Objective To investigate the clinical characteristics of patients with chronic myeloid leukemia (CML) in chronic phase with deletion and non-deletion of the argininosuccinate synthesis gene (ASS gene) on the derivative chromosome 9. Methods The clinical data of patients with CML initially treated with imatinib and BCR/ABL1/ASS1 3-color fusion probe to detect ASS gene deletion were analyzed. The patients were divided into deletion group (n=27) and non-deletion group (n=92). Clinical characteristics, treatment effects, and prognosis were analyzed. Results The average age of 119 patients was 37.22±12.72 years old. The sokal score differed between the deletion and non-deletion groups (χ²=4.304, P=0.038). No statistically significant difference in other general characteristics was found (P > 0.05). The 3-month CCyR rate, 6-month CCyR rate, and BCR-ABL^IS≤ 1% rate in the deletion group were lower than those in the non-deletion group (P < 0.05). The median follow-up of 119 patients was 35.0 (3.0-60.0) months. The PFS in the deletion group was lower than that in the non-deletion group (χ²=4.293, P=0.038). Overall survival was not significantly different between the two groups (χ²=0.008, P=0.931). Conclusion The deletion of the ASS gene in patients with chronic CML is related to the poor efficacy of imatinib treatment, poor prognosis, and high risk of disease progression.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.

Objective:To investigate the technical points and clinical effect of thulium fiber laser lobes-enucleation of the prostate (ThuLLEP).Methods:A total of 90 patients underwent ThuLLEP and plasmakinetic enucleation of prostate (PKEP) in our hospital from November 2018 to December 2020 were collected. The age of patients in the two groups was (67.7±6.8) years and (65.7±7.1) years, the prostate volume was 56.0 (46.0-83.5) ml and 61.0 (53.5-79.5) ml, the serum PSA was 3.6 (2.2-6.0) ng/ml and 4.4 (1.8-7.3) ng/ml, the international prostate symptom score (IPSS) was 27 (22-31) and 28 (23-30), the quality of life score (QOL) was 5 (5-6) and 5 (5-6), the maximum urinary flow rate (Q max) was (8.5±5.7) ml/s and (7.8±3.8) ml/s, the post-void residual volume (PVR) was 127 (47-250) ml and 100 (27-209) ml. The differences had no statistical significance ( P>0.05). The glands were bluntly dissected to establish the surgical capsule plane on both sides of the verumontanum after the verumontanum being located. And then the middle lobe was removed. The glands formed grooves at 12 o'clock after vaporization, which served as anatomical marker. The left and right lobes were removed step by step. Finally, tissue crushing was performed. The PKEP group was enucleated by three lobes enucleation. Perioperative indicators were compared between the two groups. Results:All the operations were completed successfully. The median operative time in ThuLLEP and PKEP groups was 60 (50-73) minutes and 75 (60-100) minutes, the postoperative bladder irrigation time was 2.8 (2.3-3.6) d and 3.8 (2.6-4.7) d, the catheter indwelling time was 4.1 (3.7-4.9) d and 4.9 (4.7-6.0) d, the postoperative hospital stay was 5 (4-6) d and 6 (5-7) d. The decreased hemoglobin was 8.0 (1.5-14.5) g/L and 15.0 (6.5-21.0) g/L. The differences had statistical significance ( P<0.05). Follow-up was performed for 6 months after surgery. The median IPSS score of the two groups was 5 (2-11) and 6 (3-9), the QOL score was 1 (1-2) and 1 (1-2) respectively, which had statistical significance compared with the preoperative parameters ( P<0.05), but no statistical significance between the two groups ( P>0.05). The ThuLLEP group had 1 case of postoperative blood transfusion, 1 case of transient urinary incontinence and 2 cases of urethral stricture. The PKEP group had 1 case of fever and blood transfusion, 3 cases of transient urinary incontinence and 3 cases of urethral stricture. Conclusions:ThuLLEP has definite clinical effect because of less bleeding, quicker recovery and fewer complications. The relatively simple operation steps are beneficial for beginners to master.

Alzheimer's disease (AD) is a degenerative neurological disease with unclear pathogenesis. The disease progress/trajectory of AD patients can be adequately described by establishing quantitative pharmacological disease progression model. Integrating biomarker information into the model can provide more insight to understand the potential pathological mechanisms and facilitate the optimization of future trial design. Several empirical and semi-mechanism disease progression models have been published. This mini-review is expected to offer some references for the further AD clinical research and new drug development.

AIM: Belimumab is a fully humanized IgGl-X monoclonal antibody, which can specifically bind to soluble B cell stimulating factor (BLyS) preventing BLyS from binding to B cells to promote B cell apoptosis. It is the first drug approved by the FDA for the treatment of systemic lupus erythematosus (SLE). Based on data from global clinical literature of the drug, this study evaluated the effect of belimumab in the treatment of SLE through modeling analysis, quantitatively expressed its pharmacodynamic characteristics, and explored its potential influencing factors to establish the efficacy of belimumab in the treatment of SLE, which could provide a reference for the development of drugs for the treatment of SLE. METHODS: Literature retrieval was conducted in Pubmed database. The clinical studies of belimumab in the treatment of SLE were included. Data, including the demography and baseline characteristics, dosage, administration methods, efficacy and safety of belimumab, was extracted to establish an analysis sets. Then a pharmacodynamic model was developed to evaluate the pharmacodynamic characteristics of the drug. The robustness of the model was evaluated via a variety of model evaluation methods. RESULTS: A total of 5 articles containing efficacy data were included in this analysis, involving 11 dosage groups (3 493 subjects). The results of covariate screening showed that race (Asian population or non-Asian population), age, course of disease, positive anti-dsDNA had no significant effect on the therapeutic effect of belimumab in SLE and there were no factors that had significant influence on model parameters. Model evaluation showed that the model established in this study can better describe the dose-effect relationship of belimumab in the treatment of SLE. The final model indicated that the response rate of the efficacy index SRI was close to the peak (approximately 99% of the peak level) at the 52nd week. The SRI response rates of placebo, belimumab 1 mg/kg intravenous injection, 10 mg/kg intravenous injection, and 200 mg subcutaneous injection were 46.1%, 52.9%, 57.9%, and 60.9%, respectively. After deducting the placebo effect, the SRI response rates (drug pure effect) of belimumab 1 mg/kg intravenously, 10 mg/kg intravenously, and 200 mg subcutaneously at 52 weeks were 6.8%, 11.8%, and 14.8%, respectively. CONCLUSION: The efficacy (SRI response rate) of belimumab in the treatment of SLE patients was close to its peak in the 52nd week. The SRI response rates of belimumab 1 mg/kg intravenously, 10 mg/kg intravenously, and 200 mg subcutaneously in the 52nd week were 52.9%, 57.9%, and 60.9%, respectively.

AIM: To study the ways of calculating area under the plasma concentration-time curve (AUC) in non-compartment model pharmacokinetics by comparing the accuracy & precision of every method. METHODS: Three methods were used to calculate the area under 0-T curve (AUC

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

OBJECTIVE： To establish a method for simultaneous determination of 4 triglyceride anti-tumor components in Coix lacryma seed oil. METHODS： HPLC-ELSD was adopted. The determination was performed on Inertsil ODS-3 C18 column with mobile phase consisted of acetonitrile-isopropanol （57 ∶ 43， V/V） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， and the sample size was 10 μL. Evaporative light scattering detector was used， the drift tube temperature was 70 ℃， and the gas flow rate was 2 L/min. Using glycerol trioleateas internal standard， relative correction factors （RCF） of linolein trilinolein， 1，2-linoleic acid-3-palmitic acid glyceride and 1-palmitic acid-2-oleic acid-3-linoleic acid glyceride were calculated respectively. The contents of above 3 components in C. lacryma seed oil were calculated by RCF. The contents of 4 components in C. lacryma seed oil were determined by external standard. The results of content determination by quatitative analysis of multi-components by single marker （QAMS） were compared with external standard method. RESULTS： The linear ranges were 0.15-4.50 μg for linolein trilinolein， 0.15-4.50 μg for 1，2-linoleic acid-3-palmitate， 0.35-10.50 μg for 1-palmitic acid-2-oleic acid-3-linoleic acid glyceride， 0.35-10.50 μg for glycerol trioleate （r≥0.999 5）. The limits of quantification were 0.13， 0.06， 0.07， 0.12 μg. The limits of detection were 0.04， 0.02， 0.02， 0.03 μg， respectively. RSDs of precision， stability， and repeatability tests were less than 2.0％（n＝6）. The average recoveries were 95.43％-102.67％（RSD＜2.0％， n＝6）. Average RCFs of linolein trilinolein， 1，2- linoleic acid-3-palmitic acid glyceride and 1-palmitic acid-2- oleic acid-3-linoleic acid glyceride were 0.31， 0.88， and 1.21， respectively. RCFs reproducibility was perfect under different experiment conditions. There was no significant difference in results of content determination between QAMS and external standard method （P＞0.05）. CONCLUSIONS： The method is simple， rapid， accurate and reliable. It is used for simultaneous determination of linolein trilinolein， 1， 2-linoleic acid-3-palmitate， 1-palmitic acid-2-oleic acid-3-linoleic acid glyceride and glycerol trioleateas in C. lacryma seed oil.