Objective To use direct dilution method to pretreat human urine, and to determine 19 elements in human urine using inductively coupled plasma mass spectrometry, and to evaluate the uncertainty of the entire experimental process. Methods The relevant mathematical models were established according to JJF 10591-2012 ^“Evaluation and Expression of Measurement Uncertainty^” and CNAS-GL006 ^“Guidance for Evaluation of Uncertainty in Chemical Analysis^”. Taking molybdenum as an example, the uncertainty sources in the determination of 19 elements in human urine by inductively coupled plasma method were analyzed and evaluated, including sample pretreatment, sample repeated measurement, standard solution preparation and standard curve fitting. Results The extended uncertainty of molybdenum in human urine is 2.12μg/L, and the measurement result of molybdenum is (44.8±2.12)μg/L. The measurement result of 19 elements in human urine ranges from less than the detection limit to 601μg/L, and the extended uncertainty range is 0.38~33.6μg/L.Conclusion It was found from the calculation that the uncertainty of the determination result was mainly affected by the uncertainty of the sample repeated measurement and the standard curve fitting. By adjusting the range of standard curve and increasing the number of parallel sample measurement, the uncertainty was reduced and the quality of detection was improved.

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

The clinical manifestations of colorectal polyps are consistent with the characteristics of dampness, stickiness and heaviness. The TCM constitutions in the prone population are mostly related to dampness. The pathological changes of intestinal flora imbalance, intestinal micro inflammation, neuroendocrine immune network and abnormal aquaporin in colorectal polyps are consistent with the research results of modern mechanism of dampness pathogen. This article believed that the TCM pathogenesis of colorectal polyps caused by damp pathogen is the accumulation of spleen deficiency and dampness caused by improper diet, poor emotion and other factors, and the interweaving of various diseases and pathogens to form tangible foreign bodies. According to the pathogenic characteristics of damp pathogen and the pathogenic factors of colorectal polyps, the influence of damp pathogen on the pathogenesis of colorectal polyps was discussed, in order to provide an effective TCM theoretical basis for the diagnosis and treatment of colorectal polyps in clinic.

Based on the theory of "mutual interference of clear and turbid Qi" in Huangdi Neijing（《黄帝内经》）， this study explored the pathogenesis of spleen and stomach diseases and the therapeutic effects of Banxia Xiexintang on them. It suggested that "mutual interference of clear and turbid Qi" represents a pathological state of Yin and Yang disturbance and imbalance in Qi circulation due to the mixture of clear and turbid Qi， which can elucidate the pathogenesis of spleen and stomach diseases. According to this theory， the pathogenesis of spleen and stomach diseases was summarized as Qi disorder in spleen and stomach， disharmony between Ying Qi and Wei Qi， and conflict between cold and heat. Banxia Xiexintang， as a crucial prescription for treating spleen and stomach diseases， achieves its therapeutic effects by dispersing stagnation with pungent flavor， descending adverse Qi with bitterness， regulating Ying Qi and Wei Qi， and harmonizing cold and heat. By regulating Qi circulation， balancing internal and external factors， and addressing deficiency and excess， it can rectify the pathological state of "mutual interference of clear and turbid Qi" of spleen and stomach diseases. Modern research reveals that Banxia Xiexintang can modulate gastrointestinal motility， restore mucosal immune barrier function of the digestive system， and exhibit optimal therapeutic effects when combined with both cold-cool and warm-hot medicines， aligning with its therapeutic role under the theory of "mutual interference of clear and turbid Qi". By delving into the essence of the "mutual interference of clear and turbid Qi" theory and exploring the pathogenesis of spleen and stomach diseases and the therapeutic effects of Banxia Xiexintang based on this theory， this study further elucidated the inherent connection between spleen and stomach diseases and the "mutual interference of clear and turbid Qi" theory， offering insights and theoretical references for the clinical diagnosis and treatment of spleen and stomach diseases.

Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.

Objective:To explore the application effects of the goal-oriented teaching method based on mind mapping in the teaching of stomatology practical courses.Methods:From September 2022 to September 2023, 52 fourth-year students of clinical stomatology at Harbin Medical University were divided into test group and control group for practical teaching, with 26 cases in each group. The test group received goal-oriented teaching based on mind mapping, while the control group received traditional teaching, for 20 class hours in both groups. The two groups were compared in terms of general data, theoretical and practical assessment scores, the score of the self-rating scale of self-directed learning (SRSSDL) and the score of critical thinking disposition inventory-Chinese version (CTDI-CV) before and after training, and student satisfaction with teaching activities. SPSS 25.0 software was used to perform the t-test or χ2 test. Results:After completing the practical training courses, the test group showed significantly higher scores than the control group in multiple-choice questions [(16.85±1.39) vs. (15.33±2.21)], fill-in-the-blank questions [(17.21±1.98) vs. (16.01±2.02)], short answer questions [(17.47±2.27) vs. (15.23±2.45)], case analysis [(34.36±2.79) vs. (32.57±3.02)], and practical assessment [(84.69±4.73) vs. (80.57±4.21)] (all P<0.05). The SRSSDL score and CTDI-CV score were improved in both groups, and were significantly higher in the test group [(215.29±10.42) and (357.49±17.80)] than in the control group [(200.23±11.42) and (342.23±17.26)] (both P<0.05). The students of the test group were significantly more satisfied with teaching activities than those of the control group ( P<0.05). Conclusions:Compared with the traditional teaching method, the goal-oriented teaching method based on mind mapping is more effective in stomatology practical teaching, which can improve students' self-directed learning ability and critical thinking ability, promote their mastery of theoretical knowledge, enhance their clinical practice ability, and increase their satisfaction with teaching activities.

Objective:To examine the effects of Zishenwan Prescription on bile acid metabolism in mice with diabetic encephalopathy; To explore its mechanism of improvement of diabetic encephalopathy.Methods:Male C57BL/6J mice were used to replicate the mouse model of type 2 diabetes mellitus by using high-fat chow and a single intraperitoneal injection of streptozotocin (120 mg/kg). The mice were screened for diabetic encephalopathy by using the Morris water maze test after 8 weeks of continuous stimulation with hyperglycemia, and were divided into model group and Zishenwan Prescription group according to random number table method, with 12 mice in each group. The mice in the Zishenwan Prescription group were treated with the crude extract of Zishenwan Prescription (9.36 g/kg) by gavage, and the normal group and the model group were treated with the same volume of distilled water once a day for 8 weeks. At the end of the treatment, Morris water maze test was used to investigate the cognitive function of diabetic encephalopathy mice; cresyl violet staining was used to detect the number of granule neurons in the hippocampus; serum and feces were collected to detect the content of bile acids by liquid-liquid coupling; hepatic bile acid synthase CYP7a1 and CYP27a1, farnesol X receptor (FXR), fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), and ileocecal apical sodium-dependent bile acid transporter protein (ABST) mRNA levels were detected by using fluorescence quantitative PCR assay.Results:Compared with the model group, mice in the Zishenwan Prescription group had shorter evasion latency time ( P<0.05 or P<0.01), decreased time to first reach the platform ( P<0.01), increased number of times to traverse the platform ( P<0.01), and reduced neuronal cell damage in hippocampal area; mice in the Zishenwan Prescription group showed decreased serum and fecal total bile acid content ( P<0.05 or P<0.01); the liver CYP7a1 and CYP27a1 mRNA expressions increased ( P<0.01), and FXR and FGF15 mRNA expressions decreased ( P<0.01); ileal ABST mRNA expression decreased ( P<0.01). Conclusion:Zishenwan Prescription may regulate bile acid metabolism, inhibit FRX-FGF15/FGFR4 signaling and ABST expression to promote new bile acid synthesis and conjugated bile acid reabsorption, and thus improve cognitive function in diabetic encephalopathy mice.

Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.

Objective To investigate the effects of atorvastatin calcium on thyroid function, immune response and C-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway in rats with hypothyroidism. Methods A total of 30 healthy adult male SD rats were randomly divided into control group, hypothyroid group (PTU group) and atorvastatin calcium treatment group (ACT group), with 10 rats in each group. Rats in the PTU group and the ACT group were injected with PTU subcutaneously at the dorsum of the neck every day for 28 consecutive days; instead of PTU, rats in the control group were injected subcutaneously with 0.3 mL of saline. After 2 weeks of PTU treatment, rats in the ACT group were gavaged with 3 mL of atorvastatin calcium saline solution (containing 5 mg/kg of atorvastatin calcium), which was administered once daily; the control group was gavaged with an equal amount of saline in the same way. The body weight, food intake and water intake of rats were measured weekly. The histopathological changes of the thyroid gland were observed in histopathological sections of rats in each group. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), interferon γ (IFN-γ) and interleukin-4 (IL-4) in serum; quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression levels of IFN-γ, IL-10, Foxp3 and IL-4; western blot was performed to determine the levels of p-JNK/JNK and p-p38/p38 MAPK. Results Compared with control group, PTU-induced hypothyroidism rats showed a significant decrease in body mass and food and water consumption (P < 0.05). After 2 weeks of treatment with atorvastatin calcium, the body mass loss of PTU rats was inhibited, food and water consumption was improved, and the differences were statistically significant (P < 0.05). Atorvastatin calcium was able to significantly increase the serum T3 and T4 levels and decrease the serum TSH level in hypothyroid rats (P < 0.05). Atorvastatin calcium treatment was able to significantly alleviate histopathological changes such as follicular cell proliferation and related hypertrophy induced by PTU, and increase follicular size (P < 0.05). After treatment with atorvastatin calcium, the spleen mass of PTU rats increased significantly, and the expression of IFN-γ mRNA in hypothyroid rats decreased significantly, but the expression levels of IL-10 mRNA, Foxp3 mRNA and IL-4 mRNA increased significantly (P < 0.05). After treatment with atorvastatin calcium, the levels of p-JNK/JNK and p-p38/p38 MAPK in thyroid tissue of hypothyroid rats decreased significantly (P < 0.05). Conclusion Atorvastatin calcium treatment for hypothyroidism has the function of promoting the normalization of thyroid hormone imbalance, balancing Th1/Th2 cytokines, and inhibiting the activation of JNK/p38 MAPK signaling pathway.

L-asparaginase (L-ASN) is widely applied in the treatment of malignant tumor and low-acrylamide food production, however, the low expression level hampers its application. Heterologous expression is an effective strategy to increase the expression level of target enzymes, and Bacillus is generally used as the host for efficient production of enzymes. In this study, the expression level of L-asparaginase in Bacillus was enhanced through optimization of expression element and host. Firstly, five signal peptides (SP_SacC, SP_AmyL, SP_AprE, SP_YwbN and SP_WapA) were screened, among which SP_SacC showed the best performance, reaching an activity of 157.61 U/mL. Subsequently, four strong promoters (P43, P_ykzA-P43, P_Ubay and P_bacA) from Bacillus were screened, and tandem promoter P_ykzA-P43 showed the highest yield of L-asparaginase, which was 52.94% higher than that of control strain. Finally, three Bacillus expression hosts (B. licheniformis Δ0F3 and BL10, B. subtilis WB800) were investigated, and the maximum L-asparaginase activity, 438.3 U/mL, was reached by B. licheniformis BL10, which was an 81.83% increase compared with that of the control. This is also the highest level of L-asparaginase in shake flask reported to date. Taken together, this study constructed a B. licheniformis strain BL10/P_ykzA-P43-SP_SacC-ansZ capable of efficiently producing L-asparaginase, which laid the foundation for industrial production of L-asparaginase.
Bacillus licheniformis/metabolism* ; Asparaginase/genetics* ; Bacillus/genetics* ; Protein Sorting Signals ; Promoter Regions, Genetic/genetics* ; Bacillus subtilis/genetics* ; Bacterial Proteins