Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

ObjectiveTo explore the therapeutic effect and mechanism of Xianglian Huazhuo prescription on chronic atrophic gastritis （CAG） in rats based on the Hedgehog signaling pathway. MethodsThe CAG rat model was established by sodium salicylate， N-methyl-N′-nitro-N-nitroguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into a model group （180 mg·L^-1）， a moradan group （1.4 g·kg^-1）， and Xianglian Huazhuo Prescription groups with high， medium， and low doses （36， 9， 18 g·kg^-1）， followed by drug intervention. Hematoxylin-eosin （HE） staining was used to observe morphological changes in the gastric mucosa. Transmission electron microscopy was used to observe the ultrastructure of gastric mucosa cells. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Sonic Hedgehog （Shh）， Patched 1 （Ptch1）， and Glioma-associated oncogene homolog 1 （Gli1）. Western blot was used to detect the protein expression levels of Shh， Ptch1， and Gli1 in the gastric mucosa. Immunohistochemistry was used to observe the protein expression of the epithelial marker E-cadherin. ResultsCompared with the normal group， the CAG model group showed a reduction in gastric mucosal intrinsic glands and infiltration of inflammatory cells. The ultrastructure of gastric mucosal cells showed nuclear pyknosis， fewer mitochondria， and abnormal mitochondrial structure. The mRNA and protein expression of Shh， Ptch1， and Gli1 in the gastric mucosa were significantly decreased （P<0.05）， and E-cadherin protein expression was decreased. Compared with the model group， the intervention groups showed varying degrees of improvement in histopathological morphology and cellular ultrastructure. The mRNA and protein expression of Shh， Ptch1， Gli1， and E-cadherin increased to varying degrees. Xianglian Huazhuo Prescription upregulated the expression of key Hedgehog pathway factors and E-cadherin at both the mRNA and protein levels （P<0.05）. ConclusionXianglian Huazhuo prescription has a therapeutic effect on CAG in rats， and its mechanism may be related to activation of the Hedgehog signaling pathway and inhibition of epithelial-mesenchymal transition （EMT）.

Objective: To systematically review the development and changes in mental health policies within the National Outline for Children s Development in China from 1992 to 2030, providing a reference basis for future formulation of mental health policies among children and adolescent in China. Methods: Based on the four editions of the National Outline for Children s Development in China across different periods from 1992 to 2030, word frequency analysis was used to reveal shifts in policy priorities, and an internationally recognized framework for adolescent health policy analysis was applied to conduct a textual review. Results: Word frequency analysis revealed that the term "psychological" appeared 6 times in the National Outline for Children s Development in China (2001-2010) but increased to 20 times in the National Outline for Children s Development in China (2021-2030) (abbreviated as the National Outline of 2021), while the term "health" rose from 4 times in the National Outline for Children s Development Plan in China in the 1990s to 68 times in the National Outline of 2021. The scope of mental health policy interventions expanded to encompass five key areas:health, safety, education, welfare and legal protection. Textual analysis highlighted that the policies of the National Outline for Children s Development in China were demand driven, prioritized vulnerable groups and continuously broadened their coverage, emphasizing sustainability and appropriateness, and monitoring/evaluation mechanisms. By 2023, 42.3% of primary schools and 64.8% of secondary schools employed full time mental health education teachers. However, the National Outline for Children s Development in China lacked direct evidence of children and adolescents participation in policy formulation, and publicly available mental health data disaggregated by age and gender remained limited. Conclusion Mental health policies of children and adolescents in China have evolved from nonexistence to gradual refinement, yet institutionalized channels for youth involvement in policy development and evaluation remain insufficient, and transparency in age and gender specific mental health data needs improvement.

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

OBJECTIVE To investigate the effectiveness of resident clinical pharmacist-led medication therapy management （MTM） model in geriatric cardiology departments， and provide reference for optimizing resident pharmaceutical services. METHODS A retrospective cohort study was conducted， incorporating data from inpatients admitted to the Department of Cardiovascular Medicine in the Geriatric Medical Center of our hospital during March to August 2023 （conventional group， n＝ 903） and the same period in 2024 （MTM group， n＝963）. The conventional group received only standard pharmaceutical services （including prospective prescription review and retrospective order evaluation）， while the MTM group received additional resident clinical pharmacist-led interventions-such as medication reconciliation， personalized therapeutic drug monitoring （TDM）， standardized intravenous infusion management， and a four-stage closed-loop monitoring process-based on conventional care. The effectiveness of the MTM model was evaluated by comparing the primary outcome measures （e.g.， intravenous infusion rate， TDM target attainment rate） and secondary outcome measures [e.g.， incidence of drug-drug interactions （DDIs）， incidence of grade 3 or higher acute kidney injury， average length of hospital stay， cholesterol， and medication cost per capita] between the two groups. RESULTS Compared with the conventional group， in terms of primary outcome indexes： both the overall intravenous infusion rate and the use rate of acid-suppressive injection were significantly lowered in the MTM group （P＜0.05）； serum concentration target attainment rates for digoxin and vancomycin were increased significantly （P＜0.05）. For secondary outcome indexes， the MTM group exhibited significant decreases in the work incidence of grade 3 or higher acute kidney injury， the incidence of DDIs， the rate of patients leaving the hospital against medical advice， alanine amino-transferase， aspartate transferase and the per capita total medication cost （P＜0.05）. Additionally， there was a notable increase in the creatinine， estimated glomerular filtration rate and a significant shortening of the per capita length of hospital stay （P＜0.05）. CONCLUSIONS The resident clinical pharmacist-led MTM model can significantly optimize medication therapy processes， enhance medication safety and cost-effectiveness， thus playing a positive role in promoting rational drug use and improving patient outcomes.

Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)％,0,(42.80±6.70)％,(11.74±1.79)％;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)％,(0.5±0.15)％,(38.6±2.39)％,(1.58±0.54)％.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P＜0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P＜0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

Objective To study the impacts of tetramethylpyrazine(TMP)on the epithelial mesenchymal transformation and radiotherapy resistance of cervical cancer cells by regulating Yes-associated protein(YAP)/transcriptional coactivator(TAZ)signal pathway.Methods Human cervical cancer cell line C33A was randomly grouped into control group(without any intervention),TMP group(1.5 mg·mL-1TMP),TMP+NC group(TMP 1.5 mg·mL-1+transfection empty plasmid)and TMP+YAP1 group(TMP 1.5 mg·mL-1+transfection YAP1 overexpression plasmid).C33A-RR cells of human cervical cancer were constructed and randomly separated into control-RR group(without any intervention),radiation group(6 Gy radiation),RT group(6 Gy radiation+TMP 1.5 mg·mL-1),RTN group(6 Gy radiation+TMP 1.5 mg·mL-1+transfection empty plasmid)and RTY group(6 Gy radiation+TMP 1.5 mg·mL-1+transfection YAP1 overexpression plasmid).Western blot detected the relative expression levels of proteins;cell scratch and Transwell invasion experiments respectively examined cell migration and invasion;cell counting kit-8(CCK-8)and flow cytometry experiments respectively evaluated cell proliferation and apoptosis.Results The mobility of control group,TMP group,TMP+NC group and TMP+YAP1 group were(84.82±12.16)％,(20.67±4.48)％,(21.22±5.03)％and(76.74±0.15)％,respectively;E-cadherin protein expression levels were 0.16±0.03,0.70±0.08,0.72±0.13 and 0.19±0.04.Compared TMP group with control group of above indictors were statistically significant(all P＜0.05);compared TMP+YAP1 group with TMP group and TMP+NC group were statistically significant(all P＜0.05).YAP1 protein expression levels in control-RR group,radiation group,the RT group,RTN group and RTY group were 0.79±0.14,0.88±0.16,0.21±0.03,0.22±0.04 and 0.82±0.16,respectively;the survival rates were(100.00±0.00)％,(95.78±20.12)％,(40.13±6.07)％,(42.21±6.45)％and(90.12±18.65)％,respectively.The difference between radiation group and control-RR group were statistically significant(all P＜0.05);the differences between RT group,RTN group and radiation group,RTY group were statistically significant(all P＜0.05).Conclusion TMP can down regulate the expression of YAP/TAZ signal pathway protein,thereby inhibiting epithelial mesenchymal transformation,migration and invasion of cervical cancer cells,reducing their resistance to radiotherapy and promoting their apoptosis.

Objective To investigate the effects of perineal massage combined with hip joint exercise on the outcome of delivery and mental resilience of primipara.Methods 90 pregnant women in the third trimester(after 36 weeks)who obtained the knowledge about perineal massage from midwife clinic were randomly divided into two groups with 45 cases each.The control group received regular antenatal examination and family self-exercise;the experimental group received perineal massage and hip joint training combined treatment.The delivery outcome,birth experience and maternal mental resilience of the two groups were compared.Results the number of vaginal delivery in the experimental group were higher than that in the control group(P<0.05);the second stage of labor was significantly shorter than that of the control group(P<0.05);the perineal integrity rate was higher than that of the control group(P<0.05);the scores of all dimensions in delivery experience questionnaire were higher than that of the control group(P<0.05);the scores of all dimensions in maternal mental resilience were higher than those of the control group(P<0.05)after intervention.Conclusion The perineal massage which conducted by midwives combined with hip movement can effectively improve the quality of delivery,relieve the negative emotions of pregnant women,improve the psychological elasticity level of pregnant women,and improve the delivery outcomes.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Pharmaceutical cocrystals are one of the effective strategies to improve the solubility and bioavailability of poorly water-soluble drugs. However, the phase transformation of cocrystals during dissolution can lead to the recrystallization of the parent drugs, and thus negating the solubility advantage of cocrystals. The introduction of suitable excipients into the cocrystal formulation may inhibit the phase transformation during dissolution, resulting in the enhanced dissolution and bioavailability of poorly soluble drugs. In addition, the complex gastrointestinal environment and absorption behavior of drugs can have significant impacts on the oral bioavailability of cocrystals. This review summarizes the recent studies of the dissolution and absorption of pharmaceutical cocrystals, and aims to provide guidance for the rational design of pharmaceutical cocrystal formulations.