Clinical analysis of twin-to-twin transfusion syndrome combined with necrotizing enterocolitis / 中国小儿急救医学

Objective:To investigate clinical characteristics and high-risk factors of prognosis of twin-to-twin transfusion syndrome(TTTS) combined with necrotizing enterocolitis(NEC).Methods:The clinical data of 102 children with TTTS admitted to the NICU at the Third Affiliated Hospital of Zhengzhou University from January 2017 to January 2020 were collected.Fifty-one pairs(102 cases)of twins without TTTS who were hospitalized at the same time and in the same gestational age were selected as the control group, and the relevant case data were collected and compared.The clinical data of 14 children with NEC in TTTS group were analyzed retrospectively.Results:(1)The average gestational age of TTTS group was(32.24±2.12)weeks, and that was (32.47±1.84) weeks in control group, with no statistical significance( P>0.05). The average birth weight of TTTS group was(1 547.63±523.80)g, which was lower than that of control group(1 658.71±454.13)g( P<0.05). There were 14 children in TTTS group with NEC, with an incidence of 13.7%(14/102), and seven children in the control group with NEC, with an incidence of 6.9%(7/102)( P<0.05). The proportion of very low birth weight infants, NEC occurrence within 2 weeks and mortality in TTTS group were higher than those in control group( P<0.05). (2)Compared with the non-NEC group, the NEC group of TTTS children had lower birth weight, the incidence of intrauterine distress and severe postnatal asphyxia, and the rate of sepsis were significantly higher than those in non-NEC group( P<0.05). (3)Among TTTS children, NEC was diagnosed in ten donors(71.4%) and four recipients(28.6%), with statistically significant difference between two groups( P<0.05). (4)The early clinical symptoms of TTTS complicated with NEC were mainly bloody stools, abdominal distension, poor response, apnea, and vomiting. Conclusion:TTTS is one of the risk factors for NEC, which the occurrence time of TTTS combined with NEC is not completely consistent with the classic NEC, which is more likely to occur within 2 weeks after birth.Children with TTTS complicated with NEC mostly occur in donor infants, and fetal distress in utero, severe asphyxia and sepsis are the high risk factors.The early clinical symptoms of TTTS combined with NEC are not significantly different from those of common NEC, mainly including bloody stools, abdominal diste, poor response, apnea, and vomiting.Vigilance should be raised when similar digestive symptoms appear in children.

Medial parapatellar soft tissue overlapping suture in total knee arthroplasty for severe osteoarthritis with permanent patellar dislocation: early and mid-term results / 南方医科大学学报

OBJECTIVE@#To evaluate the early and mid-term clinical results of medial parapatellar soft tissue overlapping suture in total knee arthroplasty for treatment of severe osteoarthritis combined with permanent patellar dislocation.@*METHODS@#We retrospectively analyzed the data of 12 patients (12 knees) diagnosed with severe knee osteoarthritis combined with permanent patellar dislocation undergoing total knee arthroplasty with medial parapatellar soft tissue overlapping suture. Knee Society Score (KSS), University of California Los Angeles (UCLA) activity-level rating, Visual Analog Scale (VAS) pain score, and knee range of motion of the patients were assessed before and 2 years after the surgery. Anteroposterior and lateral radiographs of the knee joint, full-length standing radiographs of the lower limbs and patellar axial radiographs were evaluated.@*RESULTS@#The mean Knee Society Score of the patients increased from 34.2±11.1 before surgery to 73.5±6.3 at two years after the surgery (P < 0.001). The UCLA activity-level rating increased from an average of 3.8 ± 0.8 before surgery to 5.8 ± 0.6 at two years postoperatively (P=0.003). The mean VAS pain score decreased from 42.8±6.0 before surgery to 20.1±3.7 (P < 0.001) and the range of motion of the knee joint increased from 74.6±8.9 degrees to 97.5±4.5 degrees at two years (P < 0.001). The radiographs showed no signs of subluxation or dislocation of the patella in all the patients.@*CONCLUSIONS@#Medial parapatellar soft tissue overlapping suture in total knee arthroplasty can achieve good early and mid-term clinical results for treatment of severe osteoarthritis combined with permanent patellar dislocation.

One-stage total knee arthroplasty combined with open reduction and internal fixation for knee osteoarthritis complicated with tibial stress fracture / 中华创伤骨科杂志

Objective:To explore one-stage total knee arthroplasty (TKA) combined with open reduction and internal fixation (ORIF) for knee osteoarthritis complicated with tibial stress fracture.Methods:The 3 patients were retrospectively analyzed who had been treated for knee osteoarthritis complicated with tibial stress fracture at Department of Orthopedics, Ganzhou District People＇s Hospital from March 2018 to March 2020. They were all female, aged from 54 to 76 years (average, 66 years). There were 2 transverse fractures and one short oblique fracture; all of them had knee varus deformity. The Hospital for Special Surgery (HSS) scores averaged 37.6 (from 28 to 50) for the left knee and 28.3 (from 22 to 39) for the right knee. One-stage TKA was performed for the articular surface while ORIF for the right tibial stress fracture for all patients. Recorded were fracture union time, HSS knee score and range of articular motion.Results:The 3 patients were followed up for 25 to 44 months (average, 32 months).The fracture union time ranged from 4 to 7 months (average, 5 months). The last follow-ups revealed no such complications as prosthesis loosening, peri-prosthesis osteolysis or joint instability. Knee varus deformity was corrected in all patients. The HSS knee scores at the last follow-up averaged 89.6 (from 88 to 91) for the left knee and 88.3 (from 85 to 90) for the right knee.Conclusion:In the treatment of knee osteoarthritis complicated with tibial stress fracture, one-stage TKA combined with ORIF can restore the function of knee joint, leading to fine curative effects.

Intelligent identification of the big data of liver injury-related adverse drug reactions based on text database / 临床肝胆病杂志

Objective To establish the intelligent identification method for the big data of liver injury-related adverse drug reaction (ADR) based on the construction of text database. Methods With the keywords including "drug-induced liver injury" and "abnormal liver function" and a search time of January 1, 2012 to December 31, 2016, 5% (4152 cases) of the case reports of liver injury-related ADR were retrieved and extracted from the China Adverse Drug Reaction Monitoring System, and then based on clinical reevaluation by physicians, these cases were classified into "negative cases", "suspected cases", and "confirmed cases". On this basis, key elements (including ADR name, biochemical parameter, and clinical symptoms) were identified. An intelligent identification method for liver injury-related ADR was established based on the correlation analysis between key elements and clinical reevaluation and the receiver operating characteristic (ROC) curve for determining cut-off values, and the method of cross validation was used to evaluate the performance of this intelligent identification method. Results The formula for the evaluation and identification of liver injury-related ADR was as follows: total score (M)=symptom score+index score+ADR name score. This formula showed the best discriminatory ability to distinguish "negative case" from "suspected case" or "confirmed case" at M=5 (area under the ROC curve [AUC]=0.97), with a sensitivity of 99.57% and a specificity of 84.61%, and it showed the best discriminatory ability to distinguish "confirmed case" from "suspected case" or "negative case" at M=12 (AUC=0.938), with a sensitivity of 87.93% and a specificity of 85.98%. Conclusion This method provides reference and basis for intelligent identification and evaluation of big data on liver injury-related ADR and is expected to effectively reduce the burden of manual processing of ADR big data and provide effective tools and methodological demonstration for early risk signal identification and warning of liver injury-related ADR.

Research and verification of quality evaluation method of Epimedii Folium based on quantitative analysis of multi-components by single marker / 中国中药杂志

The quality control of Epimedii Folium, composed of diverse constituents, is single at present. In view of this, an eva-luation method of 13 chemical constituents based on quantitative analysis of multi-components by single marker(QAMS) was established to further explore the composition differences of raw products and alcohol extracts in different batches and the influence of alcohol extraction on the composition, so as to provide a reference for improving the quality evaluation and control of Epimedii Folium. The fingerprints of different batches of Epimedii Folium were constructed by ultra-high performance liquid chromatography(UPLC) to evaluate the inter-batch consistency. The changes of the flavonoids in Epimedii Folium during alcohol extraction were analyzed based on determined levels and heat map, and the reasons for the changes were preliminarily discussed. With icariin, the quality control component recorded in the Chinese Pharmacopoeia, as the internal reference, the stability of the relative correction factors of chemical components under different conditions was investigated to obtain the relative correction factors. Then the determination results of QAMS and the external standard method were compared to verify the accuracy of QAMS. The results revealed that all batches of Epimedii Folium met the requirements specified in the Chinese Pharmacopoeia, and the fingerprints of Epimedii Folium from the same place of origin exhibited a high similarity. Raw products and alcohol extracts of Epimedii Folium could be clearly distinguished by prenylated flavonoids, which are potential biomarkers for quality control. Additionally, the glycoside hydrolysis in the alcohol extraction was preliminarily explored. The QAMS method has good accuracy, durability, and repeatability in determining 13 chemical components in Epimedii Folium under different experimental conditions. No significant difference in the results obtained by the two methods was observed. This study can provide a reference for comprehensive, rapid and reasonable quality evaluation of Epimedii Folium.

Anti-inflammatory target prediction of Gentianae Radix et Rhizoma based on network pharmacology and construction of a bioassay method for its quality control / 中国中药杂志

Based on the heat-clearing and detoxifying effects of Gentianae Radix et Rhizoma, the network pharmacology is mainly used to predict the potential targets of Gentianae Radix et Rhizoma for anti-inflammatory activity and to perform the experimental verification. A method for detecting the biological potency of Gentianae Radix et Rhizoma based on verifiable targets has been established to provide a reference for improving the quality evaluation and control standards of Gentianae Radix et Rhizoma. High performance liquid chromatography can be used to construct chemical fingerprints of different batches of Gentianae Radix et Rhizoma. Constructing a component-target-disease network of Gentianae Radix et Rhizoma for its anti-inflammatory activity was applied to screen potential anti-inflammatory components and related targets of Gentianae Radix et Rhizoma, and to verify the target of Gentianae Radix et Rhizoma by using biological evaluation methods. Detecting the biological potency of different batches of Gentianae Radix et Rhizoma extracts was used to inhibit COX-2 enzyme activity based the verifiable target cyclooxygenase-2(COX-2). The results showed that different batches of Gentianae Radix et Rhizoma accorded with the pharmacopoeia testing regulations, and the chemical fingerprints have a high similarity(similarity>0.93), suggesting that there is no significant difference in the characteristics of the chemical components. Based on network pharmacology predictions, 18 candidate targets were found to have potential direct interactions with the ingredients in Gentianae Radix et Rhizoma. Among them, the most important target is COX-2. Based on the experimental verification of recombinant human COX-2 protease activity inhibition, Gentianae Radix et Rhizoma can inhibit the COX-2 enzyme activity in a dose-dependent manner. It can function with a low concentration(0.75 mg·mL~(-1)), which preliminarily confirmed the accuracy of network pharmacology prediction. The biological potency detection method of Gentianae Radix et Rhizoma based on COX-2 inhibitory activity was optimized and established. The qualitative response parallel line method was used to calculate the biological potency of anti-inflammatory activity, which ranged from 23.04 to 46.60 U·mg~(-1). For network pharmacology prediction, it can screen and clarify the possible targets of traditional Chinese medicine rapidly, which can guide the establishment of a biological evaluation method for the quality of medicinal materials with related activities. Compared with chemical fingerprints, the biological potency testing can better detect quality fluctuations of traditional Chinese medicine.

Surgical strategies for anteromedial tibial plateau compression fracture complicated with posterolateral corner injury / 中华创伤骨科杂志

Objective:To discuss the surgical strategies for anteromedial tibial plateau compression fracture complicated with posterolateral corner injury.Methods:From 2015 January to 2020 July, 18 patients with anteromedial tibial plateau compression fracture complicated with posterolateral corner injury were admitted to Department Ⅲ of Orthopaedics, Zhongshan Hospital of Traditional Chinese Medicine. They were 11 males and 7 females, aged from 28 to 57 years (average, 38.6 years). By the CT three-column theory, all their fractures were medial column ones; by the Fanelli classification, there were 5 cases of type B and 13 cases of type C. Seventeen patients with fresh fracture were treated with arthroscopic ligament reconstruction and meniscus repair followed by primary reduction and fixation of tibial plateau fracture. The one patient with obsolete injury was treated with high tibial osteotomy around the knee joint and reconstruction of the anterior cruciate ligament. Recorded were the patients' fracture healing time, knee Lysholm score, joint range of motion and complications.Results:The 17 patients with fresh injuries were followed up for 12 to 24 months (average, 18.4 months). Their fracture healing time ranged from 12 to 24 weeks (average, 17.7 weeks). By one year after surgery, their knee extension reached 0° and their knee flexion from 120° to 135° (average, 131.9°); their knee Lysholm scores ranged from 88 to 95 points (average, 91.2 points). The one patient with old injuries was followed up for 18 months, with fracture healing time of 18 weeks, knee range of motion from 0° to 120° and knee Lysholm score of 86 points by one year after operation. None of the patients reported such complications as neurovascular injury, wound infection, internal fixation failure or nonunion.Conclusion:For anteromedial tibial plateau compression fracture complicated with posterolateral corner injury, primary repair and reconstruction can restore knee joint stability, leading to fine therapeutic outcomes.

Landscape of Hepatobiliary Adverse Drug Reactions Related to Preparations Containing Psoraleae Fructus and Its Application in Pharmacovigilance / 中国结合医学杂志

OBJECTIVE@#To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance.@*METHODS@#A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed.@*RESULTS@#There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion.@*CONCLUSIONS@#Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.

Epidemiological analysis of liver injury related to bone diseases / 中国中药杂志

A total of 1 392 reports on liver injury associated adverse drug reaction(LI-ADR) related to bone diseases were retrospectively analyzed based on national ADR monitoring system [18.75% of the patients used traditional Chinese medicine(TCM) alone and 68.68% used Western medicine alone]. This kind of cases accounted for 2.5% of all drug-related liver injury adverse reactions, ranking top ten of all drug categories. The number of reported cases and the proportion of serious cases showed an increasing trend from 2012 to 2016. The average age of the patients was(54.2±15.8) years old, and there was little difference in overall gender(male-female 1.04∶1). However, the number of female patients with rheumatoid arthritis was significantly higher than that of male patients(male-female 1∶2.6), while the number of male patients with gout was significantly higher than that of female patients(male-female 7.16∶1). The overall prognosis was good, with the recovery and improvement rate of 85.27%. The time from medication to liver injury varied due to different medicines. The median time to liver injury was 27 days in TCM alone group, later than 11 days in Western me-dicine alone group(P<0.05). Drugs for bone diseases have been one of the important categories for clinical drug-induced liver injury, and the number of reported cases on liver injury caused by drugs for bone diseases is increasing, so we should pay close attention to the safe and rational use of them. The LI-ADRs of male and female were different due to their different diseases, and the latency of adverse reactions in TCM group was generally longer than that in Western medicine group. In clinical medication, liver function should be monitored according to different diseases and characteristics of drugs to prevent the risk of liver injury.

Erratum: Author correction to 'Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome' Acta Pharmaceutica Sinica B 9 (2019) 734-744

[This corrects the article DOI: 10.1016/j.apsb.2019.02.003.].

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Application of an effect-constituents index for the quality evaluation of the traditional Chinese medicine rhubarb / 药学学报

To explore the application of an effect-constituents index (ECI) for the quality evaluation of rhubarb, we carried out the simultaneous determination of 12 chemical components by ultra-performance liquid chromatography and used the ICR mouse constipation model to determine the diarrhea biopotency of these 12 components. With the diarrhea biopotency of sennoside A as a reference, the diarrhea biopotency weight coefficient of each chemical component was obtained. A multi-component chemical quantitative analysis combined with the biopotency weight coefficients for rhubarb was developed, named the diarrhea ECI. Animal experiment ethics requirements were approved by the Animal Experimental Ethics Committee of the 302 Hospital of the People's Liberation Army (Grant Number: IACUC-2015-012). The results showed that there were significant differences in the content of the 12 chemical components in different batches of processed products of rhubarb. Especially worthy of attention was the content of aloe-emodin-8-O-β-D-glucoside in sample Rh03, nearly 40-fold higher than that in Rh07 (4.79 vs 0.12 mg·g-1), and the content of rhein-8-O-β-D-glucoside in sample Rh03, nearly 45 times higher than that in Rh07 (3.56 vs 0.08 mg·g-1). The actual measured diarrhea biopotencies of the 12 chemical components ranged from 61.65 ± 4.28 to 233.84 ± 5.58 U·mg-1. The calculated diarrhea effect-constituents indices of 16 rhubarb samples ranged from 1.07 (Rh15) to 19.38 (Rh03), and the actual measured diarrhea biopotencies of 16 rhubarb samples based the ICR mouse constipation model ranged from 23.84 U·g-1 (Rh16) to 310.94 U·g-1 (Rh05). The correlation between the diarrhea ECIs and the actual measured diarrhea biopotencies of 16 rhubarb samples was good (r = 0.969 5), suggesting that the diarrhea effect-constituents indices may be the most suitable for evaluating the quality of different rhubarbs with regard to diarrhea.

Comparative study on the suitability of chemical fingerprint and anti-platelet aggregation/anti-inflammatory biopotency in the overall quality evaluation of Xiaojin pills / 药学学报

Xiaojin pills, the first choice for clinical treatment of breast hyperplasia, were selected to explore the suitability of a bioactivity assay with chemical fingerprinting for the development of an overall quality evaluation assay. The liposoluble and water-soluble fraction fingerprints of Xiaojin pills were established. The ability to inhibit platelet aggregation and the rate of inhibition of cyclooxygenase-2 (COX-2) for 16 batches of Xiaojin pills from several manufacturers was analyzed; the chemical fingerprints of these samples were correlated with the bioactivity and chemical analysis. The animal protocol was approved by the Committee on the Ethics of Animal Experiments of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Approval, ID: 2018BL-002. Results showed that the antiplatelet aggregation activity of 16 batches was 0.712-1.278 U∙mg-1, with a relative standard deviation (RSD) of 15.4%. COX-2 inhibition was 52.07%-68.95% and the RSD was 8.91%. The results showed that there was little difference in the biological effects of these samples. However, the chemical fingerprint consistency of these 16 batches of Xiaojin pills was poor, and the similarity of nearly half of the samples was less than 0.9. The total peak area of Xiaojin pills was 32.74%-165.37% across samples, showing very poor chemical consistency. In order to explore the reasons for the poor chemical consistency despite good consistency in the biological assays, the fingerprint chromatogram was analyzed by multivariate statistical analysis. The main chromatographic peaks were identified. The results showed that the similarity of Xiaojin pills was mainly determined by the prominent chromatographic peaks 17, 18, 20, 23 and 27 in the liposoluble fingerprints, which were identified from Liquidambaris resina and Angelica sinensis Radix. However, Liquidambaris resina and Angelicae sinensis Radix had almost no anti-platelet aggregation activity or COX-2 inhibitory effect at the normal prescription ratio. As a result, the ability to utilize chemical fingerprints to evaluate the quality consistency of Xiaojin pills is limited. The selection of biological evaluation methods that reflect clinical efficacy could make up for the shortcomings of chemical evaluation methods for quality assessment, and provide new ideas and methods for the overall quality evaluation of complex Chinese patent medicines.

Construction and application of effect-related near-infrared spectroscopy for traditional Chinese medicines — Exemplification by rhubarb dispensing granules / 药学学报

Consistency in quality of traditional Chinese medicine granules is an important factor to ensure reproducible clinical efficacy. In this study rhubarb dispensing granules were utilized to construct an efficacious near-infrared spectroscopy (eNIRS) assay by combining NIRS and biopotency. A NIR method for assaying rhubarb dispensing particles was established, and information on different batches was collected. The diarrhea-inducing biopotency of rhubarb dispensing granules was determined based on a constipation model induced by diphenoxylate in mice. The animal protocol was approved by the Animal Ethic Committee​ of 302 Hospital of Chinese PLA People's Liberation Army (ID: IACUC-2019-0010). Ten anthraquinones were determined in rhubarb dispensing granules by UPLC. The correlation between NIR and biopotency was analyzed and five characteristic bands that correlated highly with bioactivity were identified, including 4 011-4 390, 4 859-5 461, 7 012-7 493, 10 992-11 312 and 11 871-12 489 cm-1. There were some differences in the main bands of different chemical constituents. In summary, five active bands based on NIRS were identified and found to be able to achieve rapid on-line detection of rhubarb dispensing granule quality. This research model may also provide reference for quality control of other Chinese medicine dispensing granules.

Quality evaluation of different processed products of Aconiti Lateralis Radix Praeparata combining bioassay and toxicity detection / 药学学报

There are many kinds of processed products of Aconiti Lateralis Radix Praeparata (ALRP), but their differences in toxicity and efficacy have not been identified. The minimum premature ventricular contraction (PVC) method was used to evaluate the biological toxicity of eight processed products. The results showed that the minimal toxic dose (MTD) of an ethanol extract of Shengfupian (SFP) was 0.16 g·kg-1, which was much lower than that of Heishunpian (HSP), Baifupian (BFP), Baofupian (BAP), Paofuzi (PFZ) or Zhengfupian (ZFP), with MTDs ranging from 2.64 to 5.75 g·kg-1. No cardiotoxicity was detected with Chaofupian (CFP) and Paotianxiong (PTX). A novel +dp/dtmax assay for acute heart failure in rats was developed to evaluate the cardiac activity. It was found that all eight processed products had cardiac effects, with Shengfupian showing the strongest cardiotonic effect and the ability to restore damaged cardiac function to normal within 15 minutes of injection. Heishunpian, Baifupian and the three other products displayed moderate activity, while Paofuzi and Paotianxiong were the weakest. An LC-MS/MS method was utilized to determine the content of 13 alkaloids in water extracts. The results demonstrated that hypertoxic aconitine, mesaconitine, and hypaconitine could not be detected, higenamine was only present in Shengfupian, and salsolinol was about 4-56 times higher in Shengfupian than in other products. A correlation analysis showed that salsolinol had the best correlation with the cardiotonic index, with a correlation coefficient as high as 0.817, while the three monoester alkaloids failed to correlate with the cardiotonic effect. Higenamine and salsolinol were cardiotonic, while the 11 other components had no cardiotonic activity. This study establishes methods for precise evaluation of cardiotoxicity and cardiac activity, reveals the toxicity and efficacy of common processed products, and identifies the key quality markers for cardiac activity, providing scientific support for the quality evaluation and clinical application of processed products of aconite.

Measurement of antiplatelet aggregation and potency of hirudo / 药学学报

The objective of this work was to develop a bioassay to quantify the antiplatelet aggregation activity of hirudo for quality evaluation and control. Antithrombin activity of hirudo extracted by high temperature decoction was determined by thrombin titration. Antiplatelet aggregation activity of hirudo was determined through pharmacodynamic experiments in vitro and in vivo using a bioassay we developed for quantifying inhibition of platelet aggregation. Methodological investigation was carried out and the titers of 12 batches of hirudo samples were determined. During the experiment, the disposal of animals is in accordance with the ethical standards of animal experiments. The results showed that the antithrombin activity of hirudo decocted at high temperature decreased significantly and almost lost its activity. Hirudo inhibited platelet aggregation and results in vivo and in vitro were consistent. These assays were employed to test 12 batches of hirudo. The results demonstrated that the biopotency of 12 batches was 113.49, 96.13, 121.22, 127.33, 83.48, 108.72, 131.41, 127.95, 76.90, 126.27, 132.89 and 573.53 U·mg-1. The method was reliable and reproducible and can be used to assess the quality of hirudo.

Metabolomic screening for diagnostic biomarkers of drug-induced chronic liver injury related cirrhosis / 药学学报

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

Analysis of epidemiological characteristics of drug induced liver injury associated with Baixianpi Preparations / 中国中药杂志

A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade Ⅲ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.

Pathogens and clinical features of preterm infants with sepsis / 中国当代儿科杂志

OBJECTIVE@#To investigate the pathogen composition and clinical features of preterm infants with sepsis, and to provide a basis for early identification and treatment of sepsis in preterm infants.@*METHODS@#A retrospective analysis was performed for the clinical data of 371 preterm infants with sepsis who had a positive blood culture between January 2014 and May 2018. According to the time of onset, the preterm infants were divided into an early-onset group (an age of onset of <7 days) with 73 preterm infants and a late-onset group (an age of onset of ≥7 days) with 298 preterm infants. The two groups were compared in terms of pathogen composition and clinical features (initial symptoms, laboratory examination results at the time of onset, comorbidities, and prognosis).@*RESULTS@#There was a higher proportion of infants with Klebsiella pneumoniae infection in the late-onset group (P<0.05), while there was a higher proportion of infants with Escherichia coli, Streptococcus agalactiae or Listeria infection in the early-onset group (P<0.05). The early-onset group had a significantly higher proportion of infants with dyspnea than the late-onset group (P<0.05). Compared with the late-onset group, the early-onset group had significantly shorter time to negative conversion of blood culture, duration of antibiotic use before infection, and indwelling time of deep venous catheterization (P<0.05), and the late-onset group had a significantly higher incidence rate of neonatal necrotizing enterocolitis than the early-onset group (P<0.05). The early-onset group had a significantly higher rate of treatment withdrawal than the late-onset group (P<0.05).@*CONCLUSIONS@#Preterm infants with sepsis lack typical clinical manifestations and laboratory examination results at the time of onset. There are certain differences in pathogen composition and clinical features between preterm infants with early- and late-onset sepsis. Possible pathogens for sepsis should be considered based on age in days at the time of onset and related clinical features.