OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China， and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI， Wanfang Data， PubMed and Web of Science were systematically searched， and the retrieval time was from the inception to December 31st， 2023. The summary and analysis were performed from the aspects of theme selection， indicator system construction， evaluation methods， comprehensive decision-making， quality control， etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs， Chinese patent medicines， cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8， all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making， quality control， or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However， there are still issues and challenges such as incomplete evaluation methods and standards， few cases of evaluation results being converted into decision-making， and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored； when the evidence-based basis is insufficient， real-world research should be conducted as much as possible， so as to accelerate the policy transformation of evaluation results.

Objective To observe the value of multi-slice spiral CT(MSCT)post-processing technologies for diagnosing otosclerosis.Methods Clinical data and original axial plain MSCT of 47 patients with otosclerosis(92 ears)and 65 patients with non-otosclerosis hearing impairment(79 ears)were retrospectively enrolled.MSCT post-processing images,including multi-planar reformation(MPR)of stapes and cochleas and curved planar reformation(CPR)of ossicular chains were obtained.The diagnostic value of original MSCT images alone and raw data of MSCT combing with post-processing images for diagnosing otosclerosis were compared.Results Otosclerosis was correctly diagnosed in 66 ears according to original MSCT images alone,but in 89 ears combined with MSCT post-processing images.The sensitivity of original MSCT images alone and combined with MSCT post-processing images was 71.74％and 96.74％,respectively,and the diagnostic accuracy was 81.29％and 96.49％,respectively,those of the latter were both higher than of the former(both P＜0.05),which had specificities being not significantly different(92.41％vs.96.20％,P＞0.05).Conclusion Combining with post-processing technologies could increase the sensitivity and accuracy of MSCT for diagnosing otosclerosis.

Background Maternal exposure to bisphenol A (BPA) during pregnancy is closely related to adverse growth and development conditions such as preterm birth and low birth weight, but the relevant mechanisms are still unclear. UDP-glucuronosyltransferases (UGTs) can regulate the excretion of BPA conjugating with glucuronic acid through urine, which is one of the important pathways for BPA elimination. Objective To explore the changes in the expression of UGTs in placenta and fetal liver of rats before birth induced by maternal exposure to BPA during pregnancy. Methods Thirty SPF-grade healthy SD pregnant rats were randomly divided into five groups: control group, 0.05, 0.5, 5, and 50 mg·kg⁻¹ BPA groups. The pregnant rats were exposed to BPA dissolved in corn oil via oral gavage daily from gestational day (GD) 5 to GD 19. After anesthesia, the pregnant rats were sacrificed on GD 20 and the placentas were collected. Body length, tail length, and weight of the fetal rats were measured. Fetal liver tissues were then separated, and organ weights were measured. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to determine the mRNA and protein levels of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in the placenta and fetal liver tissues in each group. Results There were no differences in body length and tail length of the pups after maternal exposure to BPA during pregnancy. The fetal body weight and placenta weight in the 5 and 50 mg·kg⁻¹ BPA groups and the liver weight in the 5 mg·kg⁻¹ BPA group reduced compared with the control group (P<0.05). The results of UGTs expressions in placenta showed that compared with the control group, the UGT1A1 mRNA levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) and the UGT1A1 protein level in placenta of the 50 mg·kg⁻¹ BPA group increased (P<0.05); the UGT1A6 mRNA and protein levels in placenta of each BPA group did not change (P>0.05); the UGT1A9 mRNA level in placenta of the 50 mg·kg⁻¹ BPA group and the UGT1A9 protein levels in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05); while the levels of UGT2B1 mRNA in placenta of the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). The results of UGTs expressions in fetal liver showed that compared with the control group, the UGT1A1, UGT1A6, UGT1A9, and UGT2B1 mRNA levels of each BPA group increased (P<0.05); no obvious alternation was observed in UGT1A6 protein levels in each BPA group (P>0.05); the relative protein levels of UGT1A9 in fetal liver in the 50 mg·kg⁻¹ BPA group increased (P<0.05); conversely, the relative protein levels of UGT2B1 in fetal liver in the BPA groups (exposure dose≥0.5 mg·kg⁻¹) reduced (P<0.05). Conclusion Maternal exposure to BPA during pregnancy can elevate the UGT1A1 gene and protein expressions, inhibit the UGT1A9 gene and protein expressions and UGT2B1 gene expressions in placenta. Besides, maternal exposure to BPA during pregnancy can raise the gene expressions of UGT1A1, UGT1A6, UGT1A9, and UGT2B1 in fetal liver, as well as the protein expression of UGT1A9, but inhibit the protein expression of UGT2B1. These changes may contribute to fetal developmental abnormalities after maternal exposure to BPA during pregnancy.

Objective To explore the abnormal changes of resting state functional connectivity of pain networks in patients with cervical discogenic pain(CDP).Methods The resting-state functional magnetic resonance imaging(rs-fMRI)data of 40 patients with CDP and 40 age-and gender-matched healthy controls(HC)were collected.The seed of posterior insula(PI)was used to define the pain network,and seed-based whole-brain functional connectivity analyses were performed to explore the difference of functional connectivity between CDP patients and HC,the associations between functional connectivity and clinical measures were analyzed.Results The functional connectivity between bilateral PI and bilateral thalamus(THA)was increased,and the functional connectivity between left PI and middle cingulate cortex(MCC),left postcentral gyrus(PoCG)and MCC were decreased in CDP patients.Moreover,the func-tional connectivity between right PI and left THA was positively correlated with visual analogue scale(VAS),and the functional connectivity between left PoCG and MCC was negatively correlated with VAS.Conclusion Functional connectivity abnormalities exist in pain network resting state of CDP patients,which may provide an imaging basis for revealing the neuropathological mechanism of pain in CDP patients.

OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs， the methods such as literature research， expert interviews， and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators， 13 secondary indicators， and 34 tertiary indicators， totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators， with a total score of 40 points （30 points for some drugs） and a total score of 150 points （or 140 points）. The scoring results showed that the highest score was atorvastatin， followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia； the rapid evaluation quantitative scoring table constructed in this study is comprehensive， systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.

Humans ; Phosphorylation ; Serine/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Signal Transduction ; Neovascularization, Pathologic

Objective:To analyze the medication characteristics and prescription law of Ye Tianshi and Wu Jutong in the treatment of spleen and stomach diseases based on data mining method; To provide reference for clinical treatment of spleen and stomach diseases.Methods:Records related to spleen and stomach diseases in the Lin Zheng Zhi Nan Yi An and Wu Ju Tong Yi An were collected. SPSS Statistics 26.0, SPSS Modeler 18.0 and other software were used to conduct statistical analysis on the frequency, properties and efficacy of Chinese materia medica. The association analysis and clustering analysis were carried out on high-frequency drugs. Results:A total of 423 medical records, 231 kinds of Chinese materia medica (2 752 times) were included in the Lin Zheng Zhi Nan Yi An. A total of 83 medical records, 115 kinds of Chinese materia medica (753 times) were included in Wu Ju Tong Yi An. The Chinese materia medica used by Ye Tianshi and Wu Jutong to treat spleen and stomach diseases was mainly warm, mild and cold, with pungent, sweet and bitter as the main tastes; they mainly belonged to the spleen, lung and stomach meridians, and their main functions included clearing heat, diverting water and dampness, regulating qi, resolving phlegm, relieving cough, and tonifying deficiency. 6 second-order association rule combinations and 5 effective clusters were obtained for Ye Tianshi's treatment of spleen and stomach diseases, and 15 second-order association rule combinations and 6 effective clusters for Wu Jutong's treatment. Conclusions:Ye Tianshi and Wu Jutong's medication attributes in the treatment of spleen and stomach diseases are basically similar. They often use the method of bitter catharsis to regulate the qi movement of spleen and stomach, and the products of sweet and mild infiltration are used to eliminate dampness and heat. Compared with Ye Tianshi, Wu Jutong used few tonic, heat-clearing, phlegm-resolving, cough-relieving and asthma-relieving drugs, and more diuretics and qi-regulating drugs.

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
Anemia, Aplastic/genetics* ; Epigenesis, Genetic ; Fanconi Anemia/genetics* ; Germ Cells ; Hematologic Neoplasms/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Retrospective Studies

Objective:To investigate the molecular genetic and clinical characteristics of MEF2D-BCL9 fusion gene-positive acute B-cell lymphoblastic leukemia (B-ALL), and to provide the reference for the diagnosis and treatment of the disease.Methods:The medical record and experimental examination data of a 18-year-old female MEF2D-BCL9 fusion gene-positive B-ALL patient were retrospectively analyzed. The clinical manifestations and biological characteristics of MEF2D-BCL9 fusion gene-positive B-ALL were summarized.Results:This 18-year-old female patient was treated in a local hospital in December 2018 and was diagnosed as B-ALL. She achieved complete remission after chemotherapy and recurred at 6 months after the initial onset, and then she was admitted to Hebei Yanda Ludaopei Hospital in the 9 months after the initial onset.MEF2D-BCL9 fusion gene was detected through RNA-sequencing (RNA-seq) and verified by using polymerase chain reaction and Sanger sequencing. Bone marrow cell morphology was similar to mature B cells with vacuoles but without characteristic chromosome karyotype abnormalities. The patient achieved remission after VLD regimen chemotherapy, chimeric antigen receptor T-cell (CAR-T) therapy and bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). She has maintained complete remission for 2 years at the last follow-up in February 2022.Conclusions:MEF2D-BCL9 fusion gene-positive B-ALL is characterized with high risk, early relapse and poor prognosis. These patients may benefit from CAR-T and allo-HSCT. It further emphasizes the importance of taking MEF2D-BCL9 fusion gene into the detection or identification by using RNA-seq, particularly for those newly diagnosed B-ALL patients in children and adolescents with specific bone marrow morphology.