Effect of panretinal photocoagulation combined with intravitreal Conbercept in the treatment of proliferative diabetic retinopathy with different stages / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effectiveness of panretinal photocoagulation(PRP)combined with intravitreal conbercept(IVC)for patients with different stages of proliferative diabetic retinopathy(PDR).METHODS: Retrospective study. The medical records for 100 patients(100 eyes)with PDR treated with PRP combined with IVC from January 2018 to June 2020 were reviewed, including 34 eyes with early PDR(group A), 43 with high-risk PDR(group B), and 23 with fibrovascular PDR(group C). The baseline information, best corrected visual acuity(BCVA), central macular thickness(CMT), the rate of vitrectomy and retinal detachment of the patients in the three groups at 1, 3, 6mo and the last follow-up after combination treatment were observed.RESULTS: The patients were followed up for 14.60±11.64mo(6-52mo), with a mean age of 54.22 ±9.32 years. We found 15 eyes(15.0%)who underwent vitrectomy after the combination treatment. The vitrectomy rates of the three groups were 2.9% in group A, 13.9% in group B, and 34.7% in group C. We found no instances of retinal detachment after the treatments. Most patients demonstrated improved BCVA and CMT values with the treatments.CONCLUSION: PRP combined with IVC is safe and effective in patients with different PDR stages.

Effect of Anchang Decoction on intestinal flora and fecal calcitonin in rats with severe ulcerative colitis / 国际中医中药杂志

Objective:To investigate the effects of Anchang Decoction on intestinal microflora and faecal calprotectin (FC) in rats with severe ulcerative colitis based on probiotics.Methods:Totally 50 rats were taken to prepare a model of severe ulcerative colitis. The rats who successfully modeled were divided into model group, Anchang Decoction low-, medium-, high-dosage groups, Lizhu Changle group, and mesalazine group, with 5 rats in each group. Another 6 rats were set and the blank group. Lizhu Changle group received Lizhu Changle suspension (containing 50 million live bacteria/ml) for gavage; Anchang Decoction low-, medium-, high-dosage groups received Anchang Decoction 1, 5, 10 ml/(kg·d) for gavage; Mesalazine group received Mesalazine suspension (10.5 mg/100 g) for gavage. Rats in the blank group and model group were gavaged with the same volume of normal saline for 7 days. Body mass and disease activity index (DAI) before and after administration were measured. 16s rDNA of lactobacillus and bifidobacterium in feces of rats was detected. FC content of rats was detected by ELISA.Results:Compared with the model group, the weight of rats in each administration group increased ( P<0.05), DAI score decreased ( P<0.05), and the level of calprotectin in feces decreased ( P<0.05), and there was no significant difference in the levels of lactobacillus and bifidobacterium in each administration group ( P>0.05). Conclusion:Anchang Decoction can improve the intestinal micro-ecology by regulating the level of calprotectin in rats with severe ulcerative colitis, thereby playing a therapeutic role.

Effects of manipulator operation task and troubleshooting task on blood pressure indexes of oceanauts / 中华劳动卫生职业病杂志

Objective: To explore the characteristics and rules of blood pressure changes in oceanauts during simulated operation of manipulator and troubleshooting tasks with different difficulty. Methods: In July 2020, 8 deep-sea manned submersible oceanauts, 6 males and 2 females, were selected as objects. In the 1∶1 model of Jiaolong deep-sea manned submersible, the oceanauts performed manipulator operation tasks and troubleshooting tasks with different difficulties, measured the continuous blood pressure of the oceanauts, filled in the NASA Task Load Index (NASA-TLX scale) after the completion of a single mission, and the changes of systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (MAP) and mental workload were analyzed. Results: In a single task, the SBP, DBP and MAP of the oceanauts increased first and then decreased. The blood pressure values at the third minute were significantly lower than those at the first minute (P<0.01), and those at the fifth minute were significantly higher than those at the third minute (P<0.01). When performing the same task, compared with the quiet state, SBP, DBP and MAP increased when the oceanauts performed low difficulty, high difficulty, high difficulty+2-back manipulator operation task and troubleshooting task (P<0.05). When the task difficulty was the same, the SBP and MAP of oceanauts performing manipulator operation tasks were higher than those of oceanauts performing troubleshooting tasks (P<0.05). Compared with low difficulty tasks, the scores of NASA-TLX scale for oceanauts performing high difficulty manipulator operationtasks were significantly higher (P<0.05). Compared with the low difficulty task and high difficulty task, the scale score of the high difficulty+2-back troubleshooting task was significantly higher (P<0.05). When the task difficulty was the same, the scale scores of low difficulty and high difficulty manipulator operation tasks were significantly higher than those of troubleshooting tasks (P<0.05). SBP, DBP, MAP of No. 1, No. 3, No. 4, No. 5, and No. 7 oceanauts (all of whom had 6 years of diving) were positively correlated with NASA-TLX scale scores (r>0.8, P<0.05) . Conclusion: In the process of manned deep-sea diving, when the oceanauts perform manipulator operation tasks and troubleshooting tasks, with the increase of task difficulty, the mental load of oceanauts increases, and the blood pressure index increases significantly in a short time. At the same time, improving the proficiency of operation can reduce the variation range of blood pressure indexes. Blood pressure can be used as an effective reference to evaluate the difficulty of operation and guide scientific training.

Hospitalization costs of pediatric community-acquired pneumonia in Shanghai / 中华儿科杂志

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Screening of differentially expressed genes for colorectal cancer and prediction of potential traditional Chinese medicine: based on bioinformatics / 中国中药杂志

This study screened and analyzed the differentially expressed genes(DEGs) between colorectal cancer(CRC) tissues and normal tissues with bioinformatics techniques to predict biomarkers and Chinese medicinals for the diagnosis and treatment of CRC. The microarray data sets GSE21815, GSE106582, and GSE41657 were downloaded from the Gene Expression Omnibus(GEO), and the DEGs were screened by GEO2 R, followed by the Gene Ontology(GO) tern enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the DEGs based on DAVID. The protein-protein interaction network was constructed by STRING, and MCODE and Cytohubba plug-ins were used to screen the significant modules and hub genes in the network. UCSC, cBioPortal, and Oncomine were employed for hierarchical clustering, survival analysis, Oncomine analysis, and correlation analysis of clinical data. Coremine Medical was applied to predict the Chinese medicinals acting on hub genes. A total of 284 DEGs were screened out, with 146 up-regulated and 138 down-regulated. The up-regulated genes were mainly involved in cell cycle, NLRs pathway, and TNF signaling pathway, and the down-regulated genes were related to mineral absorption, nitrogen metabolism, and bicarbonate reabsorption in proximal tubules. The 15 hub genes were CDK1, CDC20, AURKA, MELK, TOP2 A, PTTG1, BUB1, CDCA5, CDC45, TPX2, NEK2, CEP55, CENPN, TRIP13, and GINS2, among which CDK1 and CDC20 were regarded as core genes. The high expression of CDK1 and CDC20 suggested poor prognosis, and they significantly expressed in many cancers, especially breast cancer, lung cancer, and CRC. The expression of CDK1 and CDC20 was correlated with gender, tumor type, TNM stage, and KRAS gene mutation. The potential effective medicinals against CRC were Scutellariae Radix, Scutellariae Barbatae Herba, Arnebiae Radix, etc. The significant expression of CDK1 and CDC20 can help distinguish tumor tissues from normal tissues, and is related to survival prognosis. Thus, the two can be used as biomarkers for the diagnosis and treatment of CRC. This study provides a reference for related drug development.

Rhodiola crenulata extract decreases fatty acid oxidation and autophagy to ameliorate pulmonary arterial hypertension by targeting inhibiton of acylcarnitine in rats / 中国天然药物

Pulmonary arterial hypertension (PAH) is a devastating pulmonary circulation disease lacking high-efficiency therapeutics. The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata, a well-known traditional chinese medicine with cardiopulmonary protection capacity, on PAH by exploiting functional lipidomics. The rat model with PAH was successfully established for first, following Rhodiola crenulata water extract (RCE) treatment, then analysis of chemical constituents of RCE was performed, additional morphologic, hemodynamic, echocardiographic measurements were examined, further targeted lipidomics assay was performed to identify differential lipidomes, at last accordingly mechanism assay was done by combining qRT-PCR, Western blot and ELISA. Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls, mostly assigned to acylcarnitines, phosphatidylcholines, sphingomyelin associated with the PAH development. Excitingly, RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH. Furthermore, RCE was observed to reduce autophagy, confirmed by significantly inhibited PPARγ, LC3B, ATG7 and upregulated p62, and inactivated LKB1-AMPK signal pathway. Notably, we accurately identified the constituents in RCE, and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy. Altogether, RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH. This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.

Clinical efficacy of posterior percutaneous endoscopic cervical discectomy for single level cervical spondylopathy with intraspinal ossification / 中国骨伤

OBJECTIVE@#To evaluate the effectiveness and security of posterior percutaneous endoscopic cervical discectomy (PPECD) in the treatment of single level cervical spondylopathy with intraspinal ossification.@*METHODS@#Twenty three patients with single level cervical spondylopathy with intraspinal ossification were treated by posterior percutaneous endoscopic cervical discectomy between August 2017 and July 2019. There were 16 males and 7 females, aged from 29 to 74 years old with an average of (50±13) years.The disease duration were 3 to 120 months with a median of 6 months. There were 9 cases of cervical spondylotic radiculopathy, 6 cases of cervical spondylotic myelopathy, and 8 cases of mixed cervical spondylopathy. According to the characteristics of ossification, 17 cases were osteophytes on the posterior edge of the vertebral body;3 cases were protrusion ossification;3 cases were posterior longitudinal ligament ossification. According to the position of ossification in spinal canal, 14 cases were medial and lateral type, 5 cases were central type, and 4 cases were mixed type. Posterior percutaneous cervical endoscopic cervical discectomy in patients performed by the same surgeon. Japanese Orthopaedic Association (JOA) score and visual analogue scale(VAS) were compared separately before and after operation. At 3 months after operation, clinical effect was assessed according to modified Macnab standard.@*RESULTS@#All operations were successful. The operative time was 30 to 155 (69.1±27.2) min. The bedridden time was 2 to 3(3.0±0.9) h, length of postoperative hospitalization was 2 to 7(4.1± 1.5) d. Three dimensional CT reconstruction of the cervical spine at 3 days after operation showed that ossified tissue of 13 cases were completely removed, and 10 cases were left after operation, and the residual was located at the posterior edge and/or center of the upper vertebral body. VAS score at discharge from hospital was significantly lower than that before operation (@*CONCLUSION@#For an experienced surgeon, percutaneous posterior cervical endoscopic discectomy is safe and reliable in treating single level cervical spondylopathy with intraspinal ossification, and can obtain good clinical results.

Research progress on the antitumor effect of flavonoid derivatives / 药学学报

Malignant tumors seriously endanger human life and health, and their treatment has always been a research focus of scientists all over the world. Natural flavonoids and their derivatives have a variety of biological activities, especially regarding antitumor growth, with unique biological activities. They can interfere with the growth cycle of tumor cells, change the mitochondrial membrane potential, promote apoptosis, and can reduce the immune escape of tumor cells and prevent tumor metastasis by improving human immunity. In the human body, they regulate the biological signal transduction, leading to the up-regulation of pro-apoptotic protein expression. They inhibit the growth of solid tumors by regulating the growth of vascular epithelial cells and blocking the formation of blood vessels in tumor tissue. Recent studies have shown that these compounds can play an important role in the treatment of various human tumors and are expected to be developed into new antitumor drugs. This review summarizes the recent research results on the antitumor mechanism of flavonoids and their ability to inhibit tumor growth.

Multi-compound pharmacokinetic research on Chinese herbal medicines: identifying potentially therapeutic compounds and characterizing their disposition and pharmacokinetics / 药学学报

Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.

Investigation of Host-guest Complexation Between 4-Sulfonylcalix 6 Arene and 15 Alkaloids from Traditional Chinese Medicines and Inhibitory Effect of Binding System on Proliferation of HepG2 and H9c2 Cells / 中国实验方剂学杂志

Objective:To investigate bonding ability between 4-sulfonylcalix ［6］ arene （SCA6） and 15 alkaloids （matrine， allomatrine， dauricine， daurisoline， quinidine， quinine， crotaline， vincristine， gelsemine， koumine， tetrandrine， aloperine， oxymatrine， sophocarpine and sinomenine）， and to evaluate viability<italic> in vitro</italic> of HepG2 and H9c2 cells with 12 alkaloids/SCA6 bonding systems （except allomatrine， oxymatrine， sinomenine）. Method:Fluorescence competitive titration was used to determine the binding constants of alkaloids and SCA6， the inhibitory effect of alkaloid/SCA6 complex on proliferation of HepG2 and H9c2 cells was investigated by cell counting kit-8 （CCK-8）. Result:All the 15 alkaloids had good bonding with SCA6 at the ratio of 1∶1 （the binding constants >1×10⁵ mol·L^-1， <italic>R</italic>²>0.98）， the aloperine （quinolizidine alkaloids） and SCA6 had the biggest binding constant （20.55×10⁶ mol·L^-1）. In addition to gelsemine， crotaline， matrine and sophocarpine， 8 alkaloids （including aloperine， tetrandrine， dauricine， daurisoline， quinidine， quinine， vincristine and koumine） exhibited significant anti-tumor effects on HepG2 cells. Except for daurisoline， the anti-proliferation effect of the other 11 alkaloids before and after binding with SCA6 had no difference in HepG2 cells. In addition to gelsemine， crotaline， matrine and sophocarpine， the anti-proliferation effect of the other 8 alkaloids before and after binding with SCA6 had no difference in H9c2 cells. Conclusion:SCA6 shows intense binding ability with bisbenzylisoquinoline， quinolizidine and indole alkaloids. It can improve the solubility of alkaloids without affecting their anti-tumor activity， which provides a reference for subsequent related applications of SCA6 as a drug delivery carrier.

Attentional Connectivity-based Prediction of Autism Using Heterogeneous rs-fMRI Data from CC200 Atlas

Autism spectrum disorder (ASD) is a developmental syndrome characterized by obvious drawbacks in sociality and communication. It has crucial significance to exactly discern the individuals with ASD and typical controls (TC). Previous imaging studies on ASD/TC identification have made remarkable progress in the exploration of objective as well as crucial biomarkers associated with ASD. However, glaring deficiency is manifested by the investigation on solely homogeneous and small datasets. Thus, we attempted to unveil some replicable and robust neural patterns of autism using a heterogeneous multi-site brain imaging dataset from ABIDE (Autism Brain Imaging Data Exchange). Experiments were carried out with an attention mechanism based on Extra-Trees algorithm, taking the study object of brain connectivity measured with the resting-state functional magnetic resonance imaging (fMRI) data of CC200 atlas. With cross-validation strategy, our proposed method resulted in a mean classification accuracy of 72.2% (sensitivity=68.6%, specificity=75.4%). It raised the precision of ASD prediction by about 2% and specificity by 3.2% in comparison with the most competitive reported effort. Connectivity analysis on the optimal model highlighted informative regions strongly involved in the social cognition as well as interaction, and manifested lower correlation between the anterior and posterior default mode network (DMN) in autistic individuals than controls. This observation is concordant with previous studies, which enables our proposed method to effectively identify the individuals with risk of ASD.

Recommendations of Clinical Practice Guidelines of Stroke Rehabilitation / 中国康复理论与实践

@#Objective To analyze the contents of the recommendations of stroke clinical rehabilitation guidelines in order to provide advice for the development and implementation of stroke rehabilitation guidelines.Methods PubMed, EMBASE, CNKI, China Biology Medicine disc, Wanfang databases and guideline-related websites were retrieved from the date of establishment to January 2020, to collect stroke clinical rehabilitation guidelines. The main content, recommendations based on evidence, the type of evidences, and the scope of evidence classification had been explored based on World Health Organization Handbook for Guideline Development-2nd Edition.Results A total of twelve guidelines were included in this study, one in Chinese and eleven in English. They were from the United States (3 guidelines), United Kingdom (3 guidelines), Canada (3 guidelines), Australia (2 guidelines) and China (1 guidelines), and published from September, 2005 to February, 2019. Three articles (25.0%) used the Appraisal of Guidelines for Research and Evaluation (AGREE) for quality evaluation, and two articles (16.7%) used Grading of Recommendations Assessment, Development and Evaluation (GRADE) as the grading system. The recommendations covered the areas such as: cognitive dysfunction (4 dimensions) with a recommendation of cognitive function assessment at most (7 guidelines, 66.7%), language and swallowing dysfunction (5 dimensions) with a recommendation of swallowing-related complications at most (10 guidelines, 83.3%), motor dysfunction (6 dimensions) with a recommendation of spasm treatment at most (10 guidelines, 83.3%), and psychological and behavioral dysfunction (4 dimensions) with a recommendation for assessment or monitoring at most (6 guidelines, 50.0%). There were many recommendations in these areas, but the types of evidence were different, and observational studies and/or randomized controlled trials accounted for most.Conclusion There are different types of evidence and levels of recommendation strength. It is proposed for future guideline developers in stroke rehabilitation to follow World Health Organization Handbook for Guideline Development-2nd Edition to improve the quality and the overall implementation of the rehabilitation guidelines, and to improve the quality and safety of rehabilitation.

Report Quality of Clinical Practice Guidelines of Rehabilitation Based on RIGHT / 中国康复理论与实践

@#Objective To evaluate the quality of reporting of clinical practice guidelines of rehabilitation.Methods A comprehensive retrieve was performed in electronic databases of PubMed, EMBASE, CNKI, China Biology Medicine disc, Wanfang data, etc., from January 1, 2017 to January 11, 2020. Supplementary searches had been done on relevant websites. Two researchers reviewed literatures and assessed the reporting quality independently by using Reporting Items for Practice Guidelines in Healthcare (RIGHT), and any disagreements needed to be discussed in a consensus meeting.Results A total of 16 guidelines were included, with an average reporting rate of (44.8±27.9)%. Among the seven domains of RIGHT, basic information was reported the highest (57.3%), and evidence (31.3%) and other information (31.3%) was the lowest. The reporting rate was less as the guidelines published in China than in foreign contries (OR = 0.80, 95%CI 0.56-1.16), in original version than in update version (OR = 0.79, 95%CI 0.54-1.16); and higher as developed by various societies or associations than developed by non-societies or associations (OR = 1.15, 95%CI 0.82-1.61), however, no statistically significant difference was found in above comparisons.Conclusion Current clinical practice guidelines of rehabilitation reported with low quality. It is proposed that future guideline developers should report guidelines after RIGHT statements, including key information and content, in order to improve the quality of reporting guidelines.

Quality of Evidence and Strength of Recommendations of Clinical Practice Guidelines of Rehabilitation Based on GRADE / 中国康复理论与实践

Objective:To analyze the results of Grading of Recommendations Assessment, Development and Evaluation (GRADE) for clinical practice guidelines of rehabilitation. Methods:Clinical practice guidelines of rehabilitation were systematically retrieved from PubMed, EMBASE, CNKI, China Biology Medicine disc, Wanfang database and the guideline-related websites until January 11, 2020. Two researchers independently screened guidelines using Grading of Recommendations Assessment, Development and Evaluation (GRADE), and extracted and analyzed the results. Results:A total of 83 clinical practice guidelines of rehabilitation were included, in which 46 (55.4%) applied grading systems. Only four (4.8%) guidelines applied GRADE, including 44 recommendations, in which 39 guidelines (88.6%) had quality of evidence. Among the evidences citied in the recommendations, low quality evidences were the most (34.1%); among the recommendations, weak recommendations were more (56.8%). The quality of strong recommendation supporting evidence was higher than that of weak recommendation (χ2 = 8.218,P < 0.05). Conclusion:The application of the GRADE grading system in clinical practice guidelines of rehabilitation remains to be improved. It is proposed for guideline makers to further implement the methodology of guidelines and GRADE to improve the reliability and applicability of the clinical practice guidelines of rehabilitation more effectively.

Clinical Practice Guidelines of Rehabilitation: Composition of Expert Group and Situation of Conflict of Interest / 中国康复理论与实践

@#Objective To evaluate and analyze the panel composition and conflict of interest management of clinical practice guidelines of rehabilitation.Methods Clinical practice guidelines of rehabilitation were systematically retrieved from PubMed, EMBASE, China Biology Medicine disc, CNKI, Wanfang Data and Medlive database, the National Institute for Health and Care Excellence, National Guideline Clearinghouse, The Scottish Intercollegiate Guidelines Network, World Health Organization (WHO) and Guidelines International Network until January 11, 2020. Two researchers independently screened and cross-checked the literatures, and extracted the basic information of included guidelines, including the title, formulating institution, published journol, as well as the expert group, the number of expert group, the specific division of labor and their discipline, affiliation and the geographic location, the statement and management of conflict of interest, types of conflicts of interest, and whether to accept fund and the source of the fund.Results A total of 84 guidelines were finally included, 17 domestic ones and 67 foreign ones, in which, 52 (61.9%) reported the expert panel; 22 (26.2%) reported the number of expert panel groups, 21 (25.0%) indicated the specific division of work among the members of the expert panel, 74 (88.1%) reported the names of the members of the expert panel, 47 (56.0%) reported the subjects and specialties of the panelists, 70 (83.3%) reported the affiliation and location of panelists, 14 (16.7%) mentioned the management of conflicts of interest, and 25 (29.8%) reported if there were conflicts of interest. Only five of the 16 funded guidelines stated that there was no conflict of interest between the funding and the development of the guidelines. Among them, the reporting rate of expert panel was significantly higher in foreign countries than in China (χ2 = 9.542, P < 0.01), the reporting rate of name of expert panel members and specific division of labor were higher in foreign countries than in China ( χ2 > 4.155, P < 0.05), and the reporting rate of conflict of interest management was also higher in foreign countries than in China ( P < 0.05). There was no significant difference in whether there was a conflict of interest, whether it was funded and the type of funding at home and abroad ( P > 0.05). Conclusion In gerenal, clinical practice guidelines of rehabilitation published at home and abroad are necessary to be improved in the reporting quality of expert group formulation and division of labor, conflict of interest reporting and management. It is proposed that future guideline developers should follow the WHO Handbook for Guideline Development, assign roles of experts, strengthen the management and reporting of conflicts of interest, and standarderize the development process and reporting of the guidelines.

Changes in neutrophil function in septic liver injury and its effect on prognosis: a prospective observational study / 中华危重病急救医学

To explore the changes in polymorphonuclear neutrophils (PMN) function in peripheral blood of patients with sepsis and liver injury and its prognostic value. Methods A prospective observational study was conducted. The patients who met the criteria of Sepsis-3 admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from March to August in 2019 were enrolled as the research objects, and the patients were divided into sepsis without liver injury group and sepsis with liver injury group; non-sepsis patients who were hospitalized at the same time were enrolled as non-sepsis group; and the healthy people in the physical examination center were enrolled as healthy control group. The gender, age, white blood cell (WBC), PMN and procalcitonin (PCT) were recorded when the patients were admitted to ICU as well as the people on the day of physical examination. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores were calculated. The 28-day mortality was recorded. The quantitative level of neutrophil extracellular traps (NETs) which reflected by circulating free DNA (cf-DNA/NETs) in peripheral plasma was determined by PicoGreen fluorescence quantitative detection; the qualitative level of NETs was detected by immunofluorescence staining. PMN was extracted from the healthy control group, sepsis without liver injury group and sepsis with liver injury group and cultured in vitro, the quantitative level of cf-DNA/NETs in cell supernatant was determined by PicoGreen fluorescence quantitative detection. The patients were divided into two groups according to 28-day outcome of sepsis patients with liver injury. Receiver operating characteristic (ROC) curve was plotted, and the area under ROC curve (AUC) was calculated to analyze the prognostic value of NETs in sepsis patients with liver injury. Results Finally, 21 sepsis patients without liver injury, 15 sepsis patients with liver injury, 20 with non-sepsis and 20 with healthy examination were enrolled. There was no significant difference in gender or age among the four groups, indicating that the patients in each group were comparable. The levels of cf-DNA/NETs in peripheral blood, WBC and PMN of the sepsis with and without liver injury groups were significantly higher than those of the healthy control group and non-sepsis group, PCT, APACHE Ⅱ score, SOFA score and 28-day mortality were significantly higher than those of the non-sepsis group, and the levels of cf-DNA/NETs in peripheral blood, PCT and 28-day mortality of the sepsis with liver injury group were significantly higher than those of the sepsis without liver injury group [cf-DNA/NETs (μg/L): 481.60±275.86 vs. 169.76±57.05, PCT (μg/L): 11.29 (1.79, 67.10) vs. 1.11 (0.19, 4.09), 28-day mortality: 73.3% (11/15) vs. 38.1% (8/21), all P < 0.05]. The results of PMN in vitro showed that there was no NETs in normal culture of healthy control group, and a small amount of NETs was detected in sepsis with and without liver injury groups. After stimulation of PMN stimulator phorbol-12-myristate-13-acetic acid (PMA), more NETs were produced in neutrophils of three groups compared with normal culture. Quantitative analysis showed that the level of cf-DNA/NETs in cell supernatant of the sepsis with liver injury group was significantly higher than that of the sepsis without liver injury group (μg/L: 1 872.29±258.44 vs. 1 313.55±147.45, P < 0.01). In 15 sepsis patients with liver injury, 4 patients survived for 28 days (26.7%) and 11 died (73.3%). The cf-DNA/NETs level of the dead group on the day of admission was significantly higher than that of the survival group (μg/L: 582.36±160.05 vs. 241.17±96.14, P < 0.05). ROC curve analysis showed that the AUC of NETs level in peripheral blood for predicting 28-day death of sepsis patients with liver injury was 0.932 [95% confidence interval (95%CI) was 0.787-1.000]; when the best cut-off value was 266.81 μg/L, the sensitivity was 90.9%, the specificity was 75.0%, and the approximate index was 0.659. Conclusions The function of NETs in sepsis patients with liver injury has been further changed. The level of peripheral blood NETs has a certain guiding value for the prognosis of sepsis patients with liver injury.

High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

Anti-nociceptive effect of patchouli alcohol: Involving attenuation of cyclooxygenase 2 and modulation of mu-opioid receptor / 中国结合医学杂志

OBJECTIVE@#To explore the anti-nociceptive effect of patchouli alcohol (PA), the essential oil isolated from Pogostemon cablin (Blanco) Bent, and determine the mechanism in molecular levels.@*METHODS@#The acetic acid-induced writhing test and formalin-induced plantar injection test in mice were employed to confirm the effect in vivo. Intracellular calcium ion was imaged to verify PA on mu-opioid receptor (MOR). Cyclooxygenase 2 (COX2) and MOR of mouse brain were expressed for determination of PA's target. Cellular experiments were carried out to find out COX2 and MOR expression induced by PA.@*RESULTS@#PA significantly reduced latency period of visceral pain and writhing induced by acetic acid saline solution (P<0.01) and allodynia after intra-plantar formalin (P<0.01) in mice. PA also up-regulated COX2 mRNA and protein (P<0.05) with a down-regulation of MOR (P<0.05) both in in vivo and in vitro experiments, which devote to the analgesic effect of PA. A decrease in the intracellular calcium level (P<0.05) induced by PA may play an important role in its anti-nociceptive effect. PA showed the characters of enhancing the MOR expression and reducing the intracellular calcium ion similar to opioid effect.@*CONCLUSIONS@#Both COX2 and MOR are involved in the mechanism of PA's anti-nociceptive effect, and the up-regulation of the receptor expression and the inhibition of intracellular calcium are a new perspective to PA's effect on MOR.

Effect of N-acetyl-L-cysteine on bioavailability and brain distribution of curcumin by nasal delivery / 中国中药杂志

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.

Changes in neutrophil function in septic liver injury and its effect on prognosis: a prospective observational study / 中华危重病急救医学

Objective@#To explore the changes in polymorphonuclear neutrophils (PMN) function in peripheral blood of patients with sepsis and liver injury and its prognostic value.@*Methods@#A prospective observational study was conducted. The patients who met the criteria of Sepsis-3 admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from March to August in 2019 were enrolled as the research objects, and the patients were divided into sepsis without liver injury group and sepsis with liver injury group; non-sepsis patients who were hospitalized at the same time were enrolled as non-sepsis group; and the healthy people in the physical examination center were enrolled as healthy control group. The gender, age, white blood cell (WBC), PMN and procalcitonin (PCT) were recorded when the patients were admitted to ICU as well as the people on the day of physical examination. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores were calculated. The 28-day mortality was recorded. The quantitative level of neutrophil extracellular traps (NETs) which reflected by circulating free DNA (cf-DNA/NETs) in peripheral plasma was determined by PicoGreen fluorescence quantitative detection; the qualitative level of NETs was detected by immunofluorescence staining. PMN was extracted from the healthy control group, sepsis without liver injury group and sepsis with liver injury group and cultured in vitro, the quantitative level of cf-DNA/NETs in cell supernatant was determined by PicoGreen fluorescence quantitative detection. The patients were divided into two groups according to 28-day outcome of sepsis patients with liver injury. Receiver operating characteristic (ROC) curve was plotted, and the area under ROC curve (AUC) was calculated to analyze the prognostic value of NETs in sepsis patients with liver injury.@*Results@#Finally, 21 sepsis patients without liver injury, 15 sepsis patients with liver injury, 20 with non-sepsis and 20 with healthy examination were enrolled. There was no significant difference in gender or age among the four groups, indicating that the patients in each group were comparable. The levels of cf-DNA/NETs in peripheral blood, WBC and PMN of the sepsis with and without liver injury groups were significantly higher than those of the healthy control group and non-sepsis group, PCT, APACHE Ⅱ score, SOFA score and 28-day mortality were significantly higher than those of the non-sepsis group, and the levels of cf-DNA/NETs in peripheral blood, PCT and 28-day mortality of the sepsis with liver injury group were significantly higher than those of the sepsis without liver injury group [cf-DNA/NETs (μg/L): 481.60±275.86 vs. 169.76±57.05, PCT (μg/L): 11.29 (1.79, 67.10) vs. 1.11 (0.19, 4.09), 28-day mortality: 73.3% (11/15) vs. 38.1% (8/21), all P < 0.05]. The results of PMN in vitro showed that there was no NETs in normal culture of healthy control group, and a small amount of NETs was detected in sepsis with and without liver injury groups. After stimulation of PMN stimulator phorbol-12-myristate-13-acetic acid (PMA), more NETs were produced in neutrophils of three groups compared with normal culture. Quantitative analysis showed that the level of cf-DNA/NETs in cell supernatant of the sepsis with liver injury group was significantly higher than that of the sepsis without liver injury group (μg/L: 1 872.29±258.44 vs. 1 313.55±147.45, P < 0.01). In 15 sepsis patients with liver injury, 4 patients survived for 28 days (26.7%) and 11 died (73.3%). The cf-DNA/NETs level of the dead group on the day of admission was significantly higher than that of the survival group (μg/L: 582.36±160.05 vs. 241.17±96.14, P < 0.05). ROC curve analysis showed that the AUC of NETs level in peripheral blood for predicting 28-day death of sepsis patients with liver injury was 0.932 [95% confidence interval (95%CI) was 0.787-1.000]; when the best cut-off value was 266.81 μg/L, the sensitivity was 90.9%, the specificity was 75.0%, and the approximate index was 0.659.@*Conclusions@#The function of NETs in sepsis patients with liver injury has been further changed. The level of peripheral blood NETs has a certain guiding value for the prognosis of sepsis patients with liver injury.