Mechanism of HES1 regulating herceptin resistance in gastric cancer cells by ferroptosis / 药学学报

Drug resistance of cancer cells is the main causes of chemotherapy failure, and gene mutation or function loss is key factor to induce drug resistance. Previous studies have shown that hairy and enhancer of split 1 (HES1) is up-regulated in herceptin-resistant gastric cancer cells, and inhibition of its activity can reverse its resistance while the potential mechanism has not yet been elucidated. In this study, we employed CRISPR/Cas9 to establish HES1 knock-out cell line (△HES1/NCI N87R) to investigate the functions of HES1 in herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △HES1/NCI N87R cells based on quantitative proteomics. Gene ontology analysis was conducted by GeneSet Enrichment Analysis (GSEA) and Metascape database, and pathway enrichment analysis was done using GeneAnalytics database. The selected molecules were quantified by Western blot and some pathways were verified by using inhibitors. The results showed that the resistance to herceptin of △HES1/NCI N87R cells decreased compared to NCI N87R cells. Proteomic data demonstrated that the expression of 1 263 genes changed significantly in △HES1/NCI N87R cells, among which 761 genes were up-regulated while 502 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that ferroptosis, fatty acid β-oxidation, autophagy and glutathione metabolism, etc. exhibited notable changes in △HES1/NCI N87R cells. The functional studies showed that the levels of iron ion and malondialdehyde increased, and glutathione decreased in △HES1/NCI N87R cells. It was further found that Fer-1, a ferroptosis inhibitor, could reverse the expression of pTP53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in △HES1/NCI N87R cell, and reduce the sensitivity of △HES1/NCI N87R cells to herceptin. It is suggested that HES1 regulated the resistance of NCI N87R cells to herceptin through TP53/SLC7A11/GPX4 signaling pathway, and targeting TP53/SLC7A11/GPX4 signal axis mediated by HES1 is a potential strategy to reverse herceptin resistance in gastric cancer.

Mechanism of essential oil from Schizonepeta tenuifolia in treatment of depression based on network pharmacology and experimental verification / 中国中药杂志

This paper aimed to explore the antidepressant effect of the essential oil from Schizonepeta tenuifolia Briq.(EOST) on the treatment of depression and its mechanism by using a combination of network pharmacology and the mouse model of lipopolysaccharide(LPS)-induced depression. The chemical components in EOST were identified using gas chromatography-mass spectrometer(GC-MS), and 12 active components were selected as the study objects. The targets related to EOST were obtained by Traditional Chinese Medicines Systems Pharmacology(TCMSP) and SwissTargetPrediction database. The targets related to depression were screened out through GeneCards, Therapeutic Target Database(TTD), and Online Mendelian Inheritance in Man(OMIM) database. The Venny 2.1 was applied to screen out the common targets of EOST and depression. The targets were imported into Cytoscape 3.7.2 to generate "drug-active component-diease-target" network diagram. The protein-protein interaction(PPI) network was constructed using STRING 11.5 database and Cytoscape 3.7.2, and the core targets were screened out. DAVID 6.8 database was used for Gene Ontology(GO) func-tional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and subsequently the enrichment results were visualized through the bioinformatics platform. The mouse model of depression was induced by intraperitoneally injecting with LPS in mice. Before modeling, mice were administrated orally with EOST. The antidepressant effect of EOST was evalua-ted by tail suspension test(TST), forced swimming test(FST), and novelty suppressed feeding test(NSFT) after modeling. The content of interleukin(IL)-1β was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression levels of IL-1β and pro IL-1β in the hippocampus were determined by Western blot. There were 12 main components and 179 targets in EOAT, of which, 116 targets were related to depression, mainly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, and cyclic adenosine monophosphate(cAMP) signaling pathway. Biological processes such as synaptic signal transduction, G-protein coupled receptor signaling pathway, and chemical synaptic transmission were involved. Molecular functions such as neurotransmitter receptor activity, RNA polymerase Ⅱ transcription factor activity, and heme binding were involved. In mice experiments, the results showed that EOST at 100 mg·kg~(-1) and 50 mg·kg~(-1) significantly shortened the immobility time in TST and FST as well as the feeding latency in NSFT compared with the model group, decreased the levels of serum IL-1β and NO, and reduced the protein expression levels of IL-1β and pro IL-1β in the hippocampus. In conclusion, EOST shows a good antidepressant effect in a multi-component, multi-target, and multi-pathway manner. The mechanism may be attributed to the fact that EOST can down-regulate the protein expression levels of IL-1β and pro IL-1β, decrease the release of inflammatory factors, and reduce neuroinflammation response.

Value for combination of T1WI star -VIBE with TWIST -VIBE dynamic contrast -enhanced MRI in distinguishing lung nodules / 中南大学学报(医学版)

OBJECTIVES@#With the increasing detection rate of lung nodules, the qualitative problem of lung nodules has become one of the key clinical issues. This study aims to evaluate the value of combining dynamic contrast-enhanced (DCE) MRI based on time-resolved imaging with interleaved stochastic trajectories-volume interpolated breath hold examination (TWIST-VIBE) with T1 weighted free-breathing star-volumetric interpolated breath hold examination (T1WI star-VIBE) in identifying benign and malignant lung nodules.@*METHODS@#We retrospectively analyzed 79 adults with undetermined lung nodules before the operation. All nodules of patients included were classified into malignant nodules (n=58) and benign nodules (n=26) based on final diagnosis. The unenhanced T1WI-VIBE, the contrast-enhanced T1WI star-VIBE, and the DCE curve based on TWIST-VIBE were performed. The corresponding qualitative [wash-in time, wash-out time, time to peak (TTP), arrival time (AT), positive enhancement integral (PEI)] and quantitative parameters [volume transfer constant (Ktrans), interstitium-to-plasma rate constant (Kep), and fractional extracellular space volume (Ve)] were evaluated. Besides, the diagnostic efficacy (sensitivity and specificity) of enhanced CT and MRI were compared.@*RESULTS@#There were significant differences in unenhanced T1WI-VIBE hypo-intensity, and type of A, B, C DCE curve type between benign and malignant lung nodules (all P<0.001). Pulmonary malignant nodules had a shorter wash-out time than benign nodules (P=0.001), and the differences of the remaining parameters were not statistically significant (all P>0.05). After T1WI star-VIBE contrast-enhanced MRI, the image quality was further improved. Compared with enhanced CT scan, the sensitivity (82.76% vs 80.50%) and the specificity (69.23% vs 57.10%) based on MRI were higher than that of CT (both P<0.001).@*CONCLUSIONS@#T1WI star-VIBE and dynamic contrast-enhanced MRI based on TWIST-VIBE were helpful to improve the image resolution and provide more information for clinical differentiation between benign and malignant lung nodules.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine / 中国结合医学杂志

OBJECTIVE@#To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine.@*METHODS@#Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients.@*RESULTS@#Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD.@*CONCLUSIONS@#Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Biallelic mutations in WDR12 are associated with male infertility with tapered-head sperm / 亚洲男科学杂志(英文版)

Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility.

Relationship between pyroptosis and cardiovascular diseases and traditional Chinese medicine prevention and treatment research / 中国中药杂志

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.

Development and validation of a prognostic model based on SEER data for patients with esophageal carcinoma after esophagectomy / 南方医科大学学报

OBJECTIVE@#To develop a nomogram to predict the long-term survival of patients with esophageal cancer following esophagectomy.@*METHODS@#We collected the data of 7215 patients with esophageal carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database during the period from 2004 and 2016. Of these patients, 5052 were allocated to the training cohort and the remaining 2163 patients to the internal validation cohort using bootstrap resampling, with another 435 patients treated in the Department of Cardiothoracic Surgery of Jinling Hospital between 2014 and 2016 serving as the external validation cohort.@*RESULTS@#In the overall cohort, the 1-, 3-, and 5-year cancer-specific mortality rates were 14.6%, 35.7% and 41.6%, respectively. Age (≥80 years vs < 50 years, P < 0.001), gender (male vs female, P < 0.001), tumor site (lower vs middle segment, P=0.013), histology (EAC vs ESCC, P=0.012), tumor grade (poorly vs well differentiated, P < 0.001), TNM stage (Ⅳ vs Ⅰ, P < 0.001), tumor size (> 50 mm vs 0-20 mm, P < 0.001), chemotherapy (yes vs no, P < 0.001), and LNR (> 0.25 vs 0, P < 0.001) were identified as independent risk factors affecting long-term survival of the patients. The nomograms established based on the model for predicting the survival probability of the patients at 1, 3 and 5 years after operation showed a C-index of 0.726 (95% CI: 0.714-0.738) for predicting the overall survival (OS) and of 0.735 (95% CI: 0.727-0.743) for cancer-specific survival (CSS) in the training cohort. In the internal validation cohort, the C-index of the nomograms was 0.752 (95% CI: 0.738-0.76) for OS and 0.804 (95% CI: 0.790-0.817) for CSS, as compared with 0.749 (95% CI: 0.736-0.767) and 0.788 (95%CI: 0.751-0.808), respectively, in the external validation cohort. The nomograms also showed a higher sensitivity than the TNM staging system for predicting long-term prognosis.@*CONCLUSION@#This prognostic model has a high prediction efficiency and can help to identify the high-risk patients with esophageal carcinoma after surgery and serve as a supplement for the current TNM staging system.

Design and practice of SPOC mixed teaching based on MOOC in general medical courses / 中华医学教育探索杂志

Taking "count down your weight—start from 'diet'" as an example, this article discusses the design and practice of SPOC (small private online course) mixed teaching based on MOOC (massive open online course) in general medical courses. By designing teaching methods and teaching content, and using formative evaluation methods, the SPOC mixed teaching was implemented for 201 students from Sichuan University in the spring of 2020. According to the teaching evaluation and preliminary teaching effect, students generally believed that teaching resources were relatively abundant and the communication effects were generally recognized, as well as, it could significantly improve students' interest in and effect of general medical courses.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis / 中国天然药物

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

RUNX3 regulates trastuzumab resistance of gastric cancer cells: a metabolomic analysis based on UPLC-Q Exactive Focus Orbitrap mass spectrometry / 南方医科大学学报

OBJECTIVE@#To explore the role of Runt-related transcription factor 3 (RUNX3) in metabolic regulation of trastuzumab-resistant gastric cancer cells and investigate the mechanism of RUNX3 knockdown-mediated reversal of trastuzumab resistance.@*METHODS@#We performed a metabolomic analysis of trastuzumab-resistant gastric cancer cells (NCI N87R) and RUNX3 knockdown cells (NCI N87R/RUNX3) using ultra performance liquid chromatography (UPLC) coupled with Q Exactive Focus Orbitrap mass spectrometry (MS). Multivariate combined with univariate analyses and MS/MS ion spectrums were used to screen the differential variables. MetaboAnalyst 5.0 database was employed for pathway enrichment analysis. Differential metabolites-genes regulatory relationships were constructed based on OmicsNet database. The changes in GSH/GSSG and NADPH/NADP ratios in NCI N87R/RUNX3 cells were measured using detection kits.@*RESULTS@#The metabolic profile of NCI N87R cells was significantly altered after RUNX3 knockdown, with 81 differential metabolites identified to contribute significantly to the classification, among which 43 metabolites were increased and 38 were decreased (P < 0.01). In NCI N87R cells, RUNX3 knockdown resulted in noticeable alterations in 8 pathways involving glutamine metabolism, glycolysis, glycerophospholipid, nicotinate-nicotinamide and glutathione metabolism, causing also significant reduction of intracellular GSH/GSSG and NADPH/NADP ratios (P < 0.01). The differential metabolites-genes network revealed a regulatory relationship between the metabolic molecules and genes.@*CONCLUSION@#RUNX3 reverses trastuzumab resistance in gastric cancer cells by regulating energy metabolism and oxidation-reduction homeostasis and may serve as a potential therapeutic target for trastuzumab-resistant gastric cancer.

Protective effect of isorhamnetin on oxidative stress injury of HaCaT cells induced by H 2O 2 / 中国医师杂志

Objective:To investigate the protective effect of isorhamnetin on oxidative stress injury of HaCaT cells induced by H 2O 2. Methods:HaCaT cells were cultured in vitro and treated with different concentrations of H 2O 2 (300, 600, 900, 1 200 μmol/L) for 12 h. Cell proliferation activity was detected by cell counting kit-8 (CCK-8) assay; SOD activity was detected by superoxide dismutase (SOD) kit and malondialdehyde (MDA) content was detected by MDA assay. The oxidative stress model was established by the selection of suitable H 2O 2 concentration. HaCaT cells were pretreated with isorhamnetin at different concentrations for 12 h, and cell survival rate was detected by CCK-8 method to determine the safe concentration of isorhamnetin for subsequent experiments. HaCaT cells were pretreated with safe concentration of isorhamnetin for 12 h, and H 2O 2 was used to interfere with HaCaT cells for 12 h. Cell proliferation activity, SOD activity and MDA content were detected. Results:With the increase of H 2O 2 concentration, the cell survival rate decreased gradually, the SOD activity decreased gradually and MDA content increased gradually. Compared with the control group, the survival rate of 600, 900 and 1 200 μmol/L H 2O 2 groups was statistically significant ( P<0.05); The SOD activity and MDA content of H 2O 2 groups (300, 600, 900, 1 200 μmol/L) were significantly different from those of the control group ( P<0.05). The oxidative stress model of HaCaT cells was established by 600 μmol/L H 2O 2. HaCaT cells treated with 20, 40, 60, 80 and 100 μmol/L isorhamnetin for 12 h showed no cytotoxic effect. 20, 40 and 60 μmol/L isorhamnetin was selected for subsequent experiments. Compared with H 2O 2 groups, the cell proliferation activity in 40 and 60 μmol/L isornetin groups was significantly increased [(72.21±5.11)%, (76.08±4.91)%, P<0.05], SOD activity increased (19.81±0.38, 20.52±0.52, 15.45±3.13, P<0.05) and MDA content decreased (35.94±0.31, 22.04±0.26, 19.26±1.36, P<0.05). Conclusions:The flavonoid isorhamnetin has a protective effect on oxidative stress injury induced by H 2O 2 in HaCaT cells, suggesting that isorhamnetin may be a potential drug component in the treatment of vitiligo.

Determination of methyl pentane in workplace air by solvent desorption-gas chromatography / 中国职业医学

OBJECTIVE: To establish a solvent desorption-gas chromatography method for determination of methyl pentane in workplace air. METHODS: Methyl pentane in workplace air was collected with activated carbon tube and desorbed with carbon disulfide, then separated by DB-1 capillary column, detected by flame ionization detector, and quantified by standard curve method. RESULTS: Good linearity was obtained in the range of 1.98-6 600.00 mg/L with the correlation coefficient of 0.999 9. The minimum detection limit and the minimum quantification limit were 0.06 and 0.20 mg/L, respectively. The minimum detection concentration and minimum quantification concentration was 0.04 and 0.14 mg/m~3, respectively(calculated by collecting 1.5 L of air sample). The average desorption efficiency was 97.3%-102.2%. The within-run relative standard deviation(RSD) and the between-run RSD were 0.4%-0.9% and 0.3%-3.0%, respectively. The sampling efficiency was 96.7%-100.0% and the penetration capacity was 8.68 mg. The samples can be stored at room temperature for at least 14 days. CONCLUSION: This method is suitable for methyl pentane detection in workplace air.

Determination of volatile organic compounds in air using portable gas chromatography-mass spectrometry / 中国职业医学

OBJECTIVE: To explore a method for detecting volatile organic compounds(VOCs) in air by a portable gas chromatography-mass spectrometer(GC-MS). METHODS: A portable GC-MS hand-held probe was used for sampling and detection. All effluent components were qualitatively analyzed by the standard spectral library of the United State National Institute of Standards and Technology. The percentage of peak area of the component was calculated by normalization method. The static distribution method was adopted in the semi-quantitative and quantitative analysis using nitrogen as the diluting gas to prepare different mass concentration of 13 kinds of VOCs in the mixed standard gas. The retention time and characteristic ions were used for qualitative analysis, and the quantitated full scanning mode was used for quantitative analysis.RESULTS: The minimum detected mass concentration of the 13 chemical harmful factors was 0.02-0.10 mg/m~3, and the minimum quantitative mass concentration was 0.07-0.38 mg/m~3. The recovery rate was 84.76%-116.56%, and the within-and between-run relative standard deviations were 4.10%-12.50% and 8.17%-14.36%, respectively. CONCLUSION: The portable GC-MS instrument could be used for qualitative alalysis, peak area percentage determination, semi-quantitative and quantitative analysis of VOCs in the workplace air or sudden chemical poisoning accidents.

Effects of Pharmaceutical Management Intervention on Clinical Use of TCM Injection in Primary Medical Insti- tutions / 中国药房

OBJECTIVE：To investigate the effects of pharmaceutical management intervention on the use of TCM injection in primary medical institutions. METHODS ：Twenty grass-roots health centers in Yichun city ，Jiangxi province were randomly selected. Relying on Department of Pharmacy and Health Services of the Municipal Health Committee and the Quality Control Center for Pharmacy Affairs of the City ，Yichun People ’s Hospital took the lead in establishing the prescription evaluation criteria for TCM injection ，training pharmaceutical service skills ，conducting special reviews on prescriptions/medical orders ，improving control measures ，obtaining relevant data of drug use in primary health centers by issuing questionnaires on the use of TCM injection and randomly selecting prescriptions/medical orders for comments. The relevant data without drug administration （before intervention）from Jan. to Jun. 2018 were taken as the non-intervention group ，and the relevant data with drug administration （after intervention）from Jan. to Jun. 2019 were taken as the intervention group. The use of TCM medicine injection ，DDDs，DDC and sequencing ratio were compared before and after intervention. At the same time ，the prescriptions/medical orders of TCM injections before（1 222 copies）and after （1005 copies）intervention were randomly selected for comment and the reasonable situations of the prescriptions/medical orders were compared before and after the intervention. RESULTS ：After intervention ，total amount ， consumption sum and DDDs of top 10 TCM injections in the list of amount were significantly decreased. The reasonable rate of prescriptions and medical orders was 48.04％ before intervention ， but increased to 70.65％ after intervention. Besides ， unreasonable situations before and after intervention all manifested as inappropriate indications. After the intervention ，the unreasonable rates of Xuesaitong powder for injection （lyophilized），Xueshuantong injection ，Xingnaojing injection （two specifications），Shengmai injection ，Xueshuantong for injection （lyophilized）and Qingkailing injection were significantly lower than before intevention （P＜0.05）. CONCLUSIONS ：Pharmaceutical administration intervention can reduce the total amount and the consumption sun of TCM injection in primary medical institutions ，and promote rational drug use in the clinic.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial / 中西医结合学报

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

Evaluation of the Clinical Efficacy and Prognosis of Long-Term Maintenance Lenalidomide Therapy in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical efficacy and prognosis of patients with multiple myeloma (MM) treated by long-term maintenance lenalidomide treatment.@*METHODS@#A total of 97 patients diagnosed as MM in the Department of Hematology of First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2012 to 2019 were selected, and the basic clinical characteristics and laboratory indicators of the patients were tested and evaluated. After long-term maintenance lenalidomide treatment for patients with MM, the short-term and long-term clinical efficacy and the incidence of adverse reactions were evaluated, and factors affecting the prognosis of the patients were analyzed.@*RESULTS@#Before maintenance treatment, 47.42% of the patients (46/97) did not achieve complete remission (CR), among 52.58% (51/97) of CR patients, there were 20.62% of the patients showed minimal residual leukemia (MRD) negative. After lenalidomide maintenance treatment, the patients who did not achieve CR were reduced to 24.74% (24/97), among 75.26% (73/97) of the patients with CR, there were 47.42% of the patients showed MRD negative, the difference showed statistically significant (P<0.001). After maintenance treatment, the median pro-gression-free survival of the patients was 58 months, and the 5-year survival rate was 89.69%. The incidence of adverse reactions was 40.21% (39/97), including neutropenia (31/39, 79.49%), fatigue (21/39, 53.85%), thrombocytopenia (17/39, 43.59%) and gastrointestinal reaction (15/39, 38.46%) were the most common. The discontinuation rate was 24.74% (24/97), and the median time for discontinuation was 21 months. The main reasons for discontinuation were neutropenia (12/24, 50.00%) , thrombocytopenia (8/24, 33.33%) and gastrointestinal reactions accounted for 8.33% (2/24). Old age and positive MRD were the risk factors affecting the prognosis of the patients. The adjusted OR was 1.43 (95% CI 1.03-1.76, P=0.034) and 3.78 (95% CI 2.56-9.56, P=0.037), respectively.@*CONCLUSION@#The long-term maintenance lenalidomide treatment shows a good clinical effect on patients with MM, and MRD detection can assist the cilinical judge the prognosis of the patients. During maintenance treatment, the clinical symptoms, especially blood system damage of the patients should be take care, so as to avoid serious adverse reactions.

Correlation between cervical curvature and cervical disc bulging in young patients with neck pain / 中国骨伤

OBJECTIVE@#To explore the correlation between the curvature of the cervical spine and the degree of cervical disc bulging in young patients with cervical pain.@*METHODS@#The clinical data of 539 young patients with neck pain from January 2015 to December 2018 were retrospectively analyzed. There were 251 males and 288 females, aged 18 to 40 (32.2±6.3) years old. The cervical curvature and cervical disc bulging were measured by cervical X-ray and MRI. According to cervical curvature, the patients were divided into 175 cases of cervical lordosis group (cervical curvature > 7 mm), 163 cases of cervical erection group (0

Label-free quantitative proteomic study of RUNX3 regulating Herceptin resistance in gastric cancer cells / 药学学报

Resistance of tumor cells is a complex biological process involving multiple mechanisms and factors, in which anti-apoptosis is the most important cause of drug resistance. Previous studies have shown that the DNA binding activity of Runt related transcription factor 3 (RUNX3) increased prominently in Herceptin resistant gastric cancer cells (NCI N87R) while the relevance of which to drug resistance has not yet been confirmed. In this study, we employed CRISPR/Cas9 to establish RUNX3 knock-out cell line (△RUNX3/NCI N87R) to investigate the functions of RUNX3 in Herceptin resistance of NCI N87R cells and its potential mechanisms. We investigated proteomics profiling of △RUNX3/NCI N87R cells based on label free quantitative proteomics. Differentially expressed proteins were screened out according to fold change and significance level between △RUNX3/NCI N87R and NCI N87R cells. Pathway enrichment analysis was done using GeneAnalytics database, and gene ontology analysis was conducted by DAVID Bioinformatics Resources database. Protein-protein interaction networks were constructed based on STRING database. The results showed that △RUNX3/NCI N87R cells increased the sensitivity to Herceptin. Proteomic data demonstrated that the expression of 577 genes changed significantly in △RUNX3/NCI N87R cells, among which 191 genes were up-regulated while 386 ones down-regulated comparing with NCI N87R cells. Pathway analysis showed that autophagy, cell cycle, apoptosis, mitochondrial fatty acid β oxidation, neurogenic locus notch homolog protein 1 (NOTCH1), mammalian target of rapamycin (mTOR), Hedgehog and DNA damage response pathways exhibited notable changes based on pathway enrichment ratio and significance level (P < 0.05). These results indicated that RUNX3 knock-out altered multiple signaling pathways of NCI N87R cells. Western blotting manifested that the expression of autophagy regulatory molecules autophagy-related protein (ATG) 13, 7 and BECN1 increased remarkably while cell cycle molecules serine/threonine-protein kinase Chk2 (CHEK2) and apoptosis regulator Bcl-2 (BCL2) decreased prominently in △RUNX3/NCI N87R cells. The p-AKT expression decreased significantly in △RUNX3/NCI N87R cells compared with NCI N87R cells (P < 0.01) and was suppressed by Herceptin. These results indicated that RUNX3 knock-out altered cell cycle, increased inhibition to p-AKT by Herceptin, promoted autophagy and induced cell apoptosis of NCI N87R cells. These results suggested that RUNX3 may be a potential therapeutic target for reversing or reducing Herceptin resistance in gastric cancer cells.

Investigation on clinical application and management of food for special medical purpose in China's 592 medical institutions in 2020 / 中华临床营养杂志

Objective:To understand the current situation of clinical application and management of food for special medical purpose (FSMP) in China's medical institutions.Methods:A questionnaire was developed based on literature review, consultation with experts and multiple discussions to investigate the application and management of FSMP in hospitals. The survey was conducted in secondary and tertiary general or specialized hospitals in China. The accountable person of Clinical Nutrition Department in each hospital filled in the questionnaire with the guidance from provincial quality control center.Results:A total of 592 hospitals across 30 provinces/municipalities participated in the survey. The majority (40.5%) of prescription for FSMP with approved batch number was given by clinical nutrition departments, nutritional risk screening was conducted before using FSMP as enteral nutrition in 64.0% of the hospitals, consent from patients or their families prior to initial FSMP use was required in 94.8% of the hospitals, follow-up after FSMP use was carried out in 86.5% of the hospitals, 79.2% of the hospitals maintained electronic or paper documentation of the clinical application of enteral nutrition preparations, 41.6% of the hospitals had no organization or institution to supervise the standardized application of FSMP.Conclusion:In the future, we should strengthen the construction of FSMP professional team, establish convenient and efficient nutrition diagnosis and treatment information module, and set up special institutions to implement FSMP standardized management.

Antidepressant Effect of n-Butyl Alcohol Extracts from Xiaoyaosan via IGF-1Rβ/PI3K/Akt Pathway / 中国实验方剂学杂志

Objective:To investigate the intervention effect of <italic>n</italic>-butyl alcohol extracts from Xiaoyaosan against depression-like behavior induced by chronic unpredictable mild stress （CUMS） in model mice and the role of insulin-like growth factor-1 receptor <italic>β</italic> （IGF-1R<italic>β</italic>）/phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt） signaling pathway in such intervention. Method:The effective dose of n-butyl alcohol extracts from Xiaoyaosan was preliminarily determined in model mice with behavioral despair. Then the male C57BL/6 mice were randomly divided into the blank group， model group， fluoxetine group， Xiaoyaosan group， and the low- （20 g·kg^-1） and high-dose （40 g·kg^-1） <italic>n</italic>-butyl alcohol extract groups. The mice in all groups except for the blank group were exposed to CUMS for inducing the depression-like behavior， which was judged by the sucrose preference test （SPT）. The successfully modeled mice in the medication groups were intragastrically administered with the corresponding drugs， whereas those in the blank and model groups were treated with an equal volume of solvent for five successive weeks. Following the SPT， tail suspension test （TST）， and novelty suppressed feeding test （NSFT） at the end of the fifth week， the insulin-like growth factor-1 （IGF-1） levels in mouse serum and hippocampus were measured by enzyme-linked immunosorbent assay （ELISA）. The average optical density （<italic>IA</italic>） of Nissl bodies in mouse hippocampal CA3 region was detected by toluidine blue staining. The 5-bromo-2-deoxyuridine （Brdu） and doublecortin （DCX） expression in the dentate gyrus （DG） was assayed using immunofluorescence method. The protein expression levels of IGF-1R<italic>β</italic>， PI3K， phosphorylated-PI3K （p-PI3K）， Akt， p-Akt， cysteine aspartic acid-specific protease 3 （Caspase-3）， and cleaved Caspase-3 in the hippocampus were determined by Western blot. Result:The results of forced swimming test and TST showed that n-butyl alcohol extracts from Xiaoyaosan at 9.1 and 40 g·kg^-1 both significantly shortened the immobility time of mice （<italic>P</italic><0.05， <italic>P</italic><0.01）， indicating that the effective dose ranged from 9.1-40 g·kg^-1. Compared with the model control， the n-butyl alcohol extracts from Xiaoyaosan at 20 and 40 g·kg^-1 significantly increased the sucrose preference percentage （<italic>P</italic><0.05， <italic>P</italic><0.01）， shortened the immobility time in TST （<italic>P</italic><0.01） and the feeding latency in NSFT （<italic>P</italic><0.01）， reversed the down-regulated IGF-1 content in mouse serum and hippocampus （<italic>P</italic><0.01）， increased the AOD of Nissl bodies in the hippocampal CA3 region （<italic>P</italic><0.01）， promoted the expression of Brdu and DCX in DG （<italic>P</italic><0.05， <italic>P</italic><0.01）， and down-regulated the protein expression levels of IGF-1R<italic>β</italic> （<italic>P</italic><0.05， <italic>P</italic><0.01）， p-PI3K/PI3K （<italic>P</italic><0.05， <italic>P</italic><0.01）， p-Akt/Akt （<italic>P</italic><0.05）， and cleaved Caspase-3/Caspase-3 in the hippocampus of CUMS mice. Conclusion:The n-butyl alcohol extracts from Xiaoyaosan are equivalent to Xiaoyaosan in inhibiting expression. They alleviate the depression-like behavior in CUMS mice， induce the production of Nissl bodies in hippocampal CA3 region， enhance neuronal proliferation and differentiation in DG， and facilitate neurogenesis. All these may be related to the inhibition of over-activated IGF-1R<italic>β</italic>/PI3K/Akt pathway and the reduction of neuronal apoptosis.