Objective:To investigate the effects of Wumei-Fangfeng drug on Treg/Th17 immune balance in allergic rhinitis(AR)mice via regulating MMP9 derived from mast cell exosomes.Methods:Potential targets of Wumei and Fangfeng were screened,and the intersection was taken from the targets and AR risk genes,subsequently GO analysis and protein-protein interaction analysis were performed to screen therapeutic targets.AR mice model were constructed,mast cells and exosomes were separate from femurs of mice.Wumei-Fangfeng drug and exosomes were used to treat mice.The behavioral scores of mice in each group were evaluated,mRNA expressions of Foxp3,RORγt were detected in nasal mucosa of mice.After knocking down of MMP9 in exosomes,the behavioral score,Foxp3 and RORγt mRNA expressions were observed in AR mice.Results:Bioinformatics results showed that Wumei-Fangfeng drug may act on AR by mast cell exosomes derived IL-1β and MMP9.Compared with normal mice,mRNA expression of Foxp3 in AR mice was decreased,while RORγt mRNA expression was increased,and MMP9 expression was increased(all P<0.05).Expression of Foxp3 mRNA was increased,and expressions of RORγt and MMP9 were decreased in AR mice treated with Wumei-Fangfeng drug,however,mast cell exosomes could further counteract the effects of Wumei-Fangfeng drug,and the effects of mast cell exosomes was weakened after MMP9 knockdown.Conclusion:Wumei-Fangfeng drug regulates the imbalance of Treg/Th17 in AR mice by inhibiting the exosomal MMP9 of bone marrow-derived mast cells.

Objective:To evaluate the clinical effectiveness and safety of Jiuwei-Zhuhuang San plus amoxilcillin sodium and sulbactam sodium in the treatment of bacterial pneumonia in children. Methods:A total of 120 patients with bacterial pneumonia in children from 1 year to 14 years old were randomly divided into the study group ( n=90) and the control group ( n=30) with ratio 3 to 1, the random sequence created by SAS software. Both groups were treated with amoxilcillin sodium for basic treatment, the observation group was treated with Jiuwei-Zhuhuang San. Both groups were treated for 1 week and followed up for 1 week. The cough frequency, clinical effective rate, symptoms and signs score, Traditonal Chinese medicine (TCM) pattern scores and adverse event rate were observed. Results:Eighteen cases were dropped and eliminated in the observation group, and 4 cases were dropped and eliminated in the control group, so 72 of observation group and 26 of control group were analyzed. After treatment, the clinical effective rate of the observation group was 27.8% (20/72), and the control group was 0% (0/26), where the difference was significant ( χ2=7.445, P=0.006). The difference of TCM syndrome score before and after treatment in the observation group (-16.8 ± 8.2 vs. -11.0 ± 5.8, t=-3.858) was lower than that of the control group ( P<0.01). There was significant difference between the two groups ( Z=-2.347, P= 0.019) in the TCM syndrome. The cough frequency of the observation group was 41.7% (30/72), and the control group was 26.9% (7/26). There wasn’t any significant differences in the cough frequency between two groups ( P>0.05). There was no statistical difference in symptoms and signs score or adverse event rate between two groups ( P>0.05). Conclusion:On the basis of amoxicillin sodium and sulbactam sodium, combined use of Jiuwei-Zhuhuang San can improve the clinical effectiveness of children with bacterial pneumonia.

ObjectiveThis study aims to understand the recognition of practitioners in traditional Chinese medicine （TCM） hospitals on hospital-based health technology assessment （HB-HTA）， assessment needs， challenges， and suggestions， so as to provide references for the future work. MethodThe convenient sampling method was adopted to survey the relevant practitioners in TCM hospitals. The questionnaire included 39 questions in 4 dimensions and was distributed through the online platform Weijuanxing. ResultA total of 244 questionnaires were recovered， and the obtained data were analyzed in SPSS. The results showed that 137 practitioners were very familiar with HB-HTA and there was no significant difference in the recognition of practitioners in different occupations （F=0.251； P=0.778）. The practitioners in Hong Kong， Macao， and Taiwan had lower recognition than those in other regions. In terms of the assessment needs， 127 practitioners believed that it was very necessary to carry out HB-HTA in TCM hospitals in the future. Chinese patent medicines/Chinese herbal medicine decoction pieces （5.91） and TCM appropriate technology （5.57） had higher assessment priority scores. The assessment needs were high for the effectiveness （235 practitioners） and safety （224 practitioners） of health technology. The lack of specialized organization and standardized evaluation process system and the shortage of talents were considered to be the major challenges for the future development in this field. ConclusionThe stakeholders carrying out the health technology assessment in TCM hospitals had certain awareness of HB-HTA. Most practitioners believed that it was necessary to carry out HB-HTA in TCM hospitals in the future， while the work might face challenges such as the lack of organizations and system and the shortage of talents， which requires policy support.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years， randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine （TCM）， but the quality of the implementation of blind methods is uneven， and the evaluation criteria have not yet been formed. In this paper， the data collection methods， calculation principles， advantages， and disadvantages of two quantitative quality evaluation methods of blind methods， namely James Blinding Index （JBI） and Bang Blinding Index （BBI）， were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time， a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally， the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.