ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

Objective To investigate the effect of dihydroartemisinin(DHA)on the inflammatory response and skin wound healing in diabetic rats.Methods The ointment was prepared with Carbomer 980,Tween-80,glycerol,ultrapure water and sodium hydroxide as a base.DHA and ethyl nipagin were added and stirred evenly,resulting in DHA ointment.Fifty SPF-grade SD rats were used to create a diabetic rat model by intraperitoneal injection of streptozotocin,and 44 rats were successfully modelled.Whole skin defect wounds were created on the back of rats by using a 2.0 cm diameter circular punch.Thirty-six dorsal wounds were randomly divided into 4 groups(n=9)by the random number table.Then the wounds were applied respectively with 5%DHA,10%DHA,15%DHA and ointment base(control group)once a day for 14 consecutive days.On the 3th,7th and 14th days,the wound healing was observed,the specimens were cut from 0.2 cm of wound margin and would tissue,the histological changes were observed by HE staining.Collagen changes were observed by Masson staining,and the concentrations of interleukin 6(IL-6),interleukin 10(IL-10),and tumor necrosis factor-α(TNF-α)were detected by ELISA.The other eight rats were randomly divided into 10%DHA group and control group.The tissue was cut from the wound on the 7th day,and transcriptome sequencing was performed by high-throughput sequencing technology to screen the differentially expressed genes(DEGs)between the two groups.Gene ontology(GO)functional enrichment analysis as well as kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed.Data were analyzed by one-way ANOVA using SPSS 27.0 statistical software.Results The different concentrations of DHA groups showed better wound healing rates than the control group.The 10%DHA group has the most significant effect(P＜0.05).Compared with the control group,each DHA group showed a decrease in inflammatory cell infiltration and an increase in collagen fibre area on the 7th and 14th days(P＜0.05).The expressions of IL-6 and TNF-α in each DHA group were significantly lower than those in the control group(P＜0.05),while the expression of IL-10 was significantly higher than that in the control group(P＜0.05).Differential gene volcano map showed that the 10%DHA group remarkably up-regulated anti-inflammatory and antibacterial genes such as hypoxia inducible factor 1α(Hif-1α),Smad homolog 12(Smad12)and β-defensin 4(Defb4).The GO functional enrichment analysis indicated that the 10%DHA group was significantly enriched in inflammatory response,immune response and defense response to bacterium.The KEGG enrichment analysis showed that the 10%DHA group was significantly enriched in chemokine signaling pathway,NOD-like receptor signaling pathway and so on.Conclusion DHA may inhibit excessive inflammatory responses by modulating inflammatory factors,anti-inflammatory and antimicrobial genes,chemokine signaling pathway and NOD-like receptor signaling pathway as well as reducing inflammatory cell infiltration,thereby enhancing wound healing.

An 85-year-old male patient received left thyroxine sodium (LT4) 50 μg orally once daily for replacement therapy because of ischemic stroke and hypothyroidism. Next day, laboratory test showed that blood potassium was 3.0 mmol/L. He was given potassium chloride sustained-release tablets 1 g orally thrice daily. Six days later, the patient complained of a rapid heartbeat after slight activity. Laboratory tests showed that blood potassium was 3.3 mmol/L and a potassium magnesium aspartate tablet was administered orally thrice daily. After 8 days of potassium supplementation treatments, the patient's blood potassium level was 3.5 mmol/L, while the blood pressure increased to 163/90 mmHg. Losartan potassium 50 mg once daily was given orally. Clinical pharmacist consulted and learned that the patient continued to take his own LT4 75 μg once daily while following the doctor's instructions to take LT4 50 μg once daily. The patient was instructed to immediately stop taking his own medication and the LT4 dose was adjusted to 75 μg once daily. Thirteen days later, the patient's serum potassium returned to 4.0 mmol/L and no further discomfort occurred.

Objective:To explore and establish a standardized clinical thinking mode and decision-making pathway for lactation medication consultation services and ensure the harmonization and safety of medication for lactating women.Methods:Lactation medication consultation services for medical staffs conducted by pharmacists from June 2020 to August 2022 in Peking University Third Hospital were analyzed using methods of retrospective statistical analysis and root cause analysis. Application of mixed methods were used to establish a clinical thinking model for medication use during lactation and a clinical pathway for safe medication use during lactation. Lactation medication consultation service training for pharmacists was provided, questionnaire surveys before and after the training were conducted, and the effectiveness of improvement was evaluated.Results:A total of 1 218 medication consultation services provided by clinical pharmacists to medical staffs were collected in the hospital, including 44 cases (3.61%) related to lactation medication. Retrospective analysis showed that clinical pharmacists did not have a clear understanding of patients′ needs, incomplete consideration of drug-maternal-infant factors, and a limited way to retrieve information in the lactation medication consultation service. Based on the root cause analysis of the problems, a clinical thinking mode of "Questions (Q), Assessment (A), Search (S), and Plan (P)" (QASP) were established. Additionally, a clinical pathway for safe medication decision-making analysis and a standard medication consultation record template was developed. Compared with before training, clinical pharmacists made significant progress in clarifying factors related to lactation medication, evidence-based procedure, standardized documentation, and confidence in providing medication consulations (all P<0.001). Conclusion:The establishment of the QASP clinical thinking model and decision analysis model, based on the 3 factors of medication, mother, and baby for the consultation service of safe medication during lactation, can help clinical pharmacists carry out standardized medication consultation services for breast-feeding populations during lactation, and improve the quality of homogeneous pharmaceutical services.

An 85-year-old male patient received left thyroxine sodium (LT4) 50 μg orally once daily for replacement therapy because of ischemic stroke and hypothyroidism. Next day, laboratory test showed that blood potassium was 3.0 mmol/L. He was given potassium chloride sustained-release tablets 1 g orally thrice daily. Six days later, the patient complained of a rapid heartbeat after slight activity. Laboratory tests showed that blood potassium was 3.3 mmol/L and a potassium magnesium aspartate tablet was administered orally thrice daily. After 8 days of potassium supplementation treatments, the patient's blood potassium level was 3.5 mmol/L, while the blood pressure increased to 163/90 mmHg. Losartan potassium 50 mg once daily was given orally. Clinical pharmacist consulted and learned that the patient continued to take his own LT4 75 μg once daily while following the doctor's instructions to take LT4 50 μg once daily. The patient was instructed to immediately stop taking his own medication and the LT4 dose was adjusted to 75 μg once daily. Thirteen days later, the patient's serum potassium returned to 4.0 mmol/L and no further discomfort occurred.

Objective:To explore and establish a standardized clinical thinking mode and decision-making pathway for lactation medication consultation services and ensure the harmonization and safety of medication for lactating women.Methods:Lactation medication consultation services for medical staffs conducted by pharmacists from June 2020 to August 2022 in Peking University Third Hospital were analyzed using methods of retrospective statistical analysis and root cause analysis. Application of mixed methods were used to establish a clinical thinking model for medication use during lactation and a clinical pathway for safe medication use during lactation. Lactation medication consultation service training for pharmacists was provided, questionnaire surveys before and after the training were conducted, and the effectiveness of improvement was evaluated.Results:A total of 1 218 medication consultation services provided by clinical pharmacists to medical staffs were collected in the hospital, including 44 cases (3.61%) related to lactation medication. Retrospective analysis showed that clinical pharmacists did not have a clear understanding of patients′ needs, incomplete consideration of drug-maternal-infant factors, and a limited way to retrieve information in the lactation medication consultation service. Based on the root cause analysis of the problems, a clinical thinking mode of "Questions (Q), Assessment (A), Search (S), and Plan (P)" (QASP) were established. Additionally, a clinical pathway for safe medication decision-making analysis and a standard medication consultation record template was developed. Compared with before training, clinical pharmacists made significant progress in clarifying factors related to lactation medication, evidence-based procedure, standardized documentation, and confidence in providing medication consulations (all P<0.001). Conclusion:The establishment of the QASP clinical thinking model and decision analysis model, based on the 3 factors of medication, mother, and baby for the consultation service of safe medication during lactation, can help clinical pharmacists carry out standardized medication consultation services for breast-feeding populations during lactation, and improve the quality of homogeneous pharmaceutical services.

Objective:To analyze clinical and histopathological characteristics of infantile congenital melanocytic nevi (ICMN) .Methods:Clinical and pathological data were collected from 126 infants with confirmedly diagnosed congenital melanocytic nevi in Department of Dermatology, Xijing Hospital from January 2015 to January 2020, and were retrospectively analyzed. Chi-square test was used for comparisons of enumeration data.Results:Among the 126 patients with ICMN, 68 were males and 58 were females; 109 (86.5%) presented with skin lesions at birth; 73 (57.9%) were 2 - 3 years old at the first clinic visit. The skin lesions occurred on the head and face (76 cases, 60.3%) , trunk (24 cases, 19.1%) or extremities (26 cases, 20.6%) . There were 36 (28.6%) patients with small congenital nevi, 68 (54.0%) with M1-type medium-sized nevi, 13 (10.3%) with M2-type medium-sized nevi and 9 (7.1%) with giant nevi. Of 126 cases of ICMN, 121 (96.0%) had solitary lesions, 5 (4.0%) had multiple lesions, 44 (34.9%) had nevi with coarse hairs, 15 (11.9%) had nevi complicated by papules or hyperplastic nodules, and 6 (4.8%) had satellite lesions. Pathological subtypes included compound nevus (120 cases, 95.2%) , intradermal nevus (4 cases, 3.2%) , and junctional nevus (2 cases, 1.6%) . Under the microscope, the depth of the skin lesions was < 1 mm in 38 (30.1%) cases, 1 - 2 mm in 61 (48.4%) and > 2 mm in 25 (19.8%) , and 45 (35.7%) cases showed nevus cells infiltrating the subcutaneous fat layer or deeper tissues. Among the 126 ICMN lesions, common pathological features included nevus tissue maturation (100%, 2 cases of junctional nevi were excluded) , pigment granules in the stratum corneum (53 cases, 42.1%) , disordered/asymmetric distribution of nevus cells (80 cases, 63.5%) , scattered epidermal nevus cells (91 cases, 72.2%) , pagetoid spread of epidermal nevus cells (67 cases, 53.2%) , melanophages in the dermis (71 cases, 56.4%) , and nevus cells distributed along hair follicles/sebaceous glands (82 cases, 65.1%) . Special pathological features included nevus cells embedded in the vascular/lymphatic vessels (42 cases, 33.3%) , nevus cell lysis (45 cases, 35.7%) , fibromatous changes (25 cases, 19.8%) , involvement of the arrector pilli muscles (31 cases, 24.6%) , and mast cell infiltration (30 cases, 23.8%) . Pathological patterns of ICMN with different clinical features: the incidences of infiltration depth > 2 mm, pigment granules and columnar pigment granules in the stratum corneum were significantly higher in the giant nevi than in the small and medium-sized nevi ( χ2 = 7.93, 10.76, 5.89 respectively, all P < 0.05) ; the incidences of infiltration depth > 2 mm, epidermal spongiosis with scattered nevus cells, nevus cell nests distributed along the hair follicles/sebaceous glands, fibromatous changes and mast cell infiltration were significantly higher in the skin lesions with coarse hairs than in those without ( χ2 = 28.29, 8.11, 6.22, 7.92, 8.19 respectively, all P < 0.01) ; the incidences of pagetoid spread of epidermal nevus cells and atypical nevus cells were significantly higher in the skin lesions with papules/hyperplastic nodules than in those without papules/hyperplastic nodules ( χ2 = 4.92, 6.30 respectively, both P < 0.05) . Conclusions:The clinical and histopathological characteristics of ICMN are unique, and atypical nevus cells are common in ICMN. The diagnosis and treatment of ICMN need to be based on the combination of clinical and pathological characteristics.