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.

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.

Background Welders' exposure to welding fumes with multiple metals leads to decreased pulmonary function. Previous studies have focused on single metal exposure, while giving little attention to the impact of metal mixtures. Objective To assess the association between metal levels in urine and blood of welders and pulmonary function indicators, and to identify key metals for occupational health risk assessment. Methods Questionnaire surveys, lung function tests, urine and blood sampling were conducted among welders and control workers in a shipyard in Shanghai. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 12 metals such as vanadium, chromium, and manganese in urine and blood. Spearman correlation was applied to analyze the correlations between the metals in urine and blood. Multiple linear regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were used to analyze the relationships between mixed metal exposure and pulmonary function parameters, such as forced vital capacity (FVC), forced vital capacity as a percentage of predicted value (FVC%), forced expiratory volume in the first second (FEV₁), forced expiratory volume in the first second as a percentage of predicted value (FEV₁%), and forced expiratory volume in the first second/forced vital capacity (FEV₁/FVC). Results This study enrolled 445 subjects, including 322 welders (72.36%) and 123 controls (27.64%). The mean age of the 445 participants was (37.64±8.80) years, and 87.19% participants were male. The welders had significantly higher levels of urinary cadmium (0.88 vs 0.58 μg·L⁻¹), blood chromium (5.86 vs 5.06 μg·L⁻¹), and blood manganese (24.24 vs 21.38 μg·L⁻¹) than the controls (P<0.05). The Spearman correlation coefficients between the metals in urine and blood ranged from −0.46 to 0.68. After adjustment for confounders, the multiple linear regression indicted that the urine molybdenum of the welders was negatively correlated with FVC and FEV₁. There were also negative correlations between the molybdenum in blood and FVC, FVC%, FEV₁, and FEV₁%, and between the copper in blood and FEV₁/FVC. The WQS model showed that FEV₁ and FVC decreased by 0.112 L and 0.353 L with each quartile increase of metal mixture concentrations in urine and blood among the welders respectively, and the leading contributors were copper, zinc, vanadium, and antimony. The BKMR model showed a negative overall effect of metal mixtures in urine and blood among the welders on FVC, FVC%, FEV₁, and FEV₁%, and the univariate exposure response-relationship between the molybdenum concentration in urine or blood and FVC, FVC%, FEV₁, or FEV₁% had an approximately linear decreasing trend. Meanwhile, there may be an interaction of cadmium with manganese, nickel, or vanadium, and an interaction of vanadium with iron, molybdenum, zinc, or copper, when different metals in urine among the welders interacted with FEV₁%. Conclusion Exposure to multiple metals in welders leads to a decline in lung function, with molybdenum, antimony, copper, and zinc as the leading contributors.

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 evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

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.

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.

Objective To investigate the risk factors for clinically relevant postoperative pancreatic fistula(CR-POPF)after pancreaticoduodenectomy(PD),and to establish a predictive model for early identification of CR-POPF.Methods A total of 244 patients who underwent PD in General Hospital of Northern Theater Command from January 2019 to October 2023 were collected,and based on strict inclusion and exclusion criteria,179 patients were finally enrolled in this study.According to the presence or absence of CR-POPF,these patients were divided into non-CR-POPF group with 120 patients and CR-POPF group with 59 patients.Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for CR-POPF,and a nomogram model was established based on such factors.The receiver operating characteristic(ROC)curve was used to assess the predictive performance of the model,the calibration curve was used to evaluate the calibration degree of the model,and the clinical decision curve and the clinical impact curve were used to analyze and validate the clinical application value of the model.The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups.Results Among the 179 patients,59(33.0%)developed CR-POPF.The multivariate Logistic regression analysis showed that alanine aminotransferase/aspartate aminotransferase(odds ratio[OR]=2.221,P=0.004),main pancreatic duct diameter(OR=0.276,P=0.022),the distance between the peritoneum and the anterior pancreatic neck(OR=1.034,P=0.027),and extracellular volume fraction(OR=0.001,P=0.005)were independent risk factors for CR-POPF.Based on the above four independent risk factors,a nomogram was established to predict CR-POPF after PD,with an area under the ROC curve of 0.837,a sensitivity of 0.932,and a specificity of 0.725.The decision curve and the clinical impact curve also showed that the nomogram had good clinical practicability.Conclusion Preoperative clinical indicators combined with multi-phase CT have a good performance in predicting CR-POPF after PD,which can be used to early identify patients at high risk of pancreatic fistula before surgery and provide further guidance for clinical work.

Objective:To analyze and summarize the trends and hot spots in the field of neurological damage caused by electric welding operations, and to provide ideas for new researches by searching the domestic and international literature.Methods:In December 2022, using Web of Science Citation Index (Web of Science), China Journal Full-Text Database (CNKI) and Wanfang Database as search databases, literature search was conducted on the Chinese and English search terms related to eletrical welding operations and neurological damage. The bibliometric analysis software VOSviewer 1.6.18 and CiteSpace 6.1.6 were used to visualize the publication year, publication quantity, country, research institution and key words of the literature.Results:A total of 309 articles (112 in Chinese and 197 in English) were included in this study. The first domestic and international papers were published in 1976 and 1994 respectively, and the number of papers reached the peak in 2006 and 2018, and then showed a downward trend to varying degrees. In China, Shandong First Medical University (including Shandong Institute of Occupational Health and Occupational Disease Prevention and Shandong Academy of Medical Sciences) and Wuhan University of Science and Technology had the largest number of publications. The 309 articles were from 52 Chinese journals and 86 English journals. The co-occurrence analysis of key words showed that the domestic research mainly focused on eletrical welding operation, welding workers, neurobehavioral function and manganese, and the nervous system damage caused by manganese in welding smoke was the field of international attention. Long term exposure, risk, and performance were key buzzwords in the field.Conclusion:The research focus in the field of nervous system damage caused by electric welding operation has an obvious trend of time evolution, gradually transiting from clinical manifestations to its toxic mechanism and early biomarkers.