OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules， and determine the contents of 12 chemical components. METHODS Identification and content determination were performed by using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1% formic acid solution （gradient elution）； the electrospray ion source was used to scan in the positive ion multi-reaction detection mode. The mass charge ratio （m/z） 631.3→546.4， 631.3→921.4 was the detection ion pair for tortoiseshell glue， and the m/z 765.4→554.0， 765.4→733.0 was the detection ion pair for antler glue. The determination method for 12 chemical components was as follows： Accucore C18 column， methanol-0.1% formic acid as mobile phase （gradient elution）； scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode. RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min， respectively； the linear relationship of 12 chemical components was good within their respective concentration ranges， such as astragaloside Ⅳ， calycosin-7-O-β-D-glucoside， calycosin， chlorogenic acid， ferulic acid， betaine， amygdalin， rutin， hydroxysafflor yellow A， hyperoside， loganin， cyasterone （r＞0.999）； RSDs for precision， stability （24 h） and reproducibility tests were all less than 5%. The average sample recovery rates ranged from 98.04% to 101.08%. The average contents of 12 components were 1.83， 25.73， 13.76，56.71， 23.80， 49.82， 807.49， 15.01， 317.02， 60.21， 202.71 and 17.70 μg/g， respectively. CONCLUSIONS In this study， tortoiseshell glue and antler glue in Qixiong zuogui granules are identified， and the contents of 12 chemical components therein are determined. This provides a reference for the quality control of this granule.

OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

Objective: To investigate the doseresponse relationship between the risk of elevated blood pressure and body mass index (BMI) in primary and secondary school students in Shibei District, Qingdao, so as to provide a reference for precise interventions of elevated blood pressure. Methods: Statistical analysis was conducted on the health examination data of 92 091 primary and secondary school students in Shibei District, Qingdao, in 2022. Overweight and obesity were assessed using the standards from the Screening for Overweight and Obesity among Schoolaged Children and Adolescents, and blood pressure levels were evaluated using the Reference of Screening for Elevated Blood Pressure among Children and Adolescents Aged 7-18 Years. The relationship between BMI and elevated blood pressure was examined using analysis of variance, Chisquare test, multifactorial Logistic regression, and a combination of restricted cubic spline after data cleaning. Results: Based on the standardized scores under different age and gender, BMI was classified into 5 categories. Compared with the group of BMIZ scores 0-<1, the risk of developing high blood pressure gradually decreased with BMIZ scores (OR=0.55, 0.53, P<0.05). Conversely, the risk of developing high blood pressure increased with increasing BMIZ scores (OR=1.90, 3.71, P<0.05). Stratified analyses showed that BMI was positively associated with elevated blood pressure by gender (male, female), age (aged 7-8, 9-11, 12-14, 15-16), and waisttohip ratio (≤0.83, >0.83) (OR=1.18, 1.19, 1.15, 1.22, 1.19, 1.18, 1.19, 1.18, P<0.01). There were multiplicative interactions between BMI and gender, between BMI and age, between BMI and waisttohip ratio (OR=1.53, 1.08, 2.31, P<0.01). Restricted cubic spline analysis showed that as BMI levels increased, the risk of developing elevated blood pressure showed a nonlinear increasing trend in both the 7yearold and the 10 to 16yearold (χ2=27.56, 10.69, 6.10, 27.26, 18.32, 25.71, 10.53, 6.14, P<0.05). Conclusions The risk of elevated blood pressure in primary and secondary school students increases with BMI, showing a nonlinear doseresponse relationship. The blood pressure should be monitored regularly, and comprehensive and effective measures should be implemented to control elevated blood pressure in children and adolescents.

Objective:To compare the feasibility and safety of a new portable endoscopic system and the conventional endoscopic system for the detection and emergency treatment of abdominal trauma in animal models.Methods:Three healthy Bama pigs, which were fasted and water deprivation for 8 h before surgery and then underwent induction anesthesia. A layer-by-layer incision was made into the abdominal cavity of Bama pigs. An artificial pneumoperitoneum was established using a laparoscopic pneumoperitoneum machine. A bullet model was inserted into the abdominal cavity to build the bullet wound model. After the bullet model was removed, a shrapnel model was inserted into the mid-abdomen to build the shrapnel wound model. The two types of endoscopic system were used to detect, remove bullet model or shrapnel model of the three Bama pigs respectively. The procedure order of the two systems was assigned according to the random number table method. The surgical success, operation time, endoscopy pipeline patency, endoscopic operation satisfaction, adverse events and equipment defects were recorded.Results:Three surgeries were performed using the new portable endoscopic system and three other surgeries using the conventional endoscopic system, all of which were successful. The time of the new portable endoscopic system to find and remove the bullet model, and the shrapnel model were 232.33±11.68 s, 300.33±57.70 s, 170.00±44.44 s and 52.67±2.52 s, respectively. The corresponding time of the conventional endoscopic system were 232.67±21.20 s ( t=-0.054, P=0.962), 256.67±67.00 s ( t=0.880, P=0.472), 176.00±52.42 s ( t=-0.111, P=0.922), 58.67±14.84 s ( t=-0.832, P=0.493), respectively. There was no significant difference between the two systems ( P>0.05). The endoscopy tubes of the two endoscopic systems were both smooth. The operator was satisfied with the endoscopic procedures of both endoscopic systems, and no adverse event or device defect occurred. Conclusion:The portable endoscopic system proves to be safe and feasible for the diagnosis and treatment of abdominal trauma in animal models.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

ObjectiveTo investigate the effects of thyme herbal tea （BLX） on the proliferation of human coronavirus OC43 （HCoV-OC43） in vitro and in vivo. MethodThe chemical composition of BLX was analyzed by UPLC-MS. The cytotoxicity of BLX in HRT-18 cells and the effect of BLX treatment on the proliferation of HCoV-OC43 in cells were analyzed. Copies of viral gene were detected by real-time PCR. The effect of BLX treatment on the life cycle of HCoV-OC43 was detected by time-of-addition assay. The maximum tolerated dose of BLX and the influences of BLX on the body weight and survival time of suckling mice infected with HCoV-OC43 were determined. The expression of viral protein in the brain and lung tissue was analyzed by immunohistochemistry. ResultThere were 11 chemical components identified in BLX by UPLC-MS. BLX showed the 50% cytotoxic concentration （CC₅₀） of （13 859.56±319） mg·L^-1， the median inhibitory concentration （IC₅₀） of （1 439.09±200） mg·L^-1， and the selection index of 8.26-11.44 for HCoV-OC43 in HRT-18 cells. Compared with the cells infected with HCoV-OC43， BLX at the concentrations of 1 500， 1 000， 500 mg·L^-1 inhibited the proliferation of this virus （P<0.05， P<0.01）. BLX exhibited antiviral effect in the early stage of virus infection， and the inhibition role in the attachment stage was more significant than that in the entry stage （P<0.05）. In the suckling mice infected with HCoV-OC43， BLX at 1200 and 600 mg·kg^-1·d^-1 alleviated the symptoms， prolonged the survival period， reduced the death rate， and down-regulated the mRNA level of nucleocapsid protein in the mice. Moreover， BLX at 1 200 mg·kg^-1·d^-1 down-regulated the expression of nucleocapsid protein in the brain （P<0.01） and the lung （P<0.01）. ConclusionBLX contained multiple antiviral ingredients. It inhibited the proliferation of HCoV-OC43 both in vitro and in vivo by interference with viral attachment. This study provides theoretical reference for the treatment of acute respiratory tract infection with HCoV-OC43 and for further development and application of BLX.

OBJECTIVE To establish a clinical pharmaceutical pathway of anti-infective therapy for high-risk populations of antibiotic-associated encephalopathy （AAE）， and analyze its application effects. METHODS Clinical pharmacists developed the “AAE High-Risk Population Screening Form” and “Antibiotic AAE Risk Comparison Form” based on literature and expert opinions， and established the “Clinical Pharmaceutical Pathway of Anti-infective Treatment for AAE High-Risk Population” in our hospital. A prospective， non-randomized controlled study was conducted from May 2023 to April 2024， including 50 cases in the observation group and 50 cases in the control group among patients with pulmonary infections admitted to the Dept. of Internal Medicine in our hospital. The observation group was involved in the development of an anti-infective treatment following the clinical pharmaceutical pathway by clinical pharmacists， while the control group received routine anti-infective treatment by clinical physicians. The occurrence of AAE， the rational antibiotic drug use， and the effectiveness of initial anti-infective treatment in the two groups were observed， and the intervention measures and outcomes of AAE cases were summarized. RESULTS The anti-infective treatment clinical pharmaceutical pathway for AAE high-risk population was preliminarily established in our hospital. The analysis of the application effects showed that there was 1 case of AAE in the observation group and 8 cases in the control group， with a significantly lower incidence of AAE in the observation group than in the control group； the rational antibiotic drug use and the effectiveness of initial anti-infective treatment in the observation group were both significantly superior to those in the control group （P＜0.05）. Drug withdrawal and dressing change were the preferred effective intervention measures for AAE， and encephalopathy treatment drugs could be used as auxiliary measures for symptom relief. Timely and effective intervention was conducive to rapid symptom relief， with a total improvement rate of AAE of 88.89%. CONCLUSIONS The anti-infective treatment clinical pharmaceutical pathway for AAE high-risk population can effectively prevent the occurrence of AAE as well as contribute to promoting rational drug use and the effectiveness of initial anti-infection plans and strengthening treatment outcomes.

Background In vitro-in vivo extrapolation (IVIVE) is an approach utilizing in vitro experimental data to predict in vivo phenomena. It is a promising tool for chemical risk assessment. Objective To learn the hotspots, evolution path, and trend of IVIVE in risk assessment by literature search and bibliometric analysis, and provide reference and data support for subsequent research. Methods PubMed and Web of Science Core Collection were selected as foreign databases to search for literature about IVIVE applied in risk assessment published by December 31, 2023. The number of relevant documents in CNKI and Wanfang database was too small, so the Chinese databases were not included in this study. This study employed bibilometric analysis using VOSviewer and CiteSpace for visualizing networks categorized by author, institution, country, journal, keyword, and co-citation. Results A total of 189 articles were included in this study. The first article was published in 2006, and since then the number of publications overall showed an upward trend and increased significantly after 2016. The institution with the most publications was the United States Environmental Protection Agency (28 articles). The United States was the most productive country (87 articles), and had a close cooperation with the United Kingdom. The journal with the most publications and the highest number of citations per article was Archives of Toxicology (19 articles). The keyword co-occurrence analysis suggested that research on IVIVE in risk assessment mainly studied the methods and models of IVIVE and prediction of chemical toxicity, and toxicity, in vitro, and models were the research hotspots in this field. Keyword timeline cluster analysis suggested that the assessment objects gradually expanded from drugs to environmental chemicals, organic chemicals and food additives. The co-citation analysis suggested that articles about IVIVE in risk assessment mostly cited journals in the environment, food, and drug fields, and these articles were mainly methodological studies followed by literature reviews. Conclusion The research of IVIVE in risk assessment has developed rapidly. With the improvement of prediction models and the expansion of application scope, animal experiments in risk assessment may be greatly reduced and the efficiency of risk assessment can be increased. At present, the United States has a leading position in this field, while China has few relevant studies and needs to actively carry out international cooperation to improve the level of applied research of IVIVE. In the future, it is hoped that the IVIVE method can be further refined to improve its application and expand its research fields.

Objective:To analyze the influencing factors related to the prognosis of delayed replantation of avulsed permanent teeth.Methods:A retrospective study was conducted on the clinical data of 35 patients with 38 affected teeth underwent delayed replantation of permanent teeth.According to the prognosis after 12 to 108 months of follow-up,the replantation results of the cases were divided into-success,survival and failure groups.Survival curves were plotted using Kaplan-Meier method,Log-Rank test was used for univariate analysis,and Cox proportional risk regression models were used for multivariate analysis to assess the effects of gender,age,degree of tooth development,mode of tooth preservation and mode of endodontic treatment on the survival rate of replanted teeth.Results:Of the 38 replanted teeth,3 were successful,28 remained and 10 failed.The 9-year cumulative survival rate of the replanted teeth was 34.7％.The results showed that there were no statistically significant differences in the survival rate of the replanted teeth in the groups with different sex,age,degree of tooth development and the mode of preservation of avulsed teeth(P＞0.05).There were statistically significant differences in the cumulative survival rate of the replanted teeth among the groups with different endodontic treatment(P＜0.01),which showed that the cumulative survival rate in the root canal filling group＞continuous root canal sealing group＞pulp preserva-tion treatment group.Conclusion:For the delayed replantation of avulsed premanent teeth,survival prognosis of the teeth treated with pulp preservation is poor,early pulp extraction and root canal filling are recommended.

Objective: To investigate the recessive infection rate of healthy children and guardians in different epidemic periods of hand, foot and mouth disease (HFMD) in Qingdao, analyze the risk factors affecting recessive infection, so as to provide the basis for HFMD prevention and control. Methods: In the nonepidemic period of 2022, the random cluster sampling method was used to selected 546 children and guardians from 4 childcare institutions in Laoshan District and Pingdu City. In the epidemic period of 2023, 690 children and guardians were selected from 6 childcare institutions in Shibei District, Laoshan District and Pingdu District. A questionnair survey was conducted in the epidemic period. Logistic regression analysis was used to analyze the factors affecting the recessive infection. Dominance analysis was used to explore the relative importance of the risk factors affecting recessive infection. Results: The results showed that the recessive infection rates of healthy children and guardians in the epidemic period were 18.84% and 13.62%, respectively; the recessive infection rates were 9.09% and 4.44% in the nonepidemic period, respectively. The results of multivariate Logistic analysis showed that rural areas (OR=4.71, 95%CI=2.57-8.61) and recessive infection of guardians (OR=18.62, 95%CI=7.45-46.56) were positively correlated with recessive infection of HFMD in healthy children (P<0.05). Washing hands (OR=0.09, 95%CI=0.04-0.20), using towels alone (OR=0.17, 95%CI=0.07-0.40), and EV71 vaccination (OR=0.42, 95%CI=0.20-0.87) were negatively correlated with recessive infection of HFMD in healthy children (P<0.05). Public toilets (OR=3.02, 95%CI=1.50-6.09) and drying bedding once per quarter (OR=3.89, 95%CI=1.75-8.68) were positively correlated with recessive infection of HFMD in healthy guardians. Housing with good lighting (OR=0.31, 95%CI=0.12-0.79), and tableware disinfection (OR=0.31, 95%CI=0.15-0.65) were negatively correlated with recessive infection of HFMD in healthy guardians (P<0.05). The results showed that recessive infection of guardians was relatively the most important for healthy children (41.51%), and tableware disinfection was relatively the most important for recessive infection of guardians (28.87%). Conclusions The recessive infections of HFMD are common among healthy populations in Qingdao, and the recessive infection rate among children during the epidemic period is relatively higher. Guardians play an important role in the recessive infection of healthy children. Therefore, healthy education should be strengthened for key populations, especially to enhance parents awareness of prevention and control to reduce the occurrence of recessive infections of hand, foot and mouth disease in children and guardians.