OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules （DXQ） inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ， respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA （si-NC）， and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 （GPX4） （si-GPX4） were divided into the si-GPX4 group， the CsA group （treated with 1 μmol/L cyclosporine A）， and the DXQ- L， DXQ-M and DXQ-H groups （treated with 5%， 7% and 10% DXQ， respectively）. These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin （10 μmol/L）. The intracellular levels of total iron ions， glutathione （GSH）， reactive oxygen species （ROS）， and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally， mitochondrial membrane potential， the opening degree of mitochondrial permeability transition pore （MPTP）， and mRNA expressions of GPX4 and cyclophilin D （CypD） were detected. Furthermore， the expressions of ferroptosis-related proteins[GPX4， transferrin receptor 1 （TfR1） and ferritin heavy chain 1 （FTH1）]， as well as MPTP-related proteins [adenine nucleotide translocator （ANT）， cytochrome C （CytC）， mitochondrial calcium uniporter （MCU） and CypD] were assessed. RESULTS Compared with si-NC group， the levels of total iron ions and ROS， the expression level of mitochondrial superoxide， the opening degree of MPTP， protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly （P＜0.01）； however， GSH content， mitochondrial membrane potential， protein and mRNA expressions of GPX4， and protein expressions of FTH1， ANT and CytC were decreased or down-regulated significantly （P＜0.01）. Compared with the si-GPX4 group， the cells in the DXQ-M， DXQ-H groups showed a general improvement in the above quantitative indicators （P＜0.01 or P＜0.05）. CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway， regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis， inhibit excessive opening of MPTP to improve mitochondrial function， and ultimately suppress microglial ferroptosis.

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm²) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca²⁺ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.
Transcranial Direct Current Stimulation/methods* ; Motor Cortex/physiology* ; Neurons ; Transcranial Magnetic Stimulation

Objective:To analyze the healing effect of paeoniflorin on the wound of rats and regulation of NGF/Akt/GSK3β pathway on rats with diabetic foot.Methods:60 rats were randomly divided into normal control group, model group, low, medium and high dose paeoniflorin groups, 12 rats in each group. Diabetic foot model was established by intraperitoneal injection of streptozotocin (STZ) and electrothermal scald. Paeoniflorin groups were injected intraperitoneally with 20 mg/kg, 40 mg/kg and 80 mg/kg paeoniflorin, once a day for 21 days. The wound healing rate of the rats was measured. The fasting blood glucose was measured by blood glucose meter, HbAlc, TC, LDL-C and TG were measured by automatic biochemical analyzer. Serum CRP, IL-6, IL-1β and TNF-α were measured by ELISA. The histopathological changes of the wound were examined by HE staining, the levels of NGF, Akt and GSK3 β mRNA in skin tissue were measured by real-time quantitative polymerase chain reaction (RTq-PCR), the protein and phosphorylation levels of NGF, Akt and GSK3 β were determined by Western blot.Results:Compared with the model group, the healing rate the rats' wounded surface in the low, medium and high dose groups of paeoniflorin was increased ( P<0.05). The levels of fasting blood glucose, HbAlc, TC, LDL-C, TG levels and serum CRP, IL-6, IL-1β, TNF-α was decreased ( P<0.05). The expression of rat skin tissue NGF mRNA (0.83±0.12, 3.17±0.11, 4.54±0.25 vs. 0.31±0.06), Akt mRNA (1.71±0.14, 2.96±0.27, 4.10±0.34 vs. 0.97±0.20) increased ( P<0.05), expression of GSK3β mRNA (4.28±0.35, 2.82±0.14, 1.22±0.33 vs. 7.62±0.43) decreased ( P<0.05), expression of NGF (0.46±0.02, 0.70±0.04, 0.87±0.04 vs. 0.30±0.06), Akt (0.51±0.09, 0.63±0.03, 0.79±0.06 vs.0.41±0.05),p-NGF/NGF (0.47±0.06, 0.61±0.04, 0.83±0.07 vs. 0.25±0.03), p-Akt/Akt(0.54±0.08, 0.83±0.11,0.96±0.07 vs. 0.13±0.05) was increased( P<0.05), the expression of GSK3β (0.67±0.05, 0.54±0.04,0.45±0.03 vs. 0.86±0.05), and the ratio of p-GSK3β/GSK3β (0.78±0.09, 0.64±0.07, 0.42±0.07 vs. 0.97±0.05) was decreased ( P<0.05), and the changes of each index were dependent on the dose of paeoniflorin. Conclusion:Paeoniflorin can regulate the level of blood glucose and blood lipid, inhibit the level of serum inflammatory factors and promote the healing of the wound in diabetic foot rats, and its mechanism may be related to the regulation of NGF/Akt/GSK3β pathway.

Chinese national standard GBZ 97-2017 Judgment Standards for Occupational Radiogenic Neoplasms was published and will replace the current version Judgment Criteria for Cause of Radiogenic Neoplasms from November 1 in 2017. Background on which this new national standard was based, its main modifications and the necessity, choice for judgment value, choice for types of neoplasms were explained. Uncertainty of methodology not-modified in the GBZ 97-2017 was discussed. Possible misunderstood issues were explained. Finally, advices on correct application of the GBZ 97-2017 were proposed.

Objective To explore the role of long-term enriched environment in promoting the recovery of motor and social function in mice after ischemic brain injury. Methods Sixteen adult male ICR mice underwent permanent middle cerebral artery occlusion (MCAO). The first day after operation, they were divided into enriched environment group (n=8) and standard condition group (n=8). The mice were tested with modified Neurological Severity Score (mNSS), rotarod test and smart cage 7, 14, 21, 28 days after modeling. Results The score of mNSS and the result of rotarod test improved more in the enriched environment group than in the standard condition group 28 days after MCAO (t>2.927, P<0.05). The occupancy time in the middle of smart cage was longer in the enriched environment group than in the stan-dard condition group 7 to 28 days after MCAO (t>2.480, P<0.05) in the general move test. There was a trend of being more interested in strange mice in the enriched environment group than in the standard condition group, but the difference was not statistically significant (P>0.05) in the social behavior test; however, the occupancy time in the middle of smart cage was longer in the enriched environment group than in the standard condition group 14 to 28 days after MCAO (t>3.472, P<0.01), and the velocity of moving was higher 14 days after MCAO (P<0.05). Conclusion Enriched environment could promote the recovery of motor function, somehow of social function, in mice af-ter ischemic brain injury.

Objective To observe the effect of smoking cessation intervention combined with salmeterol and fluticasone pro‐pionate powder for inhalation on chronic obstructive pulmonary disease (COPD) patients with clinical symptoms and pulmonary function .Methods Totally 78 male long‐term smoking cases were randomly divided into control group(n= 40)and observation group(n=38) .The control group was treated with the ophylline sustained‐release tablets ,shah mette lo fluticasone;observation group received smoking cessation intervention .The smoking rate ,symptoms ,acute exacerbation ,life score and lung function (FEV1 ,FEV1/FVC) ,adverse reactions of two groups were observed .Results Two groups of symptoms were all improved ,but the observation group was better (P<0 .05) .FEV1 ,FEV1/FVC ,acute exacerbation ,scores were improved ,but the observation group was better(all P<0 .05);quit rates in the observation group was better than that of the control group(P<0 .05);and did not found adverse reactions .Conclusion The effect of smoking cessation intervention combined with salmeterol and fluticasone propionate powder for inhalation efficacy in the treatment of COPD is distinct ,can improve the pulmonary function and symptoms .

Objective To estimate the excess relative risk coefficients of stomach cancer for Chinese population attributable to ionizing radiation.Methods The excess relative risk and excess absolute risk coefficients of stomach cancer were estimated based on Life Span Study by using risk models developed by BEIR Ⅶ committee (Biological Effect of Ionizing Radiation).Guided by transportation methods from Life Span Study to Americans,we determined that transportation method for Chinese population includes both multiplicative and additive models with a weight of 0.7 and 0.3 respectively,on an arithmetic scale.Besides,curve fitting was used to obtain sex-age-specific stomach cancer baseline incidence based on Chinese cancer annual report.Then,Chinese excess relative risk coefficients of stomach cancer were obtained by substituting excess relative risk,excess absolute risk of Life Span Study and Chinese baseline incidence rate into risk transportation model.Results Excess relative risk coefficients of stomach cancer for Chinese population are 0.26/Sv for male and 0.64/Sv for female,whose exposure age is 30 years old and cancer age is 60 years old.Coefficients increase with decreased exposure age and cancer age.Conclusions Excess relative risk coefficients of stomach cancer for Chinese population are by larger higher than that of Life Span Study,and their sex-age tendency are similar.

Objective To estimate the averaged excess relative risk(ERR) in Chinese population based on the radiogenic cancer risk of leukemia in Japanese atomic bomb survivor cohort,and to discuss proper method suitable for risk transfer between populations.Methods Based on BEIR Ⅶ radiogenic cancer model and population transfer model,and the 2009 Chinese leukemia baseline rates given in 2012 Chinese Cancer Registry Annual Report,comparison was made of population incidences in seveal countries to adjust the weighting factors.Results The ERR of three subtypes of leukemia as a whole was obtained,and the weighting factors for risk transfer model was assumed.The additive factor for male was 0.2,and the multiplicative factor was 0.8,while the additive factor for female was 0.15,and the multiplicative factor was 0.85.Conclusions For the risk transfer between populations,weighting factor was adjusted as a whole to obtain the ERR value for estimating the risk to Chinese population.The risk transfer method suitable for Chinese population was obtained by using the incidence rate available for Chinese population to directly transfer radiation-induced leukemia risk to Chinese from Japanese.