Semi-rational evolution of ω-transaminase from Aspergillus terreus for enhancing the thermostability / 生物工程学报

ω-transaminase (ω-TA) is a natural biocatalyst that has good application potential in the synthesis of chiral amines. However, the poor stability and low activity of ω-TA in the process of catalyzing unnatural substrates greatly hampers its application. To overcome these shortcomings, the thermostability of (R)-ω-TA (AtTA) from Aspergillus terreus was engineered by combining molecular dynamics simulation assisted computer-aided design with random and combinatorial mutation. An optimal mutant AtTA-E104D/A246V/R266Q (M3) with synchronously enhanced thermostability and activity was obtained. Compared with the wild- type (WT) enzyme, the half-life t1/2 (35 ℃) of M3 was prolonged by 4.8-time (from 17.8 min to 102.7 min), and the half deactivation temperature (T1050) was increased from 38.1 ℃ to 40.3 ℃. The catalytic efficiencies toward pyruvate and 1-(R)-phenylethylamine of M3 were 1.59- and 1.56-fold that of WT. Molecular dynamics simulation and molecular docking showed that the reinforced stability of α-helix caused by the increase of hydrogen bond and hydrophobic interaction in molecules was the main reason for the improvement of enzyme thermostability. The enhanced hydrogen bond of substrate with surrounding amino acid residues and the enlarged substrate binding pocket contributed to the increased catalytic efficiency of M3. Substrate spectrum analysis revealed that the catalytic performance of M3 on 11 aromatic ketones were higher than that of WT, which further showed the application potential of M3 in the synthesis of chiral amines.

Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Comparison of yield of microorganisms in cord blood between two automated blood culture systems / 中国输血杂志

【Objective】 To compare the difference in the detection rate of microorganisms in cord blood between BACTEC FX and BacT/ALERT 3D automated blood culture systems, and to compare the influence of incubation time and different types of culture sample on the detection rate of microorganisms in cord blood. 【Methods】 Cord blood samples prepared from April to August 2020 in Sichuan Cord Blood Bank(n=4 358) were selected, and 20 mL of plasma was used as culture samples for microbial detection. In addition, cord blood samples prepared in the same months of 2021(n=4 057) were selected, and 19 mL of plasma plus 1 mL of final product was used as culture samples for microbial detection. The total sample size was 8 415, of which 4 849 samples(2 458 in plasma group and 2 391 in plasma plus final product group) were assigned to the BACTEC FX system, and 3 566 samples(1 900 in the plasma group and 1 666 in the plasma plus final product group) to the BacT/ALERT 3D system. All samples were cultured for 7 days, and culture data were recorded on day 5 and day 7. Positive results were confirmed by Gram staining. 【Results】 The positive rate detected by the BACTEC FX system was higher than that of the BacT/ALERT 3D system(4.08% vs 2.69%), with statistically significant difference(P0.05) detected by the BacT/ALERT 3D system. With quality control strains, there were significant differences in TTP between these two systems for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Clostridium sporogenes, and Bacillus subtilis(P0.05). 【Conclusion】 This study suggests that the selection of BACTEC FX blood culture system with incubation time of not less than 7 days and plasma plus final product as culture samples may improve the detection rate of microorganisms in cord blood.

Effects of different feeding patterns on physical and nutritional status of infants aged 6‒12 months / 上海预防医学

ObjectiveTo analyze the effects of different feeding patterns on the physical and nutritional status of children aged 6‒12 months， so as to provide reference for promoting scientific feeding and health development of infants and young children. MethodsChildren born between December 2019 and February 2020 and who had completed three follow-up visits at 6‒， 9‒ （8‒10 months） and 12‒ （11‒14 months） months old in all of the 13 communities of Minhang， Shanghai were selected. The subjects’ basic information was investigated by questionnaires. The indicators including feeding pattern， physical development （body weight， body length， head circumference） and nutritional status （the detection rate of overweight， obesity， low body weight， growth retardation， emaciation and iron deficiency anemia） were followed up in the outpatient department， with iron deficiency anemia only monitored at the 6‒ and 12‒ months old. According to different feeding patterns， the groups of 6‒ months old were divided into three groups of exclusive breast feeding （EBF）， mixed feeding （MF） and artificial feeding （AF）， while 9‒ and 12‒ months old were divided into MF and AF groups. The differences of basic information and follow-up results among the groups were analyzed. ResultsA total of 470 children were included， including 130 （27.66%）， 288 （61.28%） and 52 （11.06%） respectively in EBF， MF and AF groups at the 6‒ months old，and 319 （67.87%） and 196 （41.70%） in MF group at the 9‒ and 12‒ months old. There was no significant difference in the other follow-up results among the groups. The detection rate of iron deficiency anemia in 6‒ months old EBF （13.08%） was higher than that in MF group （5.90%） and AF group （1.92%） （χ2=8.40， P=0.010）， while it was still higher in 12‒ months old MF group （9.69%） than in AF group （2.92%） （χ2=9.68， P=0.002）. ConclusionThere is no significant difference in body weight，body length， head circumference， and the detection rates of overweight， obesity， low body weight， growth retardation and emaciation among the groups of different feeding patterns in the children aged 6‒12 months. The detection rate of iron deficiency anemia in the EBF and MF groups is significantly higher than that in the AF groups of children aged 6‒ and 12‒ months old.

Preliminary study on excitation, detection and identification of parathyroid glands autofluorescence using fluorescence laparoscopic system / 中华内分泌外科杂志

Objective:To evaluate the excitation and identification of parathyroid autofluorescence in thyroid surgery by a fluorescence laparoscopic system.Methods:The clinical data of 6 patients with papillary thyroid carcinoma who underwent Laparoscopic thyroid surgery at the Second Affiliated Hospital of Guangxi Medical University from Mar. 2022 to Apr. 2022 were collected. The autofluorescence of the parathyroid glands was detected and identified by the OptoMedic fluorescence laparoscopic system during the operation. A rapid frozen sections pathological examination of possible parathyroid tissue with autofluorescence was performed to determine whether it was parathyroid tissue.Results:Parathyroid autofluorescence with different intensities was visualized intraoperatively in all 6 patients, and it was confirmed as parathyroid tissue by rapid frozen pathological section.Conclusions:The parathyroid gland has a unique autofluorescence feature. Using this feature to identify, locate and protect the parathyroid gland during surgery can help reduce the complications of parathyroid injury.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Metabonomic Analysis of Wenfei Huaxian Granules Against Idiopathic Pulmonary Fibrosis in Mice / 中国实验方剂学杂志

ObjectiveTo investigate the changes of differential metabolites in the serum of mice at different stages of bleomycin sulfate（BLM）-induced pulmonary fibrosis modeling and administration， and the mechanism of Wenfei Huaxian granules（WHG）against idiopathic pulmonary fibrosis. MethodMice were randomly divided into control group， control group of 14 days， model group， model group of 14 days， low-dose WHG group and high-dose WHG group. BLM（0.04 U per mouse）was injected into the trachea of mice in the model group， model group of 14 days， low-dose WHG group and high-dose WHG group， and sterile normal saline was injected into the trachea of mice in the control group and control group of 14 days. Mice of low-dose WHG group and high-dose WHG group were given different doses of WHG by gavage every day after injection of BLM， and mice of control group， control group of 14 days， model group and model group of 14 days were given sterile water by gavage every day. The peripheral blood of mice in the control group of 14 days and model group of 14 days were taken to prepare serum after injection of BLM for 14 days， and the peripheral blood and other materials of mice in the other groups were taken after continuous administration for 28 days. The bronchoalveolar lavage fluid（BALF）was collected for leucocyte differential count， the pathological examination and hydroxyproline（HYP）content determination of lung tissues of mice were performed， and the small molecule metabolites in serum samples of mice in each group were determined by ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS）. Principal component analysis（PCA）and orthogonal partial least squares-discriminant analysis（OPLS-DA）were conducted to screen differential metabolites and their biological functions were analyzed. ResultCompared with the control group， a large number of continuous fibrotic foci appeared in the lung tissue of mice in the model group， the alveolitis score， fibrosis degree score and HYP content increased significantly（P<0.01）， and the total number of leukocytes， macrophages and lymphocytes in BALF increased significantly（P<0.05）. A total of 33 differential metabolites were screened between the control group of 14 days and model group of 14 days， mainly lipid metabolites， which were mainly involved in oxidative damage and inflammatory process. A total of 34 differential metabolites， mainly amino acid metabolites， were screened between the control group and model group， mainly involving nucleic acid damage and inflammatory process. Compared with the model group， the HYP content， fibrosis score and alveolitis score in the lung tissue of mice from high-dose WHG group decreased significantly（P<0.05， P<0.01）， and the total number of lymphocytes in BALF decreased significantly（P<0.05）. Compared with the model group， 27， 40 differential metabolites were identified in the serum of mice from the low-dose WHG group and high-dose WHG group separately. There were totally 9 common differential metabolites between the model group and low-dose WHG group/high-dose WHG group， which mainly involved in the metabolic pathways of inflammation related lipids metabolism， arginine and tryptophan metabolism， and the change trends in low-dose WHG group and high-dose WHG group were significantly back-regulated compared with the model group. ConclusionWHG can alleviate BLM-induced pulmonary fibrosis， collagen deposition and inflammatory reaction in mice， and its anti-fibrotic effect may be related to the adjusting of inflammatory factors， nitric oxide and oxidative stress related metabolic pathways.

Analysis of rare genotypes of thalassemia in Laibin area of Guangxi / 公共卫生与预防医学

Objective To investigate the rare genotypes and mutation frequency of thalassemia in Laibin area of Guangxi , to intervene the birth of children with moderate or severe thalassemia, and to better guide the genetic diagnosis and prenatal diagnosis. Methods A total of 282 patients of hematological phenotypes inconsistent with genotypes in Laibin City (four counties, one city and one district) were tested for rare genotypes. Results A total of 50 cases were found to carry rare thalassemia gene mutations, including 23 cases of β-globin gene mutation containing 9 types of mutations, and 27 cases of α-globin gene mutation containing 7 types of mutations. There were 4 homotypic thalassemia couples with one party carrying rare thalassemia gene mutation. After prenatal diagnosis, one case was found to be a rare mutation carrier , two cases to be a double heterozygote, and one case to be a common mutation carrier. Conclusion The data of thalassemia genotype spectrum in Laibin , Guangxi. It is suggested that when the hematological phenotype is not consistent with the genotype , it should be detected by other molecular techniques to avoid the birth of children with moderate or severe thalassemia, which is also helpful for clinical diagnosis and treatment guidance, population screening and genetic counseling.

Comparison of the predictive value of anthropometric indicators for the risk of benign prostatic hyperplasia in southern China / 亚洲男科学杂志(英文版)

This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759-0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753-0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723-0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609-0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587-0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540-0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.

Effects of propiconazole on physiological and biochemical properties of Panax notoginseng and dietary risk assessment / 中国中药杂志

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.

A real world study of anti-IgE monoclonal antibody in the treatment of allergic united airway disease / 中华预防医学杂志

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ2=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Effects of C10orf10 on growth and prognosis of glioma under hypoxia / 中南大学学报(医学版)

OBJECTIVES@#Glioma is the most common malignant tumor in the central nervous system, and the hypoxic microenvironment is prevalent in solid tumors. This study aims to investigate the up-regulation of genes under the condition of hypoxia and their roles in glioma growth, as well as their impact on glioma prognosis.@*METHODS@#The hypoxia-related dataset with glioma was screened in the Gene Expression Omnibus database (GEO), and the differentially expressed genes were analyzed between hypoxia and normoxia through bioinformatics, and chromosome 10 open reading frame 10 (C10orf10) was verified and screened in hypoxia-treated cells through real-time PCR and Western blotting. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets were downloaded to analyze the mRNA expression of C10orf10 in different grades of glioma and its impact on prognosis. The glioma specimens and follow-up data of 68 gliomas who underwent surgical treatment in Xiangya Hospital of Central South University from March 2017 to January 2021 were collected, and real-time PCR was used to detect the mRNA expression of C10orf10 in different grades of glioma, and the Kaplan-Meier method was used to analyze the relationship between the expression C10orf10 and prognosis. The glioma cells, which could interfere the expression of C10orf10, were constructed, and the effect of C10orf10 on the proliferation of glioma cells was evaluated by cell counting kit-8 (CCK-8) and colony formation assays.@*RESULTS@#Compared with the condition of normoxia, the expression levels of C10orf10 mRNA and protein were significantly up-regulated in glioma cells under hypoxia (P<0.001), and the mRNA expression level of C10orf10 in glioma tissues was up-regulated with the increase of WHO grade in glioma (P<0.001). Based on Kaplan-Meier survival analysis, the higher the mRNA expression level of C10orf10 was, the shorter the survival time of the patient was (P<0.05). And the expression of C10orf10 mRNA was higher in recurrent gliomas than that in primary gliomas in the CGGA database (P<0.001). Knockdown of C10orf10 could significantly inhibit the growth of glioma cells both under hypoxia and normoxia (both P<0.001).@*CONCLUSIONS@#The expression level of C10orf10 can promote the proliferation and prognosis of glioma, which is expected to become a prognostic marker and therapeutic target for glioma.

Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Clinical application of Flow-through bridge anterolateral thigh flap in repair of complex calf soft tissue defects / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of Flow-through bridge anterolateral thigh flap transplantation in the treatment of complex calf soft tissue defects.@*METHODS@#The clinical data of the patients with complicated calf soft tissue defects, who were treated with Flow-through bridge anterolateral thigh flap (study group, 23 cases) or bridge anterolateral thigh flap (control group, 23 cases) between January 2008 and January 2022, were retrospectively analyzed. All complex calf soft tissue defects in the two groups were caused by trauma or osteomyelitis, and there was only one major blood vessel in the calf or no blood vessel anastomosed with the grafted skin flap. There was no significant difference between the two groups in general data such as gender, age, etiology, size of leg soft tissue defect, and time from injury to operation ( P>0.05). The lower extremity functional scale (LEFS) was used to evaluate the sufferred lower extremity function of the both groups after operation, and the peripheral blood circulation score of the healthy side was evaluated according to the Chinese Medical Association Hand Surgery Society's functional evaluation standard for replantation of amputated limbs. Weber's quantitative method was used to detect static 2-point discrimination (S2PD) to evaluate peripheral sensation of the healthy side, and the popliteal artery flow velocity, toenail capillary filling time, foot temperature, toe blood oxygen saturation of the healthy side, and the incidence of complications were compared between the two groups.@*RESULTS@#No vascular or nerve injury occurred during operation. All flaps survived, and 1 case of partial flap necrosis occurred in both groups, which healed after free skin grafting. All patients were followed up 6 months to 8 years, with a median time of 26 months. The function of the sufferred limb of the two groups recovered satisfactorily, the blood supply of the flap was good, the texture was soft, and the appearance was fair. The incision in the donor site healed well with a linear scar, and the color of the skin graft area was similar. Only a rectangular scar could be seen in the skin donor area where have a satisfactory appearance. The blood supply of the distal limb of the healthy limb was good, and there was no obvious abnormality in color and skin temperature, and the blood supply of the limb was normal during activity. The popliteal artery flow velocity in the study group was significantly faster than that in the control group at 1 month after the pedicle was cut, and the foot temperature, toe blood oxygen saturation, S2PD, toenail capillary filling time, and peripheral blood circulation score were significantly better than those in the control group ( P<0.05). There were 8 cases of cold feet and 2 cases of numbness on the healthy side in the control group, while only 3 cases of cold feet occurred in the study group. The incidence of complications in the study group (13.04%) was significantly lower than that in the control group (43.47%) ( χ 2=3.860, P=0.049). There was no significant difference in LEFS score between the two groups at 6 months after operation ( P>0.05).@*CONCLUSION@#Flow-through bridge anterolateral thigh flap can reduce postoperative complications of healthy feet and reduce the impact of surgery on blood supply and sensation of healthy feet. It is an effective method for repairing complex calf soft tissue defects.

Investigation on occupational hazard factors in teaching and research places of a university / 中华劳动卫生职业病杂志

Objective: To investigate and monitor the occupational hazards in the Teaching and Research Laboratory (hereinafter referred to as the place) of a university, so as to provide basis for the occupational health work in the university. Methods: November 2014, 46 places in a university were selected by stratified random sampling, and the occupational health risk factors were investigated. Results: Indoor temperature, humidity, sulfur dioxide, nitrogen dioxide, carbon monoxide and carbon dioxide were detected in 21 sites, xylene and hydrofluoric acid were detected in 6 sites, and colony count was detected in 18 sites, the power frequency electric field intensity was measured in 23 places, and the x-ray radiation dose was measured in 4 places. Noise was measured at 21 sites, with 7 sites exceeding the standards accounting for 33.3% (7/21) ; 21 sites were detected for illumination and 10 sites for nonconformity accounting for 47.6% (10/21) ; 10 sites for Microwave Radiation and 3 sites exceeding the standards accounting for 30% (3/10) ; and 25 sites were detected for outdoor air volume and air velocity, the percentage of unqualified was 72% (18/25) in 18 sites, among which the wind velocity was statistically significant in teaching, research and experimental sites (P=0.010) . Conclusion: The occupational hazards in the teaching and research places of a university should be paid attention to, and the engineering protection and personal protection should be strengthened in the experiment.

Effect of Carvacrol on the Biological Behavior of Leukemia Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of carvacrol on the biological behavior of leukemia cells and its regulation to circ-0008717/miR-217 molecular axis.@*METHODS@#Human acute lymphoblastic leukemia cells Molt-4 were cultured in vitro, and different concentrations of carvacrol were added to the cells. si-NC and si-circ-0008717 were transfected into Molt-4 cells (si-NC group, si-circ-0008717 group). pcDNA, pcDNA-circ-0008717, anti-miR-NC, anti-miR-217 were transfected into Molt-4 cells and then added to carvacrol-treated cells (carvacrol+pcDNA group, carvacrol+pcDNA-circ-0008717 group, carvacrol+anti-miR-NC group, carvacrol+anti-miR-217 group). MTT, plate clone formation experiment, and flow cytometry were used to detect the viability of the cell, colony formation number, and apoptosis rate of cells, respectively. The RT-qPCR method was used to detect the expression levels of circ-0008717 and miR-217. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circ-0008717 and miR-217.@*RESULTS@#After carvacrol treatment, the cell viability decreased significantly (r=-0.9405), expression level of circ-0008717 decreased (r=-0.9117), colonies formed number decreased (r=-0.9256), while the cell apoptosis rate increased (r= 0.8464), and the expression level of miR-217 increased (r=0.9468). Compared with the si-NC group, the expression level of miR-217 in si-circ-0008717 group increased (P＜0.001), the cell apoptosis rate increased (P＜0.001), while cell viability decreased (P＜0001), the number of colonies formed decreased (P＜0.001). Compared with the carvacrol+pcDNA group, the cell viability of the carvacrol+pcDNA-circ-0008717 group increased (P＜0.001), the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0.001). circ-0008717 could target miR-217. The cell viability of the carvacrol+anti-miR-217 group increased (P＜0.001), and the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0001) as compared with the carvacrol+anti-miR-NC group.@*CONCLUSION@#Carvacrol can promote the expression of miR-217 by down-regulating the expression of circ-0008717, thereby reducing the proliferation and cloning ability of leukemia cells and promoting cell apoptosis.

Toxicity mechanism of Rhododendri Mollis Flos: based on serum metabolomics and network toxicology / 中国中药杂志

This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor β(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.