REVIEW doi: 10.12032/TMRCR20200728016

TMR Clinical Research

Meta-analysis of the clinical efficacy and safety of Urinary Kallidinogenase in the treatment of acute cerebral infarction

Yuan Qin1, Qian Yi2, Hui-Hui Shi2, Ya-Lin Qi2*, Jing-Yue Hu2

1Chongqing Mental Health Center, ward eight ward, 400036, . 2Military (Third Military Medical University) Daping Hospital Neurology, Chongqing 400010, China.

*Corresponding to: Ya-Lin Qi. Daping Hospital, Army Medical University (Third Military Medical University. NO. 10, Changjiang branch road, Daping, Yuzhong , Chongqing 400042, China. E-mail: [email protected].

Highlights

The treatment of cerebral infarction by Urinary Kallidinogenase can improve the neurological defect symptoms, improve the quality of life, and the adverse reaction rate is low, and the safety is good, which provides evidence-based evidence for the treatment of cerebral infarction by Urinary Kallidinogenase.

Submit a manuscript: https://www.tmrjournals.com/tcr TMR | November 2020 | vol. 3 | no. 4 | 131 doi: 10.12032/TMRCR20200728016 REVIEW

Abstract

Objective: To evaluate the clinical efficacy and safety of Urinary Kallidinogenase for Injection in the treatment of acute cerebral infarction. Methods: PubMed, The Cochrane Library, Embase, CNKI, VIP, Wan Fang and bibliographic database of Chinese medicine were searched by computer to collect randomized controlled trials of Urinary Kallidinogenase 's treatment of acute cerebral infarction. The time limit was set up until September 2019. At the same time, the references and grey literature in the literature were manually screened. Two independent researchers were screened, evaluated and extracted according to inclusion and exclusion criteria. Meta-analysis was carried out by RevMan 5.3 software. Results: A total of 17 randomized controlled trials involving 2,066 patients, including 1,033 in the experimental group, and 1,033 in the control group. meta-analysis results showed that compared with the conventional treatment, Urinary Kallidinogenase had better effect in the treatment of acute cerebral infarction [OR = 3.26, 95%CI (2.56, 4.16), P < 0.00001]; the national institule of Health Stroke Scale of the Urinary Kallidinogenase group was significantly better than that of the control group. Urinary Kallidinogenase group activity of daily living scale was better than the control group [OR = 21.33, 95%CI (6.64, 36.01), P = 0.004]; a total of 7 articles reported adverse reactions, including 19 cases in the trial group and 21 cases in the control group, the main adverse reactions were blood pressure drop, other symptoms were chest tightness, facial redness, dizziness fever, nausea and vomiting, arrhythmia, and no other serious adverse reactions. It can recover itself. Conclusion: the available evidence shows that Urinary Kallidinogenase can effectively improve the symptoms of neurological deficits and improve the ability of daily living in patients with acute cerebral infarction, and is safe. However, the quality of the study is limited. Keywords: Human urinary kallikrein, Urinary Kallidinogenase, Acute cerebral infarction, Randomized controlled trial, meta-analysis

Abbreviations: rt-PA, recombinant tissue plasminogen activator; RCT, randomized controlled trial; CT, computed tomography; MRI, magnetic resonance Imaging; NIHSS, national institutes of health stroke scale; ADL, activity of daily living; OR, odds ratio; CI, confidence interval; PNA, pentose nucleic acid; ACEI, angiotension converting enzyme inhibitors; hk1, hexokinase 1. Competing interests: The authors declare that there is no conflict of interest. Citation: Yuan Qin, Qian Yi, Hui-Hui Shi, et al. Meta-analysis of the clinical efficacy and safety of Urinary Kallidinogenase in the treatment of acute cerebral infarction. TMR Clinical Research 2020, 3(4): 131–141. Executive Editor: Shan-Shan Lin. Submitted: 12 December 2019, Accepted: 12 May 2020, Online: 28 July 2020

TMR | November 2020 | vol. 3 | no. 4 | 132 Submit a manuscript: https://www.tmrjournals.com/tcr REVIEW doi: 10.12032/TMRCR20200728016 magnetic resonance Imaging (MRI) patients with a Background cute cerebral infarction within 72 hours had no ge nder or age. No strict gravity center, liver or kidn At present, stroke has become the first cause of death ey insufficiency, no systemic bleeding or bleeding in China. It is also an important cause of disability. Its tendency. main clinical manifestations are disturbance of (3) The intervention group adopted the same routine consciousness, dysfunction and other symptoms. It has treatment, including lowering blood fat, anti-platelet a high disability rate and mortality rate [1]. Cerebral aggregation, nourishing brain cells and improving the infarction, also known as ischemic stroke, is caused by cerebral circulation. The experimental group was local cerebral vascular supply disorders leading to additionally given Urinary Kallidinogenase, while the hypoxic degeneration and necrosis of the brain tissue, control group was given placebo, inactive or active resulting in a corresponding clinical neurological drugs on the routine treatment. Two groups were given deficit 80%, which accounts for all stroke types, is the same treatment. used in the treatment of acute cerebral infarction. In (4) Outcome measures: effective rate: the National addition to recombinant tissue plasminogen activator Institutes of Health Stroke Scale (NIHSS) was used to (rt-PA), an antiplatelet drug aspirin and thrombolytic evaluate the improvement of neurological deficits at drugs, has become an international guideline for grade the end of treatment. The following criteria were A and grade I recommendation. The evidence for other adopted to improve the degree of improvement: the drugs is not yet sufficient. Therefore, it is of great basic cure was: the neurological deficit score was significance to study new drugs for improving cerebral reduced by 90%–100%, the disability degree was 0 circulation and protecting brain function. grade; significant progress was achieved: the Urinary Kallidinogenase, also known as the human neurological impairment score was reduced by 46%– Urinary Kallidinogenase (trade name, Kai Likang), is a 89%, and the disability degree was 1–3; progress: serine proteinase composed of 238 amino acids neurological deficit score decreased by 18%–45%; no extracted from the urine of healthy men. It is a new change: neurological impairment score decreased or class I drug developed in recent years in China. It has increased by 18%; deterioration: neurological been shown that the drug has a certain dose under impairment score increased 18%. Improved conversion certain dose. It can expand the small artery in ischemic to classification variable effective and invalid, which area, increase blood flow in ischemic brain tissue, and will be effectively defined as basic cure, significant improve cerebral circulation in 10 years. In October progress and progress, Total Efficiency = (Basic Cure 2005, it was approved by The State Food and Drug + Significant Progress + Progression/Total Number) × Administration and widely used in clinical practice.In 100%; NIHSS score; 3 activity of daily living scale recent years, the drug has been more widely used in (ADL) score. China, and the corresponding clinical randomized (5) Adverse reactions were defined as intracranial controlled trials (RCT) are also increasing, but the hemorrhage, extracranial blood, allergies, and research quality is uneven, so it is necessary to carry unexplained organ dysfunction. out systematic evaluation to provide evidence-based medical evidence for it. Exclusion criteria (1) Non randomized controlled trials. Materials and methods (2) There is no clear diagnosis, inclusion and exclusion criteria. Search strategy Computer (3) The course of treatment is inconsistent and there is Search strategy retrieves databases such as PubMe d, no definite criteria for evaluating the therapeutic effect. The Cochrane Library, Embase, CNKI, VIP, Wa n (4) Repeated published studies. Fang and Chinese biomedical literature database. Registry from inception to September 2019. “Stro Data extraction ke” and Chinese search terms such as “Urinary K Extraction were carried out separately by two allidinogenase”, “human urinary kinase” and “cereb researchers, and the data were screened and extracted. ral infarction” were retrieved by combining themati If there were differences, reference was made to third c words and free words. people's opinions. The relevant documents were retrieved into the literature management software Inclusion criteria NoteExpress to read the titles and abstracts, and the (1) Study type: RCT, whether or not use blindness. articles that did not meet the inclusion criteria were Language is restricted to Chinese and English. carefully read out and screened again. Finally, the data (2) The subjects met the diagnostic criteria of cere included the first author or information provider, date bral infarction diagnosed by the Fourth National C of publication, age, time of entry, sample size, onference on cerebrovascular diseases, and confirm intervention measures, course of treatment, and ed by cranial computed tomography (CT) and/or outcome criteria. Submit a manuscript: https://www.tmrjournals.com/tcr TMR | November 2020 | vol. 3 | no. 4 | 133 doi: 10.12032/TMRCR20200728016 REVIEW analysis variables to draw funnel plots for publication Quality evaluation bias detection. According to the bias risk assessment method recommended in the Cochrane Systematic Review Statistical analysis Manual 5.1.0, bias risk assessment method included The sensitivity analysis of meta-analysis was mainly bias risk assessment for RCT. The main items were: 1) used to judge whether the statistical effect size was randomization scheme; 2) group concealment; 3) blind stable and whether it had an impact on the combined method; 4) incomplete data report; 5) selective results, including the shear and complement method, outcome report; 6) other bias sources. Each item was the removal of single study method, the loss of safety evaluated by “low bias risk”, “high bias risk” or number method, and the replacement model analysis “inability to judge”. method. It mainly includes the method of scissor compensation, single research method, loss of safety Statistical analysis number method and replacement model analysis Meta-analysis was performed using RevMan 5.3 method. In this paper, the replacement mode analysis software. Mantel-Haenszel method was used for method is applied, namely, the meta effect of the statistical analysis. Heterogeneity between the studies combined effect volume of the included literatures is was explored by Q test and I2 test, if P > 0.1 or I2 < analyzed by the fixed effect model. Then the random 50%, which is considered to be of low heterogeneity effect model is used to calculate the point estimates and analyzed by fixed effect model, if P ≤ 0.1 or I2 ≥ and interval estimates of the combined values of the 50%, it is considered that heterogeneity is significant. effects, and then the changes of the final effect of the The causes of heterogeneity were also analyzed. The two models are observed. If the results are not test standard was P < 0.05. In this paper, two significant, the results of the meta-analysis are stable categories of variables are selected. Odds ratio (OR) and reliable. and 95% confidence interval (CI) are used as statistical

Figure 1 Flow chart of literature screening TMR | November 2020 | vol. 3 | no. 4 | 134 Submit a manuscript: https://www.tmrjournals.com/tcr REVIEW doi: 10.12032/TMRCR20200728016 literature only represents random grouping, and the Results specific allocation method is not described in the 17 literature [2–18]. There was no clear description of Document search results whether allocation concealment and blindness were A total of 81 related articles were retrieved from applied, the outcome data was complete and there was Chinese and English databases, excluding repetitive no selective report result. In conclusion, the risk of reading topics and abstracts. 62 articles were obtained, most literature bias in the meta-analysis was not clear. and the full text was screened and screened. 4 articles were excluded, 3 cases were reported, 6 articles were Meta-analysis results not available, 32 articles did not meet the inclusion Comparison of clinical efficacy between the criteria, and 17 papers [2–17] were finally included in Urinary Kallidinogenase group and the control the meta-analysis. All of them were Chinese literatures. group. The 16 articles were included [2–14, 16–18]. (Figure 1). The NIHSS score was improved. Conversion to categorical variables was effective and invalid, Total Basic characteristics of literature Efficiency = (Basic Cure + Significant Progress + 17 articles included [2–18]. There were 1,033 cases in Progression/Total Number) × 100%. Extracted data for the trial group and 1,033 cases in the control group. All heterogeneity test, P = 0.71, I²= 0%, and heterogeneity the studies were conducted in China, including 2 trials was small, and fixed effect model was used for meta- [5, 8]. 7 patients were included in the onset of 24 hours analysis. Results showed that the effective rate of [2, 10–12, 15–17]. 8 patients were included in the Urinary Kallidinogenase group (87.70%) was onset of 48 hours [3, 4, 6, 7, 9, 13, 14, 18]. All the.17 significantly higher than that of control group at the studies included in the onset of 72 hours were all non- end of treatment (70.44%): combined effect OR = 3.26, placebo controlled trials. They all explained the basic 95%CI [2.56, 4.16], P < 0.00001. The difference medication regimen, including lowering blood fat, anti- between the two groups was statistically significant platelet aggregation, nourishing brain cells and (Figure 3). improving cerebral circulation. All the experimental Comparison of NIHSS scores between Yuri Clin groups were injected with Urinary Kallidinogenase group and control group. A total of 14 articles were 0.15 pentose nucleic acid (PNA) + 0.9% sodium included [2–10, 12–15, 18]. Including 1,538 patients, chloride solution 100ml intravenous drip on the basis 770 in the experimental group and 768 in the control of the control group, once a day, and 14 days as a group. The meta-analysis of the random effect model course of 16 study, respectively. All patients in the 17 showed that the NIHSS score in the Urinary group were given intravenous drip [2–14, 16–18]. The Kallidinogenase group was significantly better than NIHSS was used to evaluate the improvement of that in the control group [OR = -2.56, 95%CI (-4.13, neurological deficit at the end of treatment. The -0.99), P = 0.001]. The difference was statistically improvement degree was converted into categorical significant (Figure 4). variable effective and invalid, Total Efficiency = Comparison of ADL scores between Urinary (Basic Cure + Significant Progress + Progression/Total Kallidinogenase group and control group. A total of Number) × 100%. Fourteen studies reported detailed 4 articles were included [8, 13, 14, 17]. Including 384 NIHSS score values [2–10, 12–15, 18]. The detailed patients, 192 in the experimental group and 192 in the ADL score is reported for 4 studies [8, 13, 14, 17]. control group. The meta-analysis of the random effect Three of the 17 studies reported no adverse reactions model showed that the ADL score in the Urinary [11, 17, 18]. No adverse reactions were reported in 8 Kallidinogenase group was better than that in the studies [3, 5, 7, 8, 12–14]. Adverse reactions were control group [OR = 21.33, 95%CI (6.64, 36.01), P = reported, including 3 cases of chest tightness, 4 cases 0.004], the difference was statistically significant of facial redness, 6 cases of blood pressure drop, 2 (Figure 5). cases of dizziness and fever, 2 cases of nausea and Comparison of adverse reactions between Urinary vomiting, 3 cases of arrhythmia, and no other serious Kallidinogenase group and control group. 17 studies adverse reactions. Baseline information on age, sex, included [2–18]. There are 3 studies [11, 17, 18]. No onset time and degree of neurological impairment were adverse reactions were reported. 7 studies [3, 5, 7, 8, all comparable in all studies (P > 0.05) (Table 1). 12–14]. The adverse reactions were reported. The data were extracted from Urinary Kallidinogenase group Document quality evaluation results (19 cases) and control group (21 cases). The adverse According to the bias risk assessment tool of Cochrane reactions of the two groups were compared, and the collaboration, the bias risk was assessed in the results of heterogeneity test showed that: P = 0.89, I2 = literature. The bias was as follows (Figure 2). Among 0%, the heterogeneity was small, and the fixed effect them, 4 were articles [8, 12–14]. Describe the model was used for meta-analysis. The results of meta- allocation of 1 papers using random number method analysis showed that: OR = 0.90, 95%CI [0.48, 1.69], [2]. Using the envelope method, the rest of the P = 0.75. It was suggested that the incidence of Submit a manuscript: https://www.tmrjournals.com/tcr TMR | November 2020 | vol. 3 | no. 4 | 135 doi: 10.12032/TMRCR20200728016 REVIEW Table 1 Basic information of literature Intervention measures Average age (years) Course of Included in Number Entry Outcome Control Control treatment the study Test group of time Test group indicators (days) group patients group + Zhang Danni Yuri Klein Basic 65.2±7.40 63.9±7.90 50/50 ≤48h basic 14 ①②④ 2017 [2] treatment treatment + Huang Yuri Klein Basic 14 ①②④ Xiaodong 61.14±14.85 60.62±15.20 84/84 ≤72h basic treatment 2018 [3] treatment + Hou Yuri Klein Basic 14 ①②④ Zhongquan 49.76±10.81 49.51±10.55 50/50 ≤72h basic treatment 2018 [4] treatment + Huang Yuri Klein Basic 14 ①②④ Mingna 2019 43.60±16.0 42.10±15.70 51/49 ≤24h basic treatment [5] treatment + Lin Kai Heng Yuri Klein Basic 48.52±7.77 49.03±7.45 50/50 ≤72h basic 14 ①②④ 2018 [6] treatment treatment + Chen Siqia Yuri Klein Basic 66.13±11.08 67.40±7.14 134/134 ≤72h basic 14 ①②④ 2019 [7] treatment treatment + Wang Jialiang Yuri Klein Basic 66.80±8.50 67.20±8.90 40/40 ≤24h basic 14 ①②③④ 2017 [8] treatment treatment + Wang Bin Yuri Klein Basic 54.50±10.0 56.20±9.0 54/54 ≤72h basic 14 ①②④ 2017 [9] treatment treatment + Lin Yu Yuri Klein Basic 55.27±7.14 55.21±7.12 56/56 ≤48h basic 14 ①②④ 2019 [10] treatment treatment + Liu Qingjie Yuri Klein Basic 54.60±9.80 53.30±10.60 41/38 ≤48h basic 14 ① 2018 [11] treatment treatment + Dai Sheng Yuri Klein Basic 14 ①②④ Bing 2019 62.50±10.20 60.80±9.60 30/30 ≤48h basic treatment [12] treatment + Edge step Yuri Klein Basic 14 ①②③④ chrysanthemu 60.80±5.80 60.10±6.20 38/38 ≤72h basic treatment m 2017 [13] treatment + Yi Ting Ting Yuri Klein Basic 57.28±4.27 54.87±3.25 59/59 ≤72h basic 14 ①②③④ 2019 [14] treatment treatment + Fu Sheng Qi Yuri Klein Basic 60.82±11.18 61.54±11.26 25/25 ≤48h basic 14 ②④ 2011 [15] treatment treatment + Zhang Li Yuri Klein Basic 64.0±0.92 63.0±0.65 154/154 ≤48h basic 14 ①④ 2017 [16] treatment treatment + Luo Jiahua Yuri Klein Basic 64.30±6.10 62.5±6.60 53/49 ≤48h basic 14 ①②③ 2017 [17] treatment treatment + Jiang Yuri Klein Basic 14 ①② Chenhui 2018 58.70±9.20 59.30±8.10 49/49 ≤72h basic treatment [18] treatment ① effective rate; ② national institutes of health stroke scale; ③ activity of daily living score; ④ adverse reaction.

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Figure 2 Document quality evaluation form

Figure 3 Urinary Kallidinogenase’s clinical analysis of acute cerebral infarction adverse reactions in the two groups was not showed a notch in the lower left corner, indicating the statistically significant. Considering the length of time possibility of publication bias (Figure 7). It was involved in the onset of the disease, the results of considered that the included studies were too few, the adverse reactions were affected. Considering the sample size was small, and the quality of the included difference in the onset time of the patients included, literatures was low. the results of adverse reactions were affected. Therefore, the subgroup analysis was conducted Sensitivity analysis according to the onset time of the patients ≤ 24 hours After the fixed effect model was changed to a random and ≤ 72 hours, and no significant change was effect model, the effect volume was recombined. The observed (Figure 6). results showed that there was no significant change in the effective rate, the combined effect volume or value, Publication bias 95%ci and forest map of the two groups, indicating Funnel plots were drawn for publication bias based on that the combined effect was more stable. the outcome indicator of efficiency. The funnel plots

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Figure 4 Urinary Kallidinogenase’s national institutes of health stroke scale of acute cerebral infarction

Figure 5 Urinary Kallidinogenase forest’s activity of daily living score of acute cerebral infarction

Figure 6 Forest diagram of adverse effects of Yuri Klein on acute cerebral infarction

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Figure 7 Literature publication bias funnel plot

different degrees of ischemic brain tissue. The Discussion establishment of collateral circulation can effectively reduce the death rate of cerebral infarction and Acute ischemic stroke is the most common stroke type, improve the prognosis [21]. Therefore, in the acute which seriously affects the life and quality of life of stage of cerebral infarction, how to save the ischemic patients. In recent years, the incidence of acute penumbra and promote the establishment of collateral cerebral infarction has been increasing year by year circulation is of great significance for improving the and younger. Although the mortality rate of patients prognosis of patients and improving the quality of life with acute cerebral infarction has decreased with the of patients. progress of medicine, most of them have left Urinary Kallidinogenase, namely human urine neurological deficits and affect their quality of life in excitation peptide enzyme (commodity called Kai the future. It brings great pain to patients and families LiKang), is developed in recent years, China’s [19]. After acute cerebral infarction, there are a series independent I class of new drugs. It is recommended of physiological changes in the body, including “Guidelines for the Diagnosis and Treatment of Acute aggravation of brain edema, thrombocytopenia and Ischemic Stroke in China 2014”. Urinary platelet activating inducer activity. The formation of Kallidinogenase is a tissue type kininase, a micro thrombus will further aggravate cerebral glycoprotein extracted from healthy male urine and is a ischemia and hypoxia [20]. At present, the early positive regulator in kininase kinin system. It can treatment of acute cerebral infarction is the first choice convert kinin to kallikrein and vasodilation, and kinin for thrombolysis, followed by interventional therapy, and its corresponding receptors bind to nitric oxide including mechanical thrombectomy, carotid cyclic guanosine, prostacyclin cyclic guanosine and endarterectomy and stent implantation. Although these other signal pathways, and play a variety of therapies can make vascular recanalization, there are physiological functions, such as dilating blood vessels, strict time windows. At present, the treatment schemes improving cerebral oxygen supply, blood supply and that exceed the time window mainly include energy metabolism. It can effectively improve blood defibrillator, anti-platelet agglutination, nutritive nerve, supply in ischemic penumbra area and save ischemic traditional Chinese medicine, rehabilitation treatment, brain cells. A large number of clinical studies have etc., but there are no other effective treatment schemes confirmed that Yuri Colin has a good effect in opening at present. In recent years, the concept of collateral collateral circulation, improving neurological circulation has been widely applied to the treatment of symptoms and daily living ability. acute cerebral infarction. Even after carotid artery The results of this study showed that in the clin ischemia, compensatory compensation can be made to ical treatment effect, the total effective rate of Uri

Submit a manuscript: https://www.tmrjournals.com/tcr TMR | November 2020 | vol. 3 | no. 4 | 139 doi: 10.12032/TMRCR20200728016 REVIEW nary Kallidinogenase test group in the treatment of 1. Zhou XM, Han G. Hemorheology changes in acute cerebral infarction was higher than that in t elderly patients with acute cerebral infarction he control group without the application of Urinar treated with kallidinogenase. Pract Geriatr 2018, y Kallidinogenase (OR = 3.26, 95%CI [2.56, 4.16], 32: 270–272. P < 0.00001), the difference was statistically sign 2. Zhang DN. Relationship between cerebrovascular ificant. It suggested that Urinary Kallidinogenase c reactivity and prognosis of acute cerebral ould significantly improve the degree of neurologic infarction treated by urinary kallidinogenase. J al deficit. Compared with the incidence of adverse Heilongjiang Med 2017, 41: 146–148. reactions in the two groups, the difference was n 3. Huang XD, Huang H. Efficacy and safety of ot statistically significant (OR = 0.90, 95%CI [0.4 human urinary kallidinogenase in the treatment of 8, 1.69], P = 0.75 > 0.05), indicating that in the t acute cerebral infarction. Chin Mod Med Appl reatment of acute cerebral infarction, the adverse r 2018, 12: 4–6. eactions caused by Urinary Kallidinogenase were s 4. Hou Z. Urinary kallidinogenase’s clinical effect imilar to those in the neurology department. The s analysis of acute cerebral infarction patients. J afety of clinical application is guaranteed. Through Heilongjiang Med 2018, 41: 204–205. the summary of the adverse reactions included in 5. Huang MN, Ren L, Wu XH. Urinary the literature, we can see that the most common kallidinogenase adjunctive treatment of acute adverse reaction of Urinary Kallidinogenase is mil cerebral infarction feasibility and safety. Chin d blood pressure drop, which may be related to th Med Sci 2019, 9: 53–55. e synergistic effect of the drug and some antihype 6. Lin KH, Ou LB, Liu T. Urinary kallidinogenase rtensive drugs. According to the research, ACEI dr intravenous drip in the treatment of acute cerebral ugs can enhance the concentration of hk1 and pro infarction. Chin Mod Med Appl 2018, 12: 105– kinin in the blood circulation, and enhance the ant 106. ihypertensive effect. Therefore, during the treatment 7. Chen SQ, Guo YW, Wang H, et al. Urinary of acute cerebral infarction, Urinary Kallidinogena kallidinogenase can improve short-term prognosis se should avoid using ACEI drugs. In the two gro of patients with large atherosclerosis acute ups, a small number of patients had chest tightnes cerebral infarction. J Shantou Univ Med Univ s, nausea and vomiting, flushing, dizziness, fever a 2019, 32: 92–95. nd so on, most of them were mild, and they coul 8. Wang LL. Urinary kallidinogenase for acute d relieve themselves without special treatment. middle cerebral artery infarction and its effect on According to the results of the meta-analysis, we did nerve function. Eval Anal Drug-Use Hosp Chin not search for a randomized controlled clinical study of 2017, 17: 170–172. Urinary Kallidinogenase in the treatment of acute 9. Wang B. Urinary kallidinogenase’s anti cerebral infarction. Most of the research designs in inflammatory effect and safety in acute cerebral China are not of high quality and lack of rigor. The infarction. Eval Anal Drug-Use Hosp Chin 2017, main findings are as follows: even though all studies 17: 1183–1185 are described as randomized controlled trials, only a 10. Lin Y, Peng ML, Xiao H, et al. Effect of urinary few have mentioned specific random allocation kallidinogenase in Treating 56 cases of methods. The distribution of concealment and perforating artery infarction and its impact on blindness is not mentioned. The limited number of nhiss score. Chin Foreign Med Res 2019, 17: 39– samples in the literature has a certain effect on the 41. strength of argumentation in this paper. 11. Liu QJ, Zhu S. Urinary kallidinogenase in the treatment of acute progressive cerebral infarction Conclusion clinical curative effect. Clin Med 2018, 38: 84–86. 12. Dai SG, Yan W, Liu Y, et al. Efficacy and safety To sum up, the current evidence shows that Urinary of urinary kallidinogenase in the treatment of Kallidinogenase can significantly improve the acute cerebral infarction. Chin Gen Res 2019, 17: neurological deficit degree and safety of patients with 1046–1048. acute cerebral infarction compared with conventional 13. Bian BJ. Urinary kallidinogenase in the treatment treatment. It is safe and has great significance for of acute cerebral ischemic stroke. Inner Mongolia improving the quality of life of patients. However, due Med 2017, 49: 841–842. to the limited quality and quantity of existing research, 14. Yi TT, Zheng YC, Zhang JY, et al. Clinical large sample and high quality randomized controlled observation of urinary kallidinogenase in the trials are needed to provide corresponding evidence- treatment of acute anterior circulation ischemic based medical evidence. stroke. J I Nat (Med Sci) 2019, 36: 93–94. 15. Fu SQ, Zhang SL, Ji P, et al. Effects of urinary References kallidinogenase injection on serum matrix

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