ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

ObjectiveTo investigate the chemical constituents of Chuanxiong Rhizoma-Paeoniae Radix Rubra（CRPRR） that cross the blood-brain barrier in rats with ischemic stroke， their brain-protective effects， and their impact on inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） and pharmacodynamic experiments. MethodsA focal cerebral ischemia-reperfusion injury model was established in rats via the middle cerebral artery occlusion/reperfusion （MCAO/R） method using intraluminal suture. Neurological function was evaluated using behavioral scoring. UPLC-Q-TOF-MS was employed to identify the chemical constituents of CRPRR that crossed the blood-brain barrier and entered the cerebrospinal fluid in MCAO/R model rats. Male Sprague-Dawley rats were randomly divided into six groups： sham operation group， model group， low-， medium-， and high-dose CRPRR groups （1.35， 2.7， 5.4 g·kg^-1， respectively）， and an edaravone group （5 mg·kg^-1）， with 12 rats in each group. The sham and model groups received normal saline， while the treatment groups received the respective doses of CRPRR once daily by gavage for three consecutive weeks. The brain-protective effects of CRPRR were assessed using the Longa five-point scoring method， open field test， Morris water maze， 2，3，5-triphenyltetrazolium chloride （TTC） staining， hematoxylin and eosin （HE） staining， and transmission electron microscopy. ResultsNine chemical constituents were identified in the cerebrospinal fluid containing CRPRR， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide. Animal experiment results showed that compared with the sham operation group， the model group exhibited disordered neuronal arrangement， severe vacuolation， nuclear pyknosis， and evident mitochondrial swelling. Chromatin aggregation and peripheralization were also observed. Neurological scores and the number of crossings in the central region were significantly increased （P<0.01）， while platform crossings were significantly decreased （P<0.01）， and clear infarct areas were present （P<0.01）. Serum levels and protein expression of TNF-α， IL-1β， and IL-18 were significantly elevated （P<0.01）. Compared with the model group， all dose groups of CRPRR showed marked improvement in neuronal morphology which was close to the normal level， with mitochondrial swelling alleviated and chromatin distribution more uniform. The medium- and high-dose groups significantly reduced neurological scores （P<0.01）， while the low-， medium-， and high-dose groups significantly reduced the number of central crossings （P<0.01） and infarct volume （P<0.01）， and decreased TNF-α， IL-1β， and IL-18 levels （P<0.05， P<0.01） compared with the model group. Furthermore， the medium- and high-dose groups significantly reduced TNF-α protein expression （P<0.05，P<0.01）， and the high-dose group significantly reduced IL-1β and IL-18 protein expression （P<0.01）. ConclusionThis study confirmed that CRPRR improves neurological function and alleviates brain tissue damage in MCAO/R rats. Its mechanism may be associated with the downregulation of inflammatory factors TNF-α， IL-1β， and IL-18， as well as the presence of nine active chemical constituents in cerebrospinal fluid， namely paeoniflorin， senkyunolide F， senkyunolide G， paeonimetabolin Ⅰ， paeoniflorin derivative， senkyunolide H， benzoylpaeoniflorin， senkyunolide A， and ligustilide， which are closely related to their brain-protective effects.

OBJECTIVE To investigate the current situation of pharmaceutical clinic service in medical institutions in China and provide experience and suggestions for promoting the development of pharmaceutical clinics. METHODS Questionnaire survey was used to investigate the development of pharmaceutical clinics in medical institutions of 31 provinces （autonomous regions and municipalities directly under the central government） in March to April 2023， and the descriptive analysis was conducted. The regression analysis was carried out for the influential factors of pharmaceutical clinic service. RESULTS A total of 1 368 questionnaires were distributed in this survey and 1 304 valid questionnaires were collected with the effective response rate of 95.32%. A total of 463 medical institutions carried out pharmaceutical clinic service， the rate of which was 35.51% （463/1 304）； the rates of pharmaceutical clinics in tertiary， secondary， primary and other medical institutions were 52.80%， 17.18% and 5.88%， respectively. The frequency of opening pharmaceutical clinics was 3.17 days per week on average， with an average of 5.99 visiting pharmacists in each medical institution. Among the visiting pharmacists， clinical pharmacists accounted for the vast majority （88.68%， 2 459/2 773）. There were various categories of pharmaceutical clinics， including joint clinics and pharmacist-independent clinics； among pharmacist-independent clinics， pharmaceutical specialty/specialty disease clinics were the main ones， accounting for 89.72% of the total number of pharmaceutical clinics. The value of pharmacists in pharmaceutical clinics was manifested in various forms， among which the proportion of medical institutions charging pharmaceutical clinics was 10.80%. The main experiences in developing pharmaceutical clinics were to attach importance to discipline construction and personnel training. The main difficulties in developing pharmaceutical clinics were low compensation levels and a shortage of talent.The number of clinical pharmacists， the number of visiting pharmacists in pharmaceutical clinics and additional compensation were positively correlated with the amount of pharmaceutical clinic services（P＜0.05）. CONCLUSIONS In recent years， pharmaceutical clinics have made significant progress； in the future， it is still necessary to further strengthen discipline construction and talent cultivation， pay attention to the value embodiment of pharmacists， to promote the healthy development of pharmaceutical clinics.

Objective To systematically evaluate qualitative studies on the experience of transition from adolescent to adult medical care for patients with congenital heart disease(CHD),and to provide a reference for exploring CHD transition management options and developing intervention strategies.Methods A computerized search of PubMed,Embase,Web of Science,Cochrane Library,EBSCO,CINAHL,China Knowledge Network,Wanfang database,Vipshop database,and China Biomedical Literature Database for qualitative studies on the transition experience of CHD patients from adolescence to adult medical care was conducted for the period from the establishment of the database to April 2023.The quality of the literature was evaluated using the Joanna Briggs Institute(JBI)Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research(2016),and the results were integrated using meta-integration methods.Results A total of 9 studies were included,and 49 research results were extracted,and 11 categories were summarized.The final synthesis included 4 integrated results:①Complex attitudes towards healthcare transition,with both attachment and expectation:attachment to paediatric healthcare providers,expectation of transition to adult healthcare providers.(2)Facing multiple healthcare transition challenges:lack of adequate preparation for healthcare transition,parents withdrawing from the role of disease manager,large differences in services between paediatric and adult healthcare providers.③Expect to receive multiple supports:expect to receive comprehensive health education from healthcare personnel,expect healthcare institutions to set up healthcare transition counselling clinics and achieve handover of illness,expect to receive companionship and support from parents,expect to receive understanding and help from peers.④ Per-ceived benefits of medical transition:increased ability to manage illness,role change and personal growth.Conclusion Adolescents with CHD have a complex experience of transitioning to adult healthcare,and healthcare professionals should be attentive to their feelings,encourage them to deal with challenges positively,and provide adequate information and joint parental and peer support to facilitate a smooth transition to adult healthcare for adolescents.

Objective:Laboratory evaluation of the relationship between cerebrospinal fluid and plasma indicators and intrathecal immunoglobulin G(IgG) synthesis in patients with neurological diseases, and establishment of a new diagnostic method for intrathecal IgG synthesis.Methods:This study retrospectively analyzed the content of IgG in cerebrospinal fluid samples and blood albumin in blood samples, and other test results of 410 patients with neurological diseases who visited Beijing Tiantan Hospital from 2019 to 2022. According to the results of oligoclonal bands in cerebrospinal fluid, patients were divided into intrathecal IgG synthesis group and non-intrathecal IgG synthesis group. The Mann Whitney U test was used for inter group comparison, and a bilateral test with P<0.05 indicates a statistically significant difference. Include indicators with differences between groups in logistic regression analysis, construct a predictive model, and compare it with the established quantitative formula IgG index. Results:There were significant differences in 10 indicators, including cerebrospinal fluid leukocyte count and 24-hour intrathecal IgG synthesis rate, between the intrathecal IgG synthesis group and the non-intrathecal IgG synthesis group, with P<0.05. The area under the curve (AUC) of intrathecal IgG synthesis was higher than the IgG index (AUC=0.920, 0.809, Z=31.178, P<0.001), the sensitivity was higher than the IgG index (0.825, 0.618), and the specificity was lower than the IgG index (0.876, 0.908). Conclusion:The combination of 10 indicators such as cerebrospinal fluid white blood cell count and 24-hour intrathecal IgG synthesis rate can improve the diagnostic efficacy and sensitivity of intrathecal IgG synthesis.

Objective To summarise the best evidence for postpartum follow-up acquired from patients with gestational diabetes mellitus so as to provide an evidence-based reference for establishment of a postpartum follow-up program.Methods Literature on postpartum blood glucose follow-up in patients with gestational diabetes mellitus was retrieved from 17 major databases including BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI),International Guide Collaboration Network,National Institute for Health and Care Excellence(NICE),American Diabetes Association website,Medlive,Cochrane Library,Embase,OVID,PubMed,Web of Science,Quanfang local PubMed,CNKI,Wanfang Data,VIP,and Sinomed from the inception of databases to July 2023.The literature to be retrieved included guidelines,expert consensus,evidence summaries,systematic reviews,clinical decisions,and the original studies.Results A total of 9 articles,five practice guidelines,a systematic review,an evidence summaries,an expert consensus and a clinical decisions,were included.Totally,17 pieces of best evidence were summarised from the five aspects:postpartum blood glucose,lifestyle guidance,breastfeeding,drug treatment and health education.Conclusions The summarised best evidences can provide evidence-based references for postpartum follow-up of patients with gestational diabetes.Nursing staff in hospitals and community health centres should formulate relevant follow-up plans according to the actual postpartum conditions of patients in order to prevent the incidence of postpartum Type Ⅱ diabetes.

This paper summarized Professor YE Jianzhou's experience in treating atopic dermatitis （AD） in children with the method of regulating the heart and treating the spirit. According to the clinical manifestations of itching-sleep psychological disorders in children with AD， and the physiological characteristics of "heart qi is prone to hyperactivity" and "liver qi is prone to hyperactivity" in children， it is believed that heart and spirit disharmony is an important pathogenesis of AD in children.From the concept of holism in traditional Chinese medicine， the principle of regulating the heart and treating the spirit has been proposed for treatment of AD in children， which is based on the theory of "the five zang （脏） organs store the spirit". In the acute stage， it is recommended to clear the heart， drain fire and calm the spirit with self-made Qingxin Ningshen Decoction （清心宁神汤） in modifications. In the chronic stage， the method of nourishing the heart， unblocking the meridians and calming the spirit is recommended， by using self-made Yangxin Anshen Decoction （养心安神汤） with modifications. The method to tranquilize the heart， subdue yang and contain the spirit should be implemented throughout the entire treatment， and yang-subduing and spirit-containing medicinals such as Duanlonggu （Os Draconis Praeparatum）， Duanmuli （Concha Ostreae Praeparatum） and Zhenzhumu （Concha Margaritiferae Usta） are usually used to treat the body and the spirit simultaneously. All these are offered to provide new ideas for the individualized treatment of children with AD.

OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

A 29-year-old man visited Zhongshan Hospital, Fudan University in December 2021. The patient presented with recurrent coughing, sputum, and wheezing, high level of serum total IgE, positive aspergillus fumigatus-specific IgE and extremely severe mixed ventilatory dysfunction. These features and thoracic CT results scan showed bronchiectasis and allergic bronchopulmonary aspergillosis. In consideration of his clinical characteristics, including low levels of fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO), persistent cough after birth, consanguineous marriage of his parents, etc. we ratiocinated a possibility of hereditary diseases, especially primary ciliary dyskinesia (PCD). From this perspective, whole exome sequencing (WES) was performed and the diagnosis of PCD was ultimately confirmed.

ObjectiveTo investigate the potential mechanisms of Jiawei Jingqin Decoction （加味荆芩汤） in the treatment of rosacea. MethodsFifty 8-week-old female BALB/c mice were randomly divided into normal control group， model group， and Jiawei Jingqin Decoction low， medium， and high-dose groups， with 10 mice in each group. Except for the normal control group， mice in the other groups were injected with 40μl of antimicrobial peptide LL-37 at a concentration of 320 μmol/L on the back， repeated once every 12 hours for a total of 4 injections， to induce the rosacea mouse model. The mice in the normal control group were injected with 40 μl of PBS solution at the same time. After successful modeling， the mice in the Jiawei Jingqin Decoction low， medium， and high-dose groups were orally administered Jiawei Jingqin Decoction at doses of 4.35， 8.71， and 17.42 g/（kg·d） respectively， while the mice in the normal control group and the model group were orally administered 20 ml/（kg·d） of normal saline. All groups were treated once daily for 5 days. The changes in skin lesions were observed， and the erythema area was measured and scored. Skin tissue at the injection site was collected for histopathological examination using HE staining， and the number of mast cells was detected using toluidine blue staining. The levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in the skin lesion tissues were measured using the ELISA method. The mRNA expression levels of key factors in the innate immune response pathway of rosacea disease mechanism， including Toll-like receptor 2 （TLR2）， downstream molecules serine protease kallikrein 5 （KLK5） and matrix metalloproteinase 9 （MMP-9）， as well as related inflammatory factors （IL-1β， IL-6， TNF-α）， and adaptive immune CD4⁺ T cell-related factors interferon-gamma （INF-γ） mRNA were detected using RT-qPCR. Immunohistochemical staining was performed to detect the protein expression of KLK5， MMP-9， and the number of CD4⁺ T-positive cells. Western blot analysis was used to determine the protein expression levels of CD4⁺ T cell-related factors including IFN-γ， CC chemokine receptor 5 （CCR5）， signal transducer and activator of transcription 1 （STAT1）， signal transducer and activator of transcription 3 （STAT3）. ResultsThe skin at the injection site on the back of mice in the normal control group appeared normal without any skin lesions or erythema， and histopathological examination showed no infiltration of inflammatory cells. The model group had significantly higher erythema scores and larger erythema areas compared to the normal control group （P＜0.05）， and histopathological examination revealed a significant infiltration of inflammatory cells， with some signs of deep connective tissue damage. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a significant decrease in erythema scores and erythema areas （P＜0.05）， as well as a reduction in inflammatory exudates and inflammatory cell infiltration. However， the Jiawei Jingqin Decoction low-dose group did not show significant difference （P＞0.05）， but there was a slight reduction in inflammatory cell infiltration compared to the model group. When compared to the normal control group， the rosacea skin tissues of the model group showed an increase in the number of mast cells， levels of IL-1β， IL-6， TNF-α， mRNA expression of IL-1β， IL-6， TNF-α， TLR2， INF-γ， KLK5， MMP-9， protein expression of KLK5， MMP-9， and the number of CD4⁺ T-positive cells （P＜0.05）. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a decrease in the number of mast cells， levels of IL-1β， mRNA expression of IL-1β， TNF-α， and the number of CD4⁺ T-positive cells. The Jiawei Jingqin Decoction high-dose group showed a decrease in IL-6， TNF-α levels， mRNA expression of IL-6， TLR2， INF-γ， MMP-9， protein expression of MMP-9， KLK5， and the number of CD4⁺ T-positive cells， as well as a decrease in IFN-γ and STAT1 protein expression （P＜0.05） compared to the Model group. ConclusionJiawei Jingqin Decoction has significant improvement effect on the skin symptoms of roseacne in a mouse model. Its mechanism might be related to regulating skin immune inflammatory reactions， thereby reducing the release of pathogenic factors and inflammatory factors.