Establishment of a predictive nomogram model for predicting the death of very preterm infants during hospitalization / 中国当代儿科杂志

OBJECTIVES@#To establish a nomogram model for predicting the risk of death of very preterm infants during hospitalization.@*METHODS@#A retrospective analysis was performed on the medical data of 1 714 very preterm infants who were admitted to the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University, from January 2015 to December 2019. These infants were randomly divided into a training cohort (1 179 infants) and a validation cohort (535 infants) at a ratio of 7∶3. The logistic regression analysis was used to screen out independent predictive factors and establish a nomogram model, and the feasibility of the nomogram model was assessed by the validation set. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, accuracy, and clinical applicability of the model.@*RESULTS@#Among the 1 714 very preterm infants, 260 died and 1 454 survived during hospitalization. By the multivariate logistic regression analysis of the training set, 8 variables including gestational age <28 weeks, birth weight <1 000 g, severe asphyxia, severe intraventricular hemorrhage (IVH), grade III-IV respiratory distress syndrome (RDS), and sepsis, cesarean section, and use of prenatal glucocorticoids were selected and a nomogram model for predicting the risk of death during hospitalization was established. In the training cohort, the nomogram model had an AUC of 0.790 (95%CI: 0.751-0.828) in predicting the death of very preterm infants during hospitalization, while in the validation cohort, it had an AUC of 0.808 (95%CI: 0.754-0.861). The Hosmer-Lemeshow goodness-of-fit test showed a good fit (P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 10%-60% for the training cohort and 10%-70% for the validation cohort.@*CONCLUSIONS@#A nomogram model for predicting the risk of death during hospitalization has been established and validated in very preterm infants, which can help clinicians predict the probability of death during hospitalization in these infants.

Research Progress of Transmembrane Transport of Oral Nanoparticles in Gastrointestinal Tract / 中国实验方剂学杂志

Oral nanoparticles （NPs） has gradually become a approach to improve oral bioavailability of biopharmaceutics classification system （BCS） Ⅱ， Ⅲ， Ⅳ drugs， and the transmembrane transport mechanism in the gastrointestinal tract largely depends on physicochemical characteristics of NPs. It would be beneficial to design the NPs with high transport efficiency and effectively improve the oral bioavailability of drugs by adopting a reasonable research model to analyze the transmembrane mechanism of the oral NPs and exactly reveal the relationship between the physicochemical properties and the transport mechanism of NPs. This review focused on summarizing the transmembrane approaches of oral NPs， comparing the advantages and disadvantages of the common cell models， concluding the potential interaction between the physicochemical properties and transmembrane process of NPs， and proposing the research strategy of transport mechanism based on in situ intestinal perfusion， with the purpose of discovering a suitable research model for studying the transport mechanism of different NPs， providing a basis for regulating the transport performance of the NPs to improve the oral bioavailability， and expanding the application of oral NPs in the development of new drugs.

Clinical features of very preterm infants with prelabor rupture of membranes and predictive factors for major adverse outcomes / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of very preterm infants with prelabor rupture of membranes (PROM) and predictive factors for early-onset sepsis (EOS) and death.@*METHODS@#A retrospective analysis was performed for the clinical data of the very preterm infants with PROM (with a gestational age of < 32 weeks) who were admitted to the neonatal intensive care unit from January 2018 to May 2020. According to the time from membrane rupture to delivery, the infants were divided into four groups: < 18 hours (@*RESULTS@#There was no significant difference in the incidence rates of major neonatal complications and mortality rate among the very preterm infants with different times of PROM (@*CONCLUSIONS@#Prolonged PROM does not increase the incidence of neonatal complications and mortality in very preterm infants. Adverse outcomes of very preterm infants with PROM are mainly associated with lower birth weights, lung immaturity, and systemic infection.

Overexpressing of chalcone isomerase (CHI) gene enhances flavonoid accumulation in Glycyrrhiza uralensis hairy roots / 药学学报

Chalcone isomerase (CHI) is the second rate-limiting enzyme involved in the biosynthetic pathway of flavonoids in Glycyrrhiza uralensis. Based on our previous studies, we selected the specific CHI haplotype (GenBank Accession No. KY115232) to maximize flavonoid accumulation. We constructed a plant binary expression vector for overexpression of this CHI gene by the gene fusion method and transfected the plasmid into Agrobacterium tumefaciens ACCC10060 by electroporation. The recombinant A. tumefaciens ACCC10060 subsequently was used to infect cotyledons and hypocotyls of G. uralensis to obtain transgenic hairy roots. A qRT-PCR method was used to determine the copy number of CHI and a UPLC method was used to assay the content of four flavonoids in different hairy root lines. The qRT-PCR results showed that the copy number of CHI in hairy roots was 1 or 5. UPLC results showed that the content of total flavonoids, liquiritin, liquiritigenin, and isoliquiritigenin in transgenic hairy root samples was significantly higher than that in wild-type samples. This study demonstrates that overexpression of CHI significantly increases the content of flavonoids in hairy roots of G. uralensis. This work provides a theoretical basis for clarifying the function of CHI. Three transgenic hairy root lines of G. uralensis were isolated which can be used to increase the accumulation of licorice flavonoids in vitro.

Analysis on the correlation between chalcone synthase gene polymorphism and content of liquiritin in licorice / 药学学报

Chinese pharmacopoeia stipulates that the content of liquiritin in licorice slices should be no less than 0.5%. However, there are lots of unqualified licorice slices in the herbal medicine markets. Due to the important role of functional gene polymorphism in secondary metabolism, this study attempts to analyze the influence of chalcone synthase (CHS) gene polymorphism on liquiritin biosynthesis and find out the unique haplotypes in licorice samples with high or low content of liquiritin, and to provide a basis for further analysis of molecular mechanism in flavonoid biosynthetic pathway. The contents of the 4 main flavonoids (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin) in 60 licorice samples were assayed by HPLC and the results were analyzed by Spearman and χ2 tests. The contents of the 4 main flavonoids were related to each other and obviously different in different original plants. They were highest in Glycyrrhiza uralensis samples and lowest in Glycyrriza inflate samples. Five G. uralensis samples with the highest liquiritin contents and five G. inflate samples with the lowest liquiritin contents were selected to clone the CHS cDNA sequences. 336 CHS cDNA sequences with a full length of 1 175 bp were obtained, 249 variable sites (141 missense mutation sites) were found, and 137 haplotypes were determined. 130 variable sites were found in the 336 CHS amino acid sequences and 102 types were determined. AA-3 is the major type of CHS in licorice, AA-35 is the special major type of CHS in the group with high flavonoids contents and AA-36 is the special major type of CHS in the group with low flavonoids contents. The mutation sites between AA-35 and AA-36 are I/V at 193 and V/T at 229. Discovery Studio 2.5 analysis of the three-dimensional structure of the CHS protein shows that the valine at site 229 of AA-35 is combined with malonyl-CoA. Homology analysis indicates that the homology of CHS among different species is low. This study is significant for identification of the unique haplotypes in licorices with high or low content of liquiritin and guiding the further molecular breeding of high-quantity licorice.

The molecular identification of Bupleurum medicinal species and the quality investigation of Bupleuri Radix / 药学学报

Bupleuri Radix is one of the most frequently used herbal medicines in China with a 2000-year medicinal history. However, the use of Bupleuri Radix is very confused. Twenty-five species and eight varieties of Bupleurum have been used as Bupleuri Radix in different regions of China. It is very difficult to identify these Bupleurum species using traditional morphological method. In order to establish a fast and effective method to identify these Bupleurum species, we collected 168 Bupleurum medicinal plants from 14 populations of 9 provinces, and amplified their ITS sequences. 168 ITS sequences with a full length of 600-606 bp were obtained. DNAMAN analyzing results showed that 86 variable sites were present in these sequences and 19 haplotypes (TH1-TH19) were determined. After calculating K2P distance and analyzing an NJ tree, we established a molecular identification method based on ITS sequence. Using this method,52 samples of Bupleuri Radix were identified successfully. Furthermore, we tested saikosaponin a, c, d contents in these Bupleuri Radix by HPLC and analyzed the results by ANOVA and LSD T test to evaluate the quality of Bupleuri Radix. This method is significant for effective identification of Bupleurum medicinal plants, and quality control of Bupleuri Radix in the market.

The molecular identification of licorice species and the quality evaluation of licorice slices / 药学学报

Licorice is one of the most common herbs in traditional Chinese medicine, and classified as top grade in Shen Nong Ben Cao Jing. There are three different original plants of licorice stipulated in Chinese Pharmacopeia, Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L., and Glycyrrhiza inflata Bat. However, previous investigation showed that the pharmacodynamic effects of the three licorices were quite different. It is very difficult to identify them by the classical identification methods. In order to establish a fast and effective identification method, we collected 240 licorice plants from 21 populations of 7 provinces, and amplified their ITS and psbA-trnH sequences. ITS sequences with a full length of 616 bp and psbA-trnH sequences with a full length of 389 bp were obtained separately. Using DNAMAN to analyze these sequences, 4 variable sites were found in ITS sequences and 2 ITS haplotypes were determined, and 3 variable sites were found in psbA-trnH sequences and 4 psbA-trnH haplotypes were determined. With the combination analysis of ITS and psbA-trnH sequences, the molecular identification method of original licorice was established. Using this method, 40 samples of licorice slices collected from 4 main herbal material markets in China were identified successfully. Furthermore, the contents of 2 triterpenes, 18α-glycyrrhizic acid and 18β-glycyrrhizic acid, and 4 flavonoids, liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in these licorice pieces were examined by HPLC and the results were analyzed using SPSS 21.0. This study provides a new method in identification of licorice, which may serve as a guideline for quality control of licorice slices.

Analgesic and anti-inflammatory effects of total alkaloid in Stephania kwangsiensis in vivo / 药物评价研究

Objective To study the analgesic and anti-inflammatory effects in vivo of the total alkaloids in Stephania kwangsiensis (TARS).Methods Mice were respectively ig with high,middle,and low doses of TARS.The analgesic effects of TARS were evaluated by the formaldehyde induced pain method and tail-immersion response induced by hot water in mice,and anti-inflammatory effects were observed by cotton ball granuloma,egg white induced paw swelling method in mice.Results TARS could significantly inhibit formaldehyde induced pain in mice,reduce the hind licking times,extend tail withdrawal time induced by hot water,obviously reduced the formation of granulomatous in mice;Inhibited egg white induced paw swelling.Conclusion TARS has significant analgesic and anti-inflammatory effect.

Enhancing ergosterol production in Pichia pastoris GS115 by overexpressing squalene synthase gene from Glycyrrhiza uralensis / 中国天然药物

The present study was designed to determine the effects of copy number variations (CNVs) of squalene synthase 1(SQS1) gene on the mevalonate (MVA) pathway. SQS1 gene from G. uralensis (GuSQS1) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy number of GuSQS1 were constructed. HPLC was used to assay the level of ergosterol in all transgenic P. pastoris strains containing GuSQS1. HPLC analysis showed that the contents of ergosterol in all of the transgenic P. pastoris containing GuSQS1 were higher than that in the negative control. And with the increase of copy number of GuSQS1, the content of ergosterol showed an increasing-decreasing-increasing pattern. The contents of ergosterol in 10-copy-GuSQS1 P. pastoris and 47-copy-GuSQS1 P. pastoris were significantly higher than that in the rest recombinant P. pastoris strains. In conclusion, the CNVs of GuSQS1 influence the content of secondary metabolites in the MVA pathway. The present study provides a basis for over-expressing GuSQS1 and increasing the content of glycyrrhizin in G. uralensis cultivars.

Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Catheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.</p><p><b>METHODS</b>A retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively.</p><p><b>RESULTS</b>The mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study.</p><p><b>CONCLUSIONS</b>Treatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.</p>

Analysis of cause and treatment of acute limb ischemia complicated in peripheral endovascular interventions / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the cause and treatment of acute limb ischemia in endovascular therapy of the lower extremity arterial occlusive disease.</p><p><b>METHODS</b>Clinical data of 54 cases of acute limb ischemia in the endovascular treatment of 685 cases of lower extremity arterial occlusive disease from June 2003 to April 2012 was analyzed retrospectively. There were 43 male and 11 female patients, with a mean age of 72.3 years (ranging from 56 to 82 years). The major causes which resulted in acute limb ischemia included: arterial embolization of 43 cases, arterial thrombosis of 8 cases, arterial dissection of 3 cases. The acute limb ischemia occurred in the process of balloon angioplasty/stent in 36 cases, catheter-directed thrombolysis in 17 cases, Silverhawk atherectomy in 1 cases. Thirty-two cases were treated by endovascular treatment, 9 cases by surgical procedures (bypass or embolectomy), 13 cases by the combination of endovascular therapy and surgical procedures.</p><p><b>RESULTS</b>Treatment were successfully accomplished in 50 of 54 cases, and failed in 4 cases which had surgical amputation. There were no deaths in all the patients. Forty-five of 54 cases were followed up for the average of 40.3 months. Six cases had ischemic symptoms recurrence in 43 artery embolization patients, in whom 4 cases were cured by endovascular treatment, 2 cases were cured by toe amputation. One case of bypass anastomotic stenosis and one case of stent restenosis were successfully cured by endovascular treatment in 8 arterial thrombosis patients. One cases of below-knee artery stent occlusion in 3 arterial dissection patients was cured by medical treatment. Four cases of amputation patients were followed up in good condition.</p><p><b>CONCLUSIONS</b>Most patients of acute limb ischemia complicated in endovascular therapy could be treated by endovascular therapy. Surgical procedures in time is still the best choice for the patients in whom the endovascular therapy was not satisfied.</p>

Randomized controlled study on acupuncture for treatment of diabetic paralytic squint / 中国针灸

<p><b>OBJECTIVE</b>To observe clinical therapeutic effect of acupuncture on diabetic paralytic squint.</p><p><b>METHODS</b>Seventy-two cases of diabetic paralytic squint were randomly divided into a medication group, an acupuncture group and an acupuncture and medication group. The medication group were treated with intramuscular injection of Methyl vitamin B12 250 microg, once daily; the acupuncture group were treated by acupuncture at different acupoints according to different paralytic muscles of eyes with adjuvant acupoints selected according to symptoms; the acupuncture and medication group were treated with the routine medicine and acupuncture. The treatment was given for 28 days.</p><p><b>RESULTS</b>The total effective rate of 87. 5% in the acupuncture group and 95.7% in the acupuncture and medication group were higher than 54.5% in the medication group (P < 0.05, P < 0.01), with no significant difference between the acupuncture group and the acupuncture and medication group (P > 0.05).</p><p><b>CONCLUSION</b>Acupuncture has a definite therapeutic effect on diabetic paralytic squint, which is better than that of routine medication.</p>

Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats.</p><p><b>METHOD</b>After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining,</p><p><b>RESULT</b>Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05).</p><p><b>CONCLUSION</b>Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.</p>

Study on acupuncture treatment of diabetic neurogenic bladder / 中国针灸

<p><b>OBJECTIVE</b>To probe into a better therapy for diabetic neurogenic bladder.</p><p><b>METHODS</b>The patients were randomly divided into a treatment group and a control group, 35 cases in each group. The control group were treated with intramuscular injection of Methycobal 250 microg, once every other day; the treatment group were treated with intramuscular injection of Methycobal 250 microg, once every other day, and acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Ciliao (BL 32), Huiyang (BL 35), once every day. The residual urine were compared before and after treatment in the two groups; the effective rate for improvement of symptoms were compared between the two groups. The mental and healthy nursing were conducted for the patients.</p><p><b>RESULTS</b>After treatment, the improving rate for the urgency of urination, frequency of micturition, dribbling urination, urinary incontinence and dysuria in the treatment group was significantly better than that in the control group, but with no significant difference between the two groups in prolongation of urination time. After treatment, the residual urine in the bladder significantly improved in the two groups with more significantly improved in the treatment group than in the control group.</p><p><b>CONCLUSION</b>Methycobal plus acupuncture has a better result than the simple Methyeobal for treatment of diabetic neurogenic bladder, and strengthening nursing care in the treatment can significantly enhance life quality of the patient.</p>

Tissue distribution of Aconitum alkaloids extracted from Radix aconiti preparata after oral administration to rats / 药学学报

<p><b>AIM</b>To develop an HPLC method for the determination of Aconitum alkaloids extracted from Radix aconiti preparata in rats.</p><p><b>METHODS</b>Waters 2690@996 PAD system was used. The analytical column was a Halsil 100 C18 column (250 mm x 4.6 mm ID, 5 microm). The mobile phase was water, methanol and diethyl amine at the ratio of 75:25:0.1. The flow rate was 0.9 mL.min(-1). The wavelength of the detector was 240 nm.</p><p><b>RESULTS</b>The linear ranges of aconitine in the heart, spleen, lung and kidney were 0.4-100 microg.mL(-1), the correlation coefficients were 0.9972, 0.9986, 0.9993 and 0.9994, respectively. The linear range of aconitine in liver was 2-200 microg.mL(-1) and the correlation coefficient was 0.9990. The linear ranges of hypaconitine in heart, liver, spleen, lung, kidney, brain and spinal cord were 5-100 microg.mL(-1), the correlation coefficients were 0.9994, 0.9997, 0.9998, 0.9984, 0.9998, 0.9998 and 0.9997, respectively. Detection limits (S/N = 3) of aconitine and hypaconitine were 0.4 microg.mL(-1). The recoveries of aconitine and hypaconitine ranged from 88.7% to 102.2% and 86.5% to 101.3%, respectively, and the RSD of precision of aconitine and hypaconitine was 10%.</p><p><b>CONCLUSION</b>It appears to be an accurate and effective method that can offer reference basis for in toxication of Radix aconiti preparata clinically.</p>