Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

Study on the correlation between dietary inflammatory index and reflux esophagitis / 中华消化杂志

Objective:To evaluate the correlation between inflammatory diet and reflux esophagitis (RE) with the dietary inflammatory index (DII), and to provide scientific evidence for the prevention and treatment of RE at the level of dietary guidance.Methods:From December 2021 to September 2022, 145 RE patients (RE group) who visited the First Affiliated Hospital of Xinjiang Medical University were recruited. During the same period, 145 subjects who underwent check-ups at the First Affiliated Hospital of Xinjiang Medical University were selected as the healthy control group, and age and gender were matched according to the ratio of 1 to 1. The baseline data of the 2 groups, including body mass index, the history of smoking and drinking, poor dietary habits, and physical activity intensity were collected. Dietary intake of the patients was assessed by a semi-quantitative food frequency questionnaire, and the overall DII was calculated to evaluate the potential anti-inflammatory or pro-inflammatory effects of diet. According to the tertiles of the DII of the healthy control group (33.3% and 66.7% as the cut-off), dietary inflammatory potential was divided into low (<-0.06), moderate (-0.06 to 1.11) and high pro-inflammatory potential diet (>1.11). Logistic regression model was performed to analyze the correlation between DII and RE risk. Linear trend test was used to compare the overall change trend of RE risk OR value along with the increase of DII. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The body mass index of RE group was higher than that of healthy control group( (24.11±2.57) kg/m 2 vs. (23.38 ±2.60) kg/m 2), and the difference was statistically significant ( t=-2.41, P=0.017). The proportions of smoking, drinking, over-eating, and eating within 3 h before bedtime of RE group was higher than those of the healthy control group (42.8%, 62/145 vs. 31.0%, 45/145; 31.0%, 45/145 vs. 16.6%, 24/145; 33.1%, 48/145 vs. 17.9%, 26/145; 52.4%, 76/145 vs. 13.1%, 19/145), and the differences were statistically significant ( χ2=4.28, 8.39, 8.78 and 50.86, P=0.039, 0.004, 0.003 and<0.001). While the proportions of night snacking and moderate to severe physical activity of RE group were lower than those of the healthy control group (14.5%, 21/145 vs. 24.1%, 35/145; 22.8%, 33/145 vs.37.2%, 54/145), and the differences were statistically significant ( χ2=4.34 and 7.24, P=0.037 and 0.007). The DII of RE group was higher than that of the healthy control group (1.05 (0.03, 1.62) vs. 0.34(-0.61, 1.35)), and the difference was statistically significant ( Z=8 661.50, P=0.010). Compared with the low pro-inflammatory potential diet, high pro-inflammatory potential diet had a 1.30-fold increased the risk of RE ( OR=2.30, 95% confidence interval (95% CI) 1.29 to 4.09, P=0.005). After adjusting for total energy intake, age, gender, ethnicity, body mass index, education level, and physical activity intensity, the high pro-inflammatory potential diet was still positively correlated with the risk of RE ( OR=2.58, 95% CI 1.16 to 5.76, P=0.020). In the continuous DII, the risk of RE increased by 36% for each 1 increase in DII ( OR=1.36, 95% CI 1.11 to 1.68, P=0.003). After adjusting for major confounding factors, the continuous DII was still positively correlated with the risk of RE ( OR=1.41, 95% CI 1.08 to 1.85, P=0.012; OR=1.42, 95% CI 1.05 to 1.93, P=0.023). The results of trend test showed that the higher the DII, the greater the risk of RE ( P=0.039). Conclusions:Pro-inflammatory diet is correlated with the increased risk of RE, and there is a certain dose-response relationship. Reasonable reduction of the intake of pro-inflammatory food may be beneficial to reduce the risk of RE.

Effects of oxytocin on neonatal lactation behavior expression and breastfeeding / 中国实用护理杂志

Objective:To investigate the effect of oxytocin on neonatal instinctive behavior expression and breast-feeding.Methods:A total of 71 pairs of parturient women and their newborns who delivered in the delivery room of the Affiliated Hospital of Weifang Medical College from February to May 2021 were selected. According to whether oxytocin induced labor, they were divided into the oxytocin group and the control group. Widstr?m nine stages was used to observe and record neonatal behavior. Breastfeeding was followed up 3 days and 3 months after delivery.Results:Totally 35 pairs in each group were included. In the oxytocin group, the occurrence time of neonatal head or head turning, hand in mouth, body moving to nipple, lips touching areola, licking nipple, nipple and effective sucking were (18.2 ± 5.4), (27.8 ± 8.3), (31.0 ± 10.1), (44.3 ± 14.5), (47.2 ± 15.6), (49.4 ± 16.3), (48.3 ± 13.6) min, which were significantly later than those in the control group (15.3 ± 5.3), (21.0 ± 8.1), (24.3 ± 9.0), (34.0 ± 11.4), (37.2 ± 11.9), (38.6 ± 11.8), (39.6 ± 8.7) min. The difference was statistically significant ( t values ranged from -3.10 to -2.17, P<0.05). The duration of neonatal awakening, activity, crawling and familiarity in the oxytocin group were (6.9 ± 3.2), (18.9 ± 9.3), (13.6 ± 7.9), (9.2 ± 5.1) min, which were significantly longer than those in the control group (5.1 ± 2.8), (12.3 ± 7.1), (10.3 ± 5.3), (6.7 ± 4.3) min; sucking stage duration in the oxytocin group was (35.1 ± 7.2) min, which was significantly shorter than that in the control group (39.6 ± 7.1) min; all the differences were statistically significant ( t values ranged from -3.25 to 2.28, P<0.05). The times of exclusive breast-feeding in the oxytocin group were (2.8 ± 3.1), (4.5 ± 3.3), (6.9 ± 3.0) at 24, 48 and 72 h postnatal, and the exclusive breastfeeding rate at 3 months after birth was 77.1%(27/35), which were significantly lower than those (7.6 ± 3.6), (8.9 ± 2.7), (10.3 ± 2.0) and 82.9%(29/35) in the control group, the differences were statistically significant ( t=6.05, 6.11, 5.48, χ2=0.36, P<0.05). Conclusions:The use of oxytocin during labor may affect the expression of neonatal lactation behavior and negatively affect the breastfeeding.

Oral sulfate solution versus polyethylene glycol for colonoscopy bowel preparation: a randomized controlled study in phase Ⅲ / 中华消化内镜杂志

Objective:To compare the efficacy of oral sulfate solution (OSS) and polyethylene glycol (PEG) electrolyte powder for colonoscopy bowel preparation.Methods:A total of 283 randomized patients from 9 centers in China taking OSS ( n=143) or PEG ( n=140) using two-day split bowel preparation regimen received colonoscopy and assessment. The primary index was the bowel preparation success rate [global Boston bowel preparation scale (BBPS)≥ 6 by independent assessment center]. Secondary indices included BBPS global and segmental scores, investigator satisfaction (5-point Likert scale) with the quality of bowel preparation, patient satisfaction assessed by questionnaires, and patient tolerance assessed by Sharma scale. Compliance and safety were compared between the two groups. Results:The bowel preparation success rates were 100.0% for OSS and 99.3% for PEG [adjusted difference 0.7% (95% CI: -5.3% - 6.7%), P<0.001 for non-inferiority]. The BBPS global score in OSS group was significantly higher than that in PEG group (8.1 VS 7.7, P<0.001). The segment BBPS scores were also higher in OSS group than those in PEG group for all 3 segments (right colon: 2.4 VS 2.3, P=0.002; transverse colon: 2.8 VS 2.7, P=0.018; left colon: 2.8 VS 2.7, P=0.007). Investigator Likert score in the OSS group was significantly higher than that in the PEG group (2.6 VS 2.3, P<0.001). There was no significant difference in compliance between OSS and PEG, except for the second dose (90.9% VS 82.6%, P=0.039). There was no significant difference in patient satisfaction, Sharma score or proportion of patients with tolerance-related symptoms between the two groups. Safety was comparable between the two groups, and all adverse events were mild to moderate. Conclusion:OSS has comparable efficacy with PEG, with higher BBPS scores in all segments, better investigator satisfaction, better compliance in split dose, and comparable patient tolerance and safety.

Impact of nutrition intervention and physical exercise on muscle mass and body fat among community elderly with sarcopenia: a randomized controlled study / 中华临床营养杂志

Objective:To investigate the impact of nutrition supplementation (whey protein, fish oil and vitamin D) and physical exercise (resistance and aerobic exercise) on muscle mass and body fat metrics among community elderly with sarcopenia.Method:102 eligible sarcopenic participants per inclusion and exclusion criteria were randomized into the control group (routine consultation, n=34) or the groups receiving nutrition supplementation (Nutr, n=34) or nutrition supplementation combined with exercise (Nutr+Ex, n=34) for 12 weeks. Muscle and body fat related indicators were compared across groups pre- and post-intervention. Results:Analysis of covariance showed that all indicators were significantly different between groups (all P<0.05). Further pairwise comparisons showed that compared with controls, patients in Nutr group showed increased appendicular muscle mass (ASM) by 0.837 kg ( P=0.003, 95% CI: 0.301 to 1.372) and decreased fat mass by 2.876 kg ( P<0.01, 95% CI: -3.941 to -1.812), while patients in Nutr+Ex group showed increased ASM by 0.745 kg ( P=0.010, 95% CI: 0.180 to 1.311) and decreased fat mass by 2.928kg ( P<0.01, 95% CI: -4.408 to -1.808). Other muscle-related indicators also increased while fat-related indicators decreased in both Nutr and Nutr+Ex groups. However, there is no significant difference between Nutr and Nutr+Ex groups. Conclusions:Nutrition supplementation and physical exercise contribute to muscle mass and body fat improvement among sarcopenic elderly. Lifestyle intervention based on nutrition intervention is important for the community elderly with sarcopenia.

Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death

Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

Risk factor analysis of 46 cases of ulcerative colitis complicated with thromboembolism / 中华消化杂志

Objective:To analyze the independent risk factors of ulcerative colitis (UC) with thromboembolism (TE), in order to diagnose UC with TE as early as possible and take corresponding preventive measures, so as to improve the prognosis and reduce the mortality of UC with TE.Methods:From January 1, 2011 to December 31, 2020, at the First Affiliated Hospital of Xinjiang Medical University, from January 1, 2015 to December 31, 2020, at the Second Affiliated Hospital of Xinjiang Medical University, from January 1, 2015 to December 31, 2020, at the Fifth Affiliated Hospital of Xinjiang Medical University, during hospitalization 46 patients diagnosed with UC with TE were enrolled. According to the ratio of 1∶2, at same period 92 simple UC patients were selected as control. The condition of embolization of UC patients with TE was analyzed. The clinical data(hypertension history, length of hospital stay, etc.), the degree of disease activity, laboratory test indicators (prothrombin time (PT), D-dimer, fibrin degradation product(FDP), hemoglobin(Hb), mean platelet volume(MPV), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), etc.)of the patients of UC with TE and UC without comorbidities were compared. Multivariate logistic regression was used to analyze the independent risk factors of UC with TE. Independent sample t test, Mann-Whitney U test, Chi-square test or Fisher′s exact probability method were used for statistical analysis. Results:Among the 46 cases of UC with TE, 14 cases (30.4%) had single site venous TE, mainly venous thrombosis of lower limbs; 20 cases (43.5%) had single site arterial TE, mainly myocardial infarction and cerebral infarction; 12 cases (26.1%) had multi-site TE. The proportion of patients with hypertension history and with severe active period of UC, and the levels of D-dimer, FDP, ESR and CRP in patients with UC with TE were all higher than those in patients without comorbidities(52.2%, 24/46 vs.33.7%, 31/92, 45.7%, 21/46 vs.19.6%, 18/92, (822.03±654.33) μg/L vs.(230.28±225.62) μg/L, 5.77 mg/L(6.87 mg/L) vs. 2.10 mg/L(1.55 mg/L), (46.32±28.27) mm/1 h vs.(33.08±24.30) mm/1 h, 22.05 mg/L(46.42 mg/L) vs. 5.58 mg/L(11.58 mg/L)); the hospital stay and PT were longer than those in patients without comorbidities ((12.76±10.18) d vs.(8.66±4.89) d, (14.13±6.06) s vs.(11.86±1.42) s); the Hb and MPV were lower than those in patients without comorbidities ((110.91±31.38) g/L vs.(123.83±27.67) g/L, (9.60±0.94) fL vs.(10.04±1.16) fL; and the differences were statistically significant( χ2=4.37 and 10.29, t=-5.96, Z=-5.78, t=-2.85, Z=-3.87, t=-2.58, -2.50, 2.47 and 2.47; all P<0.05). The results of multivariate logistic regression analysis showed that severe activity period of UC ( OR=3.079, 95% confidence interval (95% CI) 1.100 to 8.615), hypertension history ( OR=4.454, 95% CI 1.467 to 13.519), and D-dimer level( OR=1.003, 95% CI 1.001 to 1.005) were all independent risk factors of UC with TE(all P<0.05). Conclusions:Lower extremity venous, myocardial infarction and cerebral infarction are common in UC with TE. Severe activity period of UC, history of hypertension and D-dimer level are independent risk factors of UC with TE. These above factors should be paid attention to and corresponding prevention should be taken.

Analysis on Chemical Constituents in Rhizomes of Bergenia scopulosa by UHPLC-Q Exactive Focus MS/MS / 中国实验方剂学杂志

Objective:Ultra-high performance liquid chromatography coupled with quadrupole/electrostatic field orbital trap high resolution mass spectrometry （UHPLC-Q Exactive Focus MS/MS） was developed to rapidly analyze and identify the chemical components in the rhizomes of <italic>Bergenia scopulosa</italic>. Method:The 75% methanol extract of <italic>B</italic>.<italic> scopulosa</italic> rhizomes was analyzed on a Thermo Accucore aQ RP18 column （2.1 mm×150 mm， 2.6 μm） with the mobile phase of methanol （A） and 0.1% formic acid aqueous solution （B） for gradient elution （0-40 min 5%-95%A， 40-45 min 95%A）， the flow rate was 0.3 mL·min^-1 and the column temperature was at 30 ℃. The information of the chemical constituents was acquired in positive and negative ion modes by heated electrospray ion source （HESI）， and the scanning range was <italic>m</italic>/<italic>z</italic> 80-1 200. Result:A total of 66 chemical constituents were identified， including 2 free amino acids， 7 bergenin derivatives， 15 flavonoids， 15 organic acids， 25 glycosides， and 2 others. Conclusion:The chemical constituents in the rhizomes of <italic>B</italic>.<italic> scopulosa</italic> can be identified systematically， accurately and rapidly by this method. Among them， 8 compounds were unambiguously identified by comparing with reference substances （succinic acid， arbutin， gallic acid， protocatechuic acid， bengenin， catechin， chlorogenic acid and caffeic acid）， 51 compounds were found from <italic>B</italic>.<italic> scopulosa</italic> for the first time and 28 compounds were found from the genus <italic>Bergenia</italic> for the first time. This paper can provide an important basis for the further material basis clarification and quality assessment of <italic>B</italic>.<italic> scopulosa</italic>.

Identification of Chemical Constituents in Caulis of Erycibe schmidtii by UPLC-Q-Exactive Focus-MS/MS / 中国实验方剂学杂志

Objective:To rapidly recognize and identify the chemical constituents in caulis of Erycibe schmidtii by ultra-high performance liquid chromatography coupled with Q-Exactive Focus mass spectrometry (UPLC-Q-Exactive Focus-MS/MS). Method:Taking 80% methanol extract of E. schmidtii caulis as the test solution, the chemical constituents in caulis of E. schmidtii were analyzed and identified. Thermo Accucure aQ C18 column (2.1 mm×150 mm, 2.6 μm) was used for chromatographic separation with the mobile phase of methanol (A)-0.1% formic acid solution (B) for gradient elution (0-12 min, 5%-25%A; 12-20 min, 25%-30%A; 20-28 min, 30%-38%A; 28-40 min, 38%-42%A). Positive and negative ion monitoring modes and heated electrospray ion source (HESI) were used for mass spectrographic analysis. The scanning range was m/z 80-1 200. Result:A total of 42 chemical constituents from caulis of E. schmidtii were identified, including 12 coumarins, 14 chlorogenic acids, 1 tropane alkaloid, 1 amide and 14 esterified glycosides. Conclusion:Chemical constituents in caulis of E. schmidtii can be quickly and fully identified by UPLC-Q-Exactive Focus-MS/MS. Among them, 11 compounds are unambiguously identified by comparing with reference standards, 31 compounds are reported for the first time in this herb, 2 compounds are reported for the first time in Erycibe plants. This paper can provide the important basis for study on pharmacodynamic material base and substitute development of E. schmidtii caulis.

Content Determination of Nine Constituents in Different Medicinal Parts of Pimpinella thellungiana / 中国实验方剂学杂志

Objective:To develop a method to quantify nine constituents in different medicinal parts of Pimpinella thellungiana, in order to compare the content difference of the nine constituents, namely protocatechuic acid,gallic acid,neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,luteolin-7-O-β-D-glucuronide,isochlorogenic acid A,apigenin-7-O-β-D-glucuronide and isochlorogenic acid C. Method:The analysis was performed on an Agilent TC-C18 column (4.6 mm×250 mm,5 μm) with acetonitrile and mixed acid solution (0.1% phosphoric acid-0.1% glacial acetic acid) as mobile phase for gradient elution. The handover detection wavelengths were at 265 and 325 nm. The column temperature was 20℃, and the flow rate was 1.0 mL·min-1. The experiment data was analyzed using the software of Markerlynx XS. Result:The nine constituents of protocatechuic acid,gallic acid,neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid, luteolin-7-O-β-D-glucuronide,isochlorogenic acid A,apigenin-7-O-β-D-glucuronide and isochlorogenic acid C had a good degree of separation and a good linearity in their respective linear ranges(r>0.999 8). The average recoveries ranged from 99.11% to 100.76%,and the RSD ranged from 0.9% to 2.0% 。The results showed that the contents of the nine constituents had significant differences in different medicinal parts of P. thellungiana. The average contents of the nine constituents were the highest in leaves,which was followed by stem,and the lowest was in root. Conclusion:The study could provide evidence for the quality control,clinical application,and scientific resources utilization of P. thellungiana.

Effects of sarcopenia on the risks of osteoporosis and fragility fractures among community-dwelling middle and old age people: a systematic review and meta-analysis / 中华临床营养杂志

Objective To explore the relationship between sarcopenia and the risks of osteoporosis and fragility fractures among community-dwelling middle and old people (≥50 years) . Methods OVID/Medline, Pubmed, EMBASE, Cochrane Library, Web of Science ( SCI ) , China National Knowledge Infrastructure ( CNKI) , and Chinese WanFang Database were searched systematically for literatures related to the relationship between sarcopenia and osteoporosis and fragility fractures from January 1987 to July 2018. The searched litera-tures were screened based on the inclusion and exclusion criteria. The quality of the literatures were evaluated by using the risk assessment tool NOS ( Newcastle-Ottawa Scale) and AHRQ ( Agency for Healthcare Research and Quality) . Meta-regression analysis was used to explore the cause of heterogeneity between studies. The sub-group analysis was used to assess the differences in the risk of osteoporosis based on the important characteristic variables, such as gender, ethnicity, age, diagnostic criteria of sarcopenia, and outcome type. Sensitivity anal-ysis and trim and fill method were conducted to test the stability of the results of this Meta-analysis. Data col-lected and summarized by Stata 12. 2 software. Results A total of 23 studies in line with quality requirements were included eventually, including 56, 544 subjects. The results of this Meta-analysis were relatively robust. Compared with non-sarcopenia, the relative risk ( RR ) for osteoporosis among subjects with sarcopenia was 1. 61 (95％ CI: 1. 42～1. 82, P<0. 00001). Especially, compared with postmenopausal women RR=1. 37 (95％ CI: 1. 23-1. 53, P<0. 0001) and yellow race RR=1. 53 (95％ CI: 1. 34-1. 75, P<0. 0001), sar-copenia had a higher impact trend on the risk of osteoporosis in older men RR=2. 26 ( 95％ CI: 1. 71-2. 98, P<0. 0001 ) and Caucasian RR = 2. 03 ( 95％ CI: 1. 46-2. 81, P<0. 0001 ) . Conclusion Among community-dwelling middle and old aged people (≥50 year) , sarcopenia increases the risk of osteoporosis and fragility fracture by 61％ and 59％ -61％ significantly, respectively. Middle and old aged people should be pre-vented and screened early for sarcopenia, which attributes to identify high risk groups of fragile fractures and re-duce the risk of adverse outcomes.

Clinical and genetic analyses of juvenile myelomonocytic leukemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical and genetic features of juvenile myelomonocytic leukemia (JMML) and the association between genotype and prognosis. Methods The clinical data of 15 children who were diagnosed with JMML were collected. Next-generation sequencing was used to detect common gene mutations of JMML.@*RESULTS@#The male/female ratio was 6.5:1, and the age of onset was 19 months (range 2-67 months). Of the 15 children, 11 (73%) experienced disease onset before the age of 4 years, with abdominal distension and pyrexia as initial symptoms. All children had hepatosplenomegaly and superficial lymphadenectasis, with a number of peripheral blood mononuclear cells of >1.0×10/L and a percentage of juvenile cells of 1%-7% in peripheral blood smear. The percentage of bone marrow blasts + juvenile cells was <20%, and the percentage of monoblasts + promonocytes was 1%-10%. Of the 15 children, 10 (67%) had a higher level of hemoglobin F than the normal level at the corresponding age, with the highest level of 62.5%. All 15 children had the absence of Philadelphia chromosome, and one child had chromosome 7 deletion. All 15 children had a negative result of BCR/ABL fusion gene detection. PTPN11 gene mutation was found in 5 children (33%), NF1 mutation in 4 children (27%), CBL mutation in 3 children (20%), and RAS mutation in 3 children (20%). No children received regular chemotherapy, and one child underwent hematopoietic stem cell transplantation. The median follow-up time of 15 children was 18 months (range 1-48 months). Among the 15 children, 8 died (among whom 4 had PTPN11 gene mutation, 3 had NF1 mutation, and 1 had RAS mutation) and 7 survived. The children with PTPN11 mutation had the worst prognosis and the highest mortality rate, and those with CBL or NRAS mutation had a relatively good prognosis. The level of hemoglobin F was negatively correlated with survival time (r=-7.21, P=0.002).@*CONCLUSIONS@#In children with JMML, the type of gene mutation is associated with prognosis. The children with PTPN11 mutation often have a poor prognosis, and those with CBL or NRAS mutation have a relatively good prognosis.

Clinical Significance of CRLF2 High Expression in Bone Marrow Mononuclear Cells from Children with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL.@*METHODS@#A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method.@*RESULTS@#28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P＜0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P＜0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P＞0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P＜0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL.@*CONCLUSION@#The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.

Influence of genetic polymorphisms in drug metabolism enzymes and transporters on pharmacokinetics of different fluvastatin formulations / 中国药理学与毒理学杂志

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

Impact of sarcopenia on the risk of falls, osteoporosis, fractures, and all causes of death among elderly people: A Meta-analysis of prospective cohort studies / 中华临床营养杂志

Objective To explore the relationship between sarcopenia and the risks of falls, osteoporo-sis, fractures and all-cause mortality among elderly people. Methods This was a meta-analysis of prospective cohort studies. Databases of OVID/Medline, PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure ( CNKI) and Chinese WanFang Database were searched systematically according to the inclusion and exclusion criteria. The literatures related to the relationship between sarcopenia and falls, os-teoporosis, fractures and all-cause mortality among elderly people from January 1987 to June 2017 were identi-fied. The quality of the literature was evaluated by the risk assessment tool Newcastle-Ottawa Scale recommen-ded by the Cochrane. Meta-analysis was conducted by RevMan 5. 3 and Stata 12. 1 software. Results Totally 13 prospective cohort studies including 19 376 subjects and 3 190 outcome events were entered in meta-analysis. The relative risk ( RR) for comprehensive adverse outcome events among subjects with sarcopenia was 1. 64 times of non-sarcopenia subjects (95% CI=1. 51-1. 78, P<0. 000 01), and the RRs for fall, osteoporosis, fractures and all-cause mortality were 1. 60 (95% CI=1. 42-1. 81, P<0. 000 01), 4. 85 (95% CI=2. 18- 10. 79, P=0. 000 1), 1. 59 (95% CI=1. 40-1. 80, P<0. 000 01), 2. 08 (95% CI=1. 18-3. 69, P=0. 01) times of non-sarcopenia subjects respectively. Conclusion Sarcopenia increases the risk of falls, fractures, all-cause mortality and comprehensive adverse outcome significantly, suggesting that sarcopenia might be a pre-dictor for adverse outcomes among elderly people.

Chemcial constituents of Eclipta prostrata / 中国中药杂志

A total of twenty-two compounds were isolated from the 95% EtOH extract of Eclipta prostrata by various purification steps, and their structures were established as ecliptalignin A (1)，ecliptasaponin Ⅰ (2), ecliptasaponin Ⅱ (3), echinocystic acid (4), 3-oxo-16α-hydroxy-olean-12-en-28-oic acid (5), acacetin-7--rutinoside (6), luteoloside (7), apigenin (8), luteolin (9), acacetin (10), skullcapflavone Ⅱ (11), kaempferol (12), kaempferide (13), quercetin (14), 4',7-dihydroxyl-3',6'-dimethoxylisoflavone-7--glucoside (15), ecliptal (16), 5-hydroxymethyl-(2,2',5',2″)-terthienyl tiglate (17), psoralen (18), isopsoralen (19), wedelolactone (20), crinumaquine (21), and 2,3,9,12-tetramethoxyprotoberberine (22) mainly based on the spectroscopic techniques, of which 1 was a new lignin analogue, and 5, 6, 10-13, 15, 18, 19, 21 and 22 were isolated form this plant for the first time.

Effects of minimal residual disease level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of minimal residual disease (MRD) level on day 33 of remission induction and IKZF1 genotype on the survival of children with B-lineage acute lymphoblastic leukemia (B-ALL).</p><p><b>METHODS</b>A total of 152 children with newly-diagnosed B-ALL who had complete remission after the first cycle of the chemotherapy and had complete follow-up information were enrolled in this study. According to the MRD detection by flow cytometry on day 33 of remission induction, they were divided into three groups: standard-risk (SR) group (MRD <10; n=60), intermediate-risk (IR) group (10≤ MRD <10; n=55), and high-risk (HR) group (MRD ≥10; n=37). Nested RT-PCR was used to determine the IKZF1 genotype of all children before chemotherapy. The effects of MRD level on day 33 of remission induction and IKZF1 genotype on the recurrence-free survival (RFS) of children with B-ALL were analyzed.</p><p><b>RESULTS</b>There were 7 common IKZF1 subtypes in all the 152 children with B-ALL: IK1, IK2/3, IK4, IK6, IK8, IK9, and IK10. Of the 152 children, 130 had functional subtypes of IKZF1 and 22 had non-functional subtypes of IKZF1. During the follow-up period, relapse occurred in 26 (17%) children, and the recurrence rate was highest in the HR group (P<0.05). However, there was no significant difference in the recurrence rate between the SR group and the IR group (P>0.05). The cumulative recurrence rate of the children with non-functional subtypes of IKZF1 was significantly higher than that of those with functional types of IKZF1 (P<0.01). The predicted 5-year RFS rates in the SR, IR, and HR groups were (94.2±2.9)%, (86.7±3.8)%, and (56.2±4.5)% respectively (P<0.05). The 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 (P<0.01). There was no significant difference in the predicted 5-year RFS rate between the children with functional subtypes of IKZF1 and those with non-functional subtypes of IKZF1 in the SR group (P>0.05). However, the predicted 5-year RFS rate of the children with functional subtypes of IKZF1 was significantly higher than that of those with non-functional subtypes of IKZF1 in the IR group and the HR group (P<0.05).</p><p><b>CONCLUSIONS</b>B-ALL children with non-functional subtypes of IKZF1 have a high recurrence rate, and the recurrence rate will be even higher in B-ALL children with non-functional subtypes of IKZF1 and MRD ≥10 on day 33 of chemotherapy.</p>

Protective Effect and Mechanism of Human Lipoxin A4 on N2a Cell Injury Induced by β-Amyloid Protein 25-35 / 中国药师

Objective: To investigate the protective effect of human lipoxin A4 (LXA4) on N2a cell damage induced by β-amyloid protein 25-35 (Aβ25-35) and the underlying mechanism. Methods: Aβ25-35 was used to treat N2a cells to establish Alzheimer's disease (AD) cell injury model. Meanwhile, LXA4 was added to the experimental group at different concentrations (50, 100 and 200 nmol·L-1 ). MTT assay was used to detect the activity of N2a cells. The apoptosis was detected by Hoechst 33258-PI staining, the expression of P62 and TRAF6 mRNA was detected by RT-PCR, and the expression of P62 and TRAF6 protein was detected by Western blot. Results: Compared with that of the model group, the cell survival rate of LXA4 protective group (50,100 and 200 nmol·L-1 ) increased (P <0. 01) and the apoptosis of N2a cells induced by Aβ25-35 was reduced by LXA4 (100 and 200 nmol·L-1 ) . Compared with that of the model group, the expression of P62-mRNA and protein-P62 of N2a cells treated with Aβ25-35 increased (P <0. 05 or P <0. 01) and the expression of TRAF6-mRNA and protein-TRAF6 of N2a cells treated with Aβ25-35 were reduced (P <0. 05 or P <0. 01). Conclusion: LXA4 has protective effect on N2a cell damage induced by Aβ25-35 , and its mechanism may be related to the up-regulation of P62 gene and down-regulation of TRAF6 gene.

Cases Analysis of Pharmaceutical Care Practice Performed by Clinical Pharmacist in the Patients with Tumor / 中国药师

Objective: To explore the working methods of clinical pharmacists for improving the rationality of drug use through participating in individualized treatment practice for the patients with tumor.Methods: Clinical pharmacists participated in the individualized treatment of the patients with tumor, found out adverse drug interactions, adjusted dosage for the renal insufficiency patients, treated infection or pain and corrected inappropriate drug combination, etc.Results: Clinical pharmacists provided integrated pharmaceutical care and offered medical advice in accordance with the individualized information of patients, which improved the treatment effect and avoided potential adverse drug reactions or adverse events.Conclusion: Clinical pharmacists provide pharmaceutical care and participate in the performance of individualized treatment for cancer patients, which can effectively improve the level of drug treatment.

Pharmaceutical Care Performed by Clinical Pharmacists for One Patient with Torsade de Pointes / 中国药师

Objective: To study the entry points of pharmaceutical care performed by clinical pharmacists for patients in ICU.Methods: Clinical pharmacists participated in the medication treatment process of one case of patient with torsade de pointes by providing individualized pharmaceutical service, including antiarrhythmic drug selection, anti-infection therapy adjustment and electrolyte disorder rectification.Results: The therapeutic effect and medication safety of the patient were both improved by giving clinical pharmaceutical care.The vital signs of the patient were stable, and then the patient transferred from ICU and continued to be treated with rehabilitation therapy.Conclusion: Clinical pharmacists can play an active role in the rescue of ICU patients by the pharmaceutical thinking and provide efficient pharmaceutical care with high quality.