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Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.
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Objective To evaluate the short-term effect of self-management group project for chronic disease patients in Suzhou. Methods Eight to ten streets / towns were randomly selected from 10 cities and districts under the jurisdiction of Suzhou. Each street / town set up a chronic disease self-management group and carried out group activities. The awareness rate of chronic disease related knowledge, health management behavior and health status of the group members after and before the activities were compared to evaluate the short-term effect of the self-management group project. Results A total of 89 chronic disease self-management groups were set up in Suzhou in 2020. Among them, there were 47 hypertension groups and 42 diabetes groups. A total of 1176 people were surveyed at baseline, and 1161 people participated in the evaluation survey after the group activities. By setting up self-management groups, the awareness rates of chronic disease-related knowledge (BMI range, variety of food intake per day per week, moderate-intensity activity time per week, daily salt intake, harm of excessive salt intake, diagnostic criteria for hypertension, sodium content in low sodium salt, fasting blood glucose criteria, low-density lipoprotein control targets) in hypertension and diabetes patients after the intervention were improved compared with those before the intervention, and the differences were statistically significant (P“self-monitoring blood pressure” increased from 52.80% before the intervention to 66.32%, while the proportion of "having a blood glucose monitoring system at home" increased from 52.80% before the intervention to 66.32%, and the proportion of “self-monitoring blood glucose” increased from 25.67% before the intervention to 38.67%. The percentage of "drinking alcohol in the past 30 days" dropped from 12.14% before the intervention to 8.35%. All these differences were statistically significant. There was no difference in the number of "smoking in the past 30 days" compared with before the activity (P≥0.05). The number of days with poor health resulting from injuries in the past 30 days also decreased but the difference was not statistically significant (P≥0.05). In terms of the severity of depression, the number of people with moderate and severe depression decreased after the intervention, and the number of people who turned into mild depression increased, and the difference was statistically significant (P<0.05). Conclusion The self-management group project for chronic disease patients in Suzhou has achieved good results and is suitable for continued promotion and application in this region.
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Objective To explore the epidemiological characteristics and trend of lung cancer mortality in Suzhou, to predict the future lung cancer mortality by ARIMA model, and to provide a scientific basis for the research of lung cancer prevention and control strategy. Methods The annual change percentage (APC) was used to analyze the annual change trend of lung cancer mortality from 2001 to 2020, and the ARIMA optimal model was employed to predict the lung cancer mortality from 2021 to 2025. Results The average annual crude mortality of lung cancer in Suzhou from 2001 to 2020 was 46.45/100 000, while the standardized mortality was 23.51/100 000. In recent 20 years, the crude mortality showed an upward trend and the standardized mortality showed a downward trend (APC crude rate = 2.51%, APC standardized rate = -0.78% , P < 0.001). The standardized mortality of lung cancer in men was 3.22 times that in women. The mortality of lung cancer in people over 45 years old increased with the increase of age, but the mortality in the 30-59 years old group showed a downward trend year by year. ARIMA model predicted that the annual trend of lung cancer crude mortality will tend to be flat in the next five years. Conclusion The crude mortality rate of lung cancer in Suzhou shows an upward trend, while the standardized mortality rate decreases year by year, suggesting that we should pay attention to the prevention and control of lung cancer in the elderly, accurately identify high-risk population of lung cancer, promote health publicity and education, carry out lifestyle intervention, and popularize the early screening of lung cancer.
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Objective@#To investigate the mortality trends and life loss due to pancreatic cancer death among residents in Suzhou City from 2006 to 2020, so as to provide insights into the management of pancreatic cancer.@*Methods @#The data pertaining to the death of pancreatic cancer in Suzhou City from 2006 to 2020 were collected from the Jiangsu provincial mortality surveillance system. The crude mortality, standardized mortality, years of potential life lost ( YPL L), rate of YPLL ( YPLLR ), average years of life lost ( AYLL ) and annual percent change (APC) were calculated to analyze the changing trend in mortality and life loss due to pancreatic cancer.@*Results@#The crude mortality of pancreatic cancer was 13.57/105 in Suzhou City from 2006 to 2020, appearing a tendency towards a rise ( P<0.05) with APC of 2.95%. The standardized mortality of pancreatic cancer was 6.39/105. The crude mortality of pancreatic cancer was 15.14/105 in men and 12.06/105 in women, which both showed a tendency towards a rise ( P<0.05 ) with APC of 3.18% and 2.73%. The crude mortality of pancreatic cancer appeared a tendency towards a decline in residents at ages of 30 to 45 years and 45 to 60 years ( P<0.05 ), with APC of -4.93% and -1.63%, and appeared a tendency towards a rise in residents at ages of 60 years and greater ( P<0.05 ), with APC of 0.53%. The YPLL and YPLLR of pancreatic cancer were 55 340 person-years and 0.06% in Suzhou City from 2006 to 2020, while the AYLL of pancreatic cancer was 9.81 years per person, which appeared a tendency towards a decline ( P<0.05 ), with APC of -2.35%.@*Conclusions@#The crude mortality of pancreatic cancer appeared a tendency towards a rise in Suzhou City from 2006 to 2020, and the AYLL showed a tendency towards a decline. Health education and screening of pancreatic cancer should be reinforced among men and the elderly.
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Objective:To study the expression of methyltransferase-like protein 14 (METTL14) in epithelial ovarian cancer and its clinical significance, and to explore the effect of METTL14 expression on the proliferation, invasion and migration of ovarian cancer cells.Methods:Immunohistochemistry (IHC) was used to detect METTL14 expression in tumor tissue samples, and analyze the relationships among METTL14 expression, clinicopathological factors, and prognosis in ovarian cancer. Lentiviral vectors and small interfering RNA (siRNA) were used to up-regulate and down-regulate the METTL14 expression in ovarian cancer cell lines A2780 and SKOV3, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to detect the N6-methyladenosine (m6A) content in ovarian cancer cells. Cell counting kit-8 (CCK-8), wound healing assay, and transwell assay were used to examine the function of METTL14 expression in the cells.Results:(1) The IHC score of METTL14 protein was 6.2±3.7 in 20 samples of ovarian cancer tissues and 3.3±2.5 in 15 samples of normal ovarian tissues, and the difference was statistically significant ( t=-2.64, P=0.012). Among the patients who suffered from ovarian cancer, there were 69 cases with high expression of METTL14 protein (IHC score≥6), accounting for 57.0% (69/121), and the cases with low expression of METTL14 protein (IHC score<6) accounting for 43.0% (52/121). Compared with the patients with low expression of METTL14, the patients with high expression of METTL14 had later stages, higher rates of lymph node metastasis, abdominal metastasis, and more ascite amount. The differences were statistically significant (all P<0.05). The overall survival rate was significantly lower in patients with high METTL14 expression than the low expression ( P=0.009). (2) LC-MS/MS data showed that the relative expression of m6A in A2780 and SKOV3 cells in the lentivirus (LV)-METTL14 group were 0.213±0.024 and 0.181±0.018, which were significantly higher than those in the LV-normal control (NC) group (0.109±0.022 and 0.128±0.020; all P<0.05). While the relative expression of m6A in A2780 and SKOV3 cells in the si-METTL14 group were 0.063±0.012 and 0.069±0.015, which were significantly lower than the expression in si-NC group of 0.108±0.014 and 0.121±0.014 (all P<0.05). CCK-8 assay showed that the absorbance values were significantly lower in the si-METTL14 group compared with the si-NC group at 36, 48, 60 hours (all P<0.05); while were significantly increased in the LV-METTL14 group compared with the LV-NC group at 48, 60 hours (all P<0.01). Scratch wound assays showed that the migration rate of the si-METTL14 group was lower than those of the si-NC group, while the LV-METTL14 group were higher than the LV-NC group by 24 hours, the differences were statistically significant (all P<0.01). Cell migration and invasion were detected by transwell migration and invasion assays. After cultivated for 24 hours, the invasion cell number and the migration cell number in the si-METTL14 group were less than those in the si-NC group. While the invasion cell number and the migration cell number in the LV-METTL14 group were more than those in the LV-NC group, respectively. The differences were statistically significant (all P<0.01). Conclusion:Patients with high METTL14 expression have a worse prognosis in ovarian cancer, which may increase the m6A modification of ovarian cancer cells and promote cells proliferation, invasion and migration.
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Objective:To construct a precision teaching platform based on quality feedback, and to explore its application effect on the teaching of practice nursing students in the operating room.Methods:A total of 179 nursing students who interned in the operating room of Zhongshan Hospital Affiliated to Xiamen University from January 2018 to January 2019 were selected as the control group, while 157 nursing students who interned in this hospital operating room from February 2019 to February 2020 were selected as the research group. The control group adopted the traditional clinical teaching mode, while the research group adopted the teaching mode of precision teaching platform based on quality feedback. The assessment results of basic theoretical knowledge and operation skills after the internship were compared between the two groups of students, and their critical thinking ability before and after the internship, the comprehensive evaluation on them by surgeons after the internship and the satisfaction of interns with teaching were compared. SPSS 25.0 was used for t test and chi-square test. Results:After internship, the examination results of basic theoretical knowledge and operation skills in the research group were higher than those in the control group ( P<0.05). There was no significant difference in critical thinking ability between the two groups before internship. After internship, the critical thinking ability of the two groups were both significantly improved, and this ability of the research group improved more significantly than that of the control group ( P< 0.05). After the internship, the surgeon's comprehensive evaluation on the nursing students in the research group was higher than that in the control group, and the difference was statistically significant ( P<0.05). The total satisfaction rate of nursing students with teaching in the research group was significantly higher than that in the control group [93.63%(147/157) vs. 85.47%(153/179)], and the difference was statistically significant ( P<0.05). Conclusion:The application of precision teaching platform based on quality feedback in the teaching of practice nursing students in the operating room can significantly improve the learning effect of student nurses, improve their critical thinking ability and clinical comprehensive work ability, and improve their satisfaction with teaching.
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OBJECTIVES@#To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance.@*METHODS@#A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission.@*RESULTS@#A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05).@*CONCLUSIONS@#Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.
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Female , Humans , Infant, Newborn , Pregnancy , Case-Control Studies , Follow-Up Studies , Hyperbilirubinemia, Neonatal/therapy , Obstetrics , Patient Discharge , Retrospective StudiesABSTRACT
The count and recognition of white blood cells in blood smear images play an important role in the diagnosis of blood diseases including leukemia. Traditional manual test results are easily disturbed by many factors. It is necessary to develop an automatic leukocyte analysis system to provide doctors with auxiliary diagnosis, and blood leukocyte segmentation is the basis of automatic analysis. In this paper, we improved the U-Net model and proposed a segmentation algorithm of leukocyte image based on dual path and atrous spatial pyramid pooling. Firstly, the dual path network was introduced into the feature encoder to extract multi-scale leukocyte features, and the atrous spatial pyramid pooling was used to enhance the feature extraction ability of the network. Then the feature decoder composed of convolution and deconvolution was used to restore the segmented target to the original image size to realize the pixel level segmentation of blood leukocytes. Finally, qualitative and quantitative experiments were carried out on three leukocyte data sets to verify the effectiveness of the algorithm. The results showed that compared with other representative algorithms, the proposed blood leukocyte segmentation algorithm had better segmentation results, and the mIoU value could reach more than 0.97. It is hoped that the method could be conducive to the automatic auxiliary diagnosis of blood diseases in the future.
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Algorithms , LeukocytesABSTRACT
Objective:To analyze the medication rule of treating orthopedics in Tibetan Medicine by data mining, in order to summarize the characteristics and theory of ethnic minorities medicine for treating orthopedics and traumatology.Methods:By collecting the treatment methods of orthopedics and traumatologic diseases in books of Chinese Materia Medica·Tibetan Medicine Volume and Chinese Medical Encyclopedia·Tibetan Medicine to analyze the frequency, cluster and association rules of Tibetan Medicines by using Office Excel 2019, IBM SPSS Statistics 26.0 and IBM SPSS modeler 14.1 respectively. Results:Among the 202 Tibetan Medicine prescriptions of Orthopedic Department, 338 belongs to Chinese medicines. The top 3 Chinese medicines that are frequently appeared are Chebulae Fructus, Inula racemosa Hook.f, and Carthami Flos. The properties of those medicines are mainly cold, warm and cool, and the tastes are mainly pungent, bitter and sweet; the meridians mainly belong to liver, lung, stomach and spleen; The priscriptions mainly cover four kinds of diseases: trauma, arthralgia syndrome, lumbosacral tendon injury, chest and back tendon injury. The four kinds of cluster combinations were obtained. The core Chinese medicines were Chebulae Fructus, Terminaliae Belliricae Fructus, Phyllanthi Fructus, Cassiae Semen, Olibanum, Abelmoschus moschatus, and the common medicine pair were Chebulae Fructus- Terminaliae Belliricae Fructus, Abelmoschus moschatus- Cassiae Semen, Olibanum- Abelmoschus moschatus and so on. Conclusions:Tibetan Medicines treat orthopedics and traumatological diseases with antipyretic medicines as the main yellow water, followed by blood activating, Qi regulating and wind dampness removing medicines. With Sanguo Decoction and Sanhuang water of Tibetan medicine as the core, they are often combined with other antipyretic and blood cooling medicines and bone connecting medicines. Tibetan Medicine pays attention to the application of dry yellow water theory, which reflects the role of the core theory of Qingxie method and yellow water theory of Tibetan Medicine in the diagnosis and treatment of orthopedic and traumatologic diseases.
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Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.
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In the context of the construction of " double sinking and double upgrading" in Zhejiang province, a provincial hospital explored a pilot talent working mechanism of " provincial hospital recruit staff and county hospital get experts" in the process of cooperating with county hospitals. In view of the problem that high-quality medical human resources were difficult to sink, with the flexibility of the reform of post filing and staffing, we put forward the idea of " provincial hospital recruit staff and county hospital get experts" , established key support disciplines, recruited staff by provincial hospitals, and arranged experts to precisely " sink as needed" to help disciplines of county hospitals. It helped to explore the establishment of a long-term mechanism to promote the flow of excellent medical talents to remote mountain areas, built a " specialized community" of provincial and county hospitals, and improved the medical service capacity, medical quality and discipline construction of county hospitals.
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Objective:Patients are breathing freely during adjuvant proton pencil beam radiotherapy after breast conserving surgery. Fluctuation of the thorax may affect the position of the end of the proton beam flow, which needs to be precisely evaluated on a millimeter scale.Methods:For 20 patients with breast cancer treated with proton radiotherapy after breast conserving surgery, PET-CT scan was performed approximately 10 min after the end of proton radiotherapy. The images of PET-CT were processed for ROI determination and sampling line (profile) extraction on a Raystation RV workstation to calculate the actual difference between the predicted and real radioactivity from the same spatial location as obtained by PET acquisition R50. Then, the differences in the spatial location between the actual process of proton irradiation and the planned process were obtained. Depth difference values for each pair of sampling lines were presented. Results:For 20 patients with breast cancer with a median follow-up of 22 months (range 12 - 46 months), all patients survived at the last follow-up, and no radiation pneumonitis was observed during the follow-up period. Among the verification results of 21 cases, the depth difference of evenly distributed was (-0.75±1.89) mm in the primary field and (-0.82±2.06) mm in the secondary field; The depth difference of sequential treatment was (1.81±1.87) mm in the primary field and (1.32±1.74) mm in the secondary field; The depth difference of synchronous addition in the primary field was (-1.47±1.44) mm, and the depth difference in the secondary field was (-1.48±2.11) mm.Conclusion:The results of off-line PET-CT in vivo biological verification show that the accuracy of the dose boundary cut-off was within 3 mm in breast cancer patients, which meets the clinical and physician requirement for the precision in breast cancer treatment.
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Objective: To analyze the characteristics of heart rate variability (HRV) in patients with vestibular migraine (VM) and to explore its possible mechanism. Methods: Forty-eight patients with VM [17 males and 31 females, age (36.2±9.2) years], 44 patients with migraine [15 males and 29 females, age (34.4±9.0) years], and 30 patients with health check-ups during the same period [12 males and 18 females, age (34.6±6.5) years old] were selected as study subjects. Ambulatory ECG monitoring was performed in all subjects, and the HRV characteristics of each group were analyzed from both daytime and nighttime time phases. Time domain parameters were analyzed: standard deviation of normal to normal (SDNN), root mean square of successive differences (RMSSD), and percentage of normal to normal intervals differing by more than 50 ms (pNN50). The parameters in the frequency domain were analyzed: high frequency power (HF), low frequency power (LF), and the ratio of low frequency to high frequency power (LF/HF). Statistical analysis of the data was performed using SPSS 26.0 software. Results: At night, RMSSD (F=6.694) and HF (F=9.434) were lower in the VM and migraine groups compared to the control group, while LF/HF (F=16.049) and LF (F=9.434) were elevated compared to the control group, with statistically significant differences (P<0.05 or P<0.01), while LF was significantly elevated in the VM group compared to the migraine group, with a statistically significant (P<0.05). On the daytime measurements, mainly LF was elevated in the vestibular migraine group compared with the control group, while RMSSD was decreased compared with the control group, with statistically significant differences (P<0.05). Conclusion: Autonomic dysfunction characterized by sympathetic hyperfunction and vagal hypofunction is present in VM patients and is more pronounced at night. In addition, the degree of autonomic dysfunction may be more pronounced in VM patients than in migraine patients.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Heart Rate/physiology , Migraine Disorders , VertigoABSTRACT
Objective: To describe gastric cancer incidence in Suzhou cohort, explore the environmental risk factors of gastric cancer in Suzhou, and provide appropriate suggestions for gastric cancer prevention and control. Methods: The participants were from the Suzhou cohort of China Kadoorie Biobank. Baseline survey was conducted from 2004 to 2008, followed by long-term follow-up until December 31, 2013. After the exclusion of those who had been previously diagnosed with peptic ulcer and malignant tumor reported at baseline survey and gastric cancer within six months after enrollment, a total of 50,136 participants were included. Cox proportional risk models were used to identify risk factors of gastric cancer and their hazard ratios in Suzhou. The effect modifications of gender on the association between risk factors and gastric cancer were analyzed. Results: In the follow-up of 7.19 years (median), 374 gastric cancers cases occurred. The standardized incidence was 94.57 per 100 000 person-years. Multivariate Cox proportional risk model analysis found that age (10 years old as a age group, HR=2.20, 95%CI: 1.92-2.53, P<0.001), current smoking (HR=1.84, 95%CI: 1.10-3.07 P=0.020), consumption of preserved vegetables weekly (HR=2.28, 95%CI: 1.28-4.07, P=0.005) and daily (HR=2.05, 95%CI: 1.16-3.61, P=0.013) were risk factors for gastric cancer. Female (HR=0.44, 95%CI: 0.25-0.76, P=0.003) and refrigerator use (10 years as a limit, HR=0.85, 95%CI: 0.74-0.97, P=0.016) were protective factors for gastric cancer. Further analysis showed that there was heterogeneity between males and females in the association between refrigerator use years and the incidence of gastric cancer (P=0.009), and there was an interaction effect between gender and refrigerator use on the incidence of gastric cancer (P=0.010). Conclusions: The incidence of gastric cancer in Suzhou cohort was high. The risk factors of gastric cancer varied. There was a synergistic interaction effect between gender and refrigerator use years on the incidence of gastric cancer.
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Child , Female , Humans , Male , Cohort Studies , Incidence , Proportional Hazards Models , Prospective Studies , Risk Factors , Stomach Neoplasms/epidemiologyABSTRACT
Objective @#To investigate the prevalence of comorbid chronic obstructive pulmonary disease (COPD) and osteoporosis (OP) and its influencing factors among residents aged 40 years and older in Zhangjiagang City, Jiangsu Province, so as to provide insights into prevention of comorbid COPD and OP. @*Methods@#Permanent residents aged 40 years and older were sampled using a multi-stage stratified cluster random sampling method in Zhangjiagang City in 2019, and their pulmonary functions and bone mineral density were measured. The prevalence of comorbid COPD with OP was estimated. The demographic features, smoking, diet, exercises and physical examinations were collected, and factors affecting the prevalence of comorbid COPD with OP were identified using a logistic regression model.@*Results@#Totally 3 140 subjects were enrolled, including 1 315 men (41.88%) and 1 825 women (58.12%), and a mean age of (62.89±9.13) years. A total of 137 subjects were detected with comorbid COPD and OP, with prevalence of 4.36%. The patients with COPD alone included 19 cases with mild, 133 cases with moderate, 87 cases with severe and 26 cases with very severe COPD, and the patients with comorbid COPD and OP included 10 cases with mild, 56 cases with moderate, 56 cases with severe and 15 cases with very severe COPD. The grade of pulmonary functions was higher in patients with comorbid COPD and OP than in patients with COPD alone (Z=-12.304, P<0.001). Multivariable logistic regression analysis identified ages of 65 years and older (OR=2.703, 95%CI: 1.862-3.923), women (OR=2.897, 95%CI: 1.915-4.384) and physical labor (OR=1.540, 95%CI: 1.083-2.189) as factors affecting the development of comorbid COPD and OP.@*Conclusion@#The prevalence of comorbid COPD and OP was 4.36% among residents at ages of 40 years and older in Zhangjiagang City, and moderate and severe degree was the predominant grade of pulmonary functions. The elderly, women and physical labors are at a high risk of developing comorbid COPD and OP.
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Objective:To study the effect and mechanism of Rab4A knockout expression on proliferation, migration and invasion of gastric cancer cells. Methods:The expression of Rab4A in four human gastric cancer cell lines MGC-803, SGC-790, MKN45 and AGS was detected by Western blot. Rab4A was knocked out in AGS cells with the highest expression level, and untransfected gastric cancer cells were used as control group. Cell proliferation, migration and invasion were detected by CCK8 and Transwell assay, respectively. Western blot analysis was used to investigate the expression changes of epidermal growth factor receptor (EGFR), downstream pathway proteins AKT and β-catenin induced by Rab4A knockout. The interaction between Rab4A and MiR- 496 was detected by dual luciferase reporter gene, and the effect of MiR- 496 transfection on Rab4A expression was detected by qPCR and Western blot. GraphPad Prism 9 software was used for data analysis, t-test was used for comparison between the two groups, and normal distribution measurement data were expressed as mean ± standard deviation ( ± s). Results:The expression of Rab4A was the highest in AGS cells, and the knockdown of Rab4A inhibited the proliferation, migration and invasion of AGS cells ( P<0.05). In Rab4A knockout gastric cancer cells, the surface expression of epidermal growth factor receptor (EGFR) was significantly decreased, and the expression of downstream pathway proteins p-AKT and β-catenin was also inhibited ( P<0.05). The luciferase reporter showed that MiR- 496 could bind the 3′UTR of Rab4A. In addition, MiR- 496 down-regulated the expression of Rab4A in AGS cells( P<0.05). Conclusion:The expression of Rab4A is inhibited by MiR- 496, and the proliferation, migration and invasion of gastric cancer cells can be inhibited by down-regulating the surface expression of EGFR after inhibiting Rab4A expression.
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Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
Subject(s)
Animals , Mice , Artificial Intelligence , Cochlea/metabolism , Hair Cells, Auditory, Inner , Mitochondria , Synapses/metabolismABSTRACT
Radiotherapy uses high-energy X-rays or other particles to destroy cancer cells and medical practitioners have used this approach extensively for cancer treatment (Hachadorian et al., 2020). However, it is accompanied by risks because it seriously harms normal cells while killing cancer cells. The side effects can lower cancer patients' quality of life and are very unpredictable due to individual differences (Bentzen, 2006). Therefore, it is essential to assess a patient's body damage after radiotherapy to formulate an individualized recovery treatment plan. Exhaled volatile organic compounds (VOCs) can be changed by radiotherapy and thus used for medical diagnosis (Vaks et al., 2012). During treatment, high-energy X-rays can induce apoptosis; meanwhile, cell membranes are damaged due to lipid peroxidation, converting unsaturated fatty acids into volatile metabolites (Losada-Barreiro and Bravo-Díaz, 2017). At the same time, radiotherapy oxidizes water, resulting in reactive oxygen species (ROS) that can increase the epithelial permeability of pulmonary alveoli, enabling the respiratory system to exhale volatile metabolites (Davidovich et al., 2013; Popa et al., 2020). These exhaled VOCs can be used to monitor body damage caused by radiotherapy.
Subject(s)
Humans , Breath Tests/methods , Exhalation , Quality of Life , Respiratory System/chemistry , Volatile Organic Compounds/analysisABSTRACT
OBJECTIVE@#To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models.@*METHODS@#Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested.@*RESULTS@#KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels.@*CONCLUSION@#KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.
Subject(s)
Animals , Rats , Aerosols , Aorta, Thoracic , Calcium/metabolism , Endothelium, Vascular/metabolism , Myocardial Ischemia/metabolism , VasodilationABSTRACT
This study aimed to investigate the anti-inflammatory effect of astragaloside Ⅳ in mice with ulcerative colitis(UC) and its effect on the percentage of peripheral blood T helper(Th17) cells. Following the establishment of UC mouse model with 2% sodium dextran sulfate(DSS), mice in the positive control group and low-and high-dose astragaloside Ⅳ groups were treated with corresponding drugs by gavage. Disease activity index(DAI) was calculated, and serum interleukin-17(IL-17), tumor necrosis factor-α(TNF-α), and transforming growth factor-β(TGF-β) levels were assayed by ELISA. The pathological changes in colon tissue were observed by HE staining, and Th17/regulatory T cells(Treg) ratio in the peripheral blood was determined by flow cytometry. Western blot was conducted for detecting the relative protein expression levels of forkhead box protein P3(Foxp3) and retinoic acid-related orphan nuclear receptor γT(ROR-γt). The findings demonstrated that in normal mice, the colonic structure was intact. The goblet cells were not reduced and the glands were neatly arranged, with no mucosal erosion, bleeding, or positive cell infiltration. In the model group, the colonic mucosal structure was seriously damaged, manifested as disordered arrangement or missing of glands, vascular dilatation, congestion, and massive inflammatory cell infiltration. The pathological injury of colon tissue was alleviated to varying degrees in drug treatment groups. Compared with the normal group, the model group exhibited elevated percentage of Th17 cells, increased IL-17 and TNF-α content, up-regulated relative ROR-γt protein expression, lowered TGF-β, reduced percentage of Treg cells, and down-regulated relative Foxp3 protein expression. The comparison with the model group showed that DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the positive control group, low-dose astragaloside Ⅳ group, and high-dose astragaloside Ⅳ group were decreased, while TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression were increased. The DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, and relative ROR-γt protein expression in the low-dose astragaloside Ⅳ group were higher than those in the positive control group, whereas the content of TGF-β, percentage of Treg cells, and relative Foxp3 protein expression were lower. DAI score, pathological score, percentage of Th17 cells, IL-17 and TNF-α content, relative ROR-γt protein expression in the high-dose astragaloside Ⅳ group declined in contrast to those in the low-dose astragaloside Ⅳ group, while the TGF-β content, percentage of Treg cells, and relative Foxp3 protein expression rose. There was no significant difference between the positive control group and the high-dose astragaloside Ⅳ group. Astragaloside Ⅳ is able to inhibit inflammatory response and diminish the percentage of Th17 cells in mice with UC.