Objective:To compare the short-term effect and adverse reaction of venetoclax(VEN)combined with azacitidine(AZA)versus"7+3"regimen in newly diagnosed elder patients with acute myeloid leukemia(AML).Methods:From January 2021 to January 2022,the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed,including VEN+AZA group(41 cases)and"7+3"group(38 cases).The propensity score matching(PSM)method was used to balance confounding factors,then response,overall survival(OS),progression-free survival(PFS)and adverse reactions between the two groups were compared.Results:The ORR of VEN+AZA group and"7+3"group was 68％and 84％,respectively,and the CRc was 64％and 72％,respectively,the differents were not statistically significant(P＞0.05).In the VEN+AZA group,there were 5 non-remission(NR)patients,4 with chromosome 7 abnormality(7q-/-7),and 1 with ETV6 gene mutation.Median followed-up time between the two groups was 8 months and 12 months,respectively,and the 6-months OS was 84％vs 92％(P=0.389),while 6-months PFS was 84％vs 92％(P=0.258).The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳmyelosuppression,and the incidence rate was not statistically different(P＞0.05).The median time of neutrophil recovery in two groups was 27(11-70)d,25(14-61)d(P=0.161),and platelet recovery was 27(11-75)d,25(16-50)d(P=0.270),respectively.The infection rate of VEN+AZA group was lower than that of"7+3"group(56％vs 88％,P=0.012).The rate of lung infections of two groups was 36％and 64％,respectively,the difference was statistically significant(P=0.048).Conclusion:The short-term effect of VEN+AZA group and"7+3"regimens in eldrly AML patients are similar,but the VEN+AZA regimen had a lower incidence of infection.The presence of chromosome 7 abnormality(7q-/-7)may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

Objective To analyze the setup errors during proton and heavy ion therapy for head and head neck tumor patients fixed by thermoplastic film combined with styrofoam.Methods Totally 20 patients undergoing proton and heavy ion therapy at some hospital from January to December 2018 were selected retrospectively,of whom 10 ones had head tumors with clinical targets located in the head and the other 10 cases had head and neck tumors with clinical targets distributed in the head and neck.All the 20 patients were fixed with thermoplastic film combined with styrofoam.The head and neck images of the patients acquired after image guidance were aligned with the CT localization-based digitally reconstructed radiograph images,and the setup errors at six-dimensional directions(left-right translation,head-foot translation,forward-backward translation,isocentric rotation,pitch rotation and transverse-roll rotation)were recorded in the first five and the last five times of radiotherapy treatment.The data were processed by using the SPSS 23.0 statistical software and EXCEL.Results There were no significant differences between the head tumor patients in the setup errors at the six directions during the first and last five times of radiotherapy(P＞0.05).The head and neck tumor patients did not have obvious differences in the setup errors at the the directions of left-right translation,forward-backward translation,isocentric rotation and transverse-roll rotation(P＞0.05),while did at the directions of head-foot translation and pitch rotation(P＜0.05).The head and head neck tumor patients with the fixation by thermoplastic film combined with styrofoam had their setup errors at the six directions meet clinical requirements after calibration by the six-dimensional treatment table.Conclusion The fixation mode by thermoplastic film and styrofoam behaves well to enhance the setup repeatability for head tumor patients at the six-dimensional directions,while not so well for head neck tumor patients at the directions of head-foot translation and pitch rotation.Proper measures have to be taken to decrease the setup errors during proton and heavy ion therapy for head and head neck tumor patients.[Chinese Medical Equipment Journal,2024,45(7):56-61]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the effects of medullary differentiation-2(MD-2)in obesity-induced myocardial injury by regulating adenosine 5'-monophosphate-activated protein kinase(AMPK)activity.Methods The obese mice model was established by feeding high-fat feed.The wild-type and MD-2 gene knockout mice were randomly divided into wild-type(WT)-control group(fed normally),WT-model group(fed with high-fat diet),knockout(KO)-control group(fed normally)and KO-model group(fed with high-fat diet)with 8 mice in each group.At week 16,creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)were measured by reagent kits;the left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were measured with ultrasonic apparatus;the pathological changes in myocardial tissue were observed by hematoxylin and eosin(HE)staining and Masson staining;the protein expression of phosphorylation AMPK(p-AMPK)was measured by Western blot.Results HE staining and Masson staining results revealed significant necrosis and fibrosis of the myocardial tissue in WT-model group,while the degrees of necrosis and fibrosis in KO-model group were significantly reduced.The LVEF values of the WT-control group,WT-model group,KO-control group and KO-model group were(83.98±7.58)％,(52.03±4.91)％,(76.42±3.89)％and(73.71±4.22)％,respectively;the LVFS values of each group were(53.61±8.51)％,(24.56±3.76)％,(48.14±5.00)％and(44.07±3.74)％,respectively;the CK-MB values of each group were(49.83±15.49),(83.75±11.90),(54.03±18.66)and(66.85±12.98)U·L-1,respectively;the LDH values of each group were(12.24±3.20),(27.90±6.10),(13.55±3.55)and(15.53±2.58)U·L-1,respectively;the relative expression levels of p-AMPK in each group were 221.31±88.76,46.29±10.07,148.66±32.02 and 161.49±78.11.Compared with WT-control group,the above indicators in WT-model group,compared with WT-model group,the above indicators in KO-model group,the differences were statistically significant(all P＜0.05).Conclusion MD-2 mediates high-fat feed induced myocardial injury in obese mice by inhibiting AMPK activity.

Objective To analyze the registration status of domestic drug clinical trials for short stature children and the marketing status of growth hormone drugs in China during 2013-2023.Methods The website of National Medical Products Administration was searched to abtain the date and statistical analysis was conducted.Results A total of 31 drug clinical trials involving short stature children were registered in the platform,and the trial stages were mainly on phase Ⅱ and Ⅲ,with a total of 21(67.74％,21/31).The group leader was relatively focused on specialized hospital,which was closely related to the academic level,clinical trial experience and professional authority of the main investigators.Based on the duration of treatment for short stature,83.87％(26/31)of registered projects had clinical trials lasting for more than 52 weeks.The research trend was long-acting growth hormone(64.52％,20/31).Sponsors and researchers had high insurance awareness and enthusiasm for clinical trials,especially the protection of subjects.At present,growth hormone products from seven domestic and foreign enterprises had been approved for marketing in China.The growth hormone products were the most abundant category of biotechnology drugs that had been marketed so far.Conclusion It is expected that there will be more convenient ways of administration and better release characteristics of long-acting growth hormone products in the future,which will reduce treatment costs and enable short stature children to obtain an ideal healthy height.

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ² test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ²=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ²=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.
Infant ; Female ; Male ; Humans ; Child ; Retrospective Studies ; China/epidemiology* ; Hospitalization ; Community-Acquired Infections/therapy* ; Hospitals, Pediatric ; Pneumonia/therapy*

OBJECTIVE: To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway. METHODS: Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP. RESULTS: Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001). CONCLUSION Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.
Humans ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Drug Resistance ; Luciferases ; Lymphoma, Large B-Cell, Diffuse/pathology* ; MicroRNAs/metabolism* ; Programmed Cell Death 1 Receptor ; RNA, Messenger ; Signal Transduction

The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.

Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4⁺T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.
Female ; Humans ; Pregnancy ; HIV Infections/drug therapy* ; Incidence ; China/epidemiology* ; Infectious Disease Transmission, Vertical/prevention & control* ; Postpartum Period ; Drug Resistance, Viral/genetics* ; Antiviral Agents/therapeutic use*