Lipid peroxidation changes induced by dibutyl phthalate in allergic asthma mice / 环境与职业医学

Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.

Associations of mobile phone use with male semen quality and sex hormones / 环境与职业医学

Background Experimental studies have shown that radiofrequency electromagnetic waves emitted by mobile phones can cause adverse effects on male reproductive health, including decreased semen quality and altered sex hormones. However, the results of epidemiological studies on the relationship between mobile phone use and male semen quality are inconsistent. Furthermore, there are few epidemiological studies on the association of mobile phone use with sex hormones. Objective To explore the associations of mobile phone use with male semen quality and sex hormones. Methods A total of 2045 men visited the reproductive medicine center of a hospital in Wuhan and ordered infertility examination were recruited from December 2018 to January 2020. Information on mobile phone use was obtained using a questionnaire. Among them, 1232 and 1694 men were eligible for semen quality analyses and sex hormone analyses, respectively. Multiple linear and logistic regression models were used to analyze the associations of mobile phone use with male semen quality and sex hormones. Results After adjusting for potential confounders, there was no statistically significant associations of mobile phone use with sperm progressive motility, sperm total motility, sperm concentration, sperm count, or serum luteinizing hormone (P>0.05). However, serum total testosterone showed a declined tendency with increasing daily duration of mobile phone use (Ptrend=0.08). Compared with men with daily mobile phone use of 0-2 h, men with daily mobile phone use of 2.1-5, 5.1-8, and >8 h showed decreased serum total testosterone concentrations by 6.29% (95%CI: 0.40%-11.84%), 6.01% (95%CI: 0.60%-12.19%), and 7.87% (95%CI: 0.40%-14.79%), respectively. Conclusion Mobile phone use is not associated with male semen quality and serum luteinizing hormone, but increasing daily duration of mobile phone use is potentially associated with a tendency to lower male serum total testosterone.

Research progress of Guizhi Shaoyao Zhimu Decoction in the treatment of rheumatoid arthritis / 国际中医中药杂志

Guizhi Shaoyao Zhimu Decoction combined with drugs taken internally or external therapy show the benefits for rheumatoid arthritis patients. It can control the clinical symptoms such as swelling and pain of the joints, reduce inflammatory indicators, and has less adverse reactions. Modern pharmacological researches show that it can regulate a variety of inflammatory signaling pathways to achieve anti-inflammatory and analgesic effects, induce apoptosis of synovial cells, resist bone damage, and regulate immunity with multiple treatment targets to rheumatoid arthritis.

Effect of respiratory mechanics-guided sedation strategy on diaphragm function in mechanical ventilated patients with chronic obstructive pulmonary disease / 中华危重病急救医学

Objective:To investigate the effects of respiratory mechanics-guided sedation strategy on diaphragm function in chronic obstructive pulmonary disease (COPD) patients treated with mechanical ventilation (MV).Methods:A prospective study was conducted. Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) received invasive MV who were admitted to the Affiliated Huxi Hospital of Jining Medical University from May 2020 to May 2021 were enrolled. The patients were divided into observational group and control group by random number table method. All patients were intubated for MV, and received bronchodilators, glucocorticoid, anti-infectives, expectorant, nutritional support, analgesia and sedation. The sedatives were dexmedetomidine combined with propofol, and the analgesics were sufentanil in both groups. Respiratory mechanics monitoring was performed every 6 hours in the observational group, and the depth of sedation was adjusted according to the parameters of respiratory mechanics: when airway resistance (Raw) > 20 cmH 2O·L -1·s -1, deep sedation was given to maintain Richmond agitation-sedation scale (RASS) ≤ -3; when the Raw was 10-20 cmH 2O·L -1·s -1, the initial depth of sedation maintained to reach the RASS score of -2-0; when Raw < 10 cmH 2O·L -1·s -1, withdrawn the sedation, or given light sedation, and maintained the RASS score of -2-0. While the control group received light sedation. The patients' diaphragmatic excursions (DE) was measured by bedside ultrasound, tidal volume (VT) and respiratory rate (RR) were recorded, and the diaphragmatic rapid shallow breathing index (D-RSBI, D-RSBI = RR/DE) and diaphragmatic excursion efficiency (DEE, DEE = VT/DE) were calculated. The differences in DE, D-RSBI, and DEE before and 3 days and 5 days of treatment between the two groups were compared. The difference in the RASS score within 3 days of sedation between the two groups was compared. The differences in the duration of MV and 28-day mortality between the two groups were compared. Results:A total of 96 patients were selected. Six patients were excluded due to delirium or the duration of MV shorter than 3 days. Finally, 90 patients were enrolled, with 46 in the observational group, and 44 in the control group. There were no statistically significant differences in DE, D-RSBI or DEE before treatment between the two groups. After treatment, D-RSBI in both groups was gradually decreased, and DEE was gradually increased with time. The D-RSBI at 3 days and 5 days of treatment in the observational group were significantly lower than those in the control group (times·min -1·mm -1: 1.73±0.48 vs. 1.96±0.35 at 3 days, 1.45±0.64 vs. 1.72±0.40 at 5 days, both P < 0.05), and DEE were significantly higher than those in the control group (mL/mm: 19.7±4.3 vs. 17.1±3.9 at 3 days, 25.8±5.6 vs. 22.9±5.4 at 5 days, both P < 0.05). There was no significant difference in DE at all time points between the two groups. The RASS scores within 2 hours of sedation in the observational group were significantly lower than those in the control group (1 day: -3.78±0.92 vs. -2.34±0.68, 2 days: -2.87±1.04 vs. -2.43±0.79, both P < 0.05), while no statistical difference at 3 days was found between the two groups. The duration of MV in the observational group was significantly shorter than that in the control group (days: 5.78±2.01 vs. 6.84±2.27, P < 0.05). One patient died in each of the control group and the observational group, and there was no significant difference in the 28-day mortality between the two groups (2.3% vs. 2.2%, P > 0.05). Conclusion:For AECOPD patients undergoing MV, respiratory mechanics-guided sedation strategy can reduce D-RSBI, increase DEE, shorten the duration of MV, and have a certain protective effect on the diaphragm.

Comparison of the application effects of SARIMA, GAM and LSTM in prediction of hemorrhagic fever with renal syndrome / 中华地方病学杂志

Objective:To analyze the effects of seasonal autoregressive integrated moving average model (SARIMA), generalized additive model (GAM), and long-short term memory model (LSTM) in fitting and predicting the incidence of hemorrhagic fever with renal syndrome (HFRS), so as to provide references for optimizing the HFRS prediction model.Methods:The monthly incidence data of HFRS from 2004 to 2017 of the whole country and the top 9 provinces with the highest incidence of HFRS (Heilongjiang, Shaanxi, Jilin, Liaoning, Shandong, Hebei, Jiangxi, Zhejiang and Hunan) were collected in the Public Health Science Data Center (https://www.phsciencedata.cn/), of which the data from 2004 to 2016 were used as training data, and the data from January to December 2017 were used as test data. The SARIMA, GAM, and LSTM of HFRS incidence in the whole country and 9 provinces were fitted with the training data; the fitted model was used to predict the incidence of HFRS from January to December 2017, and compared with the test data. The mean absolute percentage error ( MAPE) was used to evaluate the model fitting and prediction accuracy. When MAPE < 20%, the model fitting or prediction effect was good, 20%-50% was acceptable, and > 50% was poor. Results:From the perspective of overall fitting and prediction effect, the optimal model for the whole country and Heilongjiang, Shaanxi, Jilin, Liaoning and Jiangxi was SARIMA ( MAPE was 19.68%, 20.48%, 44.25%, 19.59%, 23.82% and 35.29%, respectively), among which the fitting and prediction effects of the whole country and Jilin were good, and the rest were acceptable. The optimal model for Shandong and Zhejiang was GAM ( MAPE was 18.29% and 21.25%, respectively), the fitting and prediction effect of Shandong was good, and Zhejiang was acceptable. The optimal model for Hebei and Hunan was LSTM ( MAPE was 26.52% and 22.69%, respectively), and the fitting and prediction effects were acceptable. From the perspective of fitting effect, GAM had the highest fitting accuracy in the whole country data, with MAPE = 10.44%. From the perspective of prediction effect, LSTM had the highest prediction accuracy in the whole country data, with MAPE = 12.23%. Conclusions:SARIMA, GAM, and LSTM can all be used as the optimal models for fitting the incidence of HFRS, but the optimal models fitted in different regions show great differences. In the future, in the establishment of HFRS prediction models, as many alternative models as possible should be included for screening to ensure higher fitting and prediction accuracy.

Highly penetrable nanoparticles co-loading doxorubicin and IDO1 siRNA enhance tumor immunotherapy / 药学学报

There are two serious obstacles to tumor immunotherapy. Firstly, the immune response of the tumor is seriously reduced due to immunosuppressive tumor microenvironment (ITM) and low immunogenicity of tumor. The second obstacle is the dense and complex heterogeneous structures, which seriously prevent the nanoparticles (NPs) from penetrating deeper into tumor tissue. Immunogenic cell death (ICD) induced by doxorubicin (DOX) is an effective method to enhance tumor immune activity. However, interferon-γ (IFN-γ) secreted by cytotoxic T lymphocytes (CTL) after ICD induction would increase the expression of indoleamine 2,3-dioxygenase 1 (IDO1) and enhance ITM. IDO1 siRNA would reduce the expression of IDO1 protein, regulate the tumor immunosuppressive microenvironment and regulate ITM, so as to enhance the ICD effect of DOX. In this paper, a novel charge conversional, particle size reduction and highly penetrable NPs based on a pH sensitive copolymer poly(ethylene glycol)-poly-L-lysine-2,3-dimethylmaleic anhydride (mPEG-PLL-DMA, PLD) and polyamidoamine (PAMAM) dendrimers to achieve deep delivery of tumor tissue. DOX and IDO1 siRNA were encapsulated to achieve efficient tumor immunotherapy. Preparation and cell level experiments showed that PLD material had significant pH sensitivity. Results of 3D tumor penetrable experiment in vitro showed that adding the pH sensitive material PLD significantly improved the permeability of the preparation. In addition, 4T1 tumor model was established for BALB/c mice and all animal experiments were displayed in according with the requirements of the Animal Experiment Ethics Committee of Shenyang Pharmaceutical University. The results of in vivo efficacy experiments and tissue experiments evaluated that IDO1 siRNA significantly improved the ICD effect owing to DOX, so as to significantly inhibit tumor growth.

Mechanism of cleft palate in C57BL/6N mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin / 中华口腔医学杂志

Objective: To explore the molecular mechanism of cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Methods: The pregnant mice were randomly divided into TCDD-treated group (n=42) and control group (n=42). TCDD-treated group was given by gavage a single dose of TCDD (64 μg/kg) at 8: 00 AM on gestation day 10 (GD10) and the control group was given by gavage the isopyknic corn oil. At GD13-GD15, the fetal mice palate development was observed by HE staining. The mouse embryonic palatal mesenchymal cell proliferation was detected by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence. The localization and expression of maternally expressed gene3 (MEG3) in mouse embryonic palatal mesenchymal cells was detected by situ hybridization and real-time PCR (RT-PCR). The key protein expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway in mouse embryonic palatal mesenchyme were analyzed by Western blotting. The interaction of MEG3 and TGF-β receptor Ⅰ (TGF-βRⅠ) was examined by RNA binding protein immunoprecipitation (RIP). Results: At GD13 and GD14, compared with the control group, the ratio of BrdU-positive cells in the palatal mesenchyme of TCDD-treated fetuses decreased significantly (GD13, t=6.66, P=0.003; GD14, t=6.56, P=0.003). However, at GD15, the ratio of BrdU-positive cells was significantly increased (t=-5.98, P=0.004). MEG3 was mainly expressed in the nuclei of fetal mouse palatal mesenchymal cells, and the expression of MEG3 in TCDD group was significantly increased at GD13, GD14 and GD15(GD13, t=39.28, P=0.012; GD14, t=18.75, P=0.042; GD15, t=28.36, P=0.045). At GD14, TCDD decreased the levels of p-Smad2 and Smad4 in embryonic palate mesenchymal cells (p-Smad2, t=9.48, P=0.001;Smad4, t=63.10, P=0.001), whereas the expression of Smad7 was significantly increased at GD14 (t=30.77, P<0.001). The results of the RIP experiment showed that the amount of TGF-βRⅠ-bound MEG3 in mouse embryonic palatal mesenchymal cells in the TCDD group (23.940±1.301) was higher than that in the control group (8.537±1.523)(t=24.55, P<0.001). Conclusions: MEG3 is involved in the suppression of mouse embryonic palatal mesenchymal cell proliferation, functioning at least in part via interacting with the TGF-βRⅠ protein and thereby suppressing Smad signaling in the context of TCDD induced cleft palate.

Clinical experience of off-pump arch branches preferential reconstruction and whole brain perfusion in the treatment of type A / 中华胸心血管外科杂志

Objective:To introduce the early results of total aortic arch replacement (TAA) without cardiopulmonary bypass (CPB) and without interruption of cerebral blood supply, using the technique of arch branches preferential reconstruction and whole brain perfusion for brain protection.Methods:Between June 2020 and March 2021, a total of 9 Stanford type A aortic dissection patients we performed total arch replacement by using the technique of arch branches preferential reconstruction and whole brain perfusion without cardiopulmonary bypass and without interruption of blood supply to the brain. The method of this reconstruction technique is as follows: A 24F aortic cannula was inserted into the true lumen at the root of the transverse innominate artery (IA) to connect one end of the artery for cardiopulmonary bypass. The access was connected to 14F artery via Y-connector and inserted into IA cavity to maintain blood supply to brain. Without cardiopulmonary bypass, the 10 mm branch of the four branch artificial blood vessel was anastomosed with the innominate artery IA. The perfusion collateral was connected to the second end of the artery of CPB (single pump and double tubes) to continue to supply blood for IA. The left common carotid artery (LCA) and left subclavian artery (LSCA) were reconstructed by the same method. When IA and LCA were anastomosed, the distal blood supply was not interrupted. After the three branches of the aortic arch were anastomosed, we started to turn the machine, then cooled down and blocked the ascending aorta to further complete the operation of the aortic root and arch. During the period of lower body circulatory arrest, the whole brain was perfused with low flow.Results:No intraoperative death or perioperative complications occurred in all patients, and they were discharged smoothly. The cardiopulmonary bypass time was (192.4±58.1) min, the aortic clamping time was (128.3±52.4) min, the lower body circulatory arrest time was (29.1±1.3) min, and the postoperative awake time was (8.2±3.7) h.Conclusion:Off-pump arch branches preferential reconstruction can provide physiological whole brain perfusion, shorten the cardiopulmonary bypass time and aortic occlusion time, and the operation is safe and effective.

Medication Rules of Clinical Prescriptions Containing Citri Sarcodactylis Fructus Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo reveal the medication rules of the clinical prescriptions containing Citri Sarcodactylis Fructus， and to provide a basis for the modern clinical application of Citri Sarcodactylis Fructus， the development of health products and the research and development of new drugs. MethodThe clinical prescriptions containing Citri Sarcodactylis Fructus were retrieved from CNKI， Wanfang Data， and VIP， and then a basic database of prescriptions was established via the traditional Chinese medicine inheritance auxiliary platform （V2.5）， IBM SPSS V20， and Excel （Microsoft Office 2016）. The frequency and association rules of the medicines in prescriptions （compatible medicines） and the corresponding syndromes were then mined. ResultThe prescriptions were screened according to the inclusion and exclusion criteria. A total of 458 clinical prescriptions containing Citri Sarcodactylis Fructus were collected， involving 388 Chinese medicines， and the total frequency of medicines reached 6 199. The core compatible medicines （frequency > 130） of Citri Sarcodactylis Fructus included Poria （frequency of 222）， Atractylodis Macrocephalae Rhizoma （217）， Paeoniae Radix Alba （196）， Bupleuri Radix （159）， and Citri Reticulatae Pericarpium （142）. The Citri Sarcodactylis Fructus-compatible medicines with frequency > 49 were selected for further analysis， which included 34 medicines with the cumulative frequency of 3 131 （50.51% of the total frequency）. These medicines mainly have the functions of tonifying Qi， invigorating Qi， tonifying blood， alleviating edema and promoting urination， promoting digestion， and activating blood and relieving pain. They are mainly warm， cold， or mild-natured， taste bitter， sweet， or acrid， and have the tropism in the spleen， liver， stomach， or lung meridians. The association rule analysis demonstrated that 14 medicine combinations were commonly used， and the core combinations were Poria-Citri Sarcodactylis Fructus， Atractylodis Macrocephalae Rhizoma-Citri Sarcodactylis Fructus， Paeoniae Radix Alba-Citri Sarcodactylis Fructus， Bupleuri Radix-Citri Sarcodactylis Fructus， Atractylodis Macrocephalae Rhizoma-Poria-Citri Sarcodactylis Fructus， and Citri Reticulatae Pericarpium-Citri Sarcodactylis Fructus. The clinical prescriptions containing Citri Sarcodactylis Fructus were mainly used to treat 52 diseases corresponding to 11 types of traditional Chinese medicine （TCM） syndromes. Three representative syndrome types， including spleen and stomach syndromes， Qi-blood-body fluid syndromes， and gynecological syndromes were selected for further association rule analysis. In the treatment of spleen and stomach syndromes， the core compatible drugs were Atractylodis Macrocephalae Rhizoma， Poria， Paeoniae Radix Alba， Bupleuri Radix， Citri Reticulatae Pericarpium， and Pinelliae Ehizoma， which， together with Citri Sarcodactylis Fructus， formed 25 commonly used medicine combinations （16 combinations composed of 2 medicines and 9 combinations composed of 3 medicines）. In the treatment of Qi-blood-body fluid syndromes， the core compatible drugs were Poria， Paeoniae Radix Alba， Atractylodis Macrocephalae Rhizoma， Astragali Radix， Hordei Fructus Germinatus， and Bupleuri Radix， which， together with Citri Sarcodactylis Fructus， formed 23 common medicine combinations （17 combinations composed of 2 medicines， 5 combinations composed of 3 medicines， and 1 combination composed of 4 medicines）. In the treatment of gynecological syndromes， the core compatible medicines were Atractylodis Macrocephalae Rhizoma， Paeoniae Radix Alba， Angelicae Sinensis Radix， Astragali Radix， Cyperi Rhizoma， and Poria， which constituted 25 common medicine combinations （15 combinations composed of 2 medicines and 10 combinations composed of 3 medicines）. ConclusionWe employed the traditional Chinese medicine（TCM） inheritance auxiliary platform to explore the compatibility of Citri Sarcodactylis Fructus-containing clinical prescriptions and the corresponding TCM syndromes， which intuitively showcased the medication rules of Citri Sarcodactylis Fructus. Specifically， Citri Sarcodactylis Fructus was mainly combined with the medicines for tonifying Qi， invigorating Qi， tonifying blood， alleviating edema and promoting urination， promoting digestion， and activating blood and relieving pain to treat different TCM syndromes. While soothing liver， regulating Qi， harmonizing stomach， and relieving pain， the combinations tonify and activate blood， invigorate spleen， and resolve dampness. The findings are of great significance to the rational application of Citri Sarcodactylis Fructus， the development of health food， and the research of new drugs and will bolster the development of Chinese medicine industry.

Research progress of tumor microenvironmentally regulating organelle targeted drug delivery system / 药学学报

In recent years, the use of the body's immune system for anti-tumor immunotherapy has received extensive attention. However, the immunosuppressive tumor microenvironment (TME) limits the effect of immunotherapy. Therefore, overcoming the limitations of TME and immunosuppressive cells plays an important role in tumor immunotherapy. Nano agents have great potential to reprogram the immunosuppressive microenvironment and provide an effective strategy for immunotherapy. With the continuous development of active targeting nano carrier technology and the deepening of the research on drug action sites, subcellular organ targeting nano carrier materials with more accurate active targeting function have also attracted more and more attention. This review will briefly introduce the relationship between subcellular organelles and tumor, summarize the design strategy and research progress of targeted nano drug delivery system based on the characteristics of acidity, reactive oxygen species (ROS) activity, immunogenicity, and TME of immunosuppressive cells, to provide reference for the construction of subcellular pathway targeted drug delivery system in tumor immunotherapy.

Qishen Taohong Granule () as Adjuvant Therapy for Improving Cardiac Function and Quality of Life in Patients with Chronic Heart Failure: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To confirm the improvement of cardiac function and quality of life (QOL) in patients with chronic heart failure (CHF) via Chinese medicine (CM) Qishen Taohong Granule (, QTG).@*METHODS@#This study was a single-center, prospective, randomized, controlled clinical trial. Seventy-six patients from 27 to 84 years old diagnosed with CHF New York Heart Association (NYHA) class II or III in stage C were enrolled and randomly assigned at a 1:1 ratio to receive QTG or trimetazidine (TMZ), in addition to their standard medications for the treatment of CHF. The study period was 4 weeks. The primary outcomes included cardiac function evaluated by NYHA classification and left ventricular ejection fraction (LVEF), as well as QOL evaluated by CHF Integrated Chinese and Western Medicine Survival Scale (CHFQLS). The secondary outcomes included 6-min walking test (6MWT), CM syndrome score, symptom and sign scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP). All indices were measured at baseline and the end of the trial.@*RESULTS@#At the 4-week follow-up period, the effective rate according to NYHA classification in the QTG group was better than that in the TMZ group (74.29% vs. 54.29%, P<0.05). But there was no significant difference in post-treatment level of LVEF between the two groups (P>0.05). The CHFQLS scores improved by 13.82±6.04 vs. 7.49±2.28 in the QTG and TMZ groups, respectively (P<0.05). Subgroup analysis of the CHFQLS results showed that physiological function, role limitation and vitality were significantly higher in the QTG group than in the TMZ group (15.76±7.85 vs. 7.40±3.36, P<0.05; 16.00±8.35 vs. 10.53±4.64, P<0.05; 15.31±8.09 vs. 7.89±4.60, P<0.05). Compared with TMZ group, treatment with QTG also demonstrated superior performance with respect to 6MWT, CM syndrome, shortness of breath, fatigue, gasping, general edema and NT-proBNP level. No significant adverse reactions or adverse cardiac events occurred during treatment in either group.@*CONCLUSION@#In addition to conventional treatments, the use of QTG as an adjuvant therapy significantly improved cardiac function and QOL in patients with CHF class II or III in stage C. [Registration No. ChiCTR1900022036 (retrospectively registered)].

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Research progress of Curcuma kwangsiensis root tubers and analysis of liver protection and anti-tumor mechanisms based on Q-markers / 中国中药杂志

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and β-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.

Analysis on oral medication rules of traditional Chinese medicine prescriptions for prevention of COVID-19 / 中草药·英文版

Objective: To analyze the medication rules of traditional Chinese medicine (TCM) preventive oral prescriptions for COVID-19. Methods: The preventive oral prescriptions for COVID-19 published by national and provincial health and wellness committees, administrations of TCM, medical institutions at all levels, medical masters and Chinese medicine experts were collected to establish a database, manual screening was carried out according to the inclusion and exclusion criteria, and frequency statistics, association rule analysis. The mutual information method, entropy hierarchical clustering and other methods were improved through Excel and the TCM inheritance auxiliary platform V2.5 to mine the rules and characteristics of medication. Results: The selected 157 prescriptions contained a total of 130 TCMs. The top five TCMs with the highest use frequency were Glycyrrhizae Radix et Rhizoma (86), Astragali Radix (80), Lonicerea Japonicae Flos (70), Atractylodis Macrocephalae Rhizoma (62), Saposhnikoviae Radix (60). In accordance with TCM efficacy classification, most of them were medicines for qi-tonifying (279), followed by medicines for clearing heat and drying dampness (163), dispelling pathogenic wind-cold (126), resolving dampness (111), as well as dispelling pathogenic wind-heat (99). The characteristics of four-natures of the selected medicines are as follows: most of them were cold (59), followed by warm (38) and mild (21). In terms of five-taste, most of them were sweet (26) and acrid-and-bitter (24), followed by sweet-and-bitter (20), bitter (20) and acrid (15). For the meridian attribution, the five-zang organs and six-fu organs were all involved, most of them attributed to lung meridian (80), followed by stomach meridian (57) and spleen meridian (40). Based on association rule analysis, 12 commonly used medicine combinations with two or three TCMs were found. The commonly used medicinal pairs included Astragali Radix and Saposhnikoviae Radix (51), Astragali Radix and Atractylodis Macrocephalae Rhizoma (46), Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (43), Astragali Radix and Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix (38), Forsythiae Fructus and Astragali Radix (37), and so on. In addition, 14 core combinations of medicines were obtained by complex system entropy cluster analysis, on this basis, six new prescriptions were screened out based on unsupervised entropy hierarchical clustering analysis. According to The Catalogue of Edible Traditional Chinese Medicinal Materials, Traditional Chinese Medicinal Materials for Health Food, and New Resources of Food published by National Health Commission of the People's Republic of China, there are 35 species belonging to the group of edible traditional Chinese medicinal materials, 20 species belonging to the group of new resources of food, 31 species belonging to the group of traditional Chinese medicinal materials for health food, 19.11% of the preventive oral prescriptions for COVID-19 were composed of the medicines belonging to the above three groups. Besides, there are 11 toxic species, and 24.84% of the preventive oral prescriptions for COVID-19 contained toxic TCMs. Conclusion: We found that invigorating qi and resolving dampness were the main treatment used to prevent for COVID-19, combined with the methods for strengthening vital energy and eliminating pathogenic factors. Most of the preventive oral prescriptions for COVID-19 were treated in lung, spleen and stomach meridians. In the process of selecting prescriptions and using TCMs to prevent for COVID-19, the safety of preventive medicines was also emphasized. And the theory of “Preventive Treatment of Disease” was embodied in these preventive oral prescriptions for COVID-19. For the prescriptions containing toxic TCMs, special attention should be paid to their safety in clinical application.

Relationship between manganese superoxide dismutase gene Val16Ala polymorphism and susceptibility to prostate cancer: a Meta-analysis / 肿瘤研究与临床

Objective:To investigate the relationship between manganese superoxide dismutase (MnSOD) gene Val16Ala polymorphism and the susceptibility to prostate cancer.Methods:All literatures related to MnSOD gene polymorphism and susceptibility to prostate cancer were retrieved from PubMed, Embase, China Knowledge Network and Wanfang databases. The retrieval time was from the database establishment to September 19, 2018. Literature screening and data extraction were independently done by 2 investigators, and Meta-analysis was performed by using Stata 12.0 software.Results:A total of 17 studies were included in the final analysis, including 7 101 prostate cancer cases and 9 146 healthy controls (people working at hospital and the ordinary people). The results of Meta-analysis showed that MnSOD gene Val16Ala polymorphism was not associated with susceptibility to prostate cancer under the homozygous model ( OR = 1.12, 95% CI 1.02-1.23, P = 0.435), heterozygous model ( OR = 1.14, 95% CI 1.05-1.24, P = 0.765), dominant model ( OR = 1.14, 95% CI 1.05-1.23, P = 0.552) and allele comparison model ( OR = 1.07, 95% CI 1.02-1.12, P = 0.106). Conclusion:There may not be the relationship between MnSOD gene Val16Ala polymorphism and the susceptibility to prostate cancer.

Establishing minimal clinically important differences of Quality of Life Instruments for Cancer Patients-Leukemia based on the distribution-based approach / 国际肿瘤学杂志

Objective:To develop the minimal clinically important difference (MCID) of Quality of Life Instruments for Cancer Patients-Leukemia (QLICP-LE) (V2.0).Methods:The quality of life of 101 patients with leukemia in First Affiliated Hospital of Kunming Medical University and First People′s Hospital of Yunnan Province from October 2011 to May 2012 were measured. The QLICP-LE (V2.0) was used for data collection, and the MCID for the overall score and scores of various domains of QLICP-LE (V2.0) were established by using the distribution-based approach including indexes of effect size, standard error of measurement (SEM), reliable change index, standardized response mean and responsiveness statistic, and the recommended values of MCID were determined through the consensus method.Results:The MCID formulated by the above five indexes were as follows: the total scale 1.4-9.3, physical functional domain 1.6-15.6, psychological functional domain 2.9-15.6, social functional domain 2.2-18.0, common symptoms and side-effects domain 1.7-17.1, common module 1.8-10.0, and the specific module 1.1-12.1. Through the expert consensus method, it was recommended to use the MCID results calculated by 1.96SEM: the total scale was 4, physical domain was 8, psychological domain was 8, social domain was 9, common symptoms and side-effects domain was 9, common module was 4, and the specific module was 6.Conclusion:Each index of distribution-based approach has its own advantages and disadvantages, which can be selected based on actual conditions. There is clinical significance when the score change of QLICP-LE (V2.0) of leukemia patients after treatment exceeds its MCID.

Association between cell phone dependence and anxiety-depression co morbid symptoms among college students / 中国学校卫生

Objective@#To describe the prevalence of cell phone dependence and anxiety-depression co morbidity among college students, and to explore the association between cell phone dependence and anxiety-depression co morbidity among college students, in order to provide a reference basis for promoting the development of college students mental health.@*Methods@#Using a prospective study design, baseline survey was conducted in April-May 2019 among a random whole group sample of 1 135 individuals in two universities in Hefei, Anhui Province and Shangrao, Jiangxi Province, and a follow up survey was conducted in November 2019 among the sampled population, with a valid number of 1 110 individuals after matching with the baseline survey. The Self rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) was used to assess college students cell phone dependence, and the Depression Anxiety Stress Self Rating Scale (DASS-21) to assess depression, anxiety, and anxiety depression co morbidity symptoms, and the self administered Health Related Behavior and Mental Health Questionnaire for College Students to report sleep duration.@*Results@#The detection rates of cell phone dependence among college students at baseline and follow up surveys were 24.5% and 27.7%, respectively, and the detection rates of anxiety symptoms, depressive symptoms, and anxiety depression co morbidities were 28.7%, 21.3%, and 18.4%, respectively. The results of the binary Logistic regression model showed that cell phone dependence was positively associated with the risk of anxiety depression co morbid symptoms among college students at baseline ( OR =5.79, 95% CI =4.06-8.24) and after six months of follow up ( OR =2.62, 95% CI =1.86-3.69) ( P <0.01). The results of the moderating effect analysis showed that sleep duration moderated the association between cell phone dependence and anxiety depression co morbidities, and the interaction term was statistically significant ( β =0.08, 0.04, P <0.01).@*Conclusion@#Cell phone dependence in college students increases the risk of depressive and anxiety co morbid symptoms, and sleep mitigates effect of cell phone dependence on depressive and anxiety co morbid symptoms in college students.

Explore Effect of Jieyu Qutan Huazhuo Prescription on Gut-liver Axis of Rats with High-fat Diet Based on 16S rDNA Sequencing / 中国实验方剂学杂志

Objective:To study the effect of Jieyu Qutan Huazhuo prescription（JQHP） on the gut microbiota of rats with high-fat diet，and to explore the effect of Chinese medicine on the regulation of gut microflora and the restoration of gut-liver axis balance. Method:Seventy male SPF Wistar rats were randomly divided into a normal group of 10 and a model group of 60. Mice in the normal group were fed with normal diet and mice in the model group were fed high-fat diet. After 12 weeks，the model group was randomly divided into 6 groups with 10 animals in each group，namely the model group，Xuezhikang group，Liputuo group，and low，medium and high-dose groups of JQHP. The JQHP low-dose，medium-dose and high-dose rats were intragastrically daministered with 0.4，0.8，1.6 g·kg^-1，respectively， rats in Liputuo group with Liputuo 2 mg·kg^-1，rats in Xuezhikang group with Xuezhikang 0.1 g·kg^-1. The rats in the normal group and the model group were intragastrically administered with the same amount of distilled water. Stool were collected after continuous gavaging for 8 weeks，16S rRNA gene sequencing was performed，blood was collected from the abdominal aorta to detect blood lipids，and the liver tissue and ileum tissue were collected for hematoxylin and eosin （HE） staining for pathomorphological observation. Result:Compared with the normal group，the total cholesterol （TC），triglyceride （TG），and low-density lipoprotein （LDL-C） in the model group were significantly increased，while the high-density lipoprotein （HDL-C） was decreased （<italic>P</italic><0.01）. Compared with the model group，TC and TG values were decreased significantly in Xuezhikang group （<italic>P</italic><0.01），HDL-C value was increased （<italic>P</italic><0.05），and in the Liputuo group TC and TG were decreased significantly （<italic>P</italic><0.01）. Compared with the model group，the middle-dose group of JQHP had a certain alleviating effect on liver steatosis and could reduce the infiltration of inflammatory cells. The JQHP could improve the proliferation of lymphoid tissues in the ileal structure，and the middle-dose group has the most significant effect. The results of Shannon curve showed that compared with the normal group，the middle-dose group of JQHP increased significantly （<italic>P</italic><0.01）. Compared with the model group，the middle and high-dose group of JQHP increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the middle-dose group of JQHP，the other drug group decreased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Principal component diversity analysis（PCA） showed that the diversity and abundance in the middle-dose JQHP group were higher than those in other drug groups. In linear discriminant analysis（LDA），compared with the normal group，Bacteroidia，Ruminococcaceae，<italic>Bacteroides </italic>S24-7，and <italic>Rumenococcus </italic>UCG-005 were down-regulated in the model group（<italic>P</italic><0.01），while the orders of Desulfovibrionales，Erysipelotrichales and<italic> </italic>Lachnospiraceae were up-regulated in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group，the Bacteroidia，Ruminococcaceae，<italic>Bacteroides</italic> S24-7，and <italic>Rumencoccus</italic> UCG-005 in the middle-dose JQHP group were increased （<italic>P</italic><0.05，<italic>P</italic><0.01），and the orders of Erysipelotrichales were decreased （<italic>P</italic><0.01）. Compared with the middle-dose JQHP group，Bacteroidia，Ruminococcaceae，<italic>Bacteroides</italic> S24-7，and <italic>Rumencoccus</italic> UCG-005 in other drug groups were reduced（<italic>P</italic><0.05，<italic>P</italic><0.01），and the order of Erysipelotrichales and Lachnospiraceae were increased （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:JQHP can regulate the abundance and diversity of the gut microbiota，improve the state of liver tissue and ileum mucosa，regulate blood lipid levels，and restore the normal intestinal ecological environment. It may be related to the regulation of inflammation-related gut microbiota in order to restore the balance of the gut-liver axis，and the middle-dose JQHP group has the best effect.

Effect of Huluan Decoction on SIRT1/NF-κB/p53/p21 Pathway in Model Mice with Premature Ovarian Insufficiency / 中国实验方剂学杂志

Objective:To observe the effects of Huluan decoction on the expression of apoptosis-related protein silence information regulator 1 （SIRT1）， tumor suppressor gene （p53）， acetylated p53 （Ac-p53）， cyclin-dependent kinase inhibitor （p21）， and nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） p65 and changes in ovarian tissue structure of a mouse model with premature ovarian insufficiency （POI） induced by tripterygium glycosides. Method:Fifty female C57BL/6J mice were randomly divided into the blank group， model group， low- and high-dose Huluan decoction groups， and western medicine （estradiol valerate） group. After intragastric administration of tripterygium glycosides at 80 mg·kg^-1·d^-1 for 14 successive days， mice in the low- and high-dose Huluan decoction groups and western medicine group were treated with Huluan decoction at 1.6 g·kg^-1·d^-1 and 6.2 g·kg^-1·d^-1 and estradiol valerate at 0.13 mg·kg^-1·d^-1， respectively， by gavage since the 15^th day， while those in the blank group were provided with an equal amount of distilled water for 21 consecutive days. Following the last administration， the blood was sampled for detecting the levels of serum anti-Müllerian hormone （AMH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） by ELISA and the ovary was harvested for observing the morphological changes by HE staining. The mRNA expression levels of p53 and p21 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of SIRT1， p53， p21， Ac-p53， NF-<italic>κ</italic>B were assayed by Western blot. Result:Compared with the blank group， the model group exhibited a disordered estrous cycle， diminished ovarian volume， decreased number of follicles at various developmental stages， reduced AMH， and elevated FSH and LH， and elevated p53，p21，Ac-p53，NF-<italic>κ</italic>B protein expression and p53，p21 mRNA， reduced SIRT1 protein expression（<italic>P</italic><0.01）. As revealed by the comparison with the model group， each medication group displayed an increased number of follicles， elevated AMH， reduced FSH and LH （<italic>P</italic><0.01）， up-regulated SIRT1 protein expression （<italic>P</italic><0.01）， and significantly down-regulated mRNA and protein expression of aging-related genes p53， p21， and down-regulated Ac-p53，NF-<italic>κ</italic>B protein expression （<italic>P</italic><0.01）. Conclusion:Huluan decoction significantly reverses the aging process and improves ovarian function possibly by boosting the activity of SIRT1/NF-<italic>κ</italic>B/p53/p21 pathway in ovarian cells， changing the apoptotic state， increasing the growing and mature follicles， and reducing the atretic follicles.

Correlation between body mass index and increased body mass during pregnancy and adverse pregnancy outcomes in elderly pregnant women / 公共卫生与预防医学

Objective To investigate the correlation between body mass index and the increase in body mass during pregnancy and adverse pregnancy outcomes in elderly pregnant women. Methods The clinical data was collected from 1,374 pregnant women who underwent regular prenatal care checkups and delivered a child at Jiangsu Maternity and Child Health Hospital from January 1, 2020 to May 1, 2020. According to the age of pregnant women, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG), the subjects were divided into different groups. The incidence of adverse pregnancy outcomes between groups was compared, and the correlation between pregnant women's age, pre-pregnancy BMI and GWG and adverse pregnancy outcomes was analyzed. Results Compared with the non-advanced age group, the elderly group had an increase in the incidence rate of gestational diabetes (GDM) (38.66% VS 19.54%), the incidence rate of large for gestational age (LGA) (LGA) (19.75% VS 14.43%), and the cesarean section rate (55.46% VS) 34.77%), and the differences between the groups were statistically significant (t=40.773, 4.270, 35.630, P=0.001, 0.039, 0.001). There were no significant differences between the non-advanced age group and the elder group in the incidence of pregnancy-induced hypertension (PIH) (10.92% VS 8.63%), the incidence of small for gestational age (2.52% VS 2.90%), and the incidence of neonatal asphyxia ( 2.10% VS 1.23%) (t=1.265, 0.105, 1.088, P=0.261, 0.746, 0.297). ). The incidence of GDM in overweight and obese elderly pregnant women was higher than that in underweight and normal pregnant women. The incidence of GDM in the elderly pregnant women with less GWG and excessive GWG was higher than that in the normal group (P<0.05). Conclusion The pre-pregnancy body mass index and the gain in body mass during pregnancy are related to the occurrence of adverse pregnancy outcomes. It is necessary to strengthen the monitoring and management of pre-pregnancy body mass index and pregnancy body quality in elderly pregnant women.