ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker（QAMS） based on linear calibration using two reference substances（LCTRS）， explore the consistency between Hedyotis Herba dispensing granules and standard decoction， and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography（HPLC） specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules， and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C₁₈ columns， taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds， the retention times of the other 5 characteristic peaks were predicted and validated. Based on this， QAMS was developed to determine the contents of four components（deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid， and p-coumaric acid）. Then， the relative correction factors of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds， and each component was quantified accordingly. Finally， the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction， consistency of the specific chromatograms， contents and transfer rates of the indicator components as indexes， and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules， and four of them were identified by reference standards， namely deacetyl asperulosidic acid（peak 1）， deacetyl asperulosidic acid methyl ester（peak 3）， asperulosidic acid（peak 6） and p-coumaric acid（peak 7）. The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%， the contents of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid and p-coumaric acid were 6.62-19.70， 3.83-17.99， 1.57-6.69， 1.62-4.52 mg·g^-1， and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%， 34.03%-62.24%， 24.25%-43.70%， and 40.58%-73.71%， respectively. The extract rate， index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules（P1-P3）， produced by manufacturer A， were similar to those of the standard decoction prepared from the same batch of decoction pieces， and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules（P4-P10） from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield， consistency of specific chromatograms， contents and transfer rates of the four index components， the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction， indicating that the current production process is relatively reasonable.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.

Objective:To evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on tourniquet-induced hypertension (TIH) in the patients undergoing anterior cruciate ligament reconstruction.Methods:Seventy-four patients of either sex, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification I or II, with body mass index of 18-30 kg/m 2, undergoing elective anterior cruciate ligament reconstruction under general anesthesia combined with preoperative femoral nerve block, were divided into 2 groups ( n=37 each) using a random number table method: sham stimulation group (group SS) and group taVNS. Group SS received stimulation on the ear lobe and the tail of the helix of the left ear. Group taVNS received stimulation on the cymba concha and the earlobe of the left ear. Both groups received stimulation from 1 h before induction of anesthesia until the end of the procedure (frequency of 30 Hz, pulse width of 300 μs, and amplitude of the strongest current that could be tolerated by the patient in the absence of pain). The tourniquet inflation pressure was 280 mmHg, with an inflation time of 60-90 min. Systolic blood pressure, diastolic blood pressure and heart rate were recorded before tourniquet inflation to assess the development of intraoperative TIH. The consumption of intraoperative propofol, remifentanil, nitroglycerin, esmolol, norepinephrine and atropine was recorded, and the occurrence of postoperative nausea and vomiting, skin itching and headache and dizziness was also recorded. Results:Compared with group SS, the incidence of TIH and the number of patients used nitroglycerin were significantly reduced ( P<0.05), and no significant changes were found in the other parameters in group taVNS ( P>0.05). Conclusions:taVNS can decrease the occurrence of TIH in the patients undergoing anterior cruciate ligament reconstruction.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

BACKGROUND:Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth,which has a good application prospect in the treatment of bone diseases.However,how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE:To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS:Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate,and the labeling results were detected by fluorescence imaging and UV spectral scanning.Successfully labeled Cornus cervi Colla was injected into mice by gavage,and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy,and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager.The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy.Samples were taken from serum and bone at the time of the strongest fluorescence,and gel electrophoresis was carried out on serum and bone tissue protein solutions,and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION:The fluorescent markers were successfully separated by dextran gel chromatography,and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful,and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%.The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours.The fluorescence images of mice at different times were the same as those of bilateral femur and tibia,indicating that Cornus cervi Colla could play a role by entering the bone.Compared with UniProt database,secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin.It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role.