Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine （Part 8）： Quality Evaluation with AGREE Ⅱ and RIGHT / 中医杂志

ObjectiveTo evaluate the methodological and reporting quality of clinical practice guidelines for Chinese patent medicine （CPM） with internationally recognized tools the appraisal of guidelines for research and evaluation （AGEREE） Ⅱ and reporting items for practice guidelines in healthcare （RIGHT）， thereby providing refe-rence for the clinical application and future development of CPM guidelines. MethodsDatabases including CNKI， VIP， Wanfang and Sinomed were searched for CPM guidelines， as well as medlive.cn， websites of China Association of Chinese Medicine and Chinese Medical Association， and reference lists of the included papers. The quality of the guidelines was evaluated using the AGREE Ⅱand RIGHT tools， and consistency tests were performed using Interclass Correlation Coefficient， and descriptive analysis and chi-square test were used to analyze the reporting rate for each domain and the average score for each item. ResultsFinally， 140 CPM guidelines were included， of which 51 were disease-oriented and 89 were drug-oriented， all of which were issued by China. For 51 disease-oriented CPM guidelines， the highest average score of all six AGREE Ⅱ domains was 73.32% for clarity， and the lowest was 26.80% for application； for 89 drug-oriented CPM guidelines， the highest average score was 55.62% for scope and purpose， and the lowest was 31.32% for rigour of development. In terms of the seven domains of the RIGHT checklist， the highest reporting rate was 68.26% for background， and lowest was 27.45% for other areas regarding the disease-oriented CPM guidelines； the highest reporting rate was 61.31% for background， and the lowest was 4.49% for other areas regarding drug-oriented CPM guidelines. The average reporting rate was higher for disease-oriented than drug-oriented CPM guidelines in three domains of AGREE Ⅱ （rigour of development， clarity of presentation， editorial independence）， as well as four domains of RIGHT checklist （basic information， evidence， funding and declaration and management of interests， and other areas）. ConclusionThe overall methodology and reporting quality of the current CPM guidelines still need to be improved. It is recommended that future guideline development teams should strictly refer to the AGREE Ⅱ and RIGHT checklist， and take into account of the characteristics of CPM guidelines and relevant methodo-logical suggestions in the development and reporting of CPM guidelines， thereby guiding the clinical use of CPM in a better way.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine （Part 7）： Introduction and Interpretation of the Guideline Reporting Checklist / 中医杂志

The systematic and comprehensive introduction and interpretation of the Reporting Checklist of Clinical Practice Guidelines for Chinese Patent Medicines V1.0 is conducive to the presentation of high-quality clinical practice guidelines for Chinese patent medicines （CPMs）， thus improving their dissemination and use. The Reporting Checklist of Clinical Practice Guidelines for Chinese Patent Medicines V1.0 specifies the requirements for clear， complete and transparent reporting of the whole process of developing CPMs guidelines， containing 4 domains， 17 topics and 43 items， and involving the basic information， recommendations and methods of guideline development. Especially， it details the items related to the rules and regulations of the use of CPMs in the recommendations， which is helpful for improving the completeness， scientificity and practicality of the reporting of CPMs guideline.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine （Part 6）： Formation and Presentation of Recommendations / 中医杂志

Recommendation formation is a key component of clinical practice guidelines for Chinese patent medicine （CPM）， and should encompass the determination of the strength and direction of the recommendation， the rationale for the recommendation， and the methodology for implementing the recommendation. Recommendations can be formed through formal consensus and informal consensus. The strength and direction of recommendations for CPM guidelines should be determined by considering the quality of evidence for CPMs， the priority of the clinical questions， the pros and cons of efficacy and adverse effects， patient acceptance， the feasibility of the recommendation and the availability of resources， social fairness， economic benefits， and other influencing factors. In order to better guide guideline developers to consider these factors more rationally， this article provideed a detailed explanation of each factor in the context of the characteristics of TCM.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 5）： Retrieval and Synthesis of Key Information on Rational Drug Use / 中医杂志

Recommendations for Chinese patent medicine （CPM） based on key information on rational drug use are one of the important conditions for enhancing guideline enforceability as well as facilitating guideline implementation. In this study， we discussed in detail of the key information on the rational use of CPM in five aspects， which are dosage， drug discontinuation， drug-drug and drug-food interactions， safety and economy. Following the process of multi-source search， synthesis and prioritization， it is suggested to collect key information on the rational use of CPM from a multi-source search of drug instructions， policy documents， literature， and clinical experts' experiences. Then the searched information should be summarized and prioritized with the principle that taking drug instructions as the basis and other-sources information for check and supplementation. Finally， methodological recommendations for the retrieval and synthesis of key information on rational drug use in guideline recommendations has been formed.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 4）： Evidence Retrieval and Evaluation / 中医杂志

The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine， there is certain differences in terms of evidence composition， retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature， and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine， the corresponding evaluation tools have been recommended， and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally， a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed， which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 3）： Identification of Clinical Questions / 中医杂志

The identification of clinical questions for clinical practice guidelines of Chinese patent medicine （CPM） is important for subsequent evidence retrieval， evaluation of evidence quality， formation of recommendations. This paper described a methodological proposal for the identification of clinical questions for CPM guidelines to highlight the characteristics of Chinese patent medicine and reflect its effect in specific stage of the disease. Considering four aspects， namely， the drug of Chinese patent medicine （D）， the specific disease stage （S）， comparison （C）， and specific outcome （O）， DSCO framework has been proposed to formulate the clinical questions. Multi-source information through scientific research， policy or standard documents， and clinical data are suggested for collecting clinical questions， and clear selection criteria should be set to finalize the clinical questions to be addressed by the guideline. In addition， the above process needs to be transparently and publicly reported in order to ensure the clarity and completeness of the guidelines.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine： 2.Establishment of Guideline Working Group and Management of Conflict of Interests / 中医杂志

This paper summarized the key points and methods in terms of the establishment of the guideline working group and the management of conflict of interests， trying to provide reference for the development of clinical practice guidelines for Chinese patent medicine （CPM）. The establishment of the working group is the first important step for developing CPM guidelines. Considering the characteristics of the clinical practice guidelines for CPM， this study suggests that the three key elements of ‘multidisciplinarity’， ‘clinical relevance’ and ‘geographical representativeness’ should be put focus on when forming the working group. The guideline advisory committee， clinical expert group， evidence systematic evaluation group， secretary group and the external review group should be established. All group members should clarify the conflict of interest， and the process and management method of the conflict of interest should be clearly reported.

Methodology for the Development of Clinical Practice Guideline for Chinese Patent Medicine（Part 1）： Development Status and Characteristics / 中医杂志

The irrational use of Chinese patent medicines （CPM） is becoming more and more prominent， which makes the demand for clinical practice guidelines of CPM gradually increase. In order to make domestic scholars understand the latest developments and existing problems of the CPM guidelines， and promote its development， this paper introduced the concept of CPM guidelines， summarized the characteristics of the two development modes， namely “taking CPM as the key” and “taking disease/syndrome as the key”， and analyzed the current methodological status of developing and reporting CPM guidelines. Based on the existed problems， three suggestions have been put forward to optimize the quality of CPM guidelines， which were clarifying the target users and scope of CPM guidelines， establishing an open and transparent mechanism of the personnel involvement and process steps， and formulating implementable and operable recommendations for the use of CPM.

Standard on classification of Traditional Chinese Medicine ancient books / 国际中医中药杂志

The standardization of classification methods of Traditional Chinese Medicine(TCM) ancient books can provide a clear and reliable reference for all kinds of TCM ancient books collection units, which can also promote the sharing and utilization of TCM ancient books. We studied and investigated the classification methods of TCM ancient books in past dynasties. The standard on classification of TCM ancient books was formulated by compared with the classification table of Zhongguo Zhongyi Guji Zongmu, and referred to the classification table of Zhonghua Guji Zongmu. This standard specified three-level categories and classification principles of TCM ancient books, and mainly composed of basic categories, three-level category table, classification principles and examples, and instructions for use.

Emerging trends in organ-on-a-chip systems for drug screening

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

A multicenter study of the correlation between advanced glycation end products in the lens and type 2 diabetes / 中华健康管理学杂志

Objective:To investigate the relationship between advanced glycation end products (AGEs) in the lens and type 2 diabetes mellitus.Methods:226 subjects were recruited between August 14 to September 14, 2018 from the Endocrinology Department of Central South University Xiangya Hospital, the Third Hospital of Changsha City, and the Fourth Hospital of Changsha City. The OGTT test, combined with clinical indicators, were used as the gold standard. Subjects were screened for type 2 diabetes using both the lens AGE fluorescence assay and the gold standard. Drawing the receiver operating characteristic (ROC) curve, we calculated the area under the curve (AUC) and its 95% CI and calculated the AGE for the diagnosis of type 2 diabetes. Sensitivity, specificity, Youden index, Kappa value, and its 95% CI, and the optimal cut-off value were determined according to the Youden index. Taking diabetes as the outcome indicator and AGE as the binary indicator, three logistic regression models were constructed. Stratified by age and sub-center, the differences between fasting blood glucose and 2 h postprandial blood glucose were compared between the AGE-negative and AGE-positive groups to determine the relationship between AGE and diabetes. Results:The area under the ROC curve was 0.86(95% CI: 0.81-0.91). According to the Youden index, the optimal cut-off point for AGE was 0.24. At this time, the sensitivity was 82.86(95% CI: 77.81-87.91), the specificity was 77.06(95% CI: 71.43-82.7), the Youden index was 59.92(95% CI: 53.36-66.49), the Kappa value was 79.62(95% CI: 74.22-85.02). Except for the 20-39-year-old group, the fasting blood glucose and 2 h postprandial blood glucose of the AGE-positive group in different age groups, different sub-centers, and the general population were higher than those of the AGE-negative group (all P<0.05). After adjusting for the confounding effects of age, gender, and sub-center (model 3), the relative risk of diabetes in the AGE-positive group was 11.75 times higher than the AGE-negative group (95% CI: 5.61-24.60), all with P<0.001. Conclusion:There was a high correlation between AGE in the lens and the risk of type 2 diabetes. When the cut-off point of AGE is 0.24, it had high sensitivity and specificity and could be used as a practical tool for early screening of type 2 diabetes.

Relationship between preoperative frailty and postoperative cognitive dysfunction in elderly patients undergoing non-cardiac surgery / 中华麻醉学杂志

Objective:To evaluate the relationship between preoperative frailty and postoperative cognitive dysfunction (POCD) in elderly patients undergoing non-cardiac surgery.Methods:A total of 336 elderly patients of both sexes, aged≥65 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 18.6-25.1 kg/m 2, undergoing elective non-cardiac surgery under general anesthesia, were enrolled in the study.Faltering status was assessed with the Clinical Faltering Scale at 1 day before surgery.Mini-Mental State Examination score, Digital Span Test, Digit Symbol Substitution Test, Stroop Color and Word Test, Visual Word Learning Test and Trail Making Test were performed at 1 day before surgery and at 1, 7 and 30 days after surgery.The Z score was used to identify POCD.The patients was divided into non-POCD group and POCD group according to the occurrence of POCD within 30 days after surgery.Logistic regression analysis was used to identify the risk factors for POCD in elderly patients undergoing non-cardiac surgery. Results:The results of logistic regression analysis showed that preoperative frailty and diabetes mellitus were independent risk factors for POCD in elderly patients undergoing non-cardiac surgery ( P<0.05). Conclusion:Preoperative frailty is an independent risk factor for POCD in elderly patients undergoing non-cardiac surgery.

Relationship between G9a and Slack channels in dorsal root ganglia of rats with neuropathic pain / 中华麻醉学杂志

Objective:To evaluate the relationship between the euchromatic histone-lysine N-methyltransferase (G9a) and sodium-dependent activation of potassium channel (Slack) in the dorsal root ganglia (DRG) of rats with neuropathic pain (NP).Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 1 month, weighing 100-120 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (S group), vector plus sham operation group (VS group), vector plus NP group (VN group), and G9a CRISPR/Cas9 knockout plus NP group (GN group). Sham operation was performed at the age of 2 months in group S. In group VS, AAV5 1 μl was microinjected into L 4 and L 5 DRG at the age of 1 month, and sham operation was performed at the age of 2 months.In VN group and GN group, AAV5 and G9a CRISPR/Cas9 knockout plasmid 1 μl were microinjected into L 4 and L 5 DRG at the age of 1 month, and NP model was established by spinal nerve ligation (SNL) at the age of 2 months.Six rats in each group were selected to measure the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) before microinjection (T 0), before SNL (T 1), and at 3, 5 and 7 days after SNL (T 2-4). The animals were sacrificed after the last behavioral testing, the DRGs of lumbar segment (L 4, 5) were removed for determination of the expression of G9a, dimethylation of histone H3 at lysine 9(H3K9me2) and Slack (by Western blot). At 7 days after establishing the model, 6 rats from each group were selected to culture the primary DRG neurons.The frequency and amplitude of Slack current in DRG neurons and miniature excitatory post-synaptic currents (mEPSCs) in the spinal dorsal horn were measured by whole-cell patch-clamp technique. Results:Compared with group S, the TWL was significantly shortened and the MWT was decreased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was up-regulated, the expression of Slack was down-regulated, the amplitude and frequency of Slack currents in DRG neurons were decreased, and the frequency of mEPSCs was increased in group VN ( P<0.05), and no significant change was found in the parameters mentioned above in group VS ( P>0.05). Compared with group VN, the TWL was significantly prolonged and the MWT was increased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was down-regulated, the expression of Slack was up-regulated, the amplitude and frequency of Slack currents in DRG neurons were increased, and the frequency of mEPSCs was decreased in group GN ( P<0.05). Conclusion:The mechanism of NP is related to up-regulating the expression of G9a in DRG, thus inhibiting the expression and opening of Slack channels in rats.

Observation on the effect of improved supine position to prevent pressure injuries in emergency patients under observation / 中国实用护理杂志

Objective:To discuss the effect of improved supine position on the prevention of pressure injuries of emergency patients under observation and their comfort levels.Methods:A total of 114 patients in our Emergency Observation Ward were randomly divided into the intervention group and control group, 57 patients in each. Patients in the control group were treated with routine supine position and pressure injury prevention nursing; while patients in the intervention group were treated with improved supine position nursing intervention. Then, the incidence of pressure injury, its risk score and its comfort evaluation were compared between patients under observation in the two groups.Results:The incidence of pressure injury of the intervention group was obviously lower than that in the control group ( Z value was -2.426, P<0.05). The scores of sensation, humidity, activity, friction and shear force of patients in the intervention group were 3.36 ± 0.59, 2.92 ± 0.47, 3.21 ± 0.52 and 2.61 ± 0.29 respectively, which were significantly higher than those in the control group, specifically 2.87 ± 0.51, 2.24 ± 0.38, 2.76 ± 0.44 and 2.04 ± 0.32. The difference was statistically significant ( t value was 4.74-9.96, P<0.01). In addition, the scores of the physiological and psychological comfort level of patients in the prevention group were 15.41±2.49 and 27.26 ± 3.42 respectively, which were significantly higher than 11.01±1.97 and 22.14± 3.23 in the control group. The difference was statistically significant ( t value was 10.46, 8.21, P<0.05). Conclusions:The improved supine position nursing method can effectively lower the occurrence of pressure injury in emergency patients under observation and enhance patients’ comfort degree. Therefore, it is applicable to emergency patients under observation.

Compiling principles and methods of standard on Classification of Traditional Chinese Medicine Ancient Books / 国际中医中药杂志

It is urgent to establish a standard for the classification and management of ancient books for Traditional Chinese Medicine (TCM) industry. This paper formulated the compiling principles on classification of TCM ancient books through the investigation and research. The categories were set and adjusted by comparing with the classification of Zhongguo Zhongyi Guji Zongmu and Zhonghua Guji Zongmu. Based on the comparason, the standard on classification of TCM ancient books was established. According to the classification standard, 8 663 kinds of TCM ancient books were reclassified. This standard can provide a clear and reliable reference for all kinds of collection units, promote the unification of classification methods of TCM ancient books, and promote the sharing and utilization of TCM ancient books.

Application of medical waterproof film combined with non-woven tape fixed endotracheal tube in cleft lip/palate surgery / 中国实用护理杂志

Objective:To investigate the effect of applying waterproof film combined with non-woven tape fixation of endotracheal tube in cleft lip and palate operation.Methods:From July 2018 to December 2018, 72 cases of cleft palate and cleft lip were selected from the operating room of the First Affiliated Hospital of Zhengzhou University The cases were randomly divided into the control group (suture and thread fixation method) and the experimental group (medical waterproof lamination combined with non-woven cloth), with 36 cases in each group. The duration of catheter fixation, intraoperative catheter fixation and postoperative catheter-related complications were compared between the two groups.Results:There were statistically significant differences between the experimental group and the control group in the duration of catheter fixation, surgeon satisfaction score and incidence of needle stab injury and needle stab bleeding: (1.15±0.63) min, (4.50±0.56), 0 case, 0 case in the experimental group, and those in the control group were (2.36±0.56) min, (3.83±1.13), 6 cases, 6 cases ( t values were 0.000, 14.435, χ2 values were 72.000, 6.545, P<0.01 or 0.05). Compared with the control group, there were no statistically significant differences in operation time, intraoperative oxygen saturation, catheter fixation direction, incidence of tube tearing, and incidence of postoperative scar ( P>0.05) in the experimental group. Conclusions:Medical waterproof film combined with non-woven tape fixed endotracheal intubation can obviously shorten the preoperative endotracheal intubation fixing time, improve the surgeon satisfaction. At the same time, it is effective in preventing postoperative complications caused by fixation with needle and silk thread.

Effect of ketogenic diet on seizures, electroencephalogram and neurobehavioral development in children with epilepsy / 中华实用儿科临床杂志

Objective:To investigate the effects of ketogenic diet on seizures, electroencephalogram(EEG) changes and neurobehavioral development in children diagnosed with epilepsy.Methods:A total of 122 children diagnosed with spastic epilepsy in Nanyang Central Hospital from March 2016 to March 2019 were enrolled.The patients were divided into the observation group and the control group, by the computerized random number table method with 61 cases in each group.The children in the control group were treated with conventional therapy, and the children in the observation group were combined with the ketogenic diet on the basis of conventional treatment.The Gesell developmental schedules scale scores were compared between the two groups to evaluate seizure control and EEG improvement.Results:The seizure control in the observation group was significantly better than that in the control group [78.69%(48/61 cases) vs.54.10%(33/61 cases)], and the difference was statistically significant ( χ2 = 12.114, P <0.05). The EEG improvement in the observation group was significantly better than that in the control group [81.97%(50/61 cases) vs.55.74%(34/61 cases)], and the difference was statistically significant ( χ2=13.623, P<0.05). After 12 months of treatment, the children in the observation group had significantly higher fitness, gross motor, fine motor, language, and personal social, and total development quotient scores than the control group [(56.64±13.29) scores vs.(46.04±12.86) scores, (54.84±12.18) scores vs.(47.62±11.91) scores, (54.44±10.70) scores vs.(44.31±11.56) scores, (51.48±12.99) scores vs.(42.04±11.18) scores, (57.88±11.04) scores vs.(47.42±13.16) scores, (275.28±54.71) scores vs.(227.42±55.79) scores], the differences were statistically significant ( t=5.997, 5.887, 6.003, 5.889, 6.007, 6.010, all P<0.05). Conclusion:The ketogenic diet can significantly reduce seizures, improve EEG and neurobehavioral development in children with epilepsy.

Matrix metalloproteinase regulates natural killer cells function in methicilin-resistant staphylococcus aureus sepsis / 中华急诊医学杂志

Objective:To investigate the characteristics of natural killer (NK) cell subsets and function in methicillin-resistant staphylococcus aureus (MRSA) sepsis, and to assess the influence of matrix metalloproteinase (MMP) to NK cell function in MRSA sepsis patients.Methods:Twenty-one MRSA sepsis patients who were hospitalized in our department between January 2017 and June 2018 were enrolled. Eleven healthy individuals were served as healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated. NK cell subsets were investigated by flow cytometry. NK cell function was assessed by measuring CD107a, CD69, and CD16 expression in co-culture system between PBMCs and different target cells. MMP mRNA was semi-quantified by real-time PCR in purified NK cells. The influence of NK cell function was assessed by measuring CD107a expression in co-culture system between NK cells with MMP inhibitor stimulation and target cells.Results:There was no significant difference of total NK cell percentage between healthy controls and MRSA sepsis patients ( P>0.05). CD56brightCD16 -NK [(5.36±1.02)% vs (4.30±0.89)%] and CD56 -CD16 +NK [(24.04±2.92)% vs (9.70±1.54)%] percentage was elevated ( P<0.05), while CD56dimCD16 +NK percentage [(71.22±13.03)% vs (87.64±7.05)%, P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% vs(18.80±1.49)%] was decreased ( P<0.0001), while CD16 MFI was increased [(247.1±50.31) vs (189.4±57.54), P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients ( P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% vs (25.87±6.23)%, P=0.018]. Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.

Effects of a Reinforcing and Reducing Method of Acupuncture on Interstitial Fluid Pressure in Subcutaneous Tissue of Minipig / 医用生物力学

Objective To study the effect of the reinforcing and reducing method of acupuncture reported in first Chapter the Nine Needles and Twelve Yuan of the Miraculous Pivot on interstitial fluid pressure (IFP) in subcutaneous tissue of minipig, and to investigate its biomechanical mechanism of regulating the interstitial fluid. Methods Nine healthy minipigs were randomly selected for reinforcing method (pull or press) and reducing method (wave a big pinhole), and tested on soft skin tissues of the abdomen. The IFP in the normal state (NS), the low volume (LV) state (by extracting interstitial fluid) and the high volume (HV) state (by injecting saline solution) was measured before and after acupuncture. Results In the normal state, pulling and pressing the needle could obviously increase IFP, while reducing method could significantly decrease IFP, leading to a rapid decrease in 5 min after acupuncture. In the LV state, pulling and pressing the needle could increase IFP. However, in 10 min after acupuncture, the descend rates of IFP were relatively slower. In the HV state, the reducing method could significantly decrease IFP, and the changing trend in 5 min after acupuncture was different from that of the control group. Conclusions The reinforcing and reducing method of acupuncture could increase or decrease IFP, which proved that the acupuncture method could regulate IFP in the opposite direction. The research findings provide a new scientific basis for using reinforcing and reducing method of acupuncture in clinic.

Association of plasma kallikrein and bradykinin receptor 1 with prognosis of cerebral infarction in elderly rats after ischemic stroke / 中华老年医学杂志

Objective:To explore the correlation of plasma kallikrein and bradykinin receptor 1 with prognosis of cerebral infarction in elderly rats after ischemic stroke.Methods:A total of 40 male Sprague-Dawley rats were randomly divided into 4 groups: the stroke model group(intraperitoneally injected with 150 μl 0.9% saline, n=10), the DX-88 group(intravenously injected with kallikrein inhibitor DX-88 30 μl/time, n=10), the R-954 group(intravenously injected with bradykinin B1 receptor antagonist R-954 30 μl/time, n=10)and the DX-88 combined with R-954 treatment group(intravenously injected with DX-88 and R-954, n=10). Protein expression levels of plasma kallikrein and bradykinin receptor 1 were determined by Western blotting.mRNA expression levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and caspase-3 were analyzed by using qRT-PCR.A neurologic function scale was used to score cerebral nerve injury and calculate the middle cerebral infarction area and cerebral swelling in experimental rats.Cerebral blood-brain barrier permeability was assessed by the cerebral infarction area.Results:Neurological injury scores decreased in the DX-88, R-954 and DX-88 + R-954 groups compared with the stroke model group(5.35±1.35, 6.49±1.16, 4.92±0.92 vs.11.17±2.18, F=15.589, P=0.022). Compared with the stroke model group, the cerebral infarction area was reduced in the DX-88, R-954 and DX-88+ R-954 groups[(4.35±1.05) mm 2, (5.43±0.26) mm 2, (3.88±0.13) mm 2vs.(8.26±1.24) mm 2, F=13.476, P=0.034)]. The extent of brain swelling was smaller in the DX-88, R-954 and DX-88+ R-954 groups than in the stroke model group[(31.28±7.45) %, (35.19±8.57) %, (19.68±3.14) % vs.(74.26±15.66) %, F=16.587, P=0.026)]. Plasma kallikrein protein levels were lower in the DX-88 and DX-88+ R-954 groups than in the stroke model group( P<0.05). The expression of bradykinin-1 receptor mRNA was lower in the R-954 and DX-88+ R-954 groups than in the stroke model group( P<0.05). The above results indicated that antagonism of plasma kallikrein and bradykinin receptor 1 played an important role.mRNA transcription levels of IL-1β, TNF-α and caspase-3 were higher in the stroke model group than in the DX-88, R-954 and DX-88+ R-954 groups( F=12.665、14.574 and 13.665, P=0.021、0.015 and 0.003). Conclusions:Inhibiting plasma kallikrein and bradykinin receptor 1 may provide protection against cerebral nerve injury in cerebral ischemia, and improve the prognosis of cerebral infarction.