1.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 .
2.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.
3.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.