1.Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice.
Wanze TANG ; Zhen DING ; Huanqing GAO ; Qinnan YAN ; Jingping LIU ; Yingying HAN ; Xiaoting HOU ; Zhengwei LIU ; Litong CHEN ; Dazhi YANG ; Guixing MA ; Huiling CAO
Acta Pharmaceutica Sinica B 2023;13(11):4535-4552
Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.
2.A case -control study of the effects of surgical history on chemotherapy -induced nausea and vomiting
Bo SUN ; Erfeng ZHANG ; Lu CHEN ; Xun LIU ; Shufang LI ; Huanqing MA ; Lili PAN ; Danna LIU ; Huipin WANG
China Pharmacy 2022;33(19):2378-2383
OBJECTIVE To explore the influence of surgical history on chemotherapy -induced nausea and vomiting (CINV). METHODS A retrospective case -control study was adopted ,with 824 patients undergoing chemotherapy as the object . A total of 27 items were collected ,including demographic data ,medical history data ,pre-chemotherapy data ,and chemotherapy treatment status. Logistic regression model was used to analyze the relationship between the history of surgery and the risk of CINV . The multiple models were constructed to correct potential confounding factors ,and subgroup analysis was performed on patients with surgical history . RESULTS The incidence of CINV was higher in patients with surgical history . The statistical result before adjustment was [OR=1.72,95%CI(1.31,2.28),P<0.001];after adjusting potential confounding factors ,the statistical result was [OR=1.78,95% CI(1.28,2.48),P=0.001]. In the subgroup analysis ,the time between surgery and chemotherapy was different , and the impact of surgical history on CINV was different ,and the results were statistically significant (P=0.027). The risk of CINV showed decreasing trend with the time ,and the results were statistically significant (P for trend ≤0.050). Compared with patients who had not undergone surgery ,patients who had undergone surgery within one year had a higher risk of CINV [OR= 2.33,95%CI(1.52,3.59),P<0.001]. CONCLUSIONS Patients with surgical history are more prone to CINV ,and the risk of CINV shows a downward trend in the length of time from surgery .
3.Exploration of Risk Factors for Prevention Failure of Chemotherapy-related Nausea and Vomiting with Palonosetron Combined with Dexamethasone
Bo SUN ; Danna LIU ; Xun LIU ; Erfeng ZHANG ; Huanqing MA ; Xiaoli ZHAO ; Lu CHEN ; Tiandong KONG
China Pharmacy 2021;32(21):2640-2646
OBJECTIVE:To explore t he risk factors that may lead to the ineff ectiveness of using palonosetron combined with dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV),and to provide a reference for the rational choice and use of antiemetic drugs. METHODS :In a retrospective case-control study ,871 patients who used palonosetron combined with dexamethasone to prevent CINV in a tertiary cancer hospital from 2016 to 2020 were selected as the object. Totally 32 related data such as demographic data ,living habits ,medical history ,examination information and treatment information were counted as variables. Combined with single factor regression ,multi-factor regression, likelihood ratio forward or backward stepwise 163.com regression were used to comprehensively screen the factors for many times. The standard target factors screened by stepwise E-mail:kongtiandong@126.com regression were included in the multivariate Logistic regression analysis,and the regression model was evaluated by the ROC c urve. RESULTS :The multivariate Logistic regression model fitted well(AUC in ROC was 0.83,but 0.82 after screening ). The results showed that there were 15 statistically significant independent influential factors ,including 12 independent risk factors ,ie. poor nutritional status (OR=2.11,95%CI(1.05,4.22),P=0.036), history of gastrointestinal disease (OR=2.76,95%CI(1.87,4.07),P<0.001),abnormal electrolyte level (OR=2.54,95%CI (1.74,3.69),P<0.001),nausea and vomiting 24 h before chemotherapy (OR=8.47,95%CI(3.28,21.91),P<0.001),history of chemotherapy-induced vomiting (OR=3.20,95% CI (2.18,4.71),P<0.001),high risk level of vomiting caused by chemotherapy(OR=3.16,95%CI(2.38,4.20),P<0.001),application of opioid combined with non-steroidal analgesics (OR= 4.18,95%CI(2.06,8.49),P<0.001),the use of other drugs that stimulate the intestine and stomach (OR=2.49,95%CI(1.28, 4.83),P=0.007),history of surgery (OR=1.88,95%CI(1.34,2.63),P<0.001),high level of albumin (OR=1.05,95%CI (1.01,1.08),P=0.015),multiple days of single chemotherapy (OR=1.69,95%CI(1.11,2.56),P=0.014),and opioid analgesia medicine (OR=1.71,95%CI(1.15,2.53),P=0.007);and the following 3 independent protective factors included long time of diagnosis (OR=0.65,95%CI(0.46,0.93),P=0.019),non-first chemotherapy (OR=0.52,95%CI(0.33,0.83),P= 0.006),and drugs combined chemotherapy (OR=0.55,95%CI(0.34,0.90),P=0.018). CONCLUSIONS :Patients with the following conditions are more likely to experience CINV prevention ineffectiveness ,ie. single long-term chemotherapy ,application of chemotherapy plan with a higher risk of emesis ,history of chemotherapy-induced vomiting ,history of gastrointestinal diseases , nausea and vomiting 24 hours prior to chemotherapy ,history of surgery ,within 1 year of diagnosis ,chemotherapy for the first time,use of opioids ,use of 5-HT3 reuptake inhibitors ,malnutrition and electrolyte disorders.
4.Comparison of levator ani muscles in three-dimensional MRI-based models in women with and without pelvic organ prolapse at rest
Ping LIU ; Ruolan CHEN ; Chunlin CHEN ; Lan CHEN ; Cheng PENG ; Lu HUANG ; Jianping WANG ; Huanqing TAN ; Kedan LIAO ; Lian TANG ; Yuezhi WANG ; Lei TANG ; Shizhen ZHONG
Chinese Journal of Obstetrics and Gynecology 2015;(6):428-433
Objective Comparison of the levator ani muscles in three-dimensional (3D) MRI-based models in women with and without pelvic organ prolapse at rest to analyze the morphological characteristics of levator ani muscles in women with POP. Methods Twenty-five women with POP and 22 women with normal pelvic support were selected from Nanfang Hospital of Southern Medical University. Axial, sagittal, and coronal T2-weighted pelvic magnetic resonance scans were obtained with the women in the supine position.The 3D models were reconstructed from the source images. Morphological changes was compared within the two groups of levator ani muscles, and the 3D models were measured to determine the levator ani muscle volume (LVOL), levator plate angle (LPA), levator hiatus width (LH-W) and length (LH-L), distance between symphysis and levator sling muscle (LSG). Results There were no puborectalis avulsions in control, in POP, 3 cases of avulsions just in left, 3 cases of avulsions just in right, 7 cases in bilateral. The shape of iliococcygeus were all dome-shaped in control, 11 cases were U-shaped and 14 cases were dome-shaped in POP. The shape of levator hiatus were 7 cases of U-shape, 12 cases of V-shape, 3 cases of irregular in control; 5 cases of U-shape, 4 cases of V-shape, 16 cases of irregular in POP. POP versus control: LH-L: (68.0 ± 8.9) versus (61.6 ± 7.2) mm (P<0.05); LH-W: (41.4 ± 3.9) versus (38.0 ± 3.2) mm (P<0.05); LSG-L: (29.6 ± 7.4) versus (24.6 ± 3.7) mm (P<0.05); LSG-R: (28.4 ± 6.8) versus (23.9 ± 3.2) mm (P<0.05); LPA: (51.0 ± 11.3)° versus (40.6 ± 6.3)° (P<0.05); LVOL: (23.7 ± 5.8) versus (24.6 ± 5.0) cm3 (P>0.05). Conclusions It is possible to assess the morphologic changes of levator ani by using 3D MRI models objectively, our 3D data demonstrate larger in LVOL, LPA, LH-W, LH-L, LSG, and the changes in shape. It is helpful to diagnose and assess the specific situation of patients POP in clinic.
5.Genetic diagnosis on one case of primary pigmented nodular adrenal disease
Jie ZHU ; Xiaolong JIN ; Sheng ZHENG ; Yi JIANG ; Huanqing FENG ; Haohui CHEN ; Chengwen LU ; Bin CUI ; Xiaoying LI ; Guang NING
Chinese Journal of Endocrinology and Metabolism 2011;27(3):231-233
Primary pigmented nodular adrenal disease (PPNAD) is a kind of autosomal dominant inherited disease. Patient in the study presented with Cushing's syndrome, and clinical and pathological diagnosis of PPNAD was confirmed. It is now confirmed that there are two relevant genes and their mutations may lead to PPNAD. This study showed no mutations in the patient, surpecting if there would be an alternative mechanism or a new gene in playing the role.
6.The value of detection of small liver tumor with galactose-bovine-serum-albumin containing superparamagnetic iron oxide in rabbits
Xiaodong ZHANG ; Yikai XU ; Gang DUAN ; Bin CHEN ; Huanqing TAN ; Peng CANG ; Huali QU
Chinese Journal of Radiology 2008;42(1):29-33
Objective To discuss the value of detection of small liver tumor with Galactose-Bovine-serum-albumin containing superparamagetic(Gal-BSA-SPIO) in rabbits primarily.Methods Gal-BSA-SPIO was obtained by stabilizing small superparamagnetic iron with galactose-bovine-serum-albumin,and its size was measured.Models of liver tumor(diameter<1.5 cm) in rabbits were founded.The animals were randomly divided into groups of SPIO (n=10) and group of Gal-BSA-SPIO (n=10).Each group was further subdivided as 5 μmol Fe/kg group (n=5) and 10 μmol Fe/kg group (n=5),respectively.All animals were performed magnetic resonance imaging before and after administration of agents according to groups.SE T2WI,FSE T2WI and GRE T2WI sequences were used.Then signal of noise(SNR) of liver and contrast-noise ratio(CNR) of tumor-liver were measured and compared statistically.The histopathology study was performed for liver and tumor specimens after MR imaging.Results The mean value for the volume size was 34.4 nm,and the core particle size was 14.8 nm.The differences of liver SNR between before and after enhancement for 5 μmol Fe/kg SPIO,5 μmol Fe/kg Gal-BSA-SPIO,10 μmol Fe/kg SPIO and 10 μmol Fe/kg Gal-BSA-SPIO group were (1.92±0.42),(3.75±0.51),(3.25±0.72) and (4.73±0.34) on SE sequence,respectively;(1.56±0.18),(3.56±0.64),(3.33±0.16) and (4.83±0.16) on FSE sequence,respectively;(5.55±0.91),(9.58±0.66),(9.20±0.29) and (10.63±0.32) on GRE sequence,respectively.There were significant differences between all groups for difierent doses and agents and within all different sequences (P<0.01).The differences of tumor-liver CNR between before and after enhancement of these 4 groups were(2.22±0.68),(5.27±0.22),(4.25±0.51) and (6.97±0.63) on SE sequence,respectively;(1.73±0.41),(4.46±0.54),(3.73±0.49)and (5.39±0.39) on FSE sequence,respectively;(5.98±0.71),(11.79±0.57),(9.57±0.54)and(14.64±1.35)on GRE sequence,respectively.The differences between all groups of different doses and agents and within all sequences showed significant (P<0.01). Histopathological study revealed that Gal-BSA-SPIO was mainly distributed in hepatocytes while SPIO mainly in Kupffer cells.Conclusion Gal-BSA-SPIO is a agent with good negative enhancement effect in liver.It may be helpful for detecting small tumor of liver.
7.Diagnosis and surgical treatment of 61 cases with infective endocarditis
Shenghua LIU ; Haisheng CHEN ; Huanqing ZHONG ; Zhimin ZHONG
International Journal of Surgery 2008;35(12):816-818
Objective To summarize the diagnosis and surgical treatment of 61 cases with infective endocarditis.Methods From January 1995 to April 2008,61 cases with infective endocarditis underwent operation in our hospital.The outcomes of these patients were summarized.Results There were 4 eases of early-death.Early mortality after heart operations was 6.6%.Fifty-seven patients were followed-up for 6 months to 13 years.Five were dead.Others'cardiac function(NYHA)was as follows:classⅡin 43 cases,class Ⅲ in 9 cases.Condusion Early diagnosis,optimal surgical timing,combined internal medicine and surgical treatment are the critical factors treatment of cases with infective endocarditis.
8.Off-line experiments and analysis of independent brain--computer interface.
Qiang CHEN ; Hu PENG ; Chaohui JIANG ; Huanqing FENG
Journal of Biomedical Engineering 2006;23(3):478-482
In order to study event-related desynchronization (ERD) related to voluntary movement, we designed two experiments. In the first experiment, untrained subjects were required to imagine the action of typing with left or right index finger for about 1 second before real action, whereas they were required to type instantly after instruction in the second experiment. By analyzing spontaneous EEG signals between the instruction and the action, we predicted which finger was used. The prediction accuracy in the first experiment fell from 85% to 71% with the progress of experiment, the average accuracy being 78%, whereas the prediction result was almost random guess in the second experiment. The results demonstrate that (1) ERD patterns are significantly affected by the effective duration of motion imagination, (2) unconscious reduction of this duration can decrease the prediction accuracy. Therefore, when designing subsequent BCI experiments, we should devote our attention to the question of how to keep the effective duration of motion imagination.
Brain
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physiology
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Cortical Synchronization
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Electroencephalography
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Humans
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Man-Machine Systems
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Task Performance and Analysis
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User-Computer Interface
9.Application of high frequency component in classification of different mental tasks.
Xiang CHEN ; Jihai YANG ; Zhu YE ; Zheng LIANG ; Wei HE ; Huanqing FENG
Journal of Biomedical Engineering 2005;22(6):1259-1263
Electroencephalogram (EEG) signals of different mental tasks were preprocessed using Independent Component Analysis (ICA). Auto-Regressive (AR) model was used to extract the feature, and Back-Propagation (BP) network as the classifier. When features were extracted from 20-100 Hz high frequency range, the classification accuracy was the same as that taken from the whole frequency range and was more higher than the result of 2-35 Hz normal EEG rhythm. The explanation of this phenomenon is: brain displays different rhythm assimilation during different mental task under the effect of 60 Hz power frequency, so the high frequency components of EEG include more mental modulated information which is useful for improving the classification accuracy. The result presents a new evidence for the brain rhythm assimilation phenomenon and gives a novel feature extraction method for realizing high accuracy real-time BCI based on mental task.
Brain
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physiology
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Electroencephalography
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methods
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Evoked Potentials
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physiology
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Humans
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Principal Component Analysis
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Signal Processing, Computer-Assisted
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Thinking
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physiology
10.A comparison between thoracoscopic and open cardiac surgery in the treatment of congenital heart diseases
Haisheng CHEN ; Yunge CHENG ; Huanqing ZHONG
Chinese Journal of Minimally Invasive Surgery 2005;0(08):-
Objective To compare the efficacy between thoracoscopic and open cardiac surgery in the treatment of congenital heart diseases. Methods A total of 62 patients with congenital heart diseases were divided into two groups according to patients’ preference. There were 24 patients in the Thoracoscopic Group. The thoracoscopic operations were performed under extracorporeal circulation, including atrial septal defect repair in 8 patients and ventricular septal defect repair in 16 patients. The Open Group consisted of 38 patients, including atrial septal defect repair in 14 patients and ventricular repair in 24 patients. Results Fatal cases happened in neither of groups. There were no significant differences between the two groups in the bypass time (74?28 min vs 71?24 min; t=0.449, P=0.655), the ascending aorta cross-clamping time (29?13 min vs 28?12 min; t=0.309, P=0.758), and the postoperative mechanical ventilation time (3.2?1.1 h vs 3.3?1.1 h;t=-0.349, P=0.729), respectively. No significant variation in incidence of postoperative complications was observed between the two groups (?~2=2.646,P=0.104). As compared with the Open Group, the Thoracoscopic Group had a significantly less chest drainage volume (32?18 ml vs 66?28 ml;t=-5.290,P=0.000) and a significantly shorter postoperative hospital day (6.1?1.2 d vs 7.6?2.2 d;t=-3.059,P=0.003). Conclusions Thoracoscopic cardiac surgery for congenital heart diseases is a safe and effective technique with little invasion, quick recovery and good cosmetic results.

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