Analysis on Components Absorbed into Blood of Citri Reticulatae Pericarpium in Rats Based on Sequential Metabolism and UPLC-HRMS / 中国实验方剂学杂志

ObjectiveTo study the metabolism of chemical components from Citri Reticulatae Pericarpium（CRP）in different parts of rats by sequential metabolism and ultra performance liquid chromatography-high resolution mass spectrometry（UPLC-HRMS）. MethodSD male rats were employed as experimental subjects， and blood samples of intestinal metabolism and hepatic metabolism were prepared after administration of CRP ethanol extract by in situ intestinal perfusion， and comprehensive metabolic samples were collected after intragastric administration. UPLC-HRMS was used to analyze the samples with acetonitrile（A）-0.1% formic acid aqueous solution（B）as the mobile phase for gradient elution（0-10 min， 10%-30%A； 10-30 min， 30%-95%A； 30-31 min， 95%-10%A； 31-35 min， 10%A）at a flow rate of 0.35 mL·min-1， using a heated electrospray ionization with positive and negative ion mode scanning in the range of m/z 100-1 500. Under these conditions， the differences in the profiles of CRP ethanol extract， blank plasma and drug-containing plasma under different treatment groups were compared， and the chemical components of each sample were analyzed and identified based on the retention time， accurate relative molecular mass， primary and secondary ion fragments， and the information of reference substances. ResultA total of 44 chemical components were identified in the CRP ethanol extract， including flavone-O-glycosides， flavone-C-glycosides and polymethoxyflavonoids， etc. The results of sequential metabolism showed that 22 chemical components in CRP were detected in the intestinal metabolic sample， 18 chemical components were detected in the hepatic metabolic sample， and 9 identical chemical components（narirutin， hesperidin， meranzin， 5，7，8，3ʹ，4ʹ，5ʹ-hexamethoxy-flavone， isosinensetin， sinensetin， 3，5，6，7，8，3ʹ，4ʹ-heptamethoxyflavone， nobiletin and tangeretin）could be detected in all three metabolic samples， with a total of 22 compounds entering the blood in prototype form. ConclusionThe identified 21 components with well-defined structures entering the blood as prototypes may be potential active components of CRP， and differences in the components at different metabolic parts can provide an experimental basis for elucidating the in vivo biotransformation process of the metabolic components of CRP.

Research on hypoglycemic activity of Osmanthus fragrans var. thunbergii extract / 药学学报

This study aimed to assess the hypoglycemic activity, and in vitro inhibition of α-glucosidase, inhibition of the advanced glycation end products (AGEs), and total antioxidant capacity were used to clarify its bioactivity. Furthermore, the potential hypoglycemic active chemical constituents in the aqueous extract of Osmanthus fragrans var. thunbergii flower were characterized using high performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) method. The result showed that in vitro inhibition of α-glucosidase of the extract (IC50 = 2.11 ± 0.26 mg·mL-1) were similar to acarbose (IC50 = 2.88 ± 0.32 mg·mL-1), and it inhibited the AGEs formation and the total antioxidant capacity in a certain extent. Based on the MS fragmentation pathway analysis of reference chemical acteoside contained in this extract, and related references, 73 constituents were tentatively identified from the aqueous extract of Osmanthus fragrans var. thunbergii flower, including 58 phenylethanoids, 8 caffeoylquinic acids, 1 flavonoid vicenin-2, and 6 common organic chemicals in plant. Furthermore, 8 unknown alkaloids were characterized in this work. Among of these chemicals, 61 phenylethanoids were supposed to be detected for the first time. In conclusion, this work disclosed the potential hypoglycemic active constituents of Osmanthus fragrans var. thunbergii flower.

The status of medication review in addressing drug-related problems of elderly patients in the community / 中国药房

With the increasing aging of our population， the incidence of drug-related problems among elderly patients in the community is gradually increasing. Drug-related problems can lead to an increased incidence of adverse health outcomes such as falls and frailty in elderly patients in the community. Medication review is one of the effective means of addressing drug-related problems. The medication review models in Europe and the United States have been developed for decades to address drug-related problems； medication review model in the United Kingdom focuses on the management of drug therapy for elderly patients in aged care facilities， while the medication review models in the United States and Australia have a broader scope（covering all elderly patients in the community）， and the frequency of medication reviews in the United States and Australia are clearer and more standardized. Compared with the above countries， China’s medication review model has a late start. Our country can learn from the advanced experience of the United Kingdom， the United States， Australia and other countries， actively explore and build a drug review model suitable for China’s national conditions， so as to improve the health level of elderly patients in the community and save social public medical resources.

Association between smoking and ankylosing spondylitis: a Mendelian randomization study / 预防医学

Objective@#To evaluate the association of smoking with the risk of ankylosing spondylitis (AS) using a Mendelian randomization (MR) approach.@*Methods@#A total of 16 383 186 AS-associated single nucleotide polymorphisms (SNPs), 378 smoking initiation associated SNPs and 126 lifetime smoking score-associated SNPs were collected from three large-scale genome-wide association studies (GWAS). The association of smoking phenotypes with the risk of AS was examined using inverse-variance weighted (IVW) with AS as a outcome variable, smoking initiation and lifetime smoking score as exposure factors and SNPs with strong associations with smoking as instrumental variables, and sensitivity analyses were performed with maximum likelihood-based method, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression analysis.@*Results@# A 33.5% increased risk of AS was found among genetically predicted smokers relative to non-smokers (OR=1.335, 95%CI: 1.059-1.682), and an increase in predicted lifetime smoking by per standard deviation resulted in a 101.4% increased risk of AS (OR=2.014, 95%CI: 1.341-3.024). The maximum likelihood-based method and MR-PRESSO test showed consistent correlated effect estimations and MR-Egger regression analysis identified no evidence of pleiotropy.@*Conclusion@#It is genetically predicted that smoking is associated with an increased risk of AS.

A Clinical Analysis of Thirty-Five Patients Undergoing Aortic Reoperation

Abstract Introduction: At present, there are few reports regarding the issue of aortic reoperation due to its complexity and high risk and individual differences among patients. Methods: From November 2016 to December 2017, the data from 35 cases of aortic reoperation at our institution, out of 212 consecutive aortic repairs, were reviewed. We retrospectively summarized and analyzed their surgical indications, operative data, time interval from previous aortic repair, and outcomes. The time intervals until reoperation were analyzed for differences. Results: Patients' mean age was 40.9±14.5 years, and 25 of them were men (71.4%). The indications for reoperation were aortic valvular problem (14.3%), aneurysmal dilatation (25.7%), pseudoaneurysm formation due to anastomotic leakage (43.2%), and aortic dissection (17.1%). For patients who had underwent primarily emergency operations due to aortic dissection, the time interval until reoperation (4.8±3.2 years) was significantly shorter than that of the whole group (5.5±3.6 years, P<0.01). Among the 35 reoperations, Sun's procedure was selected for 16 patients (45.7%) with total aortic arch reconstruction. The average follow-up was 12 months (range 9-15 months). Hospital mortality was 5.7% (two patients). Among the hospital survivors there were no cases of death, rupture of residual dissection, paraplegia, or central nervous system complications during the follow-up period. Conclusion: Patients with acute aortic dissection required repeat surgery significantly earlier compared to other diseases. As to reoperation strategy, we recommend Sun's procedure as the choice for extended arch reconstruction since minimal effect on overall mortality and complication rates were found.

A polit study of using CT-radiomics based machine learning model in predicting immune cells infiltrating and prognosis of pancreatic cancer / 中华放射学杂志

Objective:To investigate the value of CT-radiomics based machine learning model in predicting the abundance of tumor infiltrating CD8 +T cells and the prognosis of pancreatic cancer patients. Methods:A total of 150 pancreatic cancer patients who underwent surgical excision and confirmed by pathology from Fudan University Shanghai Cancer Center between December 2011 and January 2017 were retrospectively enrolled. The patients were randomly divided into the training set ( n=105) and the validation set ( n=45) in a 7∶3 ratio with simple random sampling. The immunohistochemical method was used to assess the abundance of tumor infiltrating CD8 +T cells, and the patients were then divided into high infiltrating group ( n=75) and low infiltrating group ( n=75) according to the median. The prognosis between the 2 groups was evaluated using Kaplan-Meier method and log-rank test. Radiomic features were extracted from preoperative venous-phase enhanced CT images in the training set. The Wilcoxon test, the max-relevance and min-redundancy algorithm were used to select the optimal feature set. Three supervised machine learning models (decision tree, random forest and extra tree) were established based on the optimal feature set to predict the abundance of tumor infiltrating CD8 +T cells. Performance of above-mentioned models to predict the abundance of tumor infiltrating CD8 +T cells in pancreatic cancer was tested in the validation set. The evaluation parameters included area under the receiver operating characteristic curve (AUC), F1-score, accuracy, precision and recall. Results:The median overall survival time of patients in high infiltrating group and low infiltrating group were 875 days and 529 days, respectively (χ2=11.53, P<0.001). The optimal feature set consisted of 10 radiomic features in training set. In the validation set, the decision tree, random forest and extra tree model showed the AUC of 0.620, 0.704 and 0.745, respectively; corresponding to a F1-score of 0.457, 0.667 and 0.744, the accuracy of 57.8%, 68.9% and 75.6%, the precision of 66.7%, 73.7% and 80.0%, the recall of 34.8%, 60.9% and 69.6%. Conclusions:Pancreatic cancer patients with high tumor infiltrating CD8 +T cells have better prognosis than those with low tumor infiltrating CD8 +T cells. The radiomics-based extra tree model is valuable in predicting the CD8 +T cells infiltrating level in pancreatic cancer.

The predictive value of VEGF, SCCAg and miRNA let-7a in the metastasis and recurrence of laryngeal carcinoma / 中国医师杂志

Objective:To investigate the predictive value of serum vascular endothelial growth factor (VEGF), squamous cell carcinoma-associated antigen (SCCAg) and miRNA let-7a in lymph node metastasis and postoperative recurrence in patients with laryngeal cancer.Methods:A total of 82 patients with laryngeal cancer in the Second Central Hospital of Baoding from November 2017 to October 2019 were selected as the research subjects, including 18 cases of lymph node metastasis (metastasis group) and 64 cases of non metastasis (non metastasis group). The blood routine was tested before operation, and the baseline data, serum VEGF, SCCAg and miRNA let-7a levels were compared between the two groups. Logistic regression was used to analyze the related influencing factors of lymph node metastasis in patients with laryngeal cancer. The correlation between serum VEGF, SCCAg, miRNA let-7a levels and clinicopathological characteristics was analyzed. The receiver operating characteristic (ROC)curve was used to analyze the value of each index and the combined diagnosis of lymph node metastasis in patients with laryngeal cancer. After 1 year of follow-up, the serum VEGF, SCCAg and miRNA let-7a levels of patients with or without recurrent laryngeal cancer were compared. ROC curve was used to evaluate the value of VEGF, SCCAg, and miRNA let-7a in predicting the recurrence of laryngeal cancer.Results:There were statistically significant differences in tumor node metastasis (TNM) stage, degree of infiltration, degree of differentiation, serum VEGF, SCCAg, and miRNA let-7a levels between the metastasis group and non metastasis group (all P<0.05). Serum VEGF, SCCAg, miRNA let-7a levels in patients with laryngeal cancer were related to TNM stage, degree of infiltration and degree of differentiation (all P<0.05). The combined diagnosis of serum VEGF, SCCAg and miRNA let-7a levels in the diagnosis of lymph node metastasis in patients with laryngeal cancer showed that the diagnostic sensitivity and specificity were 88.89% and 70.31%, respectively. The serum VEGF and SCCAg levels of patients with recurrence after operation were higher than those without recurrence, and the level of miRNA let-7a was lower than those without recurrence (all P<0.05). The sensitivity and specificity of combined serum VEGF, SCCAg and miRNA LET-7a levels in predicting postoperative recurrence of laryngeal cancer were 72.97% and 91.11%, respectively. Conclusions:VEGF, SCCAg, miRNA let-7a in patients with laryngeal cancer have a certain correlation with clinicopathological characteristics, which can assist in the diagnosis of lymph node metastasis and help clinical prediction of postoperative recurrence in patients with laryngeal cancer, and provide a reference for the formulation of clinical treatment plans.

Prospective study on the effect of prophylactic octreotide administration in preventing pancreatic fistula after pancreatoduodenectomy / 中华胰腺病杂志

Objective:To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy (PD)associated postoperative pancreatic fistula (POPF), total complications, peri-operative death and postoperative in-hospital days.Methods:From January 2020 to August 2021, 148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial. Patients were randomly assigned into octreotide group ( n=74) and control group ( n=74). Octreotide group was subcutaneously injected with 0.1 mg (1 ml) octreotide after preoperative anesthesia, and was subcutaneously injected with the same dose every 8 hours for 5 days, with a total of 16 doses. Control group was injected with 1 ml normal saline in the same way, and relevant clinical data and indicators of the two groups were recorded. The primary endpoint was clinically relevant pancreatic fistula, and the secondary endpoints were total complications, perioperative death and postoperative in-hospital days. Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD. Results:120 patients were finally enrolled, including 61 in octreotide group and 59 in control group. There were no significant differences on age, gender ratio, body mass index, preoperative surgery rate of jaundice reduction, preoperative major biochemical indicators, operation time, intraoperative blood loss, pancreatic duct diameter, pancreatic texture and pathological type composition ratio. The total incidence of clinical relevant POPF was 8.3%, and there were no significant differences on biochemical leakage (4.9% vs 8.5%, P=0.435), grade B fistula (4.9% vs 8.5%, P=0.435) and grade C fistula (1.6% vs 1.7%, P=0.981). The total complication incidence (24.5% vs 28.8%, P=0.601), perioperative mortality (0 vs 3.3%, P=0.147) and postoperative in-hospital days (20.6±11.1 d vs 19.5±12.2 d, P=0.633) were not significantly different between two groups. Univariate analysis showed that preoperative serum albumin level <30 g/L( P<0.001) and pathological type of pancreatic ductal adenocarcinoma ( P=0.036) were independent risk factors for POPF after PD, while multivariate analysis found no statistically significant risk factors. Conclusions:Octreotide can neither reduce the incidences of POPF, total complications and postoperative mortality, nor shorten postoperative in-hospital days. However, for patients with preoperative hypoproteinemia and (or) the pathological type of pancreatic duct adenocarcinoma, the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.

Aromatase deficiency caused by mutation of CYP19A1 gene: A case report / 中南大学学报(医学版)

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.

Research progress on the regulation of mammalian energy metabolism by the circadian clock system and gut microbiota / 生理学报

The mammalian internal circadian clock system has been evolved to adapt to the diurnal changes in the internal and external environment of the organism to regulate diverse physiological functions, such as the sleep-wake cycle and feeding rhythm, thereby coordinating the rhythmic changes of energy demand and nutrition supply in each diurnal cycle. The circadian clock regulates glucose metabolism, lipid metabolism, and hormones secretion in diverse tissues and organs, including the liver, skeletal muscle, pancreas, heart, and vessels. As a special "organ" of the host, the gut microbiota, together with the intestinal microenvironment (tissues, cells, and metabolites) in a co-evolutionary process, constitutes a micro-ecosystem and plays an important role in the process of nutrient digestion and absorption in the intestine of the host. In recent years, accumulating evidence indicates that the compositions, quantities, colonization, and functional activities of the gut microbiota exhibit significant circadian variations, which are closely related to the changes of various physiological functions under the regulation of host circadian clock system. In addition, several studies have shown that the gut microbiota can produce many important metabolites such as the short-chain fatty acids through the degradation of indigestive dietary fibers. A portion of gut microbiota-derived metabolites can regulate the circadian clock system and metabolism of the host. This article mainly discusses the interaction between the host circadian clock system and the gut microbiota, and highlights its influence on energy metabolism of the host, providing a novel clues and thought for the prevention and treatment of metabolic diseases.

Effect of homologous overexpression of nucleoside diphosphate kinase on the yield and molecular weight of hyaluronic acid / 中国药科大学学报

@#To investigate the effect of nucleoside diphosphate kinase (NDK) on the synthesis of hyaluronic acid, nucleoside diphosphate kinase gene (ndk) was overexpressed along with the hyaluronic acid-producing genes in recombinant B.subtilis. Two engineered strains named Hp8tg and Pn8tg were constructed.Uniform hyaluronic acid (HA) could be obtained from both engineered strains.HA produced by both recombinant strains was confirmed by monosaccharide composition analysis, Fourier transform infrared spectometry and nuclear magnetic resonance spectroscopy.Inducing conditions of HA fermentation were optimized by response surface methodology.Overexpression of ndk could increase the production and molecular weight of HA by 1.3-fold and 1.1-fold, respectively. This study revealed for the first time that overexpression of ndk could relieve the inhibition effect of uridine diphosphate (UDP) on Class II HA synthase and increase the production and molecular weight of HA, which proves to be an efficient strategy for the production of HA, and the preparation of other polysaccharides.

Short-term effects of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection / 中国胸心血管外科临床杂志

@#Objective    To evaluate the short-term therapeutic effect of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection (ATAAD). Methods    From November 2019 to July 2020, 28 patients with ATAAD were treated by extended adventitial inversion with graft eversion anastomosis technique in the Department of Cardiovascular Surgery, Dalian Municipal Central Hospital, including 19 males and 9 females, aged 60.11±11.11 years. The intima of the ascending aorta was trimed to 5 mm above the sinotubular junction. The adventitia of the ascending aorta was longitudinally cut to the reserved intima margin along the junction of the three aortic valves. The extended adventitial inversion was sutured continuously, no coronary sinus was sutured over the aortic annulus, and the left and right coronary sinus was sutured above the coronary ostium. The anastomotic graft was everted and inserted into the aortic lumen, and the everted graft was continuously sutured at the level of sinotubular junction which was 5 mm away from the edge of graft. Results    There was no intraoperative death, intractable root hemorrhage, residual root false lumen, root dilatation, anastomotic hematoma or other complications. There was no recurrence of the pain in the back of all patients, and the results of the CT angiography were not significantly changed. In 22 patients with no regurgitation, only 1 (4.55%) patient had a mild regurgitation. In 6 patients with mild aortic regurgitation, the disappearance rate of regurgitation was 50.0% (3/6). Conclusion    The treatment of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of aortic dissection eliminates the residual dissection at the root. The anastomotic hemorrhage is prevented, the root structure of aortic dissection is reconstructed and strengthened, the root function is restored, and the possible expansion of the root is prevented. The short-term results are satisfactory.

Data mining of adverse drug reaction signals for ado-trastuzumab emtansine and brentuximab vedotin based on FAERS database / 中国药房

OBJECTIVE To analyze the adverse drug reaction （ADR）signals of ado-trastuzumab emtansine and brentuximab vedotin，so as to provide reference for clinical medication safety. METHODS Using the FDA adverse drug event reporting system （FAERS）database and OpenVigil 2.1 data platform ，the ADR of the two drugs were collected from being approved by FDA to the Sep. 30th，2021. The ADR signals were detected by frequency method and sorted according to the occurrence frequency and signal strength respectively. RESULTS & CONCLUSIONS A total of 2 319 and 3 178 ADR reports related to ado-trastuzumab emtansine and brentuximab vedotin were collected ，215 and 329 ADR signals were detected respectively. According to the occurrence frequency，the most frequent ADR s of the two drugs were thrombocytopenia （109 cases）and febrile neutropenia （198 cases）， separately，which were consistent with the drug instructions. According to the signal strength ，the spider nevus of ado-trastuzumab emtansine（report odds ratio of 451.46）and the noninfectious endocarditis of brentuximab vedotin （report odds ratio of 304.35） ranked first ，both of which were not reported in the drug instructions. It is suggested that attention should be paid not only to the most common ADR s of blood and lymphatic system caused by both drugs ，but also to the ADRs not reported in the drug instructions such as spider nevus of ado-trastuzumab emtansine and noninfective endocarditis of brentuximab vedotin.

Role of GDC-0449 in a rat model of liver fibrosis induced by carbon tetrachloride combined with 2-acetylaminofluorene / 临床肝胆病杂志

Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.

Application of pediatric early warning score ruler of children in the nursing of critically ill children in neurology department / 中国实用护理杂志

Objective:To design a pediatric early warning score (PEWS) ruler and observe the effect of its application in the nursing of critically ill children hospitalized in neurology department.Methods:A total of 200 critically ill children admitted to Department of Neurology of Hunan Children′s Hospital from 2018 to 2019. 98 cases who were hospitalized from January to September 2019 were selected as the observation group, and 102 cases who were hospitalized from January to September 2018 were set as the control group. The control group received conventional care, while the observation group conducted PEWS ruler for nursing intervention on the basis of conventional care. The differences in hospital days, ICU transfer rate, and frequency of medical intervention between the two groups were compared.Results:The hospital days of the control group and observation group were 18.17 ± 6.33 and 13.33 ± 6.38 respectively, and the difference between the two groups was significant ( t=5.38, P<0.01). The ICU transfer rate was significantly different between the control group 17.6% (18/102) and observation group 8.2% (8/98) ( χ2=3.98, P<0.05). The reduction of increased intracranial pressure, cooling, calm, sedation and oxygen breathing in the control group were 6.86% (7/102), 13.73% (14/102), 6.86% (7/102), 7.84% (8/102), while the observation group were 17.35% (17/98), 27.55% (27/98), 24.49% (24/98), 28.57% (28/98), and the differences between the two groups were significant ( χ2 values were 5.20-14.55, all P<0.05). Conclusions:The application of PEWS ruler is helpful for nurses to recognize the progress of diseases of the critically ill children. Also, it can shorten the hospitalization days of these children, reduce the ICU transfer rate, as well as improve the nursing quality for them.

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

Clinical manifestations and gene analysis of 18 cases of hereditary protein S deficiency / 中华血液学杂志

Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.

Congenital factor X deficiency: a retrospective analysis of 11 cases / 中华血液学杂志

Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.

Effects and mechanism of zidovudine on glucolipid metabolic balance in mice / 中国药科大学学报

@#To study the effects of nucleoside antiviral drug zidovudine (AZT) on the flexibility of global metabolism and liver glucolipid metabolic balance in mice, male ICR mice were given zidovudine intragastric administration for 12 weeks, and their water and food intake was recorded daily.Serum glucose (GLU) and triglyceride (TG) levels and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected after 12 weeks of administration.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed.HE staining was used to observe the pathological changes of liver.The gene levels of glucose transporter (Glut2), carnitine palmitate transferase (Cpt1α), medium chain acyl-coa dehydrogenase (Mcad), phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase) were detected by RT-PCR.Western blot was used to detect the protein levels of insulin signaling Akt, P-Akt, Glut2, Mcad and Cpt1α in liver.The results showed that zidovudine significantly decreased lipid metabolism, impaired glucose tolerance, increased liver cell volume, significantly increased liver triglyceride (TG) and non-esterified fatty acid (NEFA) content, increased Glut2 gene expression, down-regulated fatty acid oxidative metabolism genes Cpt1α, Mcad and gluconeogenesis related genes after fasting, and down-regulated protein expression of Cpt1α.The results suggest that zidovudine can induce the disorder of glucose and lipid metabolism after fasting in a dose-dependent manner.

Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma / 中南大学学报(医学版)

Hepatocellular carcinoma is one of the most common malignant tumors in the world. Although there are many options for the treatment of hepatocellular carcinoma, such as surgical resection, interventional therapy, radiotherapy, chemotherapy, targeted therapy and liver transplantation, the poor therapeutic effect seriously reduces the quality of life for patients and also increases the social and economic burden. Metformin is originally used as the first-line drug for type 2 diabetes, but it has been found to play a certain effect in the prevention and treatment of malignant tumor. The potential roles of metformin against hepatocellular carcinoma, such as regulation of the microenvironment, proliferation signal pathway, metabolism, invasion and metastasis, apoptosis, autophagy, and epigenetics of hepatoma cells. It provides a new choice for the prevention and treatment of hepatocellular carcinoma.