OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE To prepare Gambogic acid （GA） nanocapsules （GA-LNCs） and Neogambogic acid （NGA） nanocapsules（NGA-LNCs），and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ，medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ，GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ，the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs （1.92 and 2.42 mg/kg respectively ）were given intragastrically ，once a day ，for consecutive 6 weeks. The fasting blood glucose of mice ，the activities of superoxide dismutase （SOD）and glutathione peroxidase （GSH-Px），the contents of malondialdehyde （MDA），total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol （LDL-C）were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60％ water，10％ medium-chain triglyceride ，30％ polyethylene glycol monostearate （total amount of the three was 2 g）and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were （92.01±0.68）％ and（93.12±2.11）％；the drug-loading amount were （0.99±0.21）％ and（1.21±0.22）％， respectively. GA-LNCs and NGA-LNCs were yellow ，homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape ， and had obvious shell- Δ 基金项目：吉林省科技发展计划项目（No.20200404090YY）；吉 membrane structure. The particle sizes were （28.11 ± 9.76） 林省教育厅科学技术研究项目（No.JJKH20210372KJ） ＊硕士研究生 。研究方向 ：植物药 。E-mail：zhanhe0108@163. and（22.06±6.84）nm；Zeta potential were （－4.09±1.00） com and（－17.40±1.32）mV，and polydispersity were 0.93±0.06 # 通信作者：讲师，博士。研究方向：中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail：chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C （P＜0.05 or P＜0.01）in model mice ，and significantly decreased the fasting blood glucose and the serum contents of MDA ， TC， TG and LDL-C （P＜0.05 or P＜0.01）. CONCLUSIONS GA-LNCs，NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.

ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H₂O₂-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）. ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.

This study aimed to investigate the antidepressant effects of total alkaloids of Fibraurea recisa in HT22 cells damaged by corticosterone (CORT) in vitro and in a mouse model of chronic unpredictable mild stress (CUMS) as well as the underlying mechanisms.In cellular experiments,the viability of CORT-damaged HT22 cells was detected using cell counting kit-8 (CCK-8),and the cell apoptosis was detected by Hoechst 33258 staining.In animal experiments,C57BL/6N mice were randomly divided into the control group,model group,low (100 mg·kg~(-1)),medium (200 mg·kg~(-1)) and high (400 mg·kg~(-1))-dose of total alkaloids of F.recisa groups,and positive control group.After 21 days of CUMS exposure,their depressive behaviors were observed in behavioral and Morris water maze tests.The serum levels of 5-hydroxytryptamine (5-HT),dopamine (DA),and norepinephrine (NE) were assessed by ELISA.The expression levels of apoptosis-related proteins Bcl-2,Bax and cleaved caspase-3 in HT22 cells and mouse hippocampus were detected by Western blot.The results suggested that total alkaloids of F.recisa alleviated the damage of HT22 cells induced by CORT in a dose-dependent manner.The Hoechst 33258 staining uncovered that total alkaloids of F.recisa better reduced the blue spots and inhibited cell apoptosis.The results of animal experiments showed that total alkaloids of F.recisa significantly improved the depression-like behaviors of mice and increased the serum levels of 5-HT,DA and NE as compared with those in the model group.The Western blot assays revealed a significant up-regulation of Bcl-2 protein expression,but an obvious reduction in Bax and cleaved caspase-3protein expression in the total alkaloids of F.recisa group.In conclusion,total alkaloids of F.recisa inhibited depression possibly by regulating the apoptosis-related protein expression or elevating the monoamine neurotransmitter levels in the brain.
Alkaloids/pharmacology* ; Animals ; Antidepressive Agents/pharmacology* ; Depression/drug therapy* ; Disease Models, Animal ; Hippocampus ; Mice ; Mice, Inbred C57BL ; Stress, Psychological

Objective To explored the correlation between levels of serum calcium, phosphorus PTH and ⁹⁹Tc^m -MIBI in patients with hyperparathyropathy as well as to find cut off valve of serum calcium, phosphorus and PTH. Methods A total of 234 patients with hyperparathyroidism that confirmed by operation and pathology were collected from September 2017 to September 2019. Results The median PTH levels in PHPT group and SHPT group were 210.93 (122.60～529.20) pg/ml and 1842.50 (1342.50～2345.00) pg/ml, respectively. There was significant difference between the two groups (Z = − 10.83, P = 0.000). SHPT group was significantly higher than that in PHPT group. The median of Ca level of PHPT group and SHPT group was 2.86 (2.65～3.15) mmol/L and 2.43 (2.32～2.58) mmol/L, respectively. There was significant difference between the two groups (Z = −7.52, P = 0.000). The level of Ca in PHPT group was significantly higher than that in SHPT group. The median of P level in PHPT group and SHPT group was 0.80 (0.64～1.03) mmol/L and 2.26 (1.97～2.63) mmol/L respectively. There was significant difference between the two groups (Z = − 10.15, P = 0.000), and the PHPT group was significantly lower than the SHPT group. The age, gender, PTH and Ca and P value were taken as independent variables, and the results of MIBI imaging were used as dependent for logistic regression analysis. After screening, the influencing factor of PHPT group was PTH value (OR: 1.012, 95% CI: 1.002～1.023), and correlation analysis showed that r = 0.60 (P = 0.000). No related factors were found in SHPT group. ROC curves of ⁹⁹Tc^m-MIBI imaging results in PHPT group were drawn, corresponding to the areas under the maximum curve of 0.91, and the calculated cutoff value was 113.1 pg/mL. simple scatter plot of Ca value, P value and PTH value was drawn in PHPT group and SHPT group, and correlation analysis was performed. In PHPT group, Ca value and PTH value had moderate correlation (r = 0.64, P = 0.000), P value and PTH value had low correlation (r = − 0.28, P = 0.032); in SHPT group: Ca value and PTH value had low correlation (r = 0.17, P = 0.03), P value and PTH value had no correlation (P = 0.15). Conclusion The serum PTH level of PHPT was moderately correlated with MIBI imaging results. The higher the serum PTH level, the higher the positive rate of MIBI imaging, and the corresponding cutoff value of MIBI imaging was 113.1 pg/mL. There was a moderate correlation between serum Ca level and serum PTH level in PHPT, while in SHPT group low correlation between serum Ca level and serum PTH level.

With the increase of people's health awareness and the progress of medical diagostic technology in recent years, the diagnosis rate of early gastric cancer is increasing year by year. Although radical surgery has good efficacy, how to maximize the preservation of the normal anatomy and function of the stomach and improve the quality of life of patients in the pursuit of radical surgery has become a more important issue in the treatment of early gastric cancer. Under the condition of ensuring radical lymph node dissection, function-preserving gastrectomy can fully preserve gastric function by reducing the resection extent and preserving the pylorus and the vagus nerve, which has advantage of improving quality of life and has great potential in the treatment of early gastric cancer. However, there is no functional evaluation standard for function-preserving gastrectomy at present. Most of the patients are evaluated by quality of life scale, which is relatively subjective. Even though the evaluation of endoscopy, hematology and other objective means can indicate the benefit degree in quality of life brought by functional reconstruction, the evidence level is limited. Therefore, this paper discusses the research status of function-preserving gastrectomy evaluation, postoperative complications, postoperative nutritional status, auxiliary examination and other items in the evaluation of gastric function, and analyzes the prospects of research direction in this field.
Gastrectomy ; Humans ; Lymph Node Excision ; Pylorus ; Quality of Life ; Stomach Neoplasms/surgery*

The epidemic caused by coronavirus poses a serious threat to human health, but there is no specific drug or vaccine for the treatment of this kind of virus infection. Herein, this article selects typical case studies in recent years and reviews the medicinal chemistry strategies of anti-SARS-CoV, MERS-CoV and other coronavirus drugs from the perspective of medicinal chemistry, and tries to provide some clues to current drug research againstSARS-CoV-2.

Ge Gen Decoction (GGD), a Traditional Chinese Medicine prescription, is mainly used to treat infectious respiratory diseases and can relieve the symptoms of influenza A virus (IAV) infection. However, the underlying mechanism of GGD against IAV infection remains unclear. In this study, we found that GGD had moderate anti-IAV activity in vitro. GGD was more effective when given before the viral infection and targeted the viral attachment and replication stages rather than the internalization stage. In vivo, GGD treatment reduced thevirus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes in H1N1-infected mice. We observed the changes in several key immuno-related indexes in GGD administrated H1N1-infected mice with anti-IAV drug oseltamivir phosphate as the control. GGD treatment decreased the expression of TNF-α and improved Th1/Th2 immune balance to reduce the excessive immune response in H1N1-infected mice. Besides, the expression of the toll-like receptor 7 signaling pathway in H1N1-infected mice decreased after GGD treatment. Our results showed that GGD has anti-IAV activity and can modulate the immune system to relieve lung inflammation.

Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.
Drugs, Chinese Herbal ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Scutellaria baicalensis

Purpose The aim of this study was to investigate the relationship between autophagy gene Beclin1 and immune response effector classical HLA Ⅰ,Ⅱ in SKOV3 cells.To explore the role of Beclin1 in immunity in ovarian cancer cells which were transfected with the vector of Beclin1.Methods RT-PCR and Western blot were used to detect the expression of Beclin1 and HLA Ⅰ,Ⅱ in SKOV3 cells.Fluorescence microscope was carried out to observe the unique autophagosome in SKOV3 cells.MTT was used to analyze the proliferation of the Beclin1 over-expressed SKOV3 cells.Results Transfection SKOV3 cells with Beclin1 vector could induce Beclin1 transcription and translation approximately 5 and 2 times compared with empty vector group respectively.The autophagosome stained by MDC was observed by fluorescence microscope.And much more green fluorescence signal was observed in Beclin1 vector group.RT-PCR and Western blot indicated that HLA Ⅰ,Ⅱ induced by transfection with extrinsic Beclin1.The allelic transcriptions of HLA Ⅰ-A,B,C and HLA Ⅱ-DP,DQ,DR in extrinsic Beclin1 group were approximately 2,1.6,3 and 2,6,3 times compared with empty vetcor group or untreated group,respectively.The results of Western blot showed that HLA Ⅰ,Ⅱ in Beclin1 vector group induced as much as 2 and 1.6 times compared with empty vetcor group or untreated group,respectively.The results of MTT showed that the proliferation of SKOV3 cells treated with Beclin1 vector was significantly suppressed.The percentage of suppression in Beclin1 vector group at 24 h,48 h,72 h and 96 his42.6％,37.8％,24.35％,14.81％ compared with untreated group or empty vector group respectively.Conclusion The enhancement of autophagy by over-expression of Beclin1 could induce HLA Ⅰ,Ⅱ transcription and translation in SKOV3 cells.The expression of HLA Ⅰ,Ⅱ may be responsible for triggering the immune response in ovarian cancer.Over-expression of Beclin1 could inhibit the proliferation of SKOV3 cells which were transfected with extrinsic Beclin1.