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.

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 .

A 74-year-old male patient was hospitalized for cerebral infarction, hypertension, diabetes mellitus, and coronary atherosclerotic heart disease. During the hospitalization, a thyroid ultrasound examination revealed suspicious nodules. In order to make a definite diagnosis, thyroid ultrasonography was performed, during which 2.4 ml of sulphur hexafluoride microbubbles for injection and 5 ml of 0.9% sodium chloride injection were given intravenously. Ten minutes later, the patient developed fever, confusion, profuse sweating, red skin rash, and blood pressure 80/60 mmHg, and anaphylactic shock caused by sulphur hexafluoride microbubbles for injection was considered. The patient was given intravenous injection of dexamethasone 10 mg, intravenous infusion of adrenaline 1 mg dissolved in 0.9% sodium chloride injection 250 ml, intramuscular injection of promethazine 25 mg, and mask oxygen. About 3 minutes later, the patient′s consciousness gradually turned clear, and the blood pressure rose (103/72 mmHg); 1.5 hours later, the patient′s consciousness was completely recovered, the blood pressure was 143/86 mmHg, the heart rate was 98 beats/min, and the blood oxygen saturation was 0.98. Twenty-four hours later, the rash was basically disappeared, and the patient′s condition was stable.

A 74-year-old male patient was hospitalized for cerebral infarction, hypertension, diabetes mellitus, and coronary atherosclerotic heart disease. During the hospitalization, a thyroid ultrasound examination revealed suspicious nodules. In order to make a definite diagnosis, thyroid ultrasonography was performed, during which 2.4 ml of sulphur hexafluoride microbubbles for injection and 5 ml of 0.9% sodium chloride injection were given intravenously. Ten minutes later, the patient developed fever, confusion, profuse sweating, red skin rash, and blood pressure 80/60 mmHg, and anaphylactic shock caused by sulphur hexafluoride microbubbles for injection was considered. The patient was given intravenous injection of dexamethasone 10 mg, intravenous infusion of adrenaline 1 mg dissolved in 0.9% sodium chloride injection 250 ml, intramuscular injection of promethazine 25 mg, and mask oxygen. About 3 minutes later, the patient′s consciousness gradually turned clear, and the blood pressure rose (103/72 mmHg); 1.5 hours later, the patient′s consciousness was completely recovered, the blood pressure was 143/86 mmHg, the heart rate was 98 beats/min, and the blood oxygen saturation was 0.98. Twenty-four hours later, the rash was basically disappeared, and the patient′s condition was stable.

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.

A 25-year-old male patient took about 60 tablets of phenobarbital and scopolamine hydrobromide by himself (each tablet contains 30 mg phenobarbital and 0.2 mg scopolamine hydrobromide). About 1 hour later, he developed coma with paroxysmal limb convulsions. Drug poisoning was diagnosed. The patient received gastric lavage, catharsis, and intravenous injection of midazolam 10 mg for epilepsy. Six hours later, his heart rate was 53 beats/min, breathing rate was 11 times/min, and occasional convulsions and hematuria occurred. Laboratory tests showed indirect bilirubin 16.97 μmol/L, total protein 54 g/L, albumin 27.6 g/L, and thrombin time 25.0 s. Multiple organ injury was considered and blood purification treatment was given. One day later, the patient′s consciousness was restored, heart rate was 68 beats/min, breathing rate was 16 times/min, and no convulsion occurred. Laboratory tests showed indirect bilirubin 8.69 μmol/L, total protein 54.7 g/L, albumin 34.0 g/L, and thrombin time 16.7 s.

A 25-year-old male patient took about 60 tablets of phenobarbital and scopolamine hydrobromide by himself (each tablet contains 30 mg phenobarbital and 0.2 mg scopolamine hydrobromide). About 1 hour later, he developed coma with paroxysmal limb convulsions. Drug poisoning was diagnosed. The patient received gastric lavage, catharsis, and intravenous injection of midazolam 10 mg for epilepsy. Six hours later, his heart rate was 53 beats/min, breathing rate was 11 times/min, and occasional convulsions and hematuria occurred. Laboratory tests showed indirect bilirubin 16.97 μmol/L, total protein 54 g/L, albumin 27.6 g/L, and thrombin time 25.0 s. Multiple organ injury was considered and blood purification treatment was given. One day later, the patient′s consciousness was restored, heart rate was 68 beats/min, breathing rate was 16 times/min, and no convulsion occurred. Laboratory tests showed indirect bilirubin 8.69 μmol/L, total protein 54.7 g/L, albumin 34.0 g/L, and thrombin time 16.7 s.