Inhibitory effect of astaxanthin on oxidative stress damage in lens epithelial cells and its mechanism / 中华实验眼科杂志

Objective:To investigate the regulatory effect of astaxanthin on oxidative stress injury induced by hydrogen peroxide (H 2O 2) in lens epithelial cells and its possible mechanism. Methods:The HLEB-3 cells were cultured with different concentrations (0, 50, 100, 200, 500, 750 μmol/L) of H 2O 2.The cell inhibition rate was detected by the methyl thiazolyl tetrazolium (MTT) method, and the 50%inhibiting concentration (IC50) was calculated.HLEB-3 cells were cultured with different concentrations (0, 5, 10, 20, 50 μmol/L) of astaxanthin.The cell survival rate was detected by the MTT method.HLEB-3 cells were divided into four groups for 24-hour culture, namely normal control group cultured with complete medium, oxidative stress group cultured with 250 μmol/L H 2O 2, 10 μmol/L astaxanthin group cultured with 10 μmol/L astaxanthin and 250 μmol/L H 2O 2, and 20 μmol/L astaxanthin group cultured with 20 μmol/L astaxanthin and 250 μmol/L H 2O 2.The cell apoptosis rate was determined by flow cytometry.The nitric oxide (NO) concentration, superoxide dismutase (SOD) activity, glutathione (GSH) activity and malondialdehyde (MDA) content were detected by ELISA.The protein expressions of nuclear factor erythroid-2 related factor 2 (Nrf2) in nuclei, cytoplasmic Nrf2, heme oxygenase-1 (HO-1) and NAD (P) H, quinine oxidoreductase 1 (NQO1) were detected by Western bolt.The cells were divided into four groups, namely normal control-small interfering RNA (NC-siRNA) group, Nrf2-siRNA group, NC-siRNA+ astaxanthin group and Nrf2-siRNA+ astaxanthin group.The cells were transfected with NC-siRNA or Nrf2-siRNA accordingly.The cells were co-cultured for 24 hours with 0/10 μmol/L astaxanthin and 250 μmol/L H 2O 2 24 hours after transfection, respectively.The cell apoptosis rate was determined by flow cytometry.The NO concentration, SOD activity, GSH activity and MDA content were detected by ELISA. Results:With the increase of H 2O 2 concentration, the inhibition rate of HLEB-3 cells increased.There were significant differences in the inhibition rate of HLEB-3 cells treated with different concentrations of H 2O 2 ( F=12.358, P<0.05). The IC50 value of H 2O 2 on HLEB-3 cells was 264.20 μmol/L.The survival rates of HLEB-3 cells treated with 0, 5, 10, 20 and 50 μmol/L astaxanthin were (100.00±0.00)%, (102.20±1.34)%, (109.50±3.60)%, (115.40±4.13)%, (93.60±2.59)%, respectively.Then 10 μmol/L and 20 μmol/L were chosen as the experimental dose.The cell apoptosis rate of oxidative stress group was (38.50±2.38)%, which was higher than (9.20±0.24)% of normal control group, with a statistically significant difference ( P<0.05). The cell apoptosis rate of 10 μmol/L astaxanthin group was (27.60±4.33)%, which was lower than (38.50±2.38)% of oxidative stress group, but higher than (14.90±1.23)% of 20 μmol/L astaxanthin group and (9.20±0.24)% of normal control group, showing statistically significant differences (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in oxidative stress group than in normal control group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and the differences were statistically significant (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in 10 μmol/L astaxanthin group than in normal control group and 20 μmol/L astaxanthin groups, and the differences were statistically significant (all at P<0.05). There were significant differences in the relative expression levels of nuclear Nrf2, cytoplasmic Nrf2, HO-1 and NQO1 proteins among normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group ( F=43.512, 20.381, 31.014, 23.435; all at P<0.001). The relative expression of nuclear Nrf2 protein gradually decreased, and the relative expression of nuclear Nrf2, HO-1 and NQO1 proteins increased gradually in normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and there were significant differences when compared in pairs (all at P<0.05). The apoptosis rates of Nrf2-siRNA group and Nrf2-siRNA+ astaxanthin group were higher than those of NC-siRNA group and NC-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). The cell apoptosis rate was higher in NC-siRNA group than in NC-siRNA+ astaxanthin group, showing a statistically significant difference ( P<0.05). There was no significant difference in the apoptosis rate between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group ( P>0.05). The NO and MDA concentrations were higher and the SOD and GSH activities were lower in Nrf2-siRNA group than in the NC-siRNA group, with statistically significant differences (all at P<0.05). The NO and MDA concentrations were lower and the SOD and GSH activities were higher in NC-siRNA+ astaxanthin group than in NC-siRNA group and Nrf2-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). There was no significant difference in NO and MDA concentrations or the SOD and GSH activities between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group (all at P>0.05). Conclusions:Astaxanthin enhances the resistance of lens epithelial cells to H 2O 2-induced oxidative stress damage, which may be achieved by activating the Nrf2-related signaling pathway.

Efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors of gastric cardia and fundus: a multicenter study / 中华消化外科杂志

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

Effects of FasL inhibitors on corneal apoptosis and Treg after corneal transplantation in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of intravitreal injection FasL inhibitors on corneal apoptosis, Fas, FasL expression, Treg numbers in blood and lymph nodes and rejection index in rats after corneal transplantation.METHODS:A total of 24 SD rats(24 eyes)who received penetrating keratoplasty were randomly divided into two groups: PBS group received intravitreal injection of PBS(12 rats, 12 eyes)and FasL inhibitor group(12 rats, 12 eyes). Rejection index was recorded every week and blood samples and lymph node were collected at 1, 3 and 5wk after surgery to analyze the proportions of Treg. Corneal tissue was collected for detecting the expression of Fas and FasL and number of apoptosis.RESULTS: The expression of Fas, FasL in FasL inhibitor group decreased significantly compared with the PBS group(all P&#x003C;0.05); Corneal cell apoptosis significantly decreased in FasL inhibitor group, and it was the lowest at 5wk after surgery; Treg numbers in blood and lymph nodes significantly increased in FasL inhibitor group at 3wk after surgery(all P&#x003C;0.05); rejection index of corneal transplantation in the FasL inhibitor group was significantly lower than that of PBS group(all P&#x003C;0.05).CONCLUSION:Intravitreal injection of FasL inhibitors after corneal transplantation could reduce the apoptosis in all layers of cornea, increase the number of Tregs in blood and lymph nodes, and alleviate rejection.

Sleep status and influencing factors among higher vocational college students / 四川精神卫生

BackgroundSleep disorder can adversely affect human physical and mental health， with important implications for socioeconomic development. And higher vocational college students are subject to various pressures and stimuli exerted by academic studies， job seeking and family socioeconomic status， which may contribute to the onset insomnia symptom or sleep disorder. ObjectiveTo discuss the sleep status and influencing factors among higher vocational college students， and to provide references for improving their sleep status. MethodsIn January and February， 2022， a stratified random sampling method was utilized to enroll 3 300 students from five higher vocational colleges in Wenjiang district of Chengdu city. All the participants were assessed using Insomnia Severity Index （ISI）， Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and Generalized Anxiety Disorder Scale-7 （GAD-7）. Pearson correlation analysis was conducted to test the correlation of ISI with PHQ-9 and GAD-7 scores， and the Logistic regression analysis was performed to identify the influencing factors of insomnia symptom in higher vocational college students. ResultInsomnia symptom was detected in 81.90% （2 497 / 3 300） of higher vocational college students. The detection rate of insomnia symptom among vocational college students yielded statistical difference in terms of gender， family socioeconomic status， being an only child or having siblings， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom （χ2=21.032， 22.172， 8.983， 75.939， 36.781， 32.350， 54.512， 86.561， P<0.01 or 0.05）. Among higher vocational college students， ISI score was positively correlated with GAD-7 and PHQ-9 scores （r=0.620， 0.714， P<0.01）， and GAD-7 score was positively correlated with PHQ-9 score （r=0.824， P<0.01）. Gender， family socioeconomic status， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom were effective factors in predicting the insomnia symptom in higher vocational college students （P<0.01 or 0.05）. ConclusionFemale gender， average and below average family socioeconomic status， moderate-to-severe degree of psychological pressure exerted by academic studies or job seeking， spending 2~5 h， 5~7 h or >7 h on Internet per day， inadequate physical exercise and presence of depressive symptom are the risk factors for insomnia symptom in higher vocational college students.［Funded by Sichuan Provincial Primary Health Development Research Center in 2022， North Sichuan Medical College （number， SWFZ22-C-89）］

Electromyographic signals and the starting threshold voltage of orbicularis oris muscle in healthy rhesus monkeys / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of electromyography (EMG) signals and the starting threshold voltages of the orbicularis oris muscles (OOM) in healthy rhesus monkeys under different muscle movement conditions. Methods: The EMG signals and the starting threshold voltages at different time points in 4 healthy rhesus monkeys were acquired and recorded with EMG device and evoked potentiometer. The voltage amplitude variation of EMG signals was analyzed, and the voltage amplitude range of EMG signals at the beginning of OOM contraction was established. The data were statistically analyzed by one-way ANOVA. Results: The EMG of OOM in healthy monkeys in the quiet, natural and continuous mouth-closed state was linear and relatively stable, and the absolute value fluctuated between 15 and 50 μV. The EMG waveform increased rapidly during the natural lip contraction movement, and its amplitude fluctuated greatly, with the highest absolute value of the peak value reaching hundreds of microvolts. The amplitude of EMG induced by continuous mouth closure was more than thousands of microvolts. There was no significant difference in EMG amplitudes of OOM in the healthy rhesus monkey under quiet and continuous lip closure at different time points (P>0.05). There was no significant difference in threshold voltages in the state of natural lip contraction of bilateral OOM at different time points (average range: 57.17-57.47 μV) in the healthy rhesus monkeys (P>0.05). There was no significant difference in threshold voltages of OOM induced by bilateral OOM at different time points(average range: 55.38-55.99 μV) in the healthy rhesus monkeys(P>0.05). There were significant differences in the absolute values of EMG amplitudes of OOM between the three lip movement modes: (30.67±8.72) μV in quiet and natural continuous lip closure (475.12±54.72) μV in natural lip contraction, and (921.22±312.79) μV in the induced persistent lip closure, with t values of -8.48, -9.35 and -5.01 respectively, all P<0.001. Conclusions: The EMG signals of OOM show different characteristics under different muscle movement conditions, which can be used as a basis for computer to judge and recognize the movement conditions of OOM. The upper limits of the EMG threshold voltage values of OOM under different motion states are 55-60 μV.

Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Phenolic glycosides from the stems and twigs of Strychnos cathayensis and their biological activities / 药学学报

Fourteen compounds were isolated from the n-butanol fraction of the 95% aqueous ethanol extract of the stems and twigs of Strychnos cathayensis by D101 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semipreparative RP-HPLC. Their structures were elucidated as ethyl 4-O-β-D-allopyranosyl-vanillate (1), n-butyl 4-O-β-D-allopyranosyl-vanillate (2), n-butyl 4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillate (3), n-butyl 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillate (4), n-butyl 4-O-(6′-O-syringoyl)-β-D-glucopyranosyl-vanillate (5), n-butyl 4-O-α-L-rhamnopyranosyl-syringate (6), methyl 3-methoxy-4-(β-D-allopyranosyloxy) benzoate (7), pseudolaroside B (8), butyl syringate (9), glucosyringic acid (10), methyl syringate (11), methyl 4-hydroxy-3-methoxybenzoate (12), clemochinenoside C (13), and clemoarmanoside A (14), respectively, on the basis of spectroscopic data interpretation and by comparison with literature information. Compounds 1-6 are artificial products of phenolic acid esterified by ethanol or n-butanol. It is noted that the precursors (4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillic acid and 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillic acid) of compounds 3 and 4 are new compounds. The hepatoprotective, anti-inflammatory, antioxidant and cytotoxic activities of compounds 1-13 were evaluated in vitro at a concentration of 10 μmol·L-1. Compounds 1, 2 and 6-10 exhibited potential hepatic protection effects with cell survival rates ranging from 53.6% to 55.5% (acetaminophen, 45.4% at 8 mmol·L-1). Compound 4 demonstrated anti-inflammatory activity with nitric oxide inhibitory rate of 74.6%. Compounds 3 and 5 showed potential antioxidant activities with malondialdehyde inhibitory rates of 53.2% and 56.1%, respectively.

Deafness genetic mutation spectrum in nonsyndromic hearing impairment associated with enlarged vestibular aqueducts / 中国康复理论与实践

ObjectiveTo investigate the deafness genetic mutation spectrum in nonsyndromic hearing impairment (NSHI) associated with enlarged vestibular aqueducts (EVA). MethodsFrom October, 2015 to August, 2016, 85 patients with NSHI from Hubei Yichang Special Education School were examined with temporal bone CT, and 20 deafness-related gene mutations in GJB2, GJB3, SLC26A4 and mtDNA 12S rRNA were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ResultsA total of 31 patients were found EVA with temporal bone CT. Compared with non-EVA patients, the proportion of deafness-related gene mutations was more in patients with EVA (χ2 = 11.160, P = 0.001), especially for c.919-2A>G mutation of SLC26A4 (χ2 = 23.870, P < 0.001). ConclusionThe deafness gene mutation spectrum is different in NSHI patients with or without EVA. It is needed to optimize genetic testing scheme for deafness for early diagnosis and intervention of NSHI associated with EVA.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).@*METHODS@#The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.@*RESULTS@#Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).@*CONCLUSION@#D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Analysis of Long-Term Prognostic Factors Based on Nutritional Status in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the prognostic factors of patients with multiple myeloma (MM) based on nutritional status.@*METHODS@#The Controlling Nutritional Status (CONUT) score and clinical parameters at diagnosis of 203 newly diagnosed MM patients hospitalized in the department of hematology, Wuxi People's Hospital from January 1, 2007 to June 30, 2019 were analyzed retrospectively. The best cut-off value was determined by ROC curve, and the patients were divided into high CONUT group (>6.5 points) and low CONUT group (≤6.5 points); through COX regression multivariate analysis of overall survival (OS) time, CONUT, ISS stage, LDH and treatment response were selected for multiparameter prognostic stratification.@*RESULTS@#The OS of MM patients in high CONUT group was shorter. The low-risk group (≤2 points) of the multiparameter risk stratification had longer OS time and progression-free survival (PFS) time compared with the high-risk group (>2 points), and it was also effective for different age or karyotype subgroups, new drug groups containing bortezomib and transplant-ineligible subgroup.@*CONCLUSION@#The risk stratification of MM patients based on CONUT, ISS stage, LDH and treatment response is worthy of clinical application.

The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017 / 中国实验血液学杂志

OBJECTIVE@#To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients.@*METHODS@#The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively.@*RESULTS@#A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival.@*CONCLUSION@#In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

Clinical and genetic characteristics of children with primary dilated cardiomyopathy / 中国当代儿科杂志

OBJECTIVES@#To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM).@*METHODS@#A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data.@*RESULTS@#Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05).@*CONCLUSIONS@#There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.

Traditional application and modern research progress on new foreign medicinal resources / 中国中药杂志

Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.

Cloning and catalytic analysis of Isatis indigotica chalcone isomerase in vitro / 中国中药杂志

Chalcone isomerase is a key rate-limiting enzyme in the biosynthesis of flavonoids in higher plants, which determines the production of flavonoids in plants. In this study, RNA was extracted from different parts of Isatis indigotica and reverse-transcribed into cDNA. Specific primers with enzyme restriction sites were designed, and a chalcone isomerase gene was cloned from I. indigotica, named IiCHI. IiCHI was 756 bp in length, containing a complete open reading frame and encoding 251 amino acids. Homology analysis showed that IiCHI was closely related to CHI protein of Arabidopsis thaliana and had typical active sites of chalcone isomerase. Phylogenetic tree analysis showed that IiCHI was classified into type Ⅰ CHI clade. Recombinant prokaryotic expression vector pET28a-IiCHI was constructed and purified to obtain IiCHI recombinant protein. In vitro enzymatic analysis showed that the IiCHI protein could convert naringenin chalcone into naringenin, but could not catalyze the production of liquiritigenin by isoliquiritigenin. The results of real-time quantitative polymerase chain reaction(qPCR) showed that the expression level of IiCHI in the aboveground parts was higher than that in the underground parts and the expression level was the highest in the flowers of the aboveground parts, followed by leaves and stems, and no expression was observed in the roots and rhizomes of the underground parts. This study has confirmed the function of chalcone isomerase in I. indigotica and provided references for the biosynthesis of flavonoid components.

Chemical constituents from leaves of Craibiodendron yunnanense / 中国中药杂志

The present study investigated the chemical constituents from the leaves of Craibiodendron yunnanense. The compounds were isolated and purified from the leaves of C. yunnanense by a combination of various chromatographic techniques including column chromatography over polyamide, silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified by extensive spectroscopic analyses including MS and NMR data. As a result, 10 compounds, including melionoside F(1), meliosmaionol D(2), naringenin(3), quercetin-3-O-α-L-arabinopyranoside(4), epicatechin(5), quercetin-3'-glucoside(6), corbulain Ib(7), loliolide(8), asiatic acid(9), and ursolic acid(10), were isolated. Compounds 1 and 2 were two new compounds, and compound 7 was isolated from this genus for the first time. All compounds showed no significant cytotoxic activity by MTT assay.

Sensitivity baseline establishment and resistance risk assessment of Botrytis cinerea from Panax ginseng to prochloraz / 中国中药杂志

This study aimed to establish the baseline sensitivity of Botrytis cinerea from Panax ginseng to prochloraz, and ensure the fitness of prochloraz-resistant mutants and the cross-resistance of B. cinerea to prochloraz and commonly used fungicides for the prevention and control of gray mold including boscalid, pyraclostrobin, iprodione, and pyrimethanil. The sensitivity of B. cinerea from P. ginseng to fungicides was determined by the mycelial growth rate method. The prochloraz-resistant mutants were screened out through fungicide domestication and ultraviolet(UV) induction. The fitness of resistant mutants was determined through the stability of subculture, mycelial growth rate, and pathogenicity test. The cross-resistance between prochloraz and the four fungicides was determined by Person correlation analysis. The results showed that all B. cinerea strains tested were sensitive to prochloraz, and the EC_(50) value ranged from 0.004 8 to 0.062 9 μg·mL~(-1), with an average of 0.022 μg·mL~(-1). The sensitivity frequency distribution diagram showed that 89 B. cinerea strains were located within the main peak with a continuous single peak curve, and the average EC_(50) value of 0.018 μg·mL~(-1) was taken as the baseline sensitivity of B. cinerea to prochloraz. The fungicide domestication and UV induction obtained 6 resistant mutants, among which 2 strains were unstable and the other 2 strains showed decreased resistance after multiple generations of culture. Furthermore, the mycelial growth rate and spore yield of all resistant mutants were lower than those of their parents, and the pathogenicity of most mutants was lower than that of their parents. In addition, prochloraz had no obvious cross-resistance with boscalid, pyraclostrobin, iprodione, and pyrimethanil. In conclusion, prochloraz has great potential for controlling gray mold in P. ginseng, and the resistance risk of B. cinerea to prochloraz is low.

Diterpenoid constituents in Pseudolarix amabilis and their antitumor activities in vitro / 中国中药杂志

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7β-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 μmol·L~(-1), respectively.

Key quality attributes of benchmark samples of famous classical formula Kaixin Powder / 中国中药杂志

We prepared 15 batches of Kaixin Powder benchmark samples with the decoction pieces of different batches. Further, we established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples and analyzed the peaks and similarity of the chromatograms. With sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid as index components, the index component content determination method was established and 70%-130% of the mean content of each component was set as the range. The chromatograms of 15 batches of Kaixin Powder benchmark samples had a total of 22 characteristic peaks, among which 8 peaks were identified, which represented sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3,6'-disinapoyl sucrose, ginsenoside Rb_1, β-asarone, α-asarone, and dehydropachymic acid, respectively. The chromatograms shared the similarity of 0.992-0.999. The 15 batches of benchmark samples had sibiricose A5 of 0.34-0.55 mg·g~(-1), sibiricose A6 of 0.43-0.57 mg·g~(-1), polygalaxanthone Ⅲ of 0.12-0.19 mg·g~(-1), 3,6'-disinapoyl sucrose of 1.08-1.78 mg·g~(-1), ginsenoside Rb_1 of 0.33-0.62 mg·g~(-1), β-asarone of 2.34-3.72 mg·g~(-1), α-asarone of 0.11-0.22 mg·g~(-1), and dehydropachymic acid of 0.053-0.079 mg·g~(-1). This study established the specific chromatograms and index component content determination method of Kaixin Powder benchmark samples, and the method was simple, feasible, reproducible, and stable. This study provides a scientific basis for further research on the key chemical properties of the benchmark samples and preparations of Kaixin Powder.

Thoracoscopic laparoscopy-assisted Ivor-Lewis resection of esophagogastric junction cancer / 中华肿瘤杂志

Objective: To investigate the outcome of patients with esophagogastric junction cancer undergoing thoracoscopic laparoscopy-assisted Ivor-Lewis resection. Methods: Eighty-four patients who were diagnosed with esophagogastric junction cancer and underwent Ivor-Lewis resection assisted by thoracoscopic laparoscopy at the National Cancer Center from October 2019 to April 2022 were collected. The neoadjuvant treatment mode, surgical safety and clinicopathological characteristics were analyzed. Results: Siewert type Ⅱ (92.8%) and adenocarcinoma (95.2%) were predominant in the cases. A total of 2 774 lymph nodes were dissected in 84 patients. The average number was 33 per case, and the median was 31. Lymph node metastasis was found in 45 patients, and the lymph node metastasis rate was 53.6% (45/84). The total number of lymph node metastasis was 294, and the degree of lymph node metastasis was 10.6%(294/2 774). Among them, abdominal lymph nodes (100%, 45/45) were more likely to metastasize than thoracic lymph nodes (13.3%, 6/45). Sixty-eight patients received neoadjuvant therapy before surgery, and nine patients achieved pathological complete remission (pCR) (13.2%, 9/68). Eighty-three patients had negative surgical margins and underwent R0 resection (98.8%, 83/84). One patient, the intraoperative frozen pathology suggested resection margin was negative, while vascular tumor thrombus was seen on the postoperative pathological margin, R1 resection was performed (1.2%, 1/84). The average operation time of the 84 patients was 234.5 (199.3, 275.0) minutes, and the intraoperative blood loss was 90 (80, 100) ml. One case of intraoperative blood transfusion, one case of postoperative transfer to ICU ward, two cases of postoperative anastomotic leakage, one case of pleural effusion requiring catheter drainage, one case of small intestinal hernia with 12mm poke hole, no postoperative intestinal obstruction, chyle leakage and other complications were observed. The number of deaths within 30 days after surgery was 0. Number of lymph nodes dissection, operation duration, and intraoperative blood loss were not related to whether neoadjuvant therapy was performed (P>0.05). Preoperative neoadjuvant chemotherapy combined with radiotherapy or immunotherapy was not related to whether postoperative pathology achieved pCR (P>0.05). Conclusion: Laparoscopic-assisted Ivor-Lewis surgery for esophagogastric junction cancer has a low incidence of intraoperative and postoperative complications, high safety, wide range of lymph node dissection, and sufficient margin length, which is worthy of clinical promotion.