ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Objective To observe the therapeutic effects and mechanism of Xiezhuo Qutong Formula on gout.Methods(1)Animal experiments:A hyperuricemia(HUA)model was established in SD rats using hypoxanthine combined with potassium oxonate,and an acute gouty arthritis(AGA)model was induced by monosodium urate.The efficacy and safety of Xiezhuo Qutong Formula in reducing serum uric acid levels and exerting anti-inflammatory effects were evaluated.(2)Network pharmacology:The main active components and potential targets of Xiezhuo Qutong Formula were collected,along with gout-related disease targets.The intersection of these targets yielded potential therapeutic targets.A protein-protein interaction(PPI)network was constructed,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Xiezhuo Qutong Formula effectively reduced serum uric acid levels in HUA model rats without observed hepatorenal toxicity.It also decreased joint inflammation index,joint swelling degree,and inflammatory cytokine levels in AGA model rats.Network pharmacology analysis identified 156 overlapping targets between the drug and disease,among which TP53,STAT3,PIK3CA,BCL2,PIK3CD,PIK3CB,JUN,HDAC1,ESR1,and RELA may be key targets of Xiezhuo Qutong Formula in treating gout.Combined with GO and KEGG enrichment analyses,the main involved pathways include PI3K/AKT,JAK2/STAT3,and NF-κB signaling pathways.Conclusion Xiezhuo Qutong Formula exerts uric acid-lowering and anti-inflammatory effects in the treatment of gout,and its potential mechanism involves the PI3K/AKT,JAK2/STAT3,and NF-κB signaling pathways.

OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.

OBJECTIVE To investigate the monitoring of tacrolimus blood concentration in patients with nephrotic syndrome （NS），and to establish a prediction model for tacrolimus blood concentration. METHODS Data from 509 concentration monitoring sessions of 166 NS patients using tacrolimus were collected from January 1， 2020 to August 31， 2023 in Zhongshan Hospital Affiliated to Xiamen University. The relationship of efficacy and adverse drug reaction（ADR） with blood concentration was analyzed. A multilayer perceptron （MLP） prediction model was established by using the blood concentration monitoring data of 302 times from 109 NS patients with genetic information， and then verified. RESULTS In terms of efficacy， the median blood concentration of tacrolimus in the non-remission group was 2.20 ng/mL， which was significantly lower than that in the partial remission group （4.00 ng/mL， P＜0.001） and the complete remission group （3.60 ng/mL， P＝0.002）. In terms of ADR， the median blood concentration of tacrolimus in the ADR group was 5.01 ng/mL， which was significantly higher than that in the non-ADR group （3.37 ng/mL） （P＝0.001）. According to the subgroup analysis of the receiver operating characteristic curve， when the blood concentration of tacrolimus was ≥6.65 ng/mL， patients were more likely to develop elevated blood creatinine [area under the curve （AUC） was 0.764， P＜0.001）； when the blood concentration of tacrolimus was ≥6.55 ng/mL， patients were more likely to develop blood glucose （AUC＝0.615， P＝ 0.005）. The established MLP prediction model has a loss function of 0.9， with an average absolute error of 0.279 5 ng/mL between the predicted and measured values. The determination coefficient of the validation scatter plot was 0.984， indicating an excellent predictive performance of the model. CONCLUSION Tacrolimus blood concentration has an impact on both efficacy and ADR in NS patients. The use of the MLP model for predicting blood concentration exhibits high accuracy with minimal error between predicted and measured values. The model can be used as an important tool in clinical individualized medication regimens.

OBJECTIVE To correctly identify and deal with the adverse drug reaction as pancytopenia caused by isavuconazonium and to provide reference for the safe use of isavuconazonium. METHODS Clinical pharmacists analyzed a case of severe infection and renal insufficiency who experienced pancytopenia after using isavuconazonium. Clinical pharmacists screened the drugs used during hospitalization and evaluated the relationship between this adverse drug reaction and isavuconazonium， as well as the possible mechanisms， based on the half-life of the drugs and relevant literature. RESULTS & CONCLUSIONS The relationship between pancytopenia and isavuconazonium was assessed as “possibly related”. When using isavuconazonium， attention should be paid to avoiding the combination of drugs with the same mechanism or potential interaction. For patients who have a course of treatment for more than 2 weeks， have hematological abnormalities or complicated with liver and renal insufficiency， or should use it combined with other drug with same mechanism， it may be considered to increase the frequency of blood routine monitoring.

Objective To analyze the management and countermeasures of adverse nursing events in a municipal tertiary hospital in Guangxi Zhuang Autonomous Region.Methods The adverse nursing events in 2023 in a municipal tertiary hospital in Guangxi were retrospectively analyzed.Logistic regression analysis was utilized to identify the causes of these adverse events and propose suitable countermeasures.Results In 2023,a total of 121 adverse nursing events were recorded,with falls being the most prominent(42 cases,accounting for 34.71％),followed by drug extravasation,drug safety incidents and unplanned ex-tubation,accounting for 13.22％,9.92％,and 7.44％respectively.Logistic regression analysis revealed that factors such as age ≥70 years,coexisting diseases,Basel Index score ≤40,pain score ≥4,tube slip risk assessment ≥10,RASS sedation score ≥3,NGASR score ≥9,lost risk assessment score ≥ 7,GCS Coma Scale score ≤8,Stress Injury Assessment Scale score ≤10,and Morse score ≥45 were associated with the risk of adverse nursing events.In addition,inadequate awareness of nursing risks among nursing staff,ineffective patient health education methods,and non-compliance to nursing protocols were identified as primary causes of adverse nursing events.Conclusion Advanced age,combined with other diseases,and hospitali-zation scale assessment results are critical factors for adverse nursing events.Lack of nursing responsibility and risk awareness among nursing staff,inadequate system implementation,and irregular operations can increase the risk.Hospitals should optimize management systems and work processes,enhance nursing staff training,and develop targeted preventive measures for adverse nursing events to improve the quality of nursing management and reduce the risk of adverse nursing events.

Objective:To analyze the changes and clinical significance of homocysteine (Hcy), folate, and cardiac enzyme levels in patients with alcohol dependence and depression.Methods:A total of 102 patients with alcohol dependence and depression, who received treatment at Wenzhou Seventh People's Hospital from January 2022 to June 2023, were included in the observation group. The degree of alcohol dependence in patients in the observation group was assessed using the Michigan Alcoholism Screening Test (MAST). According to the assessment results, the patients in the observation group were divided into the following subgroups: mild alcohol dependence ( n = 33), moderate alcohol dependence ( n = 37), heavy alcohol dependence ( n = 15), and severe alcohol dependence ( n = 17). The severity of depression among patients in the observation group was assessed with the Hamilton Depression Scale (HAMD). Based on the assessment results, the patients in the observation group were divided into the following subgroups: mild depression ( n = 43), moderate depression ( n = 34), and severe depression ( n = 25). The cognitive function of patients in the observation group was assessed using the Montreal Cognitive Assessment Scale (MoCA). According to the assessment results, the patients in the observation group were divided into normal cognitive function ( n = 73) and cognitive impairment ( n = 29) subgroups. Thirty healthy volunteers from our hospital during the same period were included in the control group. The levels of Hcy, folate, and cardiac enzymes were compared among all groups. The correlations between Hcy, folate, and cardiac enzyme levels with HAMD, MoCA, and MAST scores were analyzed using the Pearson method. Results:The Hcy level in the observation group was (15.21 ± 1.99) μg/L, which was significantly higher than that in the control group [(11.38 ± 1.46) μg/L, t = -9.80, P < 0.001]. The levels of folate, lactate dehydrogenase (LDH), and creatine kinase (CK) in the observation group were (4.82 ± 1.77) μg/L, (122.69 ± 33.98) IU/L, and (87.83 ± 16.52) IU/L, respectively, which were significantly lower than those in the control group [(6.27 ± 1.35) μg/L, (150.56 ± 38.78) IU/L, (98.67 ± 20.29) IU/L, t = 4.16, 3.82, 2.99, all P < 0.05]. The Hcy levels in the mild , moderate, heavy, and severe alcohol dependence subgroups [(13.16 ± 1.23) μg/L, (15.35 ± 0.82) μg/L, (16.79 ± 1.38) μg/L, (17.63 ± 1.22) μg/L] increased sequentially, while the folate levels [(6.11 ± 1.51) μg/L, (4.95 ± 1.40) μg/L, (4.04 ± 0.99) μg/L, (2.70 ± 0.99) μg/L], LDH levels [(153.35 ± 27.47) IU/L, (123.29 ± 16.59) IU/L, (109.83 ± 14.41) IU/L, (73.24 ± 16.86) IU/L], and CK levels [(104.14 ± 12.78) IU/L, (86.48 ± 9.15) IU/L, (78.11 ± 7.85) IU/L, (67.71 ± 9.00) IU/L] decreased sequentially. These differences in Hcy, folate, LDH, and CK levels among the mild, moderate, heavy, and severe alcohol dependence subgroups were statistically significant ( F = 73.24, 26.53, 59.08, 53.86, all P < 0.001). The Hcy levels in the mild, moderate, and severe depression subgroups [(13.75 ± 1.54) μg/L, (15.46 ± 1.17) μg/L, (17.39 ± 1.31) μg/L] increased progressively, while the folate levels [(5.83 ± 1.77) μg/L, (4.67 ± 1.12) μg/L, (3.28 ± 1.26) μg/L], LDH levels [(138.09 ± 33.67) IU/L, (119.73 ± 26.39) IU/L, (100.24 ± 30.88) IU/L], and CK levels [(96.35 ± 15.24) IU/L, (86.73 ± 15.62) IU/L, (74.69 ± 9.71) IU/L] decreased progressively. The differenes in Hcy, folate , LDH, and CK levels among the four depression subgroups were statistically significant ( F = 56.57, 24.36, 12.23, 18.44, all P < 0.001). The Hcy levels in the cognitive impairment group [(17.01 ± 1.63) μg/L] was significantly higher than that in the normal cognitive function group [(14.50 ± 1.64) μg/L, t = -6.97, P < 0.001), and the folate, LDH, and CK levels in the cognitive impairment group were (3.76 ± 1.78) μg/L, (102.71 ± 31.08) IU/L, and (76.00 ± 13.37) IU/L respectively, which were significantly lower than those in the normal cognitive function group [(5.24 ± 1.58) μg/L, (130.63 ± 31.92) IU/L, (92.52 ± 15.31) IU/L, t = 4.11, 4.01, 5.09, all P < 0.001]. Hcy levels were positively correlated with HAMD and MAST scores ( r = 0.854, 0.846, both P < 0.05) and negatively correlated with MoCA scores ( r = -0.648, P < 0.001). Folate, LDH, and CK levels were negatively correlated with HAMD and MAST scores ( r = -0.644, -0.701; r = -0.551, -0.696; r = -0.505, -0.673; all P < 0.001), and they were positively correlated with MoCA scores ( r = 0.514, 0.436, 0.448, all P < 0.001). Conclusion:In patients with alcohol dependence and depression, abnormal levels of Hcy, folate, and cardiac enzymes were observed. These indicators were found to be associated with the severity of alcohol dependence, the level of depression, and cognitive function.

Objective:To evaluate the adjuvant role of the eCura scoring system in selecting appropriate treatment strategies after non-curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) patients.Methods:The clinicopathological data of 110 EGC patients who underwent non-curative ESD at Fujian Provincial Hospital from January 2015 to June 2019 were retrospectively analyzed. According to the eCura score, patients were divided into three lymph node metastasis (LNM) risk groups: low-risk group (79 cases), middle-risk group (22 cases), and high-risk group (9 cases). The receiver operator characteristic (ROC) curve analysis was used to test the diagnostic efficacy of eCura scoring system in predicting LNM. Logistic regression analysis was used to explore the influence of risk stratification of eCura scoring system on LNM. Kaplan-Meier method was used to evaluate cancer survival rate, which was then compared with log-rank test.Results:Thirty-five patients underwent additional standard surgery after ESD, including 22 in the low-risk group, 8 in the middle-risk group, and 5 in the high-risk group. Among them, 5 cases had LNM, including 1 case in the low-risk group and the middle-risk group respectively and 3 cases in the high-risk group. The area under the ROC curve was 0.857 (95% CI: 0.697-0.952, P=0.001), and when the cut-off value of the eCura score was set at 3, the Yuden index reached the maximum value of 0.7, with the corresponding sensitivity and specificity of 80% and 90%, respectively. Logistic regression analysis showed that the probability of LNM in the middle-risk group was about 3.00 times (95% CI: 0.17-54.57, P=0.458) as high as that in the low-risk group, and the probability of LNM in the high-risk group was about 31.50 times (95% CI: 2.14-463.14, P=0.012) of that in the low-risk group. The follow-up time was 12 to 58 months, and the median follow-up time was 40 months. There were 10 cases of recurrence, including 4 cases in the low-risk group, 3 cases in the middle-risk group and 3 cases in the high-risk group, of which 2 cases in the low-risk group were from those of additional standard surgery after ESD, and the remaining 8 cases were from those who did not receive additional standard surgery after ESD. Kaplan-Meier survival curve analysis showed that the survival rate of patients with additional surgery in the low-risk group was similar to that of patients without ( P=0.319), and the survival rate of patients with additional surgery in the middle-risk group was also similar to that of patients without ( P=0.296). The survival rate of patients with additional surgery in the high-risk group was significantly higher than that of those without ( P=0.013). Conclusion:The eCura scoring system can assist the selection of treatment strategies after non-curative resection of EGC, and can accurately predict the risk of subsequent LNM and recurrence. Close follow-up may be an acceptable option for patients with low risk of LNM, and additional standard surgical treatment may be more conducive to improving the prognosis in patients with high risk of LNM.

Objective:To evaluate type B2 vessels for predicting the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) under narrow band imaging-magnifying endoscopy (NBI-ME), and to analyse the influencing factors of over-prediction and under-prediction.Methods:A total of 86 SESCC patients with 86 lesions confirmed by postoperative pathology, who underwent NBI-ME to evaluate the invasion depth of esophageal tumor and were observed for type B2 vessels in Department of Digestive Endoscopy of Fujian Provincial Hospital from January 2015 to April 2020, were included in the case-control study. According to the postoperative pathological results, the patients were divided into the correct prediction group ( n=25) and the wrong prediction group ( n=61), and the accuracy of prediction was calculated. The wrong prediction group was further divided into the over-prediction group ( n=49) and the under-prediction group ( n=12) to find the influencing factors of over-prediction and under-prediction, respectively. Further, multivariate Logistic analysis was performed to explore the independent influential factors for the prediction. Results:The accuracy of type B2 vessels under NBI-ME for predicting the invasion depth of SESCC was only 29.07% (25/86), and the over-prediction rate and under-prediction rates were 56.98% (49/86) and 13.95% (12/86), respectively. Univariate analysis showed that the classification of type B2 area ( χ2=36.25, P<0.001), the distinct endoscopic features (nodules, thickening and obvious depression, χ2=22.90, P<0.001), and inflammation around type B2 vessels ( χ2=9.54, P=0.004) were related to the over-prediction of the invasion depth of SESCC, and the distinct endoscopic features were related to the under-prediction of the invasion depth ( P=0.016). Multivariate Logistic regression analysis showed that B2-narrow (type B2 area ≤5 mm) ( P<0.001, OR=241.988,95% CI:15.229-3 845.252) and inflammation around type B2 vessels ( P=0.033, OR=12.801, 95% CI: 1.226-133.713) were independent risk factors for over-predicting the invasion depth of SESCC, while the distinct endoscopic features were independent protective factors for over-prediction ( P<0.001, OR=0.012, 95% CI: 0.001-0.150). The distinct endoscopic feature was an independent risk factor for under-predicting invasion depth of SESCC with type B2 vessels ( P=0.027, OR=7.899, 95% CI: 1.259-49.565). Conclusion:The accuracy of predicting the invasion depth of SESCC is low only based on type B2 vessels in NBI-ME, and over-prediction is prone to occur. B2-narrow, inflammation around type B2 vessels and without nodules, thickening and obvious depression are closely related to the over-prediction of invasion depth of SESCC by type B2 in NBI-ME, and nodules, thickening and obvious depression are closely associated with the under-prediction. However, whether the combined assessment of type B2 vessels under NBI-ME and endoscopic manifestation can improve the accuracy of prediction needs to be confirmed by further studies.