Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia. We determined that CRC patients resistant to bevacizumab treatment presented with elevated levels of histone lactylation and inhibition of histone lactylation efficiently suppressed CRC tumorigenesis, progression and survival in hypoxia. Histone lactylation promoted the transcription of RUBCNL/Pacer, facilitating autophagosome maturation through interacting with BECN1 (beclin 1) and mediating the recruitment and function of the class III phosphatidylinositol 3-kinase complex, which had a crucial role in hypoxic cancer cells proliferation and survival. Moreover, combining inhibition of histone lactylation and macroautophagy/autophagy with bevacizumab treatment demonstrated remarkable treatment efficacy in bevacizumab-resistance patients-derived pre-clinical models. These findings delivered a new exploration and important supplement of metabolic reprogramming-epigenetic regulation, and provided a new strategy for improving clinical efficacy of bevacizumab in CRC by inhibition of histone lactylation.Abbreviations: 2-DG: 2-deoxy-D-glucose; BECN1: beclin 1; CQ: chloroquine; CRC: colorectal cancer; DMOG: dimethyloxalylglycine; H3K18la: histone H3 lysine 18 lactylation; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; Nala: sodium lactate; PDO: patient-derived orgnoid; PDX: patient-derived xenograft; RUBCNL/Pacer: rubicon like autophagy enhancer; SQSTM1/p62: sequestosome 1.

Determination on Tree Species Selection for Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Cultivation by Fourier Transform Infrared and Two-Dimensional Infrared Correlation Spectroscopy.

As a wood-degrading Agaricomycetes mushroom, Ganoderma lucidum can be cultivated on broad-leaf hardwoods. Generally, producers care about the yield, but not the quality of G. lucidum cultivated by different tree species. In this study, five broad-leaf hardwood tree species-Quercus variabilis Bl. (Qv), Castanea mollissima Bl. (Cm), Liquidambar formosana Hance (Lf), Dalbergia hupeana Hance (Dh), and Platycarya strobilacea Sieb. et Zucc. (Ps)-were selected for cultivating of G. lucidum. The chemical compositions of G. lucidum fruiting bodies produced by these tree species were determined by Fourier transform infrared and two-dimensional infrared correlation spectroscopy in order to select the most suitable tree species for cultivation. The overall spectra showed less discrimination of each peak variation detected and properly kept most of the primary metabolites. The second derivative unfolded the stagnation of the first spectrum and more base peaks were detected especially in the range of the first two sections. The protein content contained in G. lucidum cultivated on Ps was 92%, like that on Dh. On the other hand, only 27% similarity was determined in G. lucidum cultivated on Ps and Qv. Therefore, the correlation of this range for the protein content can help in tree species selection. The active sequence of 2DIR spectral could be determined by the active bonding of the component reacted to the perturbation. The result could provide a scientific basis for the selection of tree species and the comprehensive utilization of broad-leaf tree resources on G. lucidum cultivation.

[Quality analysis of Citri Trifoliatae Fructus in different harvest time by HPLC combined with electronic eye technology].

As a local variety of medicinal material, Citri Trifoliatae Fructus is widely used in many places, whereas its harvest time remains unclear. Therefore, studying its harvest time can make more reasonable use of this medicinal material. In this study, we determined the flavonoids content and compared the color of Citri Trifoliatae Fructus harvested in different time, aiming to guide the harvest of this medicinal material. The fresh fruits of Citrus trifoliata were collected from Xinxiang city, Henan province, graded according to the diameter range, and then dried. The contents of isonaringin, naringen, and poncirin in Citri Trifoliatae Fructus were determined by HPLC, and the color values of the samples were detected by electronic eye. The correlation analysis of the obtained data was carried out to explore the relationships of color and diameter with quality. The results showed that the contents of isonaringin, naringen, and poncirin varied significantly in different harvest time, within the ranges of 0.21-1.20, 2.21-11.59, and 3.73-23.16 mg·g~(-1), respectively. With the delay of harvest time, Citri Trifoliatae Fructus showed the color changing from green to yellow, gradually increased diameter, and gradually decreased contents of isonaringin, naringen, and poncirin. The contents of isonaringin, naringen, and poncirin were negatively correlated with the degree of red and green(a~*) and positively correlated with the degree of yellow and blue(b~*). The contents of naringen and poncirin had significantly negative correlations with the diameter. This study indicates that the quality of Citri Trifoliatae Fructus can be judged by its diameter and skin color, which provides a theoretical basis for the rational harvest of this medicinal material.

A Review on Classification and Biological Activities of Alkaloids from the Genus Zanthoxylum Species.

Many plants in the genus Zanthoxylum, belonging to the Rutaceae family, are used as folk medicines for the treatment of various diseases, which have gained much attention for their phytochemical and pharmacological activity investigations. Alkaloids are the largest secondary metabolites with structurally diverse types found in this genus and they demonstrate a wide range of biological activities. The aim of this review is to provide a summary on the isolation, classification, and biological properties of alkaloids from Zanthoxylum species, which also will bring more attention to other researchers for further biological study on alkaloids for the new drug development.

Clinical comprehensive evaluation of Danhong Injection in treatment of stroke with blood stasis syndrome / 中国中药杂志

This study systematically reviewed the existing research on Danhong Injection in the treatment of stroke with blood stasis syndrome. The methods of evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, drug economics, mathematical statistics, and health technology assessment(HTA) were employed to qualitatively and quantitatively evaluate the "6+1" dimensions(safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine) of Danhong Injection through questionnaire survey, public information, real world data, and secondary evaluation of literature. With the weights given by experts, the multi-criteria decision analysis(MCDA) model was employed to measure each dimension and highlight the clinical value of Danhong Injection. Multi-source safety evidence showed that Danhong Injection had been fully monitored and studied. The severity of adverse reactions was mostly moderate or mild, and the prognosis was good. So it was rated as grade A for safety. Compared with Ligustrazine Injection, Fufang Danshen Injection and conventional treatment of western medicine, Danhong Injection had obvious advantages in clinical response rate and NIHSS score improvement in the treatment of stroke with blood stasis syndrome. So it was rated as grade A for effectiveness. Compared with Ligustrazine Injection and Yinxing Damo Injection, Danhong Injection had a cost-effectiveness advantage in the treatment of stroke with blood stasis syndrome, and the economic results were good. According to the existing evidence, the Danhong Injection was rated as grade B for economy. Danhong Injection had won a number of national patents, which was rated as grade A for its good innovation in guaranteeing supply measures, scalability of production capacity, and production process. It had good suitability for clinicians, nurses, pharmacists, and patients using the drug, and met the needs of clinical medication, so it was rated as grade B for suitability. Danhong Injection is rich in medicinal materials, stable in price, and sustainable. However, its availability needed to be further improved due to the limitation of prescription use, so it was rated as grade B for accessibility. Danhong Injection can promote blood circulation, resolve blood stasis, warm vessels, and smooth collaterals. It had accumulated more than 30 000 pieces of empirical evidence for human use in the real world. It had prominent characteristics of traditional Chinese medicine and was rated as grade B. CSC v2.0 was used for calculation, and the clinical value of Danhong Injection was comprehensively evaluated as class A, which could be directly translated into relevant policy results of basic clinical medication management according to the Guidelines for the Management Clinical Comprehensive Evaluation of Drugs(trial version 2021).

Systematic review and Meta-analysis of efficacy and safety of gastrodin in treatment of tension-type headache / 中国中药杂志

The efficacy of gastrodin as a Chinese herbal medicine extract in the treatment of tension-type headache has been confirmed. This paper systematically reviewed the efficacy and safety of gastrodin in the treatment of tension-type headache, aiming to provide a new choice for the treatment of this disease. In this study, four Chinese databases, four English databases and two trial registries were searched from the date of establishment to September 2020. The related randomized controlled trials(RCTs) were screened out according to the predetermined criteria. The bias risk assessment tool developed by Cochrane collaboration was used to evaluate the quality of the reports. RevMan 5.4.1 was used for Meta-analysis, and GRADE system for the evidence-based evaluation on the quality of outcome indicators. A total of 177 articles were retrieved and 8 articles were finally included for analysis, with a total sample size of 1 091 cases, which included 565 cases in the treatment group and 526 cases in the control group. The overall quality of included stu-dies was not high. The results of Meta-analysis are as follows:(1)In terms of headache frequency, gastrodin group was better than wes-tern medicine group(MD=-2.90, 95%CI[-3.76,-2.03], P<0.000 01).(2)In terms of number of abnormal blood vessels in TCD, gastrodin group was better than western medicine group(MD=-88.96, 95%CI[-102.36,-75.55], P<0.000 01).(3)In terms of effective rate, gastrodin group was better than western medicine group(RR=1.47, 95%CI[1.29, 1.68], P<0.000 01). The results of subgroup analysis are as follows:(1)Effective rate based on age, for the patients upper age limit 40-46 years old, gastro-din group was better than western medicine group(RR=1.69, 95%CI[1.50, 1.90], P<0.000 01); for the patients upper age limit 55-60 years old, gastrodin group was better than western medicine group(RR=1.27, 95%CI[1.16, 1.38], P<0.000 01).(2)Effective rate based on dosage form, both the gastrodin capsules and injection groups were better than western medicine group(RR_(capsules)=1.42, 95%CI[1.08, 1.88], P=0.01; RR_(injection)=1.50, 95%CI[1.26, 1.77], P<0.000 01). GRADE evaluation showed that the above outcomes had low quality of evidence. Only one article detailed the occurrence of adverse reactions and thus the present study cannot make a positive conclusion on the safety of gastrodin in the treatment of tension-type headache. The small number and low quality of the included reports affected the reliability of the results. In the future, more high-quality randomized controlled trails are needed to improve the evaluation on the efficacy and safety of gastrodin in the treatment of tension-type headache.

Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage / 中国中药杂志

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of cerebral ischaemic stroke / 中国中药杂志

There have been many clinical trials, systematic reviews/Meta-analysis proving that Xingnaojing Injection has a good clinical efficacy in treatment of cerebral ischaemic stroke, but with fewer comprehensive descriptions. In this study, an overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treating cerebral ischaemic stroke was performed to provide current situation of evidences and basis for clinical practice. CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science were retrieved through computers. A total of 6 literatures were included in this study. By AMSTAR-2 checklist and GRADE, the quality of included systematic reviews and the efficacy of Xingnaojing Injection were evaluated. The results of AMSTAR-2 checklist showed an extremely low quality for all of the 6 systematic reviews. According to the results of GRADE evaluation, among 55 outcomes, there were 2 outcomes with a medium quality, 4 outcomes with a low quality and 49 outcomes with an extremely low quality. The 6 systematic reviews reached a consistent conclusion that Xingnaojing Injection was effective in the treatment of cerebral ischaemic stroke. This therapy could improve the total efficacy, neurological deficit scores, hemodynamic and hemodynamic parameters. However, the methodolo-gical quality of all literatures was extremely low. The evidence levels of outcomes were between extremely low to medium. The effectiveness of Xingnaojing Injection in the treatment of cerebral ischaemic stroke still needs to be further verified by more high-quality studies. In the future, relevant clinical studies and systematic reviews/Meta-analysis shall be carried out in a strict accordance with relevant regulations.

Analysis of status quo of outcome indicators of randomized controlled trials in treatment of acute ischemic stroke with acupuncture in recent three years / 中国中药杂志

To analyze the use of outcome indicators of randomized controlled trial(RCT) of acupuncture in the treatment of acute ischemic stroke in recent three years, so as to provide a basis for building a study on the core outcome indicators for the treatment of acute ischemic stroke with acupuncture. The RCTs of acupuncture treatment for acute ischemic stroke in recent three years were collec-ted through computer retrieval of eight Chinese and English databases and two clinical trial registries at home and abroad. Literature was screened out, and data was extracted. Risk of assessment bias tool Cochrane 6.1 was used for bias risk assessment, outcome indicators were summarized and analyzed. A total of 47 RCTs were included, and 3 studies were trials registration scheme. Outcome indicators were divided into 6 categories according to functional attributes, namely physical symptoms/signs, physical and chemical examination, quality of life, traditional Chinese medicine symptoms/syndromes, safety events and long-term prognosis. The study found that in addition to the common problems in previous studies covered by the status quo of outcome indicators selection of RCT of acupuncture in the treatment of acute ischemic stroke, there were also the other problems as follows: emphasis on macroscopic efficacy indicators but neglect of acupuncture specific indicators, lack of characteristic indicators and economic indicators of traditional Chinese medicine therapy, and unification of indicators measurement tool and measurement time point. In the future, the outcome indicators set for the treatment of acute ischemic stroke with acupuncture shall be established, and the core outcome indicators set shall be in line with the characteristics of traditional Chinese medicine treatment.

A novel mitochondria-targetted near-infrared fluorescent probe for selective and colorimetric detection of sulfite and its application in vitro and vivo.

Overdoses of SO2 and its derivatives (SO32-/HSO3-) in food or organisms are harmful to health. To detect SO32-/HSO3-, a novel NIR fluorescent probe 1, based upon the intramolecular charge transfer (ICT) mechanism, was developed. This probe was easily synthesized, and gave noticeable colorimetric and linear fluorescence changes at 690 nm after reaction with sulfite from 3.13 to 200 µM. Moreover, probe 1 displayed high sensitivity (LOD = 0.46 µM), excellent selectivity (among 13 kinds of anions and 3 kinds of biothiols) and quick response (within 30 min) towards SO32-/HSO3-. The SO32-/HSO3- sensing mechanism was confirmed as the Michael addition reaction. Furthermore, the probe showed wide applications for measuring SO32-/HSO3- in real samples, including sugar, tap water, wine and traditional Chinese medicine. The probe could also be used to detect SO32-/HSO3- in mitochondria of HepG2 cells and zebrafish, which suggested potential application for monitoring SO2 derivatives in clinical diagnostics.

Systematic Evaluation of Clinical Efficacy and Safety of Traditional Chinese Medicine for Post Stroke Cognitive Impairment / 中国实验方剂学杂志

Objective:To evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of post stroke cognitive impairment (PSCI). Method:Seven databases, including CNKI, WanFang, VIP, CBM, PubMed, The Cochrane library and ClinicalTrials.gov, were electronically searched for relevant randomized controlled trials (RCTs) of TCM in the treatment of PSCI. The Cochrane risk of bias assessment tool was used to evaluate the methodological quality of the included studies, descriptive analysis was carried out on the included studies, and the Meta quantitative analysis was carried out with RevMan 5.3 software. Result:A total of 16 RCTs were included with 1 296 participants, and they were assigned to the intervention group (n=649) and the control group (n=647). The results showed that TCM combined with western medicine group and TCM group were better than western medicine group in improving the scores of Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Barthel Index (BI), Activity of Daily Living (ADL), Chinese stroke scale (CSS) and National Institutes of Health stroke scale (NIHSS) of PSCI patients, and no serious adverse events were observed. Conclusion:TCM has potential advantages in improving the cognitive function of patients with PSCI, and it also has certain efficacy in improving the daily living ability and neurological impairment symptoms, and no serious adverse events have been observed. Due to the low quality of methodology included in the studies, in order to provide reliable basis for clinical decision-making, high-quality of RCTs are still needed to study the efficacy and safety of TCM for PSCI.

Development and validation of a supercritical fluid chromatography method for fast analysis of six flavonoids in Citri Reticulatae Pericarpium.

The study is aimed to develop a rapid and efficient supercritical fluid chromatography coupled with diode-array detection (SFC-DAD) method for simultaneous quantification of six flavonoids in Citri Reticulatae Pericarpium (CRP). The chromatographic parameters including stationary phase, mobile phase composition, back pressure, temperature and flow rate, were systematically optimized with single-factor test. The results indicated that the six compounds were baseline separated on an Agilent Zorbax RX-SIL column using gradient elution within 10 min. The optimized mobile phase was constituted of carbon dioxide (CO2) and methanol. And the parameters were set as follows: backpressure, 95 bar; temperature, 45 °C; flow rate, 0.8 mL/min. The optimized method showed satisfactory retention and resolution for the analytes. The method was validated to demonstrate its selectivity, linearity, precision, accuracy and robustness. Thus, the verified SFC method was successfully applied to quantification of flavonoids present in CRP samples. The results indicated that SFC has the potential to become an excellent alternative for the analysis of flavonoids in herbal medicines, owning to its intrinsic features like high efficiency, separation speed and eco-friendly characteristics.

Rapid profiling of alkaloid analogues in Sinomenii Caulis by an integrated characterization strategy and quantitative analysis.

Alkaloids, the principal constituents in the caulis of Sinomenium acutum, have gained an increasing interest over the past decades since they are widely employed as a clinical treatment for rheumatoid arthritis. In the present study, an integrated characterization strategy by combining mass defect filtering-based structure classification (MDFSC) and diagnostic fragment-ion-based extension (DFIBE) was firstly proposed for rapid profiling of alkaloids in Sinomenii Caulis (SC) via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The rectangular MDFSC window could more accurately screen the target alkaloids of different types, and the DFIBE could facilitate the acquisition of characteristic fragment ions for structural elucidation of alkaloids. High-performance liquid chromatography (HPLC) fingerprints with principal component analysis (PCA) and hierarchical clustering analysis (HCA) was established for identifying the chemical markers and simultaneous determination of sinomenine, magnoflorine, menisperine, stepharanine and ehydrodiscretine. A total of 91 alkaloids, including 82 targeted ones (26 morphinans, 22 aporphines, 20 protoberberines and 14 benzylisoquinolines) were unambiguously identified or tentatively characterized in SC, and 14 of them were reported for the first time. Sinomenine and magnoflorine could be selected as chemical markers to evaluate the quality of SC from different localities. In conclusion, the proposed method provided a potential approach for chemical profiling and holistic quality control of herbal medicines.

Identification of anti-inflammatory components in Sinomenii Caulis based on spectrum-effect relationship and chemometric methods.

The present study aimed to identify the anti-inflammatory components in Sinomenii Caulis (SC) based on spectrum-effect relationship and chemometric methods. A phytochemical investigation of SC extract was performed firstly and afforded eleven potential bioactive compounds. The HPLC fingerprints of 19 batches of SC samples were evaluated by the chemometric methods such as similarity analysis (SA) and hierarchical clustering analysis (HCA). The anti-inflammatory effects of these samples were determined by inhibition of Nitric Oxide (NO) production. Partial least squares regression (PLSR) and artificial neural network (ANN) were used to explore the spectrum-effect relationship of SC. The results indicated that there was a close correlation between chemical fingerprint and anti-inflammatory activity of SC, and peaks 8, 9, 12, 13, 14, 16, 19 and 22 might be potential anti-inflammatory compounds in SC. The verification experiments by testing individual compounds and a combination of them indicated that sinomenine (P8), magnoflorine (P13), menisperine (P16) and stepharanine (P19) were the major anti-inflammatory compounds in SC. Collectively, the present study established the spectrum-effect relationship mode of SC and discovered the anti-inflammatory compounds in SC, which could be used for exploration of bioactive components and quality control of herbal medicines.

[Identification of four Armillaria strains and their effects on quality and yield of Gastrodia elata f. glauca].

In order to improve the quality and yield of Gastrodia elata f. glauca,determine the suitable Armillaria strains for the accompanying experiment in Xiaocaoba,Yiliang,four Armillaria strains were selected. They were used for G. elata cultivation,and the gene sequence,r DNA-ITS,ß-tubulin and EF1-α of four Armillaria strains,were compared and analyzed. The yield was mesured in November which was based on previous laboratory research. The tubers were washed and steamed,then dried and powdered. The content of gastrodin and p-hydroxybenzyl alcohol was determined by UPLC,the polysaccharide was determined by phenol-concentrated sulfuric acid method. The results showed that the strains M1,M2,M3 and M4 were Armillaria gallica group but there were differences in the yield and active ingredient content when they were cultivated with the same G. elata. The yield of G. elata( Jian Ma) was the lowest when cultivated with Armillaria strain M3,but it was not the same when used M1,0. 981 kg·m-2,the highest yield in the four stains.The content of gastrodin was 0. 581%,the total content of gastrodin and p-hydroxybenzyl alcohol was 0. 595%,when accompanied with M1 strains. It was higher than other strains. The content of G. elata polysaccharide was 2. 132%,which was similar to the content of M3 strain,higher than that of M2 and M4 strain. Selecting phylogenesis of Armillaria strians,the content of active ingredient,and the yield as indicators,it was concluded concerned that the M1 strain was the best of four strains. The results will provide a theoretical basis and guidance for higher yield and quality in cultivation of G. elata in Yiliang.

Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice / 中国中药杂志

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

Clinicopathological features and prognosis analysis of the obstructive colorectal cancer / 中华消化外科杂志

Objective To explore the clinicopathological features and prognosis of the obstructive colorectal cancer (CRC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 667 CRC patients who were admitted to the Beijing Friendship Hospital Affiliated to Capital Medical University between January 2013 and December 2015 were collected.The diagnosis and treatment of CRC patients were based on colon cancer and rectal cancer clinical practice guidelines in oncology(Version 2013) of the National Comprehensive Cancer Network (NCCN) and the 7th edition of the American Joint Committee on Cancer (AJCC) cancer staging manual and the future of TNM.CRC and clinical staging were confirmed by colonoscopy,biopsy pathology and CT or MRI examination.Patients selected laparoscopic surgery or open surgery according to their conditions,and then selectively underwent postoperative adjuvant therapy based on the results of pathological examination.Observation indicators:(1) diagnosis and treatment;(2) clinicopathological features;(3) prognosis.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall and tumor-free survivals up to April,2017.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Count data were described as case and percentage,comparisons between groups were evaluated with the chi-square test.Ordinal data were analyzed using the nonparametric test.Results (1) Diagnosis and treatment:tumor locations of 677 patients:tumors located in the right hemicolon,left hemicolon and rectum were respectively detected in 213,312 and 142 patients.Preoperative clinical staging:3,47,300,298 and 19 patients were respectively detected in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ.Ninety-nine patients were complicated with intestinal obstruction,with an obstructive rate of 14.84％ (99/667),and 568 patients didn't have intestinal obstruction.Treatments of 667 patients:① Preoperative adjuvant treatment:17 non-obstructive CRC patients underwent preoperative adjuvant treatments and 650 didn't undergo preoperative adjuvant treatment.② Surgical treatment:389 and 278 patients underwent respectively open and laparoscopic surgeries,and 588 received radical resection and 79 received non-radical resection.(2) Clinicopathological features:of 99 obstructive CRC patients,tumors located in the right hemicolon,left hemicolon and rectum were respectively detected in 26,61 and 12 patients.Eighteen and 81 patients underwent respectively laparoscopic and open surgeries,including 21 with low-differentiated tumors,61 with moderate-differentiated tumors and 17 with high-differentiated tumors;71 patients received radical resection,with a number of lymph node dissected of 12±9,and 37,20 and 14 were respectively detected in stage N0,N1 and N2.Of 568 non-obstructive CRC patients,tumors located in the right hemicolon,left hemicolon and rectum were respectively detected in 187,251 and 130 patients.Two hundred and sixty and 308 patients underwent respectively laparoscopic and open surgeries,including 38 with low-differentiated tumors,420 with moderate-differentiated tumors and 110 with high-differentiated tumors;517 patients received radical resection,with a number of lymph node dissected of 15±8,and 338,155 and 24 were respectively detected in stage N0,N1 and N2.There were statistically significant differences in above indicators between obstructive CRC and non-obstructive CRC patients(x2=11.234,46.505,30.088,Z=-2.782,t=2.942,Z=-2.892,P＜0.05).(3) Prognosis:of 667 patients,584 were followed up for 18-52 months,with a median time of 36 months,including 88 with obstructive CRC (1,5,23,28 and 31patients were respectively in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ) and 469 with non-obstructive CRC (5,62,212,116 and 101 patients were respectively in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ).During the follow-up,56 obstructive CRC patients survived,including 1 in stage 0,4 in stage Ⅰ,15 in stage Ⅱ,17 in stage Ⅲ and 19 in stage Ⅳ,with an overall survival rate of 63.64％ (56/88),and overall survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 1/1,4/5,65.22％(15/23),60.71％(17/28) and 61.29％ (19/31);38 had tumor-free survival,including 1 in stage 0,4 in stage Ⅰ,15 in stage Ⅱ,13 in stage Ⅲ and 5 in stage Ⅳ,with a tumor-free survival rate of 43.18％(38/88),and tumor-free survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 1/1,4/5,65.22％ (15/23),46.43％ (13/28),16.13％ (5/31).Four hundred and forty-three non-obstructive CRC patients survived,including 5 in stage 0,58 in stage Ⅰ,181 in stage Ⅱ,106 in stage Ⅲ and 93 in stage Ⅳ,with an overall survival rate of 89.31％(443/496),and overall survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 5/5,93.55％ (58/62),85.38％ (181/212),91.38％ (106/116) and 92.08％ (93/101);384patients had tumor-free survival,including 5 in stage 0,52 in stage Ⅰ,166 in stage Ⅱ,94 in stage Ⅲ and 67 in stage Ⅳ,with a tumor-free survival rate of 77.42％ (384/496),and tumor-free survival rates in stage 0,Ⅰ,Ⅱ,Ⅲ and Ⅳ were respectively 5/5,83.87％ (52/62),78.30％ (166/212),81.03％ (94/116) and 66.34％ (67/101).There were statistically significant differences in overall survival rate and tumor-free survival rate between obstructive CRC and non-obstructive CRC patients (x2 =39.626,43.707,P＜ 0.05).The subgroup analysis:there were statistically significant differences in stage Ⅱ,Ⅲ and Ⅳ overall survival rates between obstructive CRC and non-obstructive CRC patients (x2 =6.092,17.027,11.268,P＜0.05) and in stage Ⅲ and Ⅳ tumor-free survival rates (x2 =14.148,24.116,P＜ 0.05).Conclusion The obstructive CRC commonly locates in the left hemicolon,with complex clinicopathological features and low-differentiated tumors,meanwhile,there are lower radical rate and poor prognosis.

Identification and classification of traditional Chinese medicine syndrome types among senior patients with vascular mild cognitive impairment using latent tree analysis / 中西医结合学报

<p><b>OBJECTIVE</b>To treat patients with vascular mild cognitive impairment (VMCI) using traditional Chinese medicine (TCM), it is necessary to classify the patients into TCM syndrome types and to apply different treatments to different types. In this paper, we investigate how to properly carry out the classification for patients with VMCI aged 50 or above using a novel data-driven method known as latent tree analysis (LTA).</p><p><b>METHOD</b>A cross-sectional survey on VMCI was carried out in several regions in Northern China between February 2008 and February 2012 which resulted in a data set that involves 803 patients and 93 symptoms. LTA was performed on the data to reveal symptom co-occurrence patterns, and the patients were partitioned into clusters in multiple ways based on the patterns. The patient clusters were matched up with syndrome types, and population statistics of the clusters are used to quantify the syndrome types and to establish classification rules.</p><p><b>RESULTS</b>Eight syndrome types are identified: Qi deficiency, Qi stagnation, Blood deficiency, Blood stasis, Phlegm-dampness, Fire-heat, Yang deficiency, and Yin deficiency. The prevalence and symptom occurrence characteristics of each syndrome type are determined. Quantitative classification rules are established for determining whether a patient belongs to each of the syndrome types.</p><p><b>CONCLUSION</b>A solution for the TCM syndrome classification problem for patients with VMCI and aged 50 or above is established based on the LTA of unlabeled symptom survey data. The results can be used as a reference in clinic practice to improve the quality of syndrome differentiation and to reduce diagnosis variances across physicians. They can also be used for patient selection in research projects aimed at finding biomarkers for the syndrome types and in randomized control trials aimed at determining the efficacy of TCM treatments of VMCI.</p>

Study of two kinds of Alzheimer's disease tree shrew models / 中国药理学通报

Aim To explore the optimized tree shrews model of Alzheimer's disease through comparison of the pathology changes of brain neurons between the two kinds of tree shrew models.Methods Fifty tree shrews were randomly divided into five groups with 10 in each group:control group,high dose D-galactose combined with ibotenic acid (IBO) group,low dose D-galactose combined with IBO group [intraperitoneal injection D-galactose combined with IBO injection into bilateral basal nucleus of Meynert (BNM)],high dose Aβ25-35 combined with IBO group,and low dose Aβ25-35 combined with IBO group (injection into bilateral BNM).Hematoxylin and eosin (HE) staining was used to observe the morphological changes of brain neurons.The expressions of choline acetyltransterase (ChAT) and synaptophysin(SYP) in the brains were detected by immunohistochemical staining.Western blot was used to detect the expression of amyloid beta 1-42 (Aβ1-42),amyloid precursor protein (APP) and phosphorylated tau protein (p-tau).Results The HE staining showed there were different degrees of morphological changes in the brains of model groups.The changes in the high dose D-galactose and high dose Aβ25-35 combined with IBO group were more obvious than those in low dose D-galactose and Aβ25-35 combined with IBO group.Immunohistochemical staining revealed that the levels of ChAT and SYP in the model groups decreased compared with control group,and the decline in high dose Aβ25-35 combined with IBO group was more marked than that in low dose Aβ25-35 combined with IBO group(P ＜0.01).Western blot revealed that the levels of Aβ1-42,APP,p-tau in the model groups increased compared with control group,and the rise in high dose Aβ25-35 combined with IBO group was more apparent than that in low dose Aβ25-35 combined with IBO group (P ＜ 0.05 or P ＜ 0.01).Conclusion The method of modeling by Aβ25-35 combined with IBO injection into bilateral BNM is more suitable for the establishment of Alzheimer's disease model.

Comparison of Aurantii Fructus Immaturus and Aurantii Fructus based on multiple chromatographic analysis and chemometrics methods.

To get a better understanding of the bioactive constituents in Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF), in the present study, a comprehensive strategy integrating multiple chromatographic analysis and chemometrics methods was firstly proposed. Based on segmental monitoring, a high-performance liquid chromatography (HPLC)-variable wavelength detection method was established for simultaneous quantification of ten major flavonoids, and the quantitative data were further analyzed by hierarchical cluster analysis (HCA) and principal component analysis (PCA). A strong cation exchange-high performance liquid chromatography (SCX-HPLC) method combined with t-test and one-way analysis of variance (ANOVA) was developed to determine synephrine, the major alkaloid in AFI and AF. The essential oils were analyzed by gas chromatography-mass spectrometry (GC-MS) and further processed by partial least squares discrimination analysis (PLS-DA). The results indicated that the contents of ten flavonoids and synephrine in AFI were significantly higher than those in AF, and significant difference existed in samples from different geographical origins. Also, 9 differential volatile constituents detected could be used as chemical markers for discrimination of AFI and AF. Collectively, the proposed comprehensive analysis might be a well-acceptable strategy to evaluate the quality of traditional citrus herbs.