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.

To report a case of onychocytic carcinoma in China. A 76-year-old female patient presented with a subnail mass on her left thumb for 3 years. Skin examination showed thickening of the left thumb plate whose surface was partially yellow and black in color, slight curving of the distal plate, obvious telangiectasia under the nail plate, and verrucous hyperplasia under the nail plate and at the lateral edge of the nail plate. Histopathological examination showed that the tumor grew and infiltrated downward in clumps, with obvious keratosis and necrosis in the center of the mass, and many "squamous vortex" structures, atypical cells, and pathological mitotic figures could be seen. Immunohistochemical study revealed that HK31 and HK85 were positively expressed in the squamous vortex region, K6/K16 was positively expressed in the basal part of the tumor, and HK75 was strongly expressed in the whole tumor region. The diagnosis of onychocytic carcinoma was confirmed. The patient received surgical excision combined with 3 sessions of photodynamic therapy, and no recurrence was observed during 18 months of follow-up.

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 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 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 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

Objective: To analyze the prevalence and changing trend of overweight and obesity among high school seniors in Beijing from 2009 to 2018, and to provide scientific basis for health and education departments to work out effective measures to prevent and control overweight and obesity among adolescents. Methods: The physical examination data of 700 588 high school seniors in Beijing from 2009 to 2018 were selected to describe the distribution characteristics of the detection rate of overweight and obesity, and to analyze whether there are differences in the prevalence of overweight and obesity among different genders and regions. Results: From 2009 to 2018, the prevalence rate of total overweight and obesity of high school seniors in Beijing showed an increasing trend by year ( χ 2=3.58, P <0.01). After 2016, the rising trend was more stable, and it declined for the first time in 2018. The prevalence of overweight ( χ 2=6 681.34, P <0.01) and obesity ( χ 2=15 663.08, P <0.01) were higher in male than in female. The prevalence of overweight and obesity in urban students was higher than that in suburban students (29.55%,27.95%; χ 2=211.43, P < 0.01 ), the prevalence of obesity in urban students was higher than that in suburban students from 2009 to 2013, and the prevalence of obesity in suburban students was higher than that in urban students from 2014 to 2018. The districts and counties with the highest detection rates of overweight and obesity are Shijingshan District (overweight: 19.06%, obesity: 13.99%), and the districts and counties with the lowest detection rates of overweight and obesity are Yanqing District (overweight: 13.48%, obesity: 7.18%). Conclusion From 2009 to 2018, the prevalence of overweight and obesity among high school seniors in Beijing has been increasing by year, and tends to be stable after 2016. Significant upward trend in obesity prevalence in suburban areas of Beijing has been observed.

OBJECTIVE：To investigate the clini cal features of thrombocytopenia induced by antidepressants ，and to provide reference for the rational use of clinical drugs. METHODS ：Retrieved from CNKI ，Wanfang database ，VIP，PubMed and Web of Science，during Jan. 1st in 1985 to Aug. 31st in 2020，case reports about antidepressants-induced thrombocytopenia was collected and analyzed descriptively in terms of demographic characteristics ，medication，clinical manifestations ，treatment and outcome. RESULTS：A total of 17 literatures were retrieved ，and 19 patients were included ，involving 10 male and 9 female，aged from 5 to 95 years old ，with an average of （48±24）years old. Nine kinds of drugs were involved ，including 4 cases of escitalopram ，3 cases of citalopram ，3 cases of fluoxetine ，3 cases of mirtazapine ，2 cases of amitriptyline ，1 case of sertraline ，1 case of paroxetine，1 case of mianserin and 1 case of imipramine. There were 9 cases of single drug and 10 cases of drug combination. All 19 patients suffered from thrombocytopenia at 3 d-10 years after medication ，14 of them had hemorrhage tendency. Main clinical manifestations included mucocutaneous hemorrhage ，gingival bleeding ，black stool ，hematochezia，vaginal bleeding ，ocular hemorrhage，alveolar hemorrhage. No bleeding was found in 5 cases. After drug withdrawal/changing drugs and other symptomatic treatment， platelet count of 19 patients recovered to normal ， and bleeding symptoms disappeared. CONCLUSIONS ： Thrombocytopenia caused by antidepressants has no obvious clinical features and is not easy to be found ，but it may lead to severe； bleeding symptoms if it is not found in time. The changes of platelet count should be closely monitored in clinical application of such drugs to ensure the safety of drug use.