Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

Purpose This study aims to analyze genetic mutations in patients with BCR ∷ABL negative myelopro-liferative neoplasms(MPN)and to explore their relationship with clinical features.Methods We retrospectively ana-lyzed the clinical data of 208 patients diagnosed with BCR ∷ABL negative MPN,which included 34 patients with poly-cythemia vera(PV),33 with essential thrombocytopenia(ET),and 141 with primary myelofibrosis(PMF).Mutations in driver genes were assessed in all patients.A total of 72 patients underwent next-generation sequencing(NGS)with 69-gene panel,and the relationship between gene mutations and clinical features were analyzed.Results Among the 208 MPN patients,at least one driver gene mutation(JAK2,CALR,MPL)was detected in 96.15％(200/208)of the patients.Only 0.48％(1/208)of the patients exhibited both JAK2 and CALR driver mutations.We analyzed the clinical data of 136 patients with only driver gene mutations to compare the relationship between the most common JAK2 mutations(identified in 110 patients)and clinical outcomes.The JAK2 mutation group demonstrated higher white blood cell(WBC)counts and lower platelet(PLT)counts compared to the group without JAK2 mutations.173 muta-tions in 40 genes were detected in 72 patients,per capita carried(2.40±1.40)mutations.TET2,ASXL1,and TP53 are the most prevalent non-driver gene mutations,with 44.4％(32/72)of patients exhibiting at least one mutation in these three genes.In comparison to patients without detected mutations in TET2,ASXL1,and TP53,those with muta-tions in these genes demonstrated lower hemoglobin(HGB)levels,a higher incidence of splenomegaly,and more se-vere bone marrow fibrosis.High-molecular risk category(HMR)mutations were detected in 22.22％(16/72)of the patients,and patients with HMR exhibited lower hemoglobin(HGB)levels,lower PLT counts,a higher likelihood of peripheral blood primitive cell percentage ≥ 1％,a greater incidence of splenomegaly,and more severe myelofibrosis.Mutations in the ASXL1 gene were exclusively observed in patients with PMF.Among the PMF patients with ASXL1 mutations(12 patients),there was a higher likelihood of having a peripheral blood primitive cell percentage of ≥1％,as well as a more severe degree of myelofibrosis.Conclusion Approximately 97％of patients with myeloproliferative neoplasms(MPN)exhibit positivity for driver genes,with a notably high mutation rate of the JAK2 gene.Each sub-group of MPN is characterized by distinct gene mutation patterns.Notably,ASXL1 mutations are exclusive to patients with primary myelofibrosis(PMF).Furthermore,PMF patients harboring ASXL1 mutations tend to demonstrate more pronounced bone marrow fibrosis and a greater proportion of blast cells in peripheral blood.

OBJECTIVE To analyze the occurrence of adverse drug reactions （ADR） between bevacizumab biosimilars and original drugs， and to provide data support for rational use of drugs in clinical. METHODS ADR reports of bevacizumab biosimilars and original drugs reported by Jiangsu Cancer Hospital from January to December 2022 were retrospectively analyzed. RESULTS A total of 6 818 patients were treated with bevacizumab， and 136 ADR patients were reported. The incidence of ADR caused by bevacizumab biosimilars was higher than original drugs （2.18% vs. 0.71%， P＝0.004）. In ADR reports， the main treatment plan was bevacizumab combined with other tumor drugs （129 patients）； 118 patients were cured and improved； there were 108 general reports and 28 serious reports； the main system/organ involved in ADR was the cardiovascular system； there were no statistical significance in the incidence rates of hypertension/blood pressure increase， leukocyte/platelet decrease， diarrhea and fever caused by bevacizumab biosimilars and original drugs. CONCLUSIONS The incidence of ADR related to bevacizumab biosimilars is significantly higher than that of the original drugs， but there is no significant difference in the clinical manifestation of ADR. Clinicians can use bevacizumab biosimilars or original drugs based on the willingness of patients and their families.

Objective:To explore the application value of four-dimensional automatic left ventricular quantitation(4D Auto LVQ) technology, in evaluating the myocardial mechanics in patients with different risk stratifications of hypertrophic cardiomyopathy(HCM).Methods:A total of 88 HCM patients and 20 healthy volunteers were selected from February 2020 to February 2022 in the First Affiliated Hospital of Zhengzhou University. According to the HCM Risk-SCD score, HCM patients were divided into 3 groups: low-risk group( n=49), intermediate-risk group( n=21), and high-risk group( n=18). Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including global longitudinal strain(GLS) , global circumferential strain(GCS), global area strain(GAS), global radial strain(GRS), twist and torsion. The differences in these parameters among the four groups were compared. The predictive values of conventional ultrasound parameters and myocardial mechanical parameters in patients with intermediate- and high-risk HCM patients were analyzed by ROC curve. Results:①Left ventricular end-diastolic diameter, left ventricular end-diastolic volume, left ventricular end-systolic volume, and peak systolic velocity of mitral annulus in the low-, intermediate-, and high-risk groups were lower than those in the control group while left ventricular maximal wall thickness(LVMWT) and early diastolic peak velocity of mitral value orifice/early diastolic peak velocity of mitral annulus(E/e′) were higher, left atrial diameter(LAD) and left ventricular outflow tract gradients(LVOTG) in the intermediate- and high-risk groups were higher than the low-risk group(all P<0.05). ②Compared with the control group, the GLS of HCM patients was lower, and the GLS of the intermediate- and high-risk groups was lower than the low-risk group. GCS and GRS in the intermediate- and high-risk groups were lower than those in the low-risk group. GAS in the high-risk group was lower than the low-risk and the control group, but higher than the intermediate-risk group(all P<0.05). Compared with the control group, the twist and torsion in the intermediate- and high-risk groups were higher, but lower than the low-risk group, and the differences were statistically significant(all P<0.05). ③The ROC results showed that the area under the curve(AUC) of the model containing conventional ultrasound parameters(LVWMT, LAD, and LVOTG) for predicting intermediate- and high-risk HCM patients was 0.811, with a sensitivity of 0.769 and a specificity of 0.755. The AUC of the conventional ultrasound parameters combined with myocardial mechanical parameters was 0.904, as the sensitivity was 0.667 and the specificity was 0.980. Conclusions:4D Auto LVQ can evaluate the mechanical characteristics of LV myocardium in HCM patients with different risk stratifications. Myocardial mechanical parameters combined with conventional ultrasound parameters can improve the diagnostic performance of patients with intermediate- and high-risk HCM.

OBJECTIVE To interpret the revision of the in dicators o f pharmaceutical administration in National Tertiary Public Hospitals Performance Evaluation Operational Manual （2022 edition）[hereinafter referred to as the Mannual（2022 edition）]，and to provide reference for the implementation of a new round of performance appraisal in tertiary public hospitals. METHODS The contents and revision details of the indicators of pharmaceutical administration in the Mannual（2022 edition）were described briefly，and the revised contents were interpreted and relevant suggestions were put forward. RESULTS & CONCLUSIONS The Manual（2022 edition）continued the scope of performance evaluation ，indicators’structure and sequence in the Manual（2020 edition），which focused on rational drug use and drug cost control. The Manual （2022 edition） placed more emphasis on strengthening the provision and use of essential medicines and selected drugs in the centralized drug procurement ，and further reducing the burden of medical costs in patients. It is suggested that tertiary public hospitals scientifically set indicators for the use of essential medicines ，selected drugs in the centralized drug procurement ，auxiliary drugs and antibacterial drugs in clinical departments，and improve relevant incentive mechanisms and performance assessment systems ；strengthen the interpretation of policies about essential medicines and drug centralized procurement ，as well as the training of rational drug use ；optimize in-hospital drug catalog and formulary ；formulate medication standards ，strengthen prescription review ，rational medication review and assessment ；establish and improve the drug use monitoring and evaluation and early warning system so as to standardize clinical drug use behavior by information technology ；strengthen the use of essential drugs and centrally purchase selected drugs on the basis of ensuring rationality ；control the unreasonable gradually reduce the increase in average drug costs.

OBJECTIVE：To establish quantitative e valuation system of the prophylactic use of antibiotics in orthopedic type Ⅰ incision surgery ，and to provide reference for evaluating the rational prevention use of antibiotics in this type surgery scientifically. METHODS：Based on the Guidelines of Clinical Use of Antimicrobial Agents （2015 edition），drug instructions ，related guidelines and references ，experts from relevant departments jointly discussed and formulated the evaluation criteria for the rationality of the use of antibiotics in type Ⅰ incision in orthopedic surgery. AHP method was used to assign the weights for various indexes of evaluation criteria ；TOPSIS method was used to retrospectively analyze and evaluate the rationality of 120 cases of type Ⅰ incision surgery from 3 orthopedic departments in Peking University People ’s Hospital during Sept. 1st-30th，2019. RESULTS ：Established evaluation system included 4 primary indicators （medication indication ，usage and dosage ，medication timing ，other factors ）and 12 secondary indicators. Among the secondary indicators ，indications，drug selection and timing of preoperative administration were the most important （weights were 0.209，0.140，0.117）. Among 120 cases，30.83％ of drug use were reasonable ，47.50％ were basically reasonable and 21.67％ were unreasonable. Evaluation results obtained by AHP-TOPSIS were consistent with the actual situation. CONCLUSIONS ：The rationality evaluation method of prophylactic use of antibiotics in type Ⅰ incision surgery based on AHP-TOPSIS method can quantitatively evaluate the rationality of drug use by combining multiple indicators. The method is feasible ，operable，and the evaluation results can be quantified ，which has a wide range of application.

Objective:To explore the expression and significance in regulating immune balance of programmed cell death protein 1 (PD-1) and its ligands PD-L1, PD-L2 in allergic rhinitis (AR).Methods:Eighty-two patients who received outpatient treatment due to high nasal reaction symptoms or were hospitalized due to nasal septum deviation and underwent nasal septum correction surgery in Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from May 2018 to May 2019 were enrolled, including 42 males and 40 females, with the age ranging from 14 to 38 years old. Blood, inferior turbinate nasal mucosal tissue and relevant clinical data were collected. Patients were divided into AR group and control group due to clinical manifestation, skin prick test and detection of specific IgE (sIgE) in serum. Immunohistochemistry was used to detect the expression of PD-1 and its ligands in nasal mucosa of the two groups. Flow cytometry was used to detect the proportions of PD-1 +CD4 +T cells, PD-L1 + myeloid dendritic cells (mDCs), PD-L2 +mDCs and Th2 cells in peripheral blood of the two groups. The expression levels of total IgE, sPD-1, sPD-L1 and sPD-L2 in serum of the two groups were detected by ELISA. The measurement data of normal distribution or normal distribution after the logarithm conversion to Ln were compared by t test. Pearson correlation or Spearman correlation was used to analyze the correlation among the indicators. P<0.05 was considered statistically significant. Results:The expression of PD-1 and its ligands on the surface of immune cells in the nasal mucosa of the AR group was significantly higher than that of the control group. The ratio of PD-1 +CD4 +T cells, PD-L1 +mDCs and Th2 cells in peripheral blood of AR group was significantly higher than that of the control group ((15.24±6.45)% vs (8.71±5.33)%, (8.79±2.01)% vs (5.74±2.90)%, (7.89±1.95)% vs (2.52±1.34)%, all P<0.05). There was no significant difference in the ratio of PD-L2 +mDCs between the two groups. Correlation analysis found that the proportion of PD-1 +CD4 + T cells was positively correlated with the Visual Analogue Scale (VAS) score of AR, total IgE concentration and the serum sIgE concentration ( r value was 0.501, 0.541, 0.608, respectively, all P<0.05). The proportion of PD-L1 +mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration ( r value was 0.604, 0.563, respectively, all P<0.05). The proportion of Th2 cells in peripheral blood was positively correlated with the proportion of PD-L1 +mDCs and PD-1 +CD4 +T cells ( r value was 0.538, 0.623, respectively, all P<0.05). Serum total IgE, sPD-1 and sPD-L1 in the AR group were significantly higher than those in the control group ((6.34±1.38) ng/ml vs (4.89±1.10) ng/ml, (4.40±1.01) pg/ml vs (3.79±1.21) pg/ml, (3.88±0.25) pg/ml vs (3.57±0.23) pg/ml, all P<0.05), and there was no significant difference in sPD-L2 levels between the two groups. Correlation analysis showed that sPD-L1 was positively correlated with total IgE and sIgE concentration ( r values was 0.32, 0.45, respectively, all P<0.05). Conclusions:PD-1 and PD-L1 are highly expressed on the surface of immune cells in peripheral blood and nasal mucosa of AR patients, and sPD-1 and sPD-L1 expression levels in peripheral blood of AR patients are increased. The PD-1/PD-L1 signaling pathway promote AR inflammatory response by inducing Th2 type immune response.

Ethics review as the content of the research management of forensic medicine,is the research object of forensic medicine.Focusing on ethics review of the forensic medicine research,this paper discussed on the necessity of ethics review and guiding principles of ethics committee,and appealed for the construction of ethics review in forensic medicine research.

Positive serum hepatitis B surface antigen (HBsAg) is an indication of hepatitis B virus (HBV) infection,and the clearance of HBsAg usually stands for clinical cure of chronic hepatitis B (CHB).The clearance of HBsAg is influenced by the host,virus,antiviral drugs and other factors.This paper reviews the recent research progress on the related factors of HBsAg clearance in patients with CHB.