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1.
Chinese Pharmacological Bulletin ; (12): 381-389, 2024.
Article in Chinese | WPRIM | ID: wpr-1013622

ABSTRACT

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

2.
Article in Chinese | WPRIM | ID: wpr-1005929

ABSTRACT

Objective To investigate the infection of Chlamydia pneumoniae and mycoplasma pneumoniae in adults and their association with atherosclerosis,and to provide theoretical guidance for the prevention of such diseases. Methods A case-control study was used to collect 362 patients who were diagnosed with atherosclerosis from January 2019 to December 2021 in Department of Sichuan Bazhong Central Hospital, and 370 cases who were admitted to the hospital during the same period of physical examination without any cardiovascular disease were selected as the control group, and whole blood samples of the two groups of study subjects were collected, and the infection of Chlamydia pneumoniae and mycoplasma pneumoniae was detected by PCR. Results The infection rate of Chlamydia pneumoniae was 35.49%, the infection rate of mycoplasma was 40.37%, and the co-infection rate was 11.37%;The infection rate of Chlamydia pneumoniae in the control group was 12.04%, the infection rate of mycoplasma was 15.83%, and the coinfection rate was 3.14%, and the difference between the two groups was statistically significant ( χ2=10.926, P=0.023). The effects of mycoplasma, chlamydia, and co-infection on atherosclerotic patients have sex differences, mainly manifested as higher infection rates in men; In addition, the effects of mycoplasma, chlamydia, and co-infection on atherosclerosis patients varied by age, mainly in the 55-70 years age group (P<0.05). Multivariate logistic regression results showed that Chlamydia pneumoniae infection was a risk factor for atherosclerosis (OR=1.303, 95%CI: 1.043-1.677) in the whole population, and chlamydia pneumoniae (OR=1.472, 95% CI: 1.037-1.556), mycoplasma (OR=2.003, 95%CI: 1.637-3.842) and co-infection in men (OR=1.937, 95%CI: 1.380-2.184) were risk factors for atherosclerosis, while co-infection in women (OR=1.699, 95%CI: 1.263-1.765) was a risk factor for atherosclerosis. Conclusion Chlamydia pneumoniae and mycoplasma infection are risk factors for atherosclerosis, and their impact on male groups is greater, and more attention needs to be paid to them.

3.
Chinese Journal of Pathology ; (12): 671-677, 2023.
Article in Chinese | WPRIM | ID: wpr-985756

ABSTRACT

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Prealbumin/metabolism , Stroke Volume , Cardiomyopathies/pathology , Congo Red , Ventricular Function, Right , Amyloidosis/pathology , Prognosis
4.
Chinese Journal of Epidemiology ; (12): 912-916, 2023.
Article in Chinese | WPRIM | ID: wpr-985612

ABSTRACT

Objective: To investigate the population size of transgender women (TGW) in Tianjin and analyze the characteristics of their sexual behaviors to provide a basis for AIDS prevention and control. Methods: To estimate the population size of TGW in Tianjin using the capture-recapture method. At the same time, an anonymous questionnaire was collected to conduct a multi-factor logistic analysis of the TGW population's sexual behavior. Results: A total of 213 TGW were investigated. Tianjin's estimated TGW population size was 599 (95%CI: 407-792). Multivariate logistic analysis of the use of condoms consistently showed that compared with TGW without regular sex partners, those with regular sex partners had a lower proportion of consistent condom use (aOR=0.44, 95%CI: 0.23-0.82) and had received HIV tests in the last year were more likely to adhere to condom use than those who had not been tested (aOR=2.73, 95%CI: 1.06-6.99). Conclusion: It is necessary to strengthen HIV mobilization testing among the TGW population and their regular sexual partners to improve condom use.


Subject(s)
Humans , Female , Population Density , Transgender Persons , Sexual Behavior , Sexual Partners , HIV Infections/prevention & control
5.
Chinese Journal of Epidemiology ; (12): 598-606, 2023.
Article in Chinese | WPRIM | ID: wpr-985533

ABSTRACT

Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees (P<0.001), and the axial length of the right/left eye increased in various degrees (P<0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant (P<0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m2 was the protective factor of eye axis length (HR=0.778, 95%CI: 0.659-0.918, P=0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length (HR=0.685, 95%CI: 0.592-0.793, P<0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length (HR=0.456, 95%CI: 0.534-0.761, P<0.001; HR=0.794, 95%CI: 0.705-0.895, P<0.001; HR=0.690, 95%CI: 0.619-0.768, P<0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length (HR=1.528, 95%CI: 1.018-2.293, P=0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length (HR=0.542, 95%CI: 0.404-0.726, P<0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length (HR=0.820, 95%CI: 0.698-0.965, P=0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter (HR=0.638, 95%CI: 0.534-0.761, P<0.001; HR=0.911, 95%CI: 0.848-0.978, P=0.011; HR=0.750, 95%CI: 0.702-0.801, P<0.001). The average illumination of desktop 500- lx was a protective factor of a diopter (HR=0.855, 95%CI: 0.763-0.958, P=0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.


Subject(s)
Humans , Mydriasis , Myopia/prevention & control , Refraction, Ocular , Students , Surveys and Questionnaires , Schools
6.
Chinese Journal of Oncology ; (12): 415-423, 2023.
Article in Chinese | WPRIM | ID: wpr-984738

ABSTRACT

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.


Subject(s)
Humans , Mesothelioma, Malignant , Prognosis , Nomograms , Retrospective Studies , Proportional Hazards Models
7.
Article in Chinese | WPRIM | ID: wpr-1009422

ABSTRACT

Objective To establish a stable strain of H9c2 cardiomyocytes overexpressing Cx40 and preliminarily investigate the effect of lentiviral vector-mediated Cx40 protein overexpression on the proliferation of H9c2 cells and its related mechanisms. Methods The Cx40 gene fragment was cloned from H9c2 cells by PCR and linked with lentivirus vector pLVX-IRES-Puro to obtain the recombinant plasmid pLVX-Flag-Cx40. Recombinant lentiviral particles carrying Flag-Cx40 were obtained by cotransfection with packaging plasmids into HEK293T cells. A stable expression strain (H9c2-Flag-Cx40 cell) was screened from infected H9c2 cells by purinomycin. The expression of Cx40 protein was detected by Western blot analysis, and the effect of Cx40 on H9c2 cells proliferation was determined by CCK-8 assay; cell cycle changes were measured by flow cytometry; the expression of the cell cycle protein cyclin D1 was detected by qRT-PCR and Western blot analysis. Co-immunoprecipitation (Co-IP) immunoprecipitation and Western blot analysis were used to identify the binding of Cx40 and Yes associated protein (YAP) in H9c2 cells; cytoplasmic and cytosolic proteins were isolated to detect the effect of Cx40 on the localization of YAP using Western blot analysis. Results Sequencing results showed that the recombinant pLVX-Flag-Cx40 expression vector was successfully established. A stable transfected cell line containing recombinant Flag-Cx40 lentivirus (H9c2-Flag-Cx40 cell) was successfully constructed from H9c2 cells. Compared with the control group, overexpression of Cx40 significantly reduced the proliferation of H9c2 cells, arrested the cell cycle at G0/G1 and reduced cyclin D1 expression. A significant increase in YAP expression was observed in the cytoplasm of the H9c2-Flag-Cx40 stable cell line, while the expression in the nucleus was significantly reduced. Cx40 bound to YAP in the cytoplasm and prevented it from entering the nucleus to play the role of transcriptional coactivation. Conclusion Overexpression of Cx40 induces cell-cycle arrest at G0/G1 phase and inhibits the proliferation in H9c2 cells.


Subject(s)
Rats , Humans , Animals , Cyclin D1/genetics , Transfection , Myocytes, Cardiac , HEK293 Cells , Cell Cycle Checkpoints/genetics , Cell Proliferation/genetics , Lentivirus/genetics , Genetic Vectors/genetics , Gap Junction alpha-5 Protein
8.
Article in Chinese | WPRIM | ID: wpr-1009129

ABSTRACT

OBJECTIVE@#To explore prevalence, risk factors and treatment of ankle sprain of young college student , in order to obtain accurate epidemiological data.@*METHODS@#From March 2019 to May 2019, 552 college students(1 104 sides of anke joints) from Xi'an Physical Education university were enrolled in study according to inclusion and excludion standard, including 309 males and 243 females aged from 16 to 24 years old with an average of (20.9±3.7) years old. Age, gender, and body mass indes(BMI) etc were recorded. Morbidity of acute and chronic ankle sprains of physical students, treatment after the first sprain (cold compress, cast or plaster bracing and medicine), visual analogue scale (VAS) during walking were assessed through ankle sprain questionnaire;Cumberland ankle instability tool (CAIT), Maryland foot score were applied to assess ankle function. Lateral ankle ligament injury was objectively assessed by musculoskeletal ultrasonography.@*RESULTS@#The prevalence of acute ankle sprain(AAS) was 96.20% (531/552), and the incidence of AAS was 59.96% (622/1 104). The prevalence of chronic ankle joint instability(CAI) was 16.85% (93/552), and the incidence of CAI was 8.97% (99/1 104). In the four categories of sports, college student suffered from multiple sprains in performance majors group was 22.20% (14/63), including of aerobicsand dance performance. The incidence of AAS of ball sports was 8.60%(14/163). After the first sprain, most college students(94.4%) were received cold compression, about 60% of them went to hospital;however, only 44.7% students were received standard treatmens(cast or plaster), only 35.3% of them were received hard ankle orthosis. In 552 college students, 44 students were suffered from more than 4 times of ankle sprain, and the total incidence was 7.97% (44/552). Cumberland score was 26.6±2.4, Cumberland score of students sprained ankle joint more than 4 times was (29.2±1.1), suggested it was a risk factor for ankle joint instability. VAS of students sprained ankle joint more than 4 times was higher than that of less than 4 times(P<0.05), Maryland foot score was significantly lower than that of that of <4 times(P<0.05). Musculoskeletal ultrasonography measured the thickness of anterior tibiofibular ligament(ATFL) was (2.41±0.41) mm, and the thickness of calcaneofibular ligament(CFL) was (1.92±0.21) mm, and had no statistical difference(P>0.05).@*CONCLUSION@#Ninty-four percent college students had at least once ankle sprain, ankle sprains were more common in erobics and ball sports. After the first sprain, the proportion of cast or plaster treatment was less than 50%. Sprained ankle joint more than 4 times is a risk factor, and musculoskeletal ultrasonography showed thickening of both ATFL and CFL, while no statstical difference.


Subject(s)
Female , Male , Humans , Adolescent , Young Adult , Adult , Cross-Sectional Studies , Joint Instability/epidemiology , Physical Education and Training , Universities , Ankle Injuries/therapy
9.
Article in Chinese | WPRIM | ID: wpr-972306

ABSTRACT

Heart failure is the final stage of heart disease caused by a variety of etiologies and has a high morbidity, mortality, and disability rate, making it a major challenge in the field of medicine. Cardiomyocytes, the most basic unit of the heart, are irreversible in nature and can be damaged or necrotic in various ways in the presence of heart failure. Myocardial cell injury is also an important cause of cardiac dysfunction and affects the prognosis and quality of life of patients. Therefore, reducing the level of myocardial cell damage and delaying the process of cell death can help patients with heart failure lessen the extent of cardiac damage and improve their prognosis, thereby lowering the incidence of death and disability and times of hospitalization. Ferroptosis is a new form of cell death that has been widely concerned in recent years, with studies confirming its occurrence in cardiac myocytes. As a modifiable form of cell death, interfering with ferroptosis can modulate the extent of injury and death in cardiac myocytes. Studies have shown that the inhibition of iron death has a protective effect on cardiomyocytes, thereby alleviating heart failure. Chinese medicine has been widely used in the clinical treatment of heart failure, and has the advantages of multiple approaches and entry points, with significant therapeutic effects, low side effects, and low medical costs. It also reduces the clinical side effects of western medicine, with good clinical results. The use of Chinese medicine to modulate ferroptosis may be a new direction for the future treatment of heart failure. This paper briefly elaborated on the mechanism of ferroptosis, investigated the role of ferroptosis in heart failure, and discussed the current status of research on ferroptosis in Chinese medicine interventions in heart failure, to provide references for further improving the efficacy of Chinese medicine in the treatment of heart failure.

10.
Article in Chinese | WPRIM | ID: wpr-970639

ABSTRACT

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, β-amyloid(Aβ), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.


Subject(s)
Humans , Alzheimer Disease/drug therapy , Medicine, Chinese Traditional , Acupuncture Therapy , Medicine , Amyloid beta-Peptides
11.
Article in Chinese | WPRIM | ID: wpr-969871

ABSTRACT

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC50) was calculated by using 1.25×108 CFU/ml,2.50×108 CFU/ml,3.75×108 CFU/ml,5.00×108 CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC50 concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC50=2.5×108 CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.


Subject(s)
Animals , Sheep , Larva/microbiology , Virulence , Candida glabrata , Agar , Moths/microbiology , Esterases , Aspartic Acid Proteases , Lipase
12.
Chinese Journal of Oncology ; (12): 146-152, 2023.
Article in Chinese | WPRIM | ID: wpr-969817

ABSTRACT

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.


Subject(s)
Humans , Pyroptosis , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Gasdermins , Chemoradiotherapy/adverse effects , Rectal Neoplasms/surgery , Caspases/metabolism , Diarrhea/chemically induced , Leukopenia/genetics , Genetic Variation , Dermatitis
13.
Article in Chinese | WPRIM | ID: wpr-971264

ABSTRACT

Locally advanced tumor with involvement of surrounding tissues and organs is a common situation in pelvic malignancies. Up to 10% of newly diagnosed rectal cancer cases infiltrate to adjacent tissues and organs. Satisfactory resection margins obtained by pelvic exenteration can achieve a 5-year survival rate similar to cases that without adjacent tissue invasion. The 5-year survival rate of patients with locally recurrent pelvic malignancies is almost zero if they are treated only with radiotherapy and chemotherapy. To obtain negative margins through pelvic exenteration is the only chance for a long-term survival of these patients. However, pelvic exenteration is a complicated procedure with higher morbidity and mortality. The development of fascia anatomy enables surgeons to have a deeper understanding and comprehensive application of pelvic fasciae. Meanwhile, the improvement of laparoscopic technology provides a clearer view for surgeons and enables the application of minimally invasive techniques in complex pelvic exenteration. The fascial space priority approach is based on the fascia anatomy of pelvis and giving priority to the separation of the pelvic avascular fascial spaces, which provides a reproducible surgical approach for complex pelvic exenteration.


Subject(s)
Humans , Pelvic Exenteration/methods , Pelvic Neoplasms , Neoplasm Recurrence, Local/surgery , Rectal Neoplasms/surgery , Pelvis/pathology , Retrospective Studies
14.
Asian Journal of Andrology ; (6): 152-157, 2023.
Article in English | WPRIM | ID: wpr-971026

ABSTRACT

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.


Subject(s)
Male , Humans , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , DNA-Binding Proteins/metabolism , Prolyl Hydroxylases/metabolism , Hypoxia , Prostatic Neoplasms/pathology , Glycolysis , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Cell Line, Tumor , DNA Helicases/metabolism
15.
Acta Pharmaceutica Sinica B ; (6): 1588-1599, 2023.
Article in English | WPRIM | ID: wpr-982812

ABSTRACT

Liver is the central hub regulating energy metabolism during feeding-fasting transition. Evidence suggests that fasting and refeeding induce dynamic changes in liver size, but the underlying mechanisms remain unclear. Yes-associated protein (YAP) is a key regulator of organ size. This study aims to explore the role of YAP in fasting- and refeeding-induced changes in liver size. Here, fasting significantly reduced liver size, which was recovered to the normal level after refeeding. Moreover, hepatocyte size was decreased and hepatocyte proliferation was inhibited after fasting. Conversely, refeeding promoted hepatocyte enlargement and proliferation compared to fasted state. Mechanistically, fasting or refeeding regulated the expression of YAP and its downstream targets, as well as the proliferation-related protein cyclin D1 (CCND1). Furthermore, fasting significantly reduced the liver size in AAV-control mice, which was mitigated in AAV Yap (5SA) mice. Yap overexpression also prevented the effect of fasting on hepatocyte size and proliferation. Besides, the recovery of liver size after refeeding was delayed in AAV Yap shRNA mice. Yap knockdown attenuated refeeding-induced hepatocyte enlargement and proliferation. In summary, this study demonstrated that YAP plays an important role in dynamic changes of liver size during fasting-refeeding transition, which provides new evidence for YAP in regulating liver size under energy stress.

16.
Article in Chinese | WPRIM | ID: wpr-982757

ABSTRACT

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
17.
Article in Chinese | WPRIM | ID: wpr-981723

ABSTRACT

OBJECTIVE@#To compare the mid-term clinical effect of arthroscopic surgery versus conservative treatment on the middle aged early knee osteoarthritis (EKOA) patients, with the hope to provide clinical evidence for their individual therapy.@*METHODS@#A total of 145 middle aged EKOA patients(182 knees) who received arthroscopic surgery or conservative treatment from January 2015 to December 2016 were retrospectively enrolled, including 35 males and 110 females, aged from 47 to 79 years old with an average of (57.6±6.9) years old, and the duration of disease ranged from 6 to 48 months with an average of(14.6±8.9) months. According to treatment method, patients were divided into arthroscopic surgery group (47 patients, 58 knees) and conservative treatment group(98 patients, 124 knees). Before treatment, patients presented with symptoms of knee joint, such as pain, swelling, locking, limited flexion and extension, and weakness, as well as abnormal findings in knee X-ray (without or suspicious joint space narrow, and a few of osteophyte formation) or in knee MRI (injury or degeneration of articular cartilage or meniscus, loose body in the joint cavity and synovial hyperemia edema, etc). Related data were collected, including duration of knee symptoms, presence of meniscus injury, loose body in the joint cavity or mechanical symptoms such as locking, and visual analogue scale (VAS) and Lysholm knee function score before treatment and at the latest follow-up. Statistical analysis was performed to compare the differences in VAS or Lyshilm score before or after treatment between the low groups and within each group.@*RESULTS@#Patients in the two groups were followed up from 60 to 76 months. In the arthroscopic surgery group, the incision healing was good and no surgical complications occurred. There were no significant differences in age, gender, BMI and follow-up time between the two groups(P>0.05). Before treatment, compared with conservative group, duration of symptoms in the arthroscopic group was longer (P<0.001), comorbidity rates of meniscus injury (P<0.001), free body (P=0.001) and mechanical symptoms (P<0.001) were higher, VAS (P<0.001) and Lysholm score (P<0.001) were worse. At the final follow-up, VAS and Lysholm score in either the conservative group or the arthroscopic group were significantly better than before treatment (P<0.05), while no significant differences between the two groups were found. The VAS was (1.5±1.2) scores in the arthroscopic group and (1.6±1.0)scores in the conservative group(P=0.549), and the Lysholm score was (84.9±12.5) scores in the arthroscopic group and (84.2±9.9) scores in the conservative group (P=0.676).@*CONCLUSION@#Both arthroscopic surgery and conservative treatment have satisfactory intermediate clinical effect middle- aged patients with EKOA, without statistically differences. However, most of the patients before surgery in the arthroscopic treatment group had mechanical locking symptoms caused by meniscus injury or loose body. Therefore, for the middle-aged EKOA patients with mechanical locking symptoms or without obtaining satisfactory outcome after conservative treatment, arthroscopic surgery may be considered.


Subject(s)
Male , Middle Aged , Female , Humans , Aged , Osteoarthritis, Knee/surgery , Retrospective Studies , Arthroscopy/methods , Treatment Outcome , Knee Joint/surgery
18.
Article in Chinese | WPRIM | ID: wpr-981481

ABSTRACT

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-β-D-xylosyl)-β-D-galactoside was the highest with the average content in the tested samples of 161.0 μg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 μg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 μg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.


Subject(s)
Flavonoids/analysis , Anthocyanins/analysis , Quercetin , Chromatography, High Pressure Liquid/methods , Kaempferols , Tandem Mass Spectrometry/methods , Glycosides
19.
Acta Pharmaceutica Sinica ; (12): 3204-3209, 2023.
Article in Chinese | WPRIM | ID: wpr-999095

ABSTRACT

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

20.
Acta Pharmaceutica Sinica ; (12): 3191-3197, 2023.
Article in Chinese | WPRIM | ID: wpr-999081

ABSTRACT

Licorzine granules are common preparations for children zinc deficiency. Considering the long course of treatment, the taste of licorzine granules may become a main factor affecting medication adherence. To date there have been no taste evaluation research into licorzine granules yet. In this study, both sensory evaluation and electronic tongue method were utilized to optimize licorzine granules formulations, evaluate the tastes of licorzine, excipients, optimized formulation in vivo and in vitro. As the results show, bitterness and astringency are the main unpleasant tastes generating from licorzine. Xanthan gum is the main taste-masking excipient, lowering down the bitterness and astringency of licorzine by at least one grade. Good correlation exists between the results of sensory evaluation and electronic tongue method, and an integrated combination of the two helps to obtain objective and rational research conclusions. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

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