1.Correlation of CD200-CD200R axis and diseases and its research progress
Han XU ; Yu-xin BI ; Gui-xia LI ; Jian LI ; Liu-li WANG ; Rui-jia HAO ; Xue-min ZHENG ; Rui-jing HUANG ; Jin HAN ; Fei LI ; Gen-bei WANG
Acta Pharmaceutica Sinica 2024;59(4):822-830
		                        		
		                        			
		                        			 CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target. 
		                        		
		                        		
		                        		
		                        	
2.Acupuncture for delayed sleep-wake phase disorder: a randomized controlled trial.
Xin-Tong YU ; Wen-Jia YANG ; Na ZHAO ; Rui-Long LIANG ; Xu-Qiu SUN ; Yue-Ping BI ; Yan-Yan MOU
Chinese Acupuncture & Moxibustion 2023;43(3):245-251
		                        		
		                        			OBJECTIVE:
		                        			To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD).
		                        		
		                        			METHODS:
		                        			A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups.
		                        		
		                        			RESULTS:
		                        			Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05).
		                        		
		                        			CONCLUSION
		                        			Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Acupuncture Therapy
		                        			;
		                        		
		                        			Sleep
		                        			;
		                        		
		                        			Acupuncture Points
		                        			;
		                        		
		                        			Down-Regulation
		                        			;
		                        		
		                        			Sleep Duration
		                        			
		                        		
		                        	
3.Deep chemical identification of phytoecdysteroids in Achyranthes bidentata Blume by UHPLC coupled with linear ion trap-Orbitrap mass spectrometry and targeted isolation.
Ying-Ying WANG ; Jia-Yuan LI ; Chang-Liang YAO ; Jian-Qing ZHANG ; Yang YU ; Shuai YAO ; Min GAO ; Shi-Fei WU ; Wen-Long WEI ; Qi-Rui BI ; De-An GUO
Chinese Journal of Natural Medicines (English Ed.) 2022;20(7):551-560
		                        		
		                        			
		                        			Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.
		                        		
		                        		
		                        		
		                        			Achyranthes/chemistry*
		                        			;
		                        		
		                        			Chromatography, High Pressure Liquid/methods*
		                        			;
		                        		
		                        			Gas Chromatography-Mass Spectrometry
		                        			;
		                        		
		                        			Mass Spectrometry
		                        			;
		                        		
		                        			Medicine, Chinese Traditional
		                        			;
		                        		
		                        			Spectrometry, Mass, Electrospray Ionization/methods*
		                        			
		                        		
		                        	
4.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
		                        		
		                        			OBJECTIVES:
		                        			To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
		                        		
		                        			METHODS:
		                        			A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
		                        		
		                        			RESULTS:
		                        			The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fetal Growth Retardation
		                        			;
		                        		
		                        			Gestational Age
		                        			;
		                        		
		                        			Hospitalization
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Infant, Newborn
		                        			;
		                        		
		                        			Infant, Premature
		                        			;
		                        		
		                        			Infant, Very Low Birth Weight
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Risk Factors
		                        			
		                        		
		                        	
5.Network Meta-analysis of acupuncture and moxibustion for allergic rhinitis.
Zhong-Ren SUN ; Cheng-Bin WANG ; Hong-Na YIN ; Yi-Xian LUAN ; Yu-Xiu LIU ; Rui-Qi GONG ; Na GONG ; Bi-Li-Ge WANG ; Chen-Xin MIAO
Chinese Acupuncture & Moxibustion 2021;41(11):1295-1302
		                        		
		                        			OBJECTIVE:
		                        			To review the therapeutic effect of acupuncture and moxibustion on allergic rhinitis based on the network Meta-analysis.
		                        		
		                        			METHODS:
		                        			The randomized controlled trials of acupuncture and moxibustion for allergic rhinitis were retrieved from the databases, starting from the date of establishment to August 17, 2020, i.e. the PubMed, EMbase, Cochrane Library, CNKI, Wanfang and VIP. The traditional Meta-analysis and network Meta-analysis were performed by RevMan5.3 and GeMTC0.14.3.
		                        		
		                        			RESULTS:
		                        			A total of 50 RCTs were included, including 4260 patients, involving 5 kinds of acupuncture and moxibustion therapies, such as acupuncture, moxibustion, acupoint application, acupoint thread-embedding and auricular point therapy.①In term of total effective rate, acupuncture, moxibustion and acupoint thread-embedding were superior to western medication and auricular point therapy (
		                        		
		                        			CONCLUSION
		                        			The therapeutic effect of acupuncture and moxibustion on allergic rhinitis is better than western medication, and acupoint thread-embedding has the best curative effect.
		                        		
		                        		
		                        		
		                        			Acupuncture
		                        			;
		                        		
		                        			Acupuncture Points
		                        			;
		                        		
		                        			Acupuncture Therapy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Moxibustion
		                        			;
		                        		
		                        			Network Meta-Analysis
		                        			;
		                        		
		                        			Rhinitis, Allergic/therapy*
		                        			
		                        		
		                        	
6.Value of α-synuclein concentration in cerebrospinal fluid in predicting postoperative delirium
Yuwei GUO ; Xiaopeng SUN ; Chunhui XIE ; Xu LIN ; Bin WANG ; Rui DONG ; Wei XU ; Mingshan WANG ; Xinjuan YU ; Yanlin BI
Chinese Journal of Anesthesiology 2021;41(3):282-286
		                        		
		                        			
		                        			Objective:To investigate the value of α-synuclein (α-syn) concentration in cerebrospinal fluid (CSF) in predicting postoperative delirium (POD).Methods:One thousand patients underwent elective surgery with combined epidural-spinal anesthesia in our hospital from January 2018 to September 2020 were selected.The epidural puncture was performed at L 3, 4 interspace, and 2 ml of CSF was collected after the needle reaching the subarachnoid space.The concentrations of α-syn, β-amyloid (Aβ)40, Aβ42, total tau protein (T-tau), and phosphorylated tau protein (P-tau) in CSF were determined by enzyme-linked immunosorbent assay.The concentrations of α-syn in CSF and occurrence of POD in patients of different ages were recorded.Patients were divided into POD group and non-POD group according to whether POD occurred, and frequency matching (1∶1) was performed based on five matching variables of age, ASA physical status, education level, duration of operation, and intraoperative blood loss. Results:Eight hundred and forty-one patients were finally included in the study, and the incidence of POD was 15.0%. There were 126 cases in POD group and 126 cases in non-POD group after matching. The concentrations of α-syn in CSF and incidence of POD were gradually increased with age ( P<0.05). Compared with non-POD group, the concentrations of α-syn, T-tau and P-tau in CSF were significantly increased, the concentrations of Aβ40 and Aβ42 were decreased, Aβ40/P-tau, Aβ42/P-tau, Aβ42/Aβ40 and P-tau/T-tau were decreased in POD group ( P<0.05). After confounding factors were corrected by logistic regression analysis, increased concentrations of α-syn, p-tau, and T-tau in CSF were risk factors for POD ( P<0.05). Increased concentrations of Aβ40 and Aβ42 in CSF and increased Aβ40/P-tau and Aβ42/P-tau were protective factors for POD ( P<0.05). Multiple linear regression analysis showed that the concentration of α-syn in CSF was negatively correlated with Aβ40 and Aβ42 concentrations and positively correlated with P-tau and T-tau concentrations ( P<0.05). The area under the receiver operating characteristic curve of concentrations of α-syn in CSF predicting POD was 0.895, Youden index was 0.664, sensitivity was 80.00%, and specificity was 86.36% ( P<0.001). Conclusion:The concentration of α-syn in CSF is related to the occurrence of POD, and it provides higher accuracy in predicting POD.
		                        		
		                        		
		                        		
		                        	
7.Establishment and verification of risk prediction model for postoperative delirium in elderly patients undergoing non-cardiac surgery
Chunhui XIE ; Yuwei GUO ; Xu LIN ; Bin WANG ; Rui DONG ; Wei XU ; Xinjuan YU ; Yanlin BI
Chinese Journal of Anesthesiology 2021;41(10):1206-1211
		                        		
		                        			
		                        			Objective:To establish the risk prediction models for postoperative delirium (POD) in elderly patients undergoing non-cardiac surgery and to evaluate the predictive efficacy.Methods:A total of 685 patients of both sexes, aged 65-90 yr, of American Society of Anesthesiologists (ASA) physical status Ⅰ-Ⅳ, who underwent non-cardiac elective surgery requiring tracheal intubation during general anesthesia in general surgery, orthopedics, urology, hepatobiliary and pancreatic surgery in our hospital from January 2020 to December 2020, were selected.Patients were assigned to the training set and validation set at a ratio of 7∶3 using a simple random sampling method.The clinical data of patients in the perioperative period were collected, and the patients were followed up within 1-7 days after operation (or before discharge), and the occurrence of POD was recorded.Univariate and multivariate logistic regression analysis was used to identify the independent risk factors for POD.The risk prediction model for POD was established based on the results of multivariate logistic regression analysis of the training set, a nomogram and receiver operating characteristic (ROC) curve were drawn, and the area under the curve (AUC) was calculated.The validation set was used to verify the prediction model and assess the efficacy of the risk prediction model for POD.Results:A total of 653 patients were enrolled in this study, 139 patients developed POD, and the incidence was 21.3%.The results of multivariate logistic regression analysis showed that advanced age, high ASA physical status classification, low preoperative Mini-Mental State Examination score, complication with diabetes mellitus, low years of education, high preoperative Pittsburgh Sleep Quality Index scale score, long anesthesia time and high numerical rating scale score after operation were independent risk factors for POD in elderly patients undergoing non-cardiac surgery.The risk prediction model for POD was established based on the independent risk factors mentioned above.The AUC of the training set was 0.981, the Youden index was 0.881, the sensitivity was 95.95%, and the specificity was 92.92%; the AUC of the validation set was 0.939, the Youden index was 0.795, the sensitivity was 94.44%, and the specificity was 85.09%.Conclusion:The risk prediction model for POD established based on age, ASA physical status classification, history of diabetes melittus, years of education, preoperative Mini-Mental State Examination score, preoperative Pittsburgh sleep quality index scale score, anesthesia time and postoperative numerical rating scale score has good predictive efficacy in elderly patients undergoing non-cardiac surgery.
		                        		
		                        		
		                        		
		                        	
8.Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.
Yuan Yue ZHU ; Rui Zhi ZHENG ; Gui Xia WANG ; Li CHEN ; Li Xin SHI ; Qing SU ; Min XU ; Yu XU ; Yu Hong CHEN ; Xue Feng YU ; Li YAN ; Tian Ge WANG ; Zhi Yun ZHAO ; Gui Jun QIN ; Qin WAN ; Gang CHEN ; Zheng Nan GAO ; Fei Xia SHEN ; Zuo Jie LUO ; Ying Fen QIN ; Ya Nan HUO ; Qiang LI ; Zhen YE ; Yin Fei ZHANG ; Chao LIU ; You Min WANG ; Sheng Li WU ; Tao YANG ; Hua Cong DENG ; Jia Jun ZHAO ; Lu Lu CHEN ; Yi Ming MU ; Xu Lei TANG ; Ru Ying HU ; Wei Qing WANG ; Guang NING ; Mian LI ; Jie Li LU ; Yu Fang BI
Biomedical and Environmental Sciences 2021;34(1):9-18
		                        		
		                        			Objective:
		                        			The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.
		                        		
		                        			Methods:
		                        			The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.
		                        		
		                        			Results:
		                        			A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).
		                        		
		                        			Conclusion
		                        			An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Blood Glucose/analysis*
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Diabetes Mellitus/blood*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Glucose Tolerance Test
		                        			;
		                        		
		                        			Glycated Hemoglobin A/analysis*
		                        			;
		                        		
		                        			Glycemic Index
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Uric Acid/blood*
		                        			
		                        		
		                        	
9.A study of LEF1 protein expression in diagnosis and differential diagnosis of lymphoblastic lymphoma/acute lymphoblastic leukemia
Xue CHEN ; Weiwei RUI ; Ke BI ; Yunjin WU ; Suxia ZHANG ; Long ZHANG ; Jie YU ; Bing XIU ; Xianghua YI ; Yu ZENG
Chinese Journal of Pathology 2021;50(3):207-212
		                        		
		                        			
		                        			Objective:To evaluate the expression of LEF1 protein in lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and small B-cell lymphomas, and its value in pathologic diagnosis and differential diagnosis of LBL/ALL.Methods:53 cases of LBL/ALL were collected at shanghai Tongji Hospital from January 2012 to December 2019. The protein expression of LEF1 and TdT was detected by immunohistochemistry in 53 paraffin-embedded tissue samples of LBL/ALL. The specificity and sensitivity of LEF1 and TdT in the diagnosis of LBL/ALL were compared. The expression of LEF1 protein in 77 cases of small B-cell lymphomas including chronic lymphocytic leukemia/small lymphoid lymphoma (CLL/SLL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma was studied. The correlation between LEF1 expression and overall survival (OS) and progression-free survival (PFS) was performed by univariate analysis.Results:The expression of LEF1 in LBL/ALL was 100% (53/53), the median value was 90%; the expression of TdT was 84.9% (T-LBL/ALL 78.1%, B-LBL/ALL 95.2%), the median value was 80%; the expression rate and median value of LEF1 and TdT were significantly different ( P=0.008 and 0.001 respectively). The expression of LEF1 in CLL/SLL was 14/18, the median value was 45%; LEF1 was not expressed in follicular lymphoma (0/16), mantle cell lymphoma (0/16), marginal zone lymphoma (0/19), and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma (0/8). LEF1 expression was significantly different between B-LBL/ALL and small B-cell lymphomas. The median follow-up time of LBL/ALL cases in this group was 16 months. There was no statistical difference between LEF1 expression and the OS and PFS in LBL/ALL patients. Conclusions:Immunohistochemical staining of LEF1 has high sensitivity and good specificity in the diagnosis of LBL/ALL, and its combination with TdT can improve the diagnostic rate of LBL/ALL.
		                        		
		                        		
		                        		
		                        	
10.Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial.
Jia-Bo WANG ; Zhong-Xia WANG ; Jing JING ; Peng ZHAO ; Jing-Hui DONG ; Yong-Feng ZHOU ; Guang YANG ; Ming NIU ; Xu ZHAO ; Tian-Jun JIANG ; Jing-Feng BI ; Zhe XU ; Ping ZHANG ; Dan WU ; Zhao-Fang BAI ; Yu-Ming GUO ; Si-Miao YU ; Yong-Qiang SUN ; Zi-Teng ZHANG ; Xiao-Yan ZHAN ; Peng-Yan LI ; Jin-Biao DING ; Peng-Fei ZHAO ; Xue-Ai SONG ; Jian-Yuan TANG ; Dong-Chu HE ; Zhu CHEN ; En-Qiang QIN ; Rui-Lin WANG ; Xiao-He XIAO
Chinese journal of integrative medicine 2020;26(9):648-655
		                        		
		                        			OBJECTIVES:
		                        			To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.
		                        		
		                        			METHODS:
		                        			A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.
		                        		
		                        			RESULTS:
		                        			An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).
		                        		
		                        			CONCLUSIONS
		                        			Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
		                        		
		                        		
		                        		
		                        			Administration, Inhalation
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Coronavirus Infections
		                        			;
		                        		
		                        			diagnosis
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			mortality
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Drug Administration Schedule
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Follow-Up Studies
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Integrative Medicine
		                        			;
		                        		
		                        			Interferon-alpha
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Lopinavir
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Pandemics
		                        			;
		                        		
		                        			Pneumonia, Viral
		                        			;
		                        		
		                        			diagnosis
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			mortality
		                        			;
		                        		
		                        			Risk Assessment
		                        			;
		                        		
		                        			Severe Acute Respiratory Syndrome
		                        			;
		                        		
		                        			diagnosis
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			mortality
		                        			;
		                        		
		                        			Severity of Illness Index
		                        			;
		                        		
		                        			Survival Rate
		                        			
		                        		
		                        	
            
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