups.@*RESULTS@#Compared before treatment, the morning systolic blood pressure (SBP) after treatment were decreased in the two groups (P<0.05), and the morning diastolic blood pressure (DBP) after treatment was decreased in the observation group (P<0.05). The levels of SBP and DBP after treatment in the observation group were lower than the control group (P<0.05). Compared before treatment, the total score of PSQI and NIHSS score after treatment in the observation group were decreased (P<0.01, P<0.05), which were lower than the control group (P<0.01, P<0.05), the decreasing rate of NIHSS score in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#On the basis of Xingnao Kaiqiao acupuncture, Tiaoshen Qianyang acupuncture could improve morning blood pressure and sleep quality for patients with SSD complicated with hypertension, promote the recovery of nerve function.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Blood Pressure , Humans , Hypertension/therapy , Sleep Quality , Sleep Wake Disorders/therapy , Treatment Outcome
9.
Article in Chinese | WPRIM | ID: wpr-907150

ABSTRACT

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

10.
Article in Chinese | WPRIM | ID: wpr-940982

ABSTRACT

OBJECTIVE@#To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci.@*METHODS@#A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke.@*RESULTS@#A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033).@*CONCLUSION@#Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.


Subject(s)
Aged , Genome-Wide Association Study , Humans , Ischemic Stroke , Middle Aged , Sleep/genetics , Stroke/genetics , Surveys and Questionnaires
11.
Article in Chinese | WPRIM | ID: wpr-940625

ABSTRACT

ObjectiveWe aimed to investigate the efficacy and mechanism of Yishen Shengjing Prescription (YSP) in the treatment of oligoasthenospermia in rats. MethodThe oligoasthenospermia rat model was established by injection with cyclophosphamide (35 mg·kg-1·d-1) for 5 consecutive days. Rats were randomly assigned into control group (without treating with cyclophosphamide), model group, low- (YSP-L), medium- (YSP-M), and high- (YSP-H) dose (2.91, 5.83, and 11.66 g·kg-1, respectively) groups, Wuzi Yanzongwan (WYW, 1.03 g·kg-1) group, and L-carnitine (0.17 g·kg-1) group, with 8 rats in each group. After 28 days of drug intervention, the body weight, testicular weight, and testicular index of rats were recorded. The sperm quality in epididymis was detected by computer-assisted sperm analysis (CASA) system. Hematoxylin-eosin (HE) staining was employed for observation of testicular tissue morphology. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in testicular tissue were detected by colorimetry. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) in serum were determined by enzyme-linked immunosorbent assay(ELISA). TdT-mediated dUTP nick-end labeling (TUNEL) was employed to detect the apoptosis of testicular cells. The protein levels of B cell lymphoma-2(Bcl-2), Bax, and cleaved Caspase-3 in testicular tissue were detected by Western blot. ResultCompared with the control group, the model group showed decreased body weight, testicular weight and index, sperm concentration and motility (P<0.01) and increased testicular pathological score (P<0.01). Compared with the model group, the YSP-M, YSP-H, WYW, and L-carnitine groups showed increased body weight, testicular weight, testicular index, sperm concentration and motility and decreased testicular pathological score. After modeling, the SOD level decreased (P<0.01) while the MDA content increased (P<0.01) in the testicular tissue. YSP-H, WYW, and L-carnitine reversed the SOD and MDA level changes caused by modeling. Compared with the control group, the model group exhibited declined T level (P<0.01) and increased FSH and LH levels (P<0.01). Compared with the model group, YSP, WYW, and L-carnitine increased the T level (P<0.01) and decreased the LH level (P<0.05, P<0.01). The apoptosis rate of spermatogenic cells in the model group was higher than that in the control group (P<0.01), whereas YSP-M, WYW, and L-carnitine reversed such changes (P<0.01). The model group rats showed decreased expression of Bcl-2(P<0.05) and increased expression of Bax and cleaved Caspase-3 (P<0.05, P<0.01). Compared the model group, YSP-M, YSP-H, WYW, and L-carnitine up-regulated the Bcl-2 expression and down-regulated the cleaved Caspase-3 expression (P<0.05, P<0.01). ConclusionYSP improved the sperm quality of oligoasthenospermia model rats by regulating the antioxidant system and sex hormone levels and inhibiting the apoptosis of spermatogenic cells.

12.
Article in Chinese | WPRIM | ID: wpr-940488

ABSTRACT

ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research (ICR) mice and Kunming (KM) mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments, and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction (real-time qPCR) assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment, compared with the normal mice, the ICR mice showed increased serum content of alkaline phosphatase (ALP), and 5′-nucleotidase (5′-NT), without significant difference, and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment, KM mice showed erect hair, mental malaise, and near-death 3 days after administration. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in KM mice (400 mg·kg-1) significantly increased(P<0.01), and the activity of total reactive oxygen species (SOD) in liver significantly decreased(P<0.01)compared with those in normal mice, while the serum content of 5′-NT and cholinesterase (CHE) in ICR mice (400 mg·kg-1) were significantly elevated (P<0.01). The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% (P<0.01). The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy, while those in KM mice were focal inflammation, hepatocyte hypertrophy, and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes(KEGG)and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation, bile secretion, bile acid and bile salts synthesis, and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention (P<0.01) and MRP2 was reduced in all groups with drug intervention of KM mice (P<0.01) and elevated in all groups with drug intervention of ICR mice (P<0.01) compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury (400 mg·kg-1) (P<0.05). SHP1 was highly expressed in KM mice with acute liver injury (400 mg·kg-1). The expression of FXR was diminished in ICR mice with subacute liver injury (200 mg·kg-1) (P<0.01). SOD1, CAT, and NFR2 significantly decreased in KM mice with acute liver injury (400 mg·kg-1), and CAT dwindled in KM mice with subacute liver injury (200 mg·kg-1) (P<0.01). GSTA1 and GPX1 significantly increased in KM mice with acute liver injury (400 mg·kg-1) (P<0.01) and SOD1, CAT, NRF2, and GSTA1 significantly increased in ICR mice with subacute liver injury (200 mg·kg-1) (P<0.01). CAT and NRF2 significantly increased in ICR mice with acute liver injury (400 mg·kg-1) (P<0.01). ConclusionWith the increase in the dosage of bakuchiol, the liver injury induced by oxidative stress in KM mice was gradually aggravated, and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

13.
Article in Chinese | WPRIM | ID: wpr-940470

ABSTRACT

Hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases, affecting the structures and functions of important organs of the body, such as the heart, brain, and kidney. At present, the prevalence of hypertension in China remains high. How to effectively curb the incidence of hypertension and reduce target organ damage in patients with hypertension is an urgent challenge that needs to be addressed. Traditional Chinese medicine (TCM), by virtue of its unique efficacies and advantages, is increasingly applied around the world. In TCM, "wind" is considered as a major constant factor in the development of hypertension. Some scholars believe that hypertension is located in collaterals, and the lesions of collaterals are also important reasons for the occurrence and development of hypertension. Collateral diseases and pathogenic wind are closely related to the development of hypertension as well as target organ damage in the heart, brain, and kidney. From the six-meridian syndrome differentiation for febrile diseases, "collateral" and "wind" are closely related to the Jueyin, with collateral diseases classified into Jueyin diseases and pathogenic wind beginning in the Jueyin. The occurrence, development, and persistence of hypertension are closely related to Jueyin diseases. The present study analyzed the pathogenesis and treatment of hypertension from "collateral" and "wind" of the Jueyin, and specifically discussed the relationship between hypertension and "collateral" and "wind" of the Jueyin. It is believed that the internal depression of wind and fire in the Jueyin results in the upward impulse of liver fire, and the deficiency of Jueyin can trigger the internal movement of liver wind and stirring wind due to collateral deficiency. External contraction in the Jueyin due to the induction of external wind is the important pathogenesis of the development of hypertension and the damage to target organs such as the heart, brain, and kidney. The therapeutic methods for both "collateral" and "wind" were also discussed based on the primary prescription for Jueyin, Wumei Pills. Six-meridian syndrome differentiation can guide the therapeutic principles for all diseases and inspire posterity. Exploring the pathogenesis and treatment of hypertension from “collateral" and "wind" of the Jueyin is of great significance in guiding the prevention and treatment of hypertension, reducing target organ damage in patients with hypertension, and improving the prognosis of cardiovascular and cerebrovascular diseases.

14.
Article in Chinese | WPRIM | ID: wpr-940451

ABSTRACT

ObjectiveTo explore the effects and related mechanisms of modified Shuyuwan on the decline of learning and memory in Alzheimer's disease (AD) mice. MethodForty 5-month-old SPF APP/PS1 mice were randomly divided into model group, Donepezil group, modified Shuyuwan group, modified Shuyuwan+ chloroquine (CQ) group, 10 mice in each group, the same background wild type C57BL/6J ten mice were set as the normal group. Among them, the modified Shuyuwan group was given the modified Shuyuwan decoction (10 g·kg-1), the Donepezil group was given the Donepezil hydrochloride solution (0.45 mg·kg-1), the modified Shuyuwan + CQ group was CQ (10 mg·kg-1) was injected intraperitoneally on the basis of the modified Shuyuwan group, and the normal group and the model group were given the same amount of normal saline intragastrically, once a day, for a total of 35 days. After the administration, Morris water maze experiment and new object recognition experiment to detect the spatial memory ability of mice. TdT-mediated dUTP Nick-End Labeling(TUNEL) staining to detect the apoptosis level of mouse hippocampal CA1 neurons, biochemical detection of reactive oxygen species (ROS) and superoxide in mouse hippocampal neurons dismutase (SOD) levels. transmission electron microscopy to observe the ultrastructure of neuronal mitochondria in the CA1 region of mouse hippocampus. Western blot to detect mouse hippocampal mitochondrial autophagy adaptor protein (p62) and microtubule-associated protein 1 light chain 3 Ⅱ (LC3Ⅱ), PTEN-induced kinase 1 (PINK1), E3 Ubiquitin Ligase(Parkin)protein expression level. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) detection of mouse hippocampal mitochondrial forkhead transcription factor O1 (FoxO1), PINK1, Parkin mRNA expression level. ResultCompared with the normal group, the escape latency of the model group mice increased significantly, the number of crossing platforms and the retention time in the target quadrant decreased significantly, the relative resolution index decreased significantly, and the ability to recognize new objects was weakened (P<0.05), neurons in the hippocampus CA1 area decreased. The number of dead cells increased significantly (P<0.05), the level of ROS was significantly increased (P<0.01), and the level of SOD was significantly decreased (P<0.01), the morphology of hippocampal mitochondria was severely damaged, the expression of p62 and LC3Ⅱ proteins increased (P<0.01), Parkin protein expression decreased (P<0.05), and PINK1 protein expression increased (P<0.05), FoxO1, PINK1, Parkin mRNA expressions all decreased (P<0.05). Compared with the model group, the mice's escape latency was significantly shortened after the intervention of the modified Shuyuwan, the number of crossing platforms and the proportion of residence time in the target quadrant increased significantly, the relative resolution index increased significantly, and the ability to identify new objects was enhanced (P<0.05). Apoptotic cells were significantly reduced (P<0.05). ROS levels were significantly reduced (P<0.01), and SOD levels were significantly increased (P<0.05, P<0.01), mitochondrial morphology and various structures were significantly improved, p62, LC3Ⅱ protein expression decrease (P<0.05,P<0.01), PINK1, Parkin protein expression increased (P<0.01). FoxO1, PINK1, Parkin mRNA expression increased (P<0.05, P<0.01). Compared with the modified Shuyuwan group, the evasion latency of mice in the modified Shuyuwan + CQ group increased significantly, the number of crossing platforms and the proportion of residence time in the target quadrant decreased, and the relative resolution index decreased (P<0.05), the SOD level was significantly reduced (P<0.01). The damage of mitochondrial morphology and structure increased again, the expression of p62 and LC3Ⅱ protein increased (P<0.05, P<0.01), and the expression of PINK1 and Parkin decreased significantly(P<0.05, P<0.01). FoxO1, PINK1, and Parkin mRNA expression was significantly reduced (P<0.05, P<0.01). ConclusionModified Shuyuwan can effectively improve the oxidative stress damage and learning and memory ability of AD mice. The mechanism may be related to up-regulating the expression of FoxO1, PINK1, and Parkin factors, promoting mitochondrial autophagy, reducing oxidative stress, and protecting neuronal damage.

15.
Chinese Journal of School Health ; (12): 1224-1228, 2022.
Article in Chinese | WPRIM | ID: wpr-940260

ABSTRACT

Objective@#To explore the changes in liver function of Tibetan youth living in plateau with different body mass index (BMI) during the early stage of migration to the plain, and to provide scientific basis for high attitude de adaptation.@*Methods@#A total of 3 035 Tibetan youth who firstly migrated to the plain (Shaanxi) from the plateau (Tibet) were selected as the research subjects, and were screened for symptoms of plateau de adaptation. Participants were divided into four groups: underweight, normal weight, overweight and obese, and received liver function test on the 3rd, 6th, 9th dayafter migration, respectively. Chi square test was used to detect the abnormal rate of liver function indicators among each group, and binary Logistic regression analysis was used to explore the relationship between BMI and abnormal liver function indicators.@*Results@#The alanine aminotransferase(ALT), Aspartate aminotransferase(AST), γ glutamyl transpeptidase (GGT) of overweight Tibetan male and obese Tibetan male and female adolescents, the total bile acid (TBA) of overweight Tibetan male and obese Tibetan female were higher than those of the normal weight group at the early stage of de adaptation( P <0.05). With the de adaptation for 3, 6, 9 days, the indexes showed an overall upward trend, including: direct bilirubin (DBIL) in overweight male and female adolescents, total protein (TP) and globulose (GLOB) in obese female adolescents( P <0.05). The abnormal rate of overweight group (male ALT: 13.9%), obesity group (male and female ALT, GGT: 34.3%, 26.7%, 11.4%, 13.3%; female AST:10.0%) was significantly higher than that in underweight (2.8%, 3.5%, 0, 1.0%, 1.5%) and normal group(3.5%, 3.4%, 0.9%, 3.6%, 4.1%)( χ 2=48.07, 20.55, 20.55, 17.93, 10.23 , P <0.05). Binary Logistic regression analysis showed that after adjusting for age and gender, overweight was positively correlated with abnormal ALT( OR=2.10, 95%CI =1.20-3.62). Obesity was positively correlated with abnormal ALT( OR=5.50, 95%CI =4.23-7.40) and GGT( OR=4.10, 95%CI =2.03-6.74)( P <0.05).@*Conclusion@#During the early stage of migration to the plain among Tibetan youth living on the plateau, changes in liver function indicators are related to BMI. Overweight and obese Tibetans have a higher abnormal rate of liver damage indicators. It is suggested that individuals with high risk of obesity should undergo health examination and medical supervision when migrates from plateau to plain.

16.
Article in Chinese | WPRIM | ID: wpr-939665

ABSTRACT

OBJECTIVES@#To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring.@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD.@*RESULTS@#The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05).@*CONCLUSIONS@#Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.


Subject(s)
Aminohydrolases/genetics , Case-Control Studies , Child , Female , Genetic Predisposition to Disease , Heart Defects, Congenital/genetics , Humans , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Minor Histocompatibility Antigens/genetics , Mothers , Multifunctional Enzymes/genetics , Polymorphism, Single Nucleotide , Risk Factors
17.
Acta Physiologica Sinica ; (6): 401-410, 2022.
Article in Chinese | WPRIM | ID: wpr-939575

ABSTRACT

The purpose of this paper was to study the transcriptional regulation of nuclear respiratory factor 1 (NRF1) on nuclear factor kappa B (NF-κB), a key molecule in lipopolysaccharide (LPS)-induced lung epithelial inflammation, and to clarify the mechanism of NRF1-mediated inflammatory response in lung epithelial cells. In vivo, male BALB/c mice were treated with NRF1 siRNA, followed with LPS (4 mg/kg) or 0.9% saline through respiratory tract, and sacrificed 48 h later. Expression levels of NRF1, NF-κB p65 and its target genes were detected by Western blot and real-time PCR. Nuclear translocation of NRF1 or p65 was measured by immunofluorescent technique. In vitro, L132 cells were transfected with NRF1 siRNA or treated with BAY 11-7082 (5 μmol/L) for 24 h, followed with treatment of 1 mg/L LPS for 6 h. Cells were lysed for detections of NRF1, NF-κB p65 and its target genes as well as the binding sites of NRF1 on RELA (encoding NF-κB p65) promoter by chromatin immunoprecipitation assay (ChIP). Results showed that LPS stimulated NRF1 and NF-κB p65. Pro-inflammatory factors including interleukin-1β (IL-1β) and IL-6 were significantly increased both in vivo and in vitro. Obvious nuclear translocations of NRF1 and p65 were observed in LPS-stimulated lung tissue. Silencing NRF1 resulted in a decrease of p65 and its target genes both in vivo and in vitro. In addition, BAY 11-7082, an inhibitor of NF-κB, significantly repressed the inflammatory responses induced by LPS without affecting NRF1 expression. Furthermore, it was proved that NRF1 had three binding sites on RELA promoter region. In summary, NRF1 is involved in LPS-mediated acute lung injury through the transcriptional regulation on NF-κB p65.


Subject(s)
Acute Lung Injury/genetics , Animals , Lipopolysaccharides/pharmacology , Male , Mice , NF-kappa B/metabolism , Nuclear Respiratory Factor 1/genetics , RNA, Small Interfering , Transcription Factor RelA/metabolism
18.
Article in Chinese | WPRIM | ID: wpr-936285

ABSTRACT

OBJECTIVE@#To investigate the inhibitory effect of 27-P-coumayl-ursolic acid (27-P-CAUA), the active ingredient in triterpenoids from the leaves of Ilex latifolia Thunb, against breast cancer cells and explore the underlying mechanism.@*METHODS@#CCK-8 assay was used to assess the changes in viability of breast cancer HCC-1806 cells after 27-P-CAUA treatment for 24, 48, or 72 h. The inhibitory effect of 27-P-CAUA on proliferation of the cells was determined by clonogenic assay. JC-1 was used to detect the changes in mitochondrial membrane potential and flow cytometry was performed for analyzing cell apoptosis following 27-P-CAUA treatment. Immunofluorescence assay was used to observe the expression of cl-caspase-3 and P62 in the treated cells. Western blotting was performed to observe the effect of 27-P-CAUA and chloroquine pretreatment on the expressions of LC3I/II, P62 and HER2 signaling pathway proteins in the cells.@*RESULTS@#The results of CCK-8 and clonogenic assays showed that 27-P-CAUA treatment significantly inhibited the proliferation of HCC-1806 cells (P < 0.01) with IC50 values of 81.473, 48.392 and 18.467 μmol/L at 24, 48, and 72 h, respectively. 27-P-CAUA treatment also caused obvious changes in mitochondrial membrane potential (P < 0.01) and induced cell apoptosis in HCC-1806 cells with a 3.34% increase of the early apoptosis rate. Immunofluorescence assay revealed a significant increase of cl-caspase3 expression in 27-P-CAUA-treated HCC-1806 cells, and treatment with 40 μmol/L 27-P-CAUA resulted in significant cell apoptosis (P < 0.01). 27-P-CAUA obviously reduced the expression of LC3II, caused P62 degradation and induced autophagy in HCC-1806 cells. Chloroquine pretreatment obviously blocked the autophagy-inducing effect of 27-P-CAUA. 27-P-CAUA treatment also inhibited the phosphorylation of HER2 and AKT proteins and progressively lowered the expressions of HER2 and phosphorylated AKT protein in HCC-1806 cells (P < 0.01).@*CONCLUSION@#27-P-CAUA can inhibit the proliferation and induce mitochondrial autophagy and apoptosis of HCC-1806 cells by inhibiting the HER2/PI3K/AKT signaling pathway.


Subject(s)
Apoptosis , Autophagy , Breast Neoplasms , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation , Female , Humans , Liver Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
19.
Article in Chinese | WPRIM | ID: wpr-936142

ABSTRACT

OBJECTIVE@#To explore the incidence of ischemic stroke after the onset of type 2 diabetes, and further analyze the risk factors, so as to provide a basis for further research.@*METHODS@#The data were obtained from the database of the Beijing Urban Employee Basic Medical Insurance Database. The study used a prospective design to describe the incidence of ischemic stroke in patients with type 2 diabetes. In our study, these patients were followed up for seven years. Multivariate Logistic regression models were used to analyze the risk factors of ischemic stroke in patients with type 2 diabetes.@*RESULTS@#A total of 185 813 newly diagnosed type 2 diabetes patients were enrolled, with an average age of (58.5±13.2) years, and 49.0% of them were males. A total of 10 393 patients with newly diagnosed ischemic stroke occurred in 7 years, with a cumulative incidence of 5.6% and an incidence density of 8.1/1 000 person-years. Ischemic stroke occurred in all age groups in patients with type 2 diabetes. The cumulative incidence was 1.5% (95%CI: 1.3%-1.6%) in group ≤44 years old, 3.6% (95%CI: 3.4%-3.7%) in group 45-54 years old, 5.4% (95%CI: 5.2%-5.5%) in group 55-64 years old, and 9.2% (95%CI: 9.0%-9.4%) in group ≥65 years old, and the cumulative incidence increased with age (P < 0.05). Cumulative incidence rate of the males (6.8%, 95%CI: 6.7%-7.0%) was higher than the females (4.4%, 95%CI: 4.3%-4.6%). Among the patients < 80 years old, the cumulative incidence rate of the males was higher than that of the females in all the age groups. In the patients ≥80 years of age, the cumulative incidence was higher in the females (9.2%) than in the males (7.9%). Further analysis revealed that complications, such as coronary heart disease (OR=3.18, 95%CI: 2.72-3.72), heart failure (OR=1.53, 95%CI: 1.32-1.79) and kidney failure (OR=1.45, 95%CI: 1.20-1.75) were associated with ischemic stroke in the patients with type 2 diabetes.@*CONCLUSION@#The incidence level of ischemic stroke in patients with type 2 diabetes is high. It is necessary to strengthen the management of risk factors in elderly patients, screen the complications of type 2 diabetes as early as possible, and take active preventive and control measures.


Subject(s)
Adult , Aged , Aged, 80 and over , Beijing/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Incidence , Ischemic Stroke , Male , Middle Aged , Prospective Studies , Risk Factors , Stroke/etiology
20.
Chinese Journal of Epidemiology ; (12): 728-733, 2022.
Article in Chinese | WPRIM | ID: wpr-935451

ABSTRACT

Objective: To investigate the type, length, and CG loci of HBV DNA CpG islands in HBsAg positive maternal C genotype and its relationship with intrauterine HBV transmission, so as to provide a new perspective for the study of intrauterine transmission of HBV. Methods: From June 2011 to July 2013, HBsAg-positive mothers and their newborns who delivered in the obstetrics and gynecology department of the Third People's Hospital of Taiyuan were collected. Epidemiological data were collected through face-to-face questionnaires and electronic medical records. Serum HBV markers and serum HBV DNA were detected by electrochemiluminescence and quantitative fluorescence PCR, respectively. Intrauterine transmission of HBV was determined by positive HBsAg and/or HBV DNA in femoral venous blood before injection of HBV vaccine/Hepatitis B immunoglobulin within 24 h of birth. A total of 22 mothers and their newborns with HBV DNA load ≥106 IU/ml in intrauterine transmission were selected as the intrauterine transmission group, and 22 mothers with HBV DNA load ≥106 IU/ml without intrauterine transmission were chosen as the control group by random seed method. The distribution prediction of CpG islands of HBV DNA in 39 mothers with genotype C by HBV DNA sequencing was analyzed. Results: Among 39 mothers with HBV C genotype, 19 were in the intrauterine transmission group, and 20 were in the control group. The HBV DNA of 39 patients with genotype C traditional CpG island Ⅱ and Ⅲ, while the control group had traditional CpG island Ⅰ and novel CpG island Ⅳ and Ⅴ. The length of CpG island Ⅱ and Ⅲ and the number of CG loci of CpG island Ⅱ in the intrauterine transmission group differed from those in the control group (P<0.05). The CpG island Ⅱ length ≥518 bp and the number of CG loci ≥40 in the intrauterine transmission group (11/19) were significantly higher than those in the control group (2/20) (P<0.05). The length of CpG island Ⅱ and the number of CG loci in the X gene promoter region (Xp region) were higher than those in the control group (P<0.05). In the HBV intrauterine transmission group, most of maternal (12/19) HBV DNA CpG island Ⅱ completely covered the Xp region, which was significantly higher than that in the control group (5/20), and the number of HBV DNA Xp region CG loci was higher than that in the control group (P<0.05). Conclusions: The distribution of maternal C genotype HBV DNA CpG islands is related to intrauterine transmission. The length of CpG island Ⅱ and the number of CG sites may increase the risk of intrauterine transmission of HBV.


Subject(s)
Biomarkers , CpG Islands , DNA, Viral/genetics , Female , Hepatitis B , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Mothers , Pregnancy , Pregnancy Complications, Infectious
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