Effect of fumigation therapy of Flos Farfarae in cigarette smoke-induced lung injury mice based on metabolomics / 药学学报

This study aimed to investigate the effect of Flos Farfarae (FF) fumigation on cigarette smoke-induced lung injury mice, and analyze the metabolic profile of lung tissue by metabolomics. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shanxi University (Approval number: SXULL2019014). By using HS-GC-MS to analyze volatile components of Flos Farfarae, 23 compounds were identified. The results showed that FF fumigation improved the lung tissue morphology of cigarette smoke-induced lung injury mice, lowered the levels of interleukin 6 (IL-6) and interleukin-1β (IL-1β). The lung tissue samples were applied for metabolomic analysis based on UHPLC-QTOF MS, the results showed that 70 metabolites were changed in the lung tissue of mice after cigarette exposure, and 35 of them could be regulated, including lysophosphatidylcholine (LPC), 12-HETE, adenosine, and xanthine. These metabolites, such as LPC, 12-HETE, adenosine, and xanthine were mainly associated with the body's inflammatory response. It was observed that these metabolites are primarily involved in purine metabolism, arachidonic acid metabolism, phospholipid metabolism, and pyruvate metabolism pathways. These findings suggest that the volatile terpenoids in the FF may regulate the metabolites associated with the inflammatory response in the lung tissue, such as lysophosphatidylcholine, 12-HETE, and adenosine, which could further alleviate lung inflammation induced by cigarette smoke through the metabolic pathways of purine metabolism and others. This study proved the scientific basis of the traditional application of FF fumigation, and provided a theoretical basis for the further product development.

Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.@*METHODS@#The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance.@*RESULTS@#The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05).@*CONCLUSION@#High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization / 中国中药杂志

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Application of SGRT Combined with IGRT Isocenter Dual-guided Resetting in IMRT for Breast Cancer / 中山大学学报(医学科学版)

ObjectiveThe objective is to investigate the possibility of isocenter dual-guided resetting of surface guided radiation therapy （SGRT） combined with image guided radiation therapy （IGRT） in postoperative radiotherapy for breast cancer. To assess the setup error accuracy between the new resetting mode and the traditional resetting mode. MethodsRetrospective analysis was performed on breast cancer patients who underwent ELEKTA infinity accelerator radiotherapy in sun yat-sen university cancer center from July 13， 2021 to October 15， 2022. According to different reset methods， the patients were divided into a simulation group （41 cases） and a dual-guided group （40 cases）. The simulation group was reset using a simulator， CBCT scans were performed and setup errors were recorded during the first treatment； The dual-guided group was guided by AlignRT and combined with CBCT for isocenter dual-guided resetting， and the setup error obtained by CBCT registration was recorded. The global setup errors of chest region of interest （CROI） ， the local residual errors of supraclavicular region of interest （SROI） and the resetting time of the two reset methods were calculated and compared respectively. The advantages of the CBCT error distribution in the dual-guided resetting of SGRT combined with IGRT were analyzed. ResultsThe median of the global setup errors （X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz°） of the simulation group and the median of the dual-guided group in the CROI were statistically significant （P<0.05） except the Rz and Ry directions. The local residual errors of the two groups of the SROI were calculated. The median of the errors of X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz° were statistically significant （P<0.05） except the X and Y axis. The resetting time of the simulation group was significantly longer than that of the dual-guided group （238.64±28.56） s， t=-24.555， P=0.000， and the difference was statistically significant （P<0.05）. The CBCT error distribution of the dual-guide group was analyzed， and it was found that the absolute values of translation errors of X， Y and Z axis were all within 0.4 cm， while the proportions of ≤ 0.3 cm were 95%， 93% and 93%， respectively. The proportions of rotation errors of Rx， Ry and Rz ≤ 1.5 ° were 90%， 93% and 90%， respectively. ConclusionIn postoperative radiotherapy of breast cancer， SGRT combined with IGRT for isocenter dual-guided resetting can effectively correct the rotational setup errors and residual errors， and improve the accuracy of radiotherapy with less resetting time and high feasibility， which compared with the traditional simulator resetting mode. This precise， unmarked resetting method can be widely used in clinical practice.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Association of Breastfeeding Duration with Body Composition in Children Aged 3-5 Years / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to assess the relationship between the body composition of children aged 3-5 years and breastfeeding status and duration.@*METHODS@#The study was conducted using data from the National Nutrition and Health Systematic Survey for children 0-17 years of age in China (CNHSC), a nationwide cross-sectional study. Breastfeeding information and potential confounders were collected using standardized questionnaires administered through face-to-face interviews. The body composition of preschool children was measured using bioelectrical impedance analysis. A multivariate linear regression model was used to assess the relationship between breastfeeding duration and body composition after adjusting for potential confounders.@*RESULTS@#In total, 2,008 participants were included in the study. Of these, 89.2% were ever breastfed and the median duration of breastfeeding was 12 months (IQR 7-15 months). Among children aged 3 years, the height-for-age Z-score (HAZ) for the ever breastfed group was lower than that for never breastfed group (0.12 vs. 0.42, P = 0.043). In addition, the weight-for-age Z-score (WAZ) of the ever breastfed group was lower than that of the never breastfed group (0.31 vs. 0.65, P = 0.026), and the WAZ was lower in children aged 4 years who breastfed between 12 and 23 months than in those who never breastfed. Compared to the formula-fed children, the fat-free mass of breastfed infants was higher for children aged 3 years (12.84 kg vs. 12.52 kg, P = 0.015) and lower for those aged 4 years (14.31 kg vs. 14.64 kg, P = 0.048), but no difference was detected for children aged 5 years (16.40 kg vs. 16.42 kg, P = 0.910) after adjusting for potential confounders. No significant difference was detected in the weight-for-height Z-score (WHZ), body mass index (BMI)-for-age Z-score (BAZ), fat-free mass index, and body fat indicators in the ever breastfed and never breastfed groups and among various breastfeeding duration groups for children aged 3-5 years.@*CONCLUSION@#No obvious associations were detected between breastfeeding duration, BMI, and fat mass indicators. Future prospective studies should explore the relationship between breastfeeding status and fat-free mass.

Acupuncture for treatment of tobacco withdrawal syndrome: systematic review and Meta-analysis / 中国针灸

OBJECTIVE@#To systematically review the efficacy of acupuncture for the treatment of tobacco withdrawal syndrome.@*METHODS@#The randomized controlled trials (RCTs) regarding acupuncture for treatment of tobacco withdrawal syndrome were searched in CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane, Medline and EMbase databases. The search period was from January 1st of 2011 to December 31st of 2021. After data extraction and bias risk assessment of the included literature, the Meta-analysis was performed using RevMan5.4.1 software.@*RESULTS@#Totally 23 RCTs were included, including 2 120 patients. The Meta-analysis results showed that compared with medication, acupuncture showed no significant difference at improving Fagerström test for nicotine dependence (FTND) score (MD=0.16, 95%CI: -0.08, 0.41), heaviness of smoking index (HSI) score (MD=0.11, 95%CI: -0.13, 0.36), Minnesota nicotine withdrawal scale (MNWS) score (MD=0.12, 95%CI: -0.11, 1.35), questionnaire of smoking urges (QSU) score (MD=-0.30, 95%CI: -2.78, 2.18), Hamilton depression scale (HAMD) score (MD=0.76, 95%CI: -1.54, 3.06), abstinence rate (RR=0.95, 95% CI: 0.82, 1.10) and effective rate (RR=1.01, 95%CI: 0.95, 1.07). Acupuncture was superior to sham acupuncture in reducing MNWS score (MD=-4.88, 95%CI: -5.21, -4.55, P<0.000 01). Acupuncture was superior to cognitive behavioral therapy in reducing FTND score (MD=-1.41, 95%CI: -1.74, -1.08), MNWS score (MD=-4.28, 95%CI: -5.31, -3.25) and increasing abstinence rate (RR=2.19, 95%CI: 1.39, 3.45, P<0.000 01, P<0.001).@*CONCLUSION@#Acupuncture could effectively improve tobacco withdrawal syndrome, increase abstinence rate and effective rate. Limited by the quantity and quality of the included studies, this conclusion needs to be verified by more studies.

Secular trends of age at menarche and age at menopause in women born since 1951 from a county of Shandong Province, China / 北京大学学报(医学版)

OBJECTIVE@#To describe the secular trends of age at menarche and age at natural menopause of women from a county of Shandong Province.@*METHODS@#Based on the data of the Premarital Medical Examination and the Cervical Cancer and Breast Cancer Screening of the county, the secular trends of age at menarche in women born in 1951 to 1998 and age at menopause in women born in 1951 to 1975 were studied. Joinpoint regression was used to identify potential inflection points regarding the trend of age at menarche. Average hazard ratios (AHR) of early menopause among women born in different generations were estimated by performing multivariate weighted Cox regression.@*RESULTS@#The average age at menarche was (16.43±1.89) years for women born in 1951 and (13.99±1.22) years for women born in 1998. The average age at menarche was lower for urban women than that for rural women, and the higher the education level, the lower the average age at menarche. Joinpoint regression analysis identified three inflection points: 1959, 1973 and 1993. The average age at menarche decreased annually by 0.03 (P < 0.001), 0.08 (P < 0.001), and 0.03 (P < 0.001) years respectively for women born during 1951-1959, 1960-1973, and 1974-1993, while it remained stable for those born during 1994-1998 (P=0.968). As for age at menopause, compared with women born during 1951-1960, those born during 1961-1965, 1966-1970 and 1971-1975 showed a gradual decrease in the risk of early menopause and a tendency to delay the age at menopause. The stratified analysis presented that the risk of early menopause gradually decreased and the age of menopause showed a significant delay among those with education level of junior high school and below, but this trend was not obvious among those with education level of senior high school and above, where the risk of early menopause decreased and then increased among those with education level of college and above, and the corresponding AHRs were 0.90 (0.66-1.22), 1.07 (0.79-1.44) and 1.14 (0.79-1.66).@*CONCLUSION@#The age at menarche for women born since 1951 gradually declined until 1994 and leveled off, with a decrease of nearly 2.5 years in these years. The age at menopause for women born between 1951 and 1975 was generally delayed over time, but the trend of first increase and then decrease was observed among those with relatively higher education levels. In the context of the increasing delay in age at marriage and childbearing and the decline of fertility, this study highlights the necessity of the assessment and monitoring of women' s basic reproductive health status, especially the risk of early menopause.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Role of blood markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection / 中华外科杂志

Objective: To investigate the value of inflammation,coagulation and nutrition markers in predicting the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation for treatment of periprosthetic joint infection(PJI). Methods: A retrospective study was conducted on 70 patients who undertook prosthesis removal and antibiotic-loaded bone cement spacer implantation due to PJI from June 2016 to October 2020 in the Department of Orthopedics,Henan Provincial People's Hospital. There were 28 males and 42 females,aged (65.5±11.9) years (range: 37 to 88 years). Patients were divided into two groups as the successful group and the failed group depended on whether reinfection occurred after prosthesis removal and antibiotic-loaded bone cement spacer implantation at the last follow up. Patient demographics,laboratory values (C-reactive protein (CRP),erythrocyte sedimentation rate (ESR),ESR and CRP ratio (ESR/CRP),white blood cell count(WBC),platelet count(PLT),hemoglobin(HB),total lymphocyte count(TLC),albumin、fibrinogen(FIB),CRP and albumin ratio (CAR),prognostic nutritional index(PNI)),and reinfection rates were assessed. Comparison between groups was conducted by the independent sample t test or χ2 test. Receiver operating characteristic (ROC) curve was plotted,and the area under the curve (AUC),optimal diagnostic threshold,sensitivity,and specificity were analyzed to predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation. Results: All patients were followed up for at least two years,and the follow-up time was (38.4±15.2) months (range: 24 to 66 months). Fifteen patients suffered failure after prosthesis removal and antibiotic-loaded bone cement spacer implantation,while the other 55 patients succeeded. The overall failure rate of prosthesis removal and antibiotic-loaded bone cement spacer implantation in PJI treatment was 21.4%. Level of preoperative CRP(35.9±16.2)mg/L,PLT(280.0±104.0)×109/L and CAR 1.3±0.8 in successful group were lower than CRP (71.7±47.3)mg/L,PLT (364.7±119.3)×109/L and CAR 2.5±2.0 in failed group (all P<0.05).Whereas,level of preoperative ESR/CRP (3.3±3.1), Albumin (35.3±5.2)g/L and PNI 43.6±6.2 in successful group were higher than ESR/CRP (1.6±1.4),Albumin(31.3±4.8)g/L and PNI (39.2±15.1) in failed group (all P<0.05). AUC of ROC curve,optimal threshold value,sensitivity and specificity of CRP,ESR/CRP, PLT, Albumin,CAR and PNI for the predicting failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation were 0.776(95%CI:0.660 to 0.867),35.4 mg/L,86.7%,67.3%;0.725(95%CI:0.605 to 0.825),1.0,60.0%,78.2%;0.713(95%CI:0.593 to 0.815),253,93.3%,47.3%;0.721(95%CI:0.601 to 0.822),35.7,93.3%,49.1%;0.772(95%CI:0.656 to 0.863),1.1,86.7%,67.3%;0.706(95%CI:0.585 to 0.809),45.7,100%,41.8% respectively. Conclusion: In patients with PJI,CRP>35.4,ESR/CRP≤1.0 and CAR>1.1 could predict the failure of prosthesis removal and antibiotic-loaded bone cement spacer implantation.

Association of hs-CRP with frailty and its components among the elderly over 65 years old in 9 longevity areas of China / 中华预防医学杂志

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM).@*METHODS@#From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, β2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed.@*RESULTS@#Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy.@*CONCLUSION@#The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.

Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/ HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation

Background/Aims@#The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. @*Methods@#The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosisrelated proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. @*Results@#CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells.miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. @*Conclusions@#CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

Progress of relationship between autophagy and hepatocellular carcinoma / 肿瘤研究与临床

Autophagy is an intracellular degradation process that delivers cytoplasmic constituents to the lysosome. Abnormality of autophagy is related to many human diseases, which provides a new clue to the pathophysiology of human cancer. However, the role of autophagy in normal liver physiology and the pathogenesis of liver diseases need to be further clarified. This article reviews the role of autophagy in the occurrence and development of hepatocellular carcinoma and the molecular mechanisms.

Study on the modification and anti-tumor activity of silybin derivatives for CDK4/6 targeted / 药学学报

By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I1 has a certain inhibitory effect on human HepG-2 cells, which is worth further study.

The impact of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year outcome in patients with premature coronary heart disease: results of a prospective, multicenter, observational cohort study / 中华心血管病杂志

Objective: To explore the relationship between low density lipoprotein cholesterol (LDL-C)/high density lipoprotein cholesterol (HDL-C) ratio with the severity of coronary artery disease and 2-yeat outcome in patients with premature coronary heart disease. Methods: This prospective, multicenter, observational cohort study is originated from the PROMISE study. Eighteen thousand seven hundred and one patients with coronary heart disease (CHD) were screened from January 2015 to May 2019. Three thousand eight hundred and sixty-one patients with premature CHD were enrolled in the current study. According to the median LDL-C/HDL-C ratio (2.4), the patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1 867) and high LDL-C/HDL-C group (LDL-C/HDL-C>2.4, n=1 994). Baseline data and 2-year major adverse cardiovascular and cerebrovascular events (MACCE) were collected and analyzed in order to find the differences between premature CHD patients at different LDL-C/HDL-C levels, and explore the correlation between LDL-C/HDL-C ratio with the severity of coronary artery disease and MACCE. Results: The average age of the low LDL-C/HDL-C ratio group was (48.5±6.5) years, 1 154 patients were males (61.8%); the average age of high LDL-C/HDL-C ratio group was (46.5±6.8) years, 1 523 were males (76.4%). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (1.04±0.74 vs. 0.97±0.80, P=0.002; 2.04±0.84 vs. 1.85±0.84, P<0.001; 13.81±8.87 vs. 11.70±8.05, P<0.001; 36.2% vs. 27.4%, respectively, P<0.001). Correlation analysis showed that there was a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all P<0.05). The 2-year follow-up results showed that the incidence of MACCE was significantly higher in the high LDL-C/HDL-C group than that in the low LDL-C/HDL-C group (6.9% vs. 9.1%, P=0.011). There was no significant difference in the incidence of all-cause death, cardiac death, myocardial infarction, stroke, revascularization and bleeding between the two groups. Cox multivariate regression analysis showed that the LDL-C/HDL-C ratio has no correlation with 2-year MACCE, death, myocardial infarction, revascularization, stroke and bleeding events above BARC2 in patients with premature CHD. Conclusion: High LDL-C/HDL-C ratio is positively correlated with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio is significantly higher during 2 years follow-up; LDL-C/HDL-C ratio may be an indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.

Rapid identification of the chemical compounds in the leaves of Solanum nigrum L. based on UHPLC-Q Exactive MS and molecular network technology / 药学学报

The whole herb of Solanum nigrum L. can be used as the herbal drug. In this study, UHPLC-Q Exactive high resolution mass combined with GNPS molecular network was used for the rapid characterization of the components in the leaves of S. nigrum L. A total of 157 compounds were identified, including 30 steroid alkaloids, 61 steroid saponins, 35 flavonoids, and 31 other compounds (amino acids and organic acids), by comparison with the data reported in the literature, and mass fragmentation characteristics analysis, as well as the correlation of known and unknown nodes in the GNPS molecular network. Compared with the fruits and stems, the leaves of S. nigrum L was rich in a variety of steroidal saponins, steroidal alkaloids, and flavonoids, and the results lay the foundation for the precise resources utilization of S. nigrum L.

Analysis of Fusarium oxysporum infection on changes of Astragalus metabolism by metabolomic approach / 药学学报

italic>Astragalus is a commonly used Chinese medicinal material in traditional Chinese medicine (TCM), and with the increase of planting area in recent years, the damage of Astragalus root rot has worsened year by year, which seriously affecting its quality and yield. Fusarium oxysporum is one of the main pathogens causing root rot in astragalus. In this study, UPLC-Q-TOF-MS based metabolomic approach combined with multivariate statistical analysis were used to analyze the metabolite changes of Astragalus in response to F. oxysporum infection. The results showed that 62 metabolites in the Astragalus had significant changes after inoculation of F. oxysporum. Polar metabolites included 40 flavonoids, 8 saponins, 2 nucleosides, 1 vitamin, 1 organic acid, 1 amino acid; while lipid metabolites included 3 fatty acids, 1 diradylglycerols, 2 lysophosphatidylcholine, 1 lysophosphatidylglycerol, 1 phosphatidylinositol, 1 sterol lipid. Among these differential metabolites, the relative content of flavonoids, vitamin B2, tryptophan and salicylic acid were increased, while the relative content of saponins were decreased. Correlation analysis showed that the flavonoids were positively correlated with each other, and positively correlated with most lipids, but negatively correlated with most saponins. In addition, studies have shown that F. oxysporum infection is not an influencing factor for the generation of malonyl substitution of flavonoid. This study elucidates the effect of F. oxysporum infection on Astragalus from the perspective of plant metabolism, which provides a basis for exploring the interaction mechanism between the Astragalus and F. oxysporum and further promoting molecular breeding.

Quality evaluation of Bupleuri Radix in Shanxi Province by LC-MS based pseudotargeted metabonomics / 药学学报

Bupleuri Radix is commonly used in the traditional Chinese medicine, and saikosaponins are the important active ingredients. In this study, we first established a relative quantitative method for 25 saikosaponins using ultra high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QTrap-MS) in the scheduled multiple reaction monitoring (sMRM) mode. The established method showed good intra-day and intra-day precision, linearity, repeatability and stability. Then the method was applied to compare 37 batches of Bupleuri Radix from different planting areas. The results showed that there was no significant difference in the saikosaponins composition of Bupleuri Radix from different planting areas in Shanxi Province, which indicating that Bupleuri Radix is well adapted to the environment, so it is suitable for widely planting. However, Bupleuri Radix harvested at spring and autumn were differed from those harvested at summer, which indicated that the traditional harvesting experience was reasonable. Correlation analysis showed that saikosaponins a and d were positively correlated with some saponins, and 4 saponins (such as clinoposaponin XII) showed bigger content variation were identified by coefficient of variation analysis. The LC-MS based pseudotargeted metabonomic method established in this study can be applied to the comprehensive detection of saikosaponins, which providing new method for the quality evaluation of Bupleuri Radix.