[This corrects the article DOI: 10.1016/j.apsb.2021.10.012.].

Objective:To establish a general method for the simultaneous determination of hydroxyphenyl esters and quaternary ammonium bacteriostatic agents in eye drops.Methods:The chromatographic analysis was per-formed on an Agilent C18 column(4.6 mm ×250 mm,5 μm)with 1％triethylamine solution(pH adjusted to 5.0 with phosphoric acid)as mobile phase A and methanol as mobile phase B.Gradient elution was performed at col-umn temperature of 40 ℃.The detection wavelength was 214 nm,the flow rate was 1 mL·min-1,and the injec-tion volume was 20 μL.Results:Methylparaben,ethylparaben,propylparaben,butylparaben,benzalkonium chlo-ride and benzalkonium bromide were 0.11-559.0,0.10-513.0,0.10-258.8,0.11-270.5,1.07-537.0 and 1.03-512.8 μg·mL-1,respectively.The linear range was good(r＞0.999).The average recoveries of meth-ylparaben,benzalkonium bromide and benzalkonium chloride were 104.7％(RSD=1.3％),102.6％(RSD=1.1％)and 100.9％(RSD=1.1％),respectively.The contents of bacteriostatic agent in 100 batches of eye drops from 36 varieties of 12 enterprises were determined,and the accurate results were obtained.Conclusion:This meth-od provides a reference for the content quality control and safety evaluation of bacteriostatic agents in eye drops.

Objective:To investigate the specific method, efficacy and safety of intrathecal baclofen (ITB) in the treatment of moderate and severe spasticity.Methods:The clinical features, response to ITB trial, clinical outcomes and treatment-related complications after baclofen pump implantation surgery were retrospectively analyzed in patients with moderate to severe spasticity who received ITB treatment in Hong Kong University Shenzhen Hospital from August 2022 to August 2023.Results:The study included 22 patients with moderate to severe spasticity, of whom 18 patients (81.8%) were effective in ITB trial. For these patients with effective trial, the lowest mean Modified Ashworth Scale (MAS) score of lower extremity muscle groups after ITB bolus injection was decreased significantly compared with the baseline mean value before injection (1.29±0.81 vs 3.31±1.18 , t=11.364, P<0.001), and the M/H amplitude ratio of soleus H-reflex at 4 hours after ITB bolus injection was significantly higher than the baseline value (9.61±4.66 vs 3.83±2.69, t=7.780, P<0.001). Among the 18 patients with effective ITB trial, 10 patients received baclofen pump implantation surgery with the informed consent of the patients or their guardians. Compared with the 8 patients without surgery, the baseline mean MAS score of lower extremity muscle groups of the 10 patients who received surgery was higher (3.71±1.06 vs 2.83±1.16, F=5.645, P<0.05), the maximum reduction of mean MAS score of lower extremity muscle groups of the 10 patients who received surgery was greater (2.61±0.99 vs 1.30±0.64, F=20.696, P<0.001). In 10 patients who received baclofen pump implantation surgery, the mean MAS score of lower limb muscle groups was significantly decreased in the first and sixth months after surgery compared with the baseline mean value before surgery (1.64±0.91, 1.16±0.89 and 3.71±1.06, F=39.946, P<0.001). Among them, 2 patients were followed up to 12 months after surgery, 2 patients were followed up to 18 months after surgery, and the mean MAS score of their lower limb muscle groups showed continuous improvement, and 1 patient with cerebral palsy combined with lower urinary tract hyperactive syndrome also showed significant improvement of urgent urinary incontinence after surgery. Up to the last follow-up, the daily dose of baclofen in 10 patients receiving baclofen pump implantation was (143.60±96.24) μg, and no treatment-related complications occurred. Conclusions:ITB can effectively relieve spasticity symptoms and other related neurological dysfunction in patients with moderate and severe spasticity, and the efficacy can be maintained for a long time, and treatment-related complications are rare. Preoperative ITB trial is helpful to screen out patients more suitable for baclofen pump implantation. Patients with higher grade of spasticity at baseline and better efficacy of ITB trial are more suitable for baclofen pump implantation. The soleus H reflex can effectively reflect the change of stretch reflex of lower limb muscle groups in patients with spasticity treated by ITB, and can be used to evaluate the treatment effect of ITB.

Objective:To analyze the potential biomarkers of kidney yang deficiency, kidney yin deficiency, and stasis and water stagnation in diabetic nephropathies (DN) using hydrogen nuclear magnetic resonance ( 1H-NMR)-based technology; To provide a test basis for the TCM diagnosis and typing of DN from the molecular biology point of view. Methods:This is a case-control study. Totally 90 patients with DN Ⅲ-Ⅳ in the second ward of Nephrology Department of Shanxi Integrated Traditional and Western Medicine Hospitalwere selected from November 2022 to May 2023, and were divided into the kidney yang deficiency group, the kidney yin deficiency group, and the stasis and water stagnation group based on TCM syndrome types, with 30 cases in each group; 30 healthy medical checkups were selected as the healthy control group. Urine samples were taken from each group for case-control study, and the samples were examined by 1H-NMR technology. The data were preprocessed to obtain the relevant data matrix and qualitative identification of metabolites, and multivariate statistical analyses were performed to clarify the differences between the samples and screen the metabolites that contributed to the grouping, and the key pathways were analyzed. Results:Through metabolomics technology combined with multivariate statistical analysis, a total of 12 potential biomarkers in the urine of patients with DN kidney yang deficiency were screened out, involving 6 major metabolic pathways; 15 potential biomarkers in the urine of patients with kidney yin deficiency were screened out, involving 6 major metabolic pathways; and 7 potential biomarkers in the urine of patients with stasis and water stagnation were screened out, involving 5 major metabolic pathways. Among them, glyoxylate and dicarboxylic acid metabolism, and glycine, serine and threonine metabolism were the metabolic pathways commonly involved in the three groups of syndrome types.Conclusion:There are differences among patients with kidney yang deficiency, kidney yin deficiency, and stasis and water stagnation in DN, and the discovery of potential biomarkers can provide an objective basis and reference value for TCM diagnosis of DN.

Objective:To evaluate the effect of imatinib on the endotoxemia-induced acute lung injury in mice.Methods:Sixty SPF male, 8-12 weeks, C57BL/6 mice were randomly (random) divided into 4 groups ( n=15 each): control group (group C), imatinib group (groupⅠ), endotoxemia group (group LPS) and imatinib + endotoxemia group (group I+LPS). The endotoxemia model of acute lung injury was established. After 24 hours, the mice were sacrificed. The pathological changes of lung tissues were evaluated, the lung injury scores were calculated, and the wet/dry ratios of lung tissues were measured. ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum. Detection kits were used to analyze the levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in lung tissues; The expression levels of phosphorylated nuclear factor-kappa B (p-NF-κB), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in lung tissues were analyzed by western blotting. Results:Compared with the group C, the wet/dry (W/D) ratio of lungs [(3.47±0.41) vs. (5.58±0.47)], lung injury scores [(1.25±0.89) vs. (10.25±1.75)], and the levels of TNF-α and IL-6 in serum increased in the group LPS ( P<0.05). The levels of SOD, CAT, GSH and GSH/GSSG decreased, the level of MDA increased, and the expression of p-NF-κB, Nrf2 and HO-1 protein up-regulated ( P<0.05). Compared with the LPS group, the W/D ratio of lungs [(5.58±0.47) vs.(4.62±0.38)] and lung injury scores [(10.25±1.75) vs. (7.00±1.31)] in the I+LPS group decreased ( P<0.05), and the levels of TNF-α and IL-6 in the serum decreased ( P<0.05). In lung tissues, the levels of SOD, CAT, GSH and GSH/GSSG increased (all P<0.05), the level of MDA decreased (all P<0.05), the expression of p-NF-κB protein decreased, and the expression of Nrf2 and HO-1 protein increased ( P<0.05). Conclusions:Imatinib improves sepsis-induced acute lung injury in mice, and the mechanism of actions behind may be related to the inhibition of oxidative stress.

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

Objective:To explore the diagnostic value of the toxicant and drug detection in clinical poisoning diseases and analyze the clinical characteristics of patients with positive poison test.Methods:This study was a multicenter retrospective cohort study. Sampling and clinical information data were collected between October 1, 2020 and September 30, 2022 from 41 tertiary hospitals in and around Jiangsu province. The clinical characteristics of patients with positive toxicology tests were analyzed, and the correlation between the drug sampling situation and the test results was analyzed..Results:A total of 895 patients with clinical diagnosis or suspected poisoning were enrolled in this study. Among them, 652 patients had positive results, accounting for 72.85%. Among all positive patients, 506 patients were exposed to a single poison and 147 patients were exposed to multiple poisons. The top three poisons were pesticide herbicides (202 cases, 30.98%), sedative and psychotropic drugs (151 cases, 23.16%), and pesticide insecticides (97 cases, 14.88%). Among 541 patients with clear exposure history, the positive rate was 78.19%, and among 354 patients with unclear exposure history, the positive rate was 64.69%. The top three poisons (drugs) of patients with unclear exposure history were sedative and psychotropic (82, 12.58%), herbicide (26, 3.99%), and rodenticide (22, 3.37%). Patients who admitted to hospital for unexplained consciousness disorder, abnormal blood coagulation function and multiple organ dysfunction were more likely to obtain positive poison test results.Conclusions:There is uncertainty in the exposure history of poisoning diseases, so it is necessary to improve the detection of toxic substances as soon as possible. Toxicant testing should be considered when patients have impaired consciousness, abnormal coagulation function and multiple organ dysfunction.

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.

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.