Objective:To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) in the real-world clinical setting.Methods:Clinical data of 2 221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment (225 mg/d) from December 16, 2020 to December 16, 2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients (≥ 65 years old) .Results:Among the total 2 221 patients, 511 patients (23.01%) experienced adverse events, including 8 patients (0.36%) who experienced serious adverse events. Adverse events led to dose modification in 67 patients (3.02%) and discontinuation in 18 patients (0.81%). The common adverse events were rash (407/2 221, 18.33%), pruritus (41/2 221, 1.85%), constipation (41/2 221, 1.85%), and facial edema (31/2 221, 1.40%). Thirty-six patients (1.62%) experienced ≥grade 3 adverse events. After symptomatic treatment of 511 patients with adverse reactions, 50 patients (9.78%) were healed, 271 patients (53.03%) were improved, 120 patients (23.48%) were persisted, and 70 patients (13.71%) were unknown due to loss of follow-up or other reasons. Forty-three patients (1.94%) reported 57 unintended adverse reactions. Among the 599 elderly patients, 116 patients (19.37%) experienced adverse events, including 1 patient (0.17%) who experienced serious adverse events. Adverse events led to dose modification in 25 patients (4.17%) and discontinuation in 5 patients (0.83%). The common adverse events of elderly patients were rash (88/599, 14.69%), constipation (14/599, 2.34%), facial edema (12/599, 2.00%), and pruritus (10/599, 1.67%). Twelve patients (2.00%) experienced ≥grade 3 adverse events. Among the 116 elderly patients with adverse reactions following the symptomatic treatment, 11 patients (9.48%) were healed, 58 patients (50.00%) were improved, 28 patients (24.13%) were persisted, and 19 patients (16.39%) were unknown due to loss of follow-up or other reasons. During the treatment, 1 patient (0.05%) experienced grade 2 interstitial lung disease, and no patient died due to adverse events.Conclusion:Ensartinib has a favorable safety profile in the real-world populations, with the most frequent adverse events being rash, mostly mild, and low incidence of ≥grade 3 adverse events. Overall, adverse reactions were tolerable and manageable.

OBJECTIVES: International Ovarian Tumor Analysis (IOTA) working group proposed a logistic regression (IOTA LR2) model. It is served as a risk prediction model for benign and malignant adnexal tumors. This study aims to compare the diagnostic efficiency between the IOTA LR2 model and doctors' subjective assessment on diagnosing benign and malignant adnexal mass. METHODS: The ultrasonographic images of 616 adnexal masses were retrospectively analyzed by the senior doctors' group and the junior doctors' group using the IOTA LR2 model and subjective assessment. The postoperative pathological diagnosis was used as the gold standard to compare the diagnostic efficiency of the 2 methods. RESULTS: The area under the curves of subjective assessment and IOTA LR2 model for diagnosing malignant adnexal masses were 0.86 and 0.90 for the senior doctors' group and 0.79 and 0.88 for the junior doctors' group, respectively. The sensitivity and specificity of subjective assessment for diagnosing the malignant adnexal masses were 81.0% and 91.3% for the senior doctors' group and 70.1% and 88.7% for the junior doctors' group, respectively. The sensitivity and specificity of the IOTA LR2 model for diagnosing the malignant adnexal masses were 79.6% and 88.1% for the senior doctors' group, and 79.6% and 81.7% for the junior doctors' group, respectively.There were no significant difference in the sensitivities between the senior doctors' group and junior doctors' group using the IOTA LR2 model and the senior doctors' group using subjective assessment (both P>0.05). CONCLUSIONS The diagnostic efficiency of the IOTA LR2 model is equal to the senior doctors' experiences. This model can help junior doctors to reduce the missed diagnosis of malignant adnexal masses.
Adnexal Diseases/pathology* ; Diagnosis, Differential ; Female ; Humans ; Ovarian Neoplasms/diagnostic imaging* ; Retrospective Studies

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

Objective To explore the feasibility of the deep convolutional neural network (DCNN) judging the indications and prognosis of the total knee arthroplasty based on the trained DCNN computer learning system.Methods C1FAR-10 DCNN model based on TensorFlow (an open source system,Google,USA) optimized by Alex Krizhevsky were constructed.There were 400 cases with knee osteoarthritis from different databases used for analysis.Three hundred patients underwent total knee arthroplasty,while 100 did not.X-ray of 200 preoperative cases from the 400 cases and their enlarged image (50 times) were applied for training DCNN,while the enlarged images from other 200 cases were used to test the DCNN.The correlation and the regression between judgment of the DCNN and clinical truth were analyzed.The clinical truths were rechecked three times and were confirmed by treatment results.Pearson correlation and linear regression analysis were used.The relation test of the software was only used as a reference.Results There was no significant difference between the baseline of cases for learning and test.After learning 200 cases,the DCNN judged the 10 000 cases enlarged from remaining 200 cases.The correlation between the DCNN judgment and the clinical truth was not significant (r=0.000,F=0.001,P=0.970).False positive was observed in 1 681 cases,false negative in 3 296.After enlarged to 10 000 images,the correlation between the two judgments was significant (F=11 228.735,P=0.000,r=0.727 and R2=0.529).The software detection precision was 0.860.Conclusion DCNN can be applied in judging the indications of the total knee arthroplasty.Large sample size can improve the accuracy of the judgment significantly.

Objective To develop a rotatable scalp acupuncture to enhance success rate of arteriovenous puncture during hospital treatment, field firstaid and evacuation.Methods The acupuncture was composed of a pinhead, a neilsbed, wings and a soft tube. The wings connected with each other to form a hole to hold the intermediate section of the neilsbed rotating in it. There was an index point in the middle of the head of the neilsbed, whose direction corresponded linearly with that of the inclined plane of the pinhead in the vessel.Results Clinical trials proved that the acupuncture could eliminate the failure of puncture due to tremble hands, incoordination of the patient and etc.Conclusion The acupuncture structured well is easy to operate for all conditions, and thus is worth popularizing practically.

In this study, the natural biological inducer, rat regenerating pancreatic extract (RPE), was used to induce human amniotic mesenchymal stem cells (hAMSCs) into insulin-secreting cells. We excised 60% of rat pancreas in order to stimulate pancreatic regeneration. RPE was extracted and used to induce hAMSCs at a final concentration of 20 microg/mL. The experiment methods used were as follows: morphological-identification, dithizone staining, immumofluorescence analysis, reverse transcription-PCR (RT-PCR) and insulin secretion stimulated by high glucose. The results show that the cell morphology of passge3 hAMSCs changed significantly after the induction of RPE, resulting in cluster shape after induction for 15 days. Dithizone staining showed that there were scarlet cell masses in RPE-treated culture. Immumofluorescence analysis indicated that induced cells were insulin-positive expression. RT-PCR showed the positive expression of human islet-related genes Pdx1 and insulin in the induced cells. The result of insulin secretion stimulated by high glucose indicated that insulin increasingly secreted and then kept stable with prolongation of high glucose stimulation. In conclusion, hAMSCs had the potential to differentiate into insulin-secreting cells induced by RPE in vitro.
Amnion ; cytology ; Animals ; Cell Differentiation ; physiology ; Cells, Cultured ; Humans ; Insulin-Secreting Cells ; cytology ; Mesenchymal Stromal Cells ; cytology ; Pancreas ; physiology ; surgery ; Pancreatic Extracts ; pharmacology ; Rats ; Regeneration

Objective The therapeutic effect of epigallocatechin-3-gallate (EGCG) on the collageninduced arthritis model (CIA) was observed and its immunological mechanism was analyzed. Methods EGCG was administered to CIA mice and PBS was admitted as negative control. The severity of CIA was evaluated by clinical scores and histopathological assessment (H-E staining). Immunological mechanisms inv-suppressive effect on IL-17 secretion of CD4+T cells (EGCG group: 0.41%; PBS group: 4.05% ) and inhibitive activity of C Ⅱ -reactive splenocytes proliferation. There was statistical significant difference between IKB expression and down-regulate phosphorylated IKB expression in lymph node cells of CIA mice.Conclusion EGCG can significantly ameliorate the severity of CIA. The therapeutic mechanisms may be related to inhibition of C Ⅱ -reactive splenocyte proliferation and IL-17 secretion and via inhibiting the activity of NF-κB by inducing the expression of IKB and by suppressing the expression of phosphorylated IKB in CIA mice.

The battlefield rescuing unit of the current model is always restricted by some factors such as regional environments in wartime rescuing action and peacetime disaster relief, which can lead to failure of following and deploying action, so that wounded persons can not be rescued at the first time. Aiming at the special circumstances, a forward first-aid unit composed of five doctors and nurses should be established to give emergency medical rescue with rescuing emergent equipments and medicine packed in portable packages such as portable respiring machine, defibrillator and oxygen device at the battlefront. In this way, success rate of rescuing wounded persons would be increased obviously, while mortality rate and deformity rate would be decreased greatly.

To study the effects of Cordyceps mycelia extract (CME) on portal hypertension in rats with dimethylnitrosamine (DMN) induced liver cirrhosis and probe into the mechanism of the action.

OBJECTIVETo investigate the effect of Fuzheng Huayu decoction (FHD) intervention on hepatic fibrosis.

METHODSWistar rats were randomly divided into 3 groups: rats in the normal group only treated with subcutaneous injection of saline, rats in the model group and the FHD group were made into hepatic fibrosis by subcutaneous injection of 40% carbon tetrachloride (CCl4)-olive solution and then those in the FHD group were treated with FHD by gastric perfusion after modeling. Liver samples of the rats were obtained for routine pathological observation, hydroxyproline determination and proteome quantitative determination. After then, the proteome profile was obtained through 2-dimensional electrophoresis and silver staining, and analyzed. More than 30 proteins with different expression were identified by MALDI-TOF-MS.

RESULTS(1) The integral response of vital movement such as body weight and activity of hepatic fibrosis declined in the CCl4 induced liver fibrosis rats; (2) Liver fibrosis were associated with abnormal metabolism; (3) There were four material metabolism-related protein showed by hepatic proteome mass spectrography, which expressed different between the normal and the fibrotic rats, i. e. the perchloric acid soluble protein, the phosphatidylinositol transferase, the phosphoglycerate kinase and the endoplasmic reticulum-60 protease; (4) The expressions of the above-mentioned four proteins in the FHD group were nearly the same as those of normal level.

CONCLUSION(1) Liver fibrosis is accompanied with abnormal protein synthesis and decomposition, as well as the enhanced activity of glycolysis; (2) The existence of metabolism-related proteins is one of the elements for the liver in regulating metabolism; (3) The regulation on the expressions of metablism-related proteins is one of the pathways for FHD to exert its anti-hepatic fibrosis effect.

Animals ; Carbon Tetrachloride ; Drugs, Chinese Herbal ; therapeutic use ; Hydroxyproline ; metabolism ; Liver ; metabolism ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; Male ; Phosphoglycerate Kinase ; metabolism ; Phytotherapy ; Proteins ; metabolism ; Random Allocation ; Rats ; Rats, Wistar