OBJECTIVE To explore the mechanism of action of Qingre huatan huoxue decoction against atherosclerosis （AS）based on macrophage polarization. METHODS Using atorvastatin served as the positive control， the drug-containing serum of the Qingre huatan huoxue decoction was prepared to treat RAW264.7 macrophages. Macrophage viability， apoptosis rate， and the fluorescence intensities of CD86 and CD206 were measured， along with the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）. Apolipoprotei n E-deficient （ApoE －/－ ） mice （AS model mice） fed with a high-fat diet were randomly assigned to model group， atorvastatin group （2.6 mg/kg）， and low-， medium- and high-dose groups of Qingre huatan huoxue decoction （90， 180， 360 mg/kg）， respectively. C57BL/6J mice fed with a standard diet served as the normal control group， with 10 mice per group. The treatment group mice were administered the corresponding drugs intragastrically， once daily， for 8 consecutive weeks. Serum levels of TNF-α and IL-1β were measured in all groups. Lipid deposition in the aorta （assessed by the percentage of plaque in the entire aorta and aortic root） and morphological changes in the aortic root were observed. Expression levels of CD86 and CD206 in aortic tissue， as well as the protein expression levels of inducible nitric oxide synthase （iNOS）， arginase-1 （Arg-1）， AMP-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， and peroxisome proliferator-activated receptor γ （PPAR-γ） in aortic tissues were all detected. RESULTS Cell experiment results showed that， at concentrations of 5-100 μg/mL， the drug-containing serum of the Qingre huatan huoxue decoction significantly increased RAW264.7 cell viability （ P ＜0.05）. The drug-containing serum of the Qingre huatan huoxue decoction at concentrations of 10， 50， and 100 μg/mL， along with atorvastatin， significantly reduced apoptosis rates， CD86 fluorescence intensity， and TNF-α and IL-1β levels in RAW264.7 cells， while markedly enhancing CD206 fluorescence intensity （ P ＜0.05）. Animal experiment results showed that， compared with the model group， all dosage groups of Qingre huatan huoxue decoction and the atorvastatin group showed significantly reduced/down-regulated levels of TNF-α and IL-1β in serum， along with decreased aortic total and root plaque percentages， CD86 expression， and iNOS protein expression. CD206 expression and Arg-1， p-AMPK/AMPK， PPAR-γ protein expression were significantly up-regulated （ P ＜0.05）. Pathological morphology of the aorta showed varying degrees of improvement. CONCLUSIONS The formula of Qingre huatan huoxue decoction exerts its anti-AS effects by regulating macrophage polarization， increasing the proportion of M2 macrophages， thereby effectively inhibiting AS plaque formation and reducing inflammatory responses.

ObjectiveTo analyze the temporal distribution characteristics of crisis calls and eight major counseling issues to the Shanghai mental health hotline, and to provide recommendations for improving hotline management. MethodsDescriptive statistics were used to analyze 1 106 crisis calls and the calls of eight major counseling issues to the Shanghai mental health hotline across months, time periods and weeks from October 2021 to September 2023, and the chi-square test was used to analyze whether there was any difference in the distribution of 1 106 crisis calls and the calls of eight major counseling issues across months, time periods and weeks. ResultsThere were significant differences in the number of crises calls across different months (χ²=87.816, P<0.05), time periods (χ²=161.848, P<0.05), and weekly distributions (χ²=63.329, P<0.05). The highest number of calls occurred in September, while January had the lowest. The peak call times were between 18:00‒20:00, with the fewest calls occurring between 3:00‒5:00. The day of the week with the highest number of calls was Saturday, while Wednesday had the lowest. Among the different types of counselling issues in crisis calls, the highest number of calls were related to mental disorders, while the fewest calls were related to COVID-19. ConclusionCrisis calls to the Shanghai mental health hotline are concentrated at specific times, indicating that relevant organizations should optimize resource allocation based on this time distribution.

ABSTRACT OBJECTIVE To investigate the current situation of pediatric pharmacist-managed clinic in China, and to provide reference for pediatric pharmacist-managed clinic construction and improvement. METHODS Domestic Children's hospitals, Women's & Children's Hospital, and general hospitals with pediatric unit were selected as the survey objects, questionnaires were distributed through the Wenjuanxing Application, and SPSS 26.0 was used to describe the data. The development of pediatric pharmacist-managed clinic, the qualification of visiting pharmacists, the situation of post training and training needs were analyzed. RESULTS A total of 101 valid questionnaires were collected. Pediatric pharmacist-managed clinics had been set up in 55(54.5%) hospitals, of which 35 were independent pharmacists' clinics, and most had well medical document and patient management processes. However, about 70% of hospitals did not charge registration fees, and more than half of hospitals had fewer than 5 patient-visits per day. 85.5% of the hospitals were visited by clinical pharmacists, and about half of them were senior clinical pharmacists with more than 10 years of working experience. But only 3.6% of visiting pharmacists had the right of specific prescription. In 101 hospitals relevant post training for pharmacists had been carried out in 36 hospitals, of which 25 hospitals had set up pharmacist-managed clinic. In addition to pharmaceutical expertise, more than 50% of pharmacists had a strong demand for the improvement of physician-patient communication and problem-solving ability, and 30%-40% of the demand was focused on the collection of medication history, psychological counseling ability, and case-based learning in the pharmacist-managed clinic. CONCLUSION At present, the domestic pediatric pharmacist-managed clinic shows a vigorous development trend, however, there are insufficient registration fees, visits, and post training. Appropriate service methods of pediatric pharmacist-managed clinic should be actively explored, and a pediatric specialized training system for should be well constructed to improve the competency.

Abstract OBJECTIVE To analyze the drug-drug interaction during the use and treatment of nirmatrelvir/ritonavir tablets in children, and to provide reference for rational drug use in clinical practice. METHODS All hospitalized pediatric patients with using nirmatrelvir/ritonavir tablets from December 23, 2022 to February 8, 2023 in Children's Hospital, Zhejiang University School of Medicine were collected. The use of nirmatrelvir/ritonavir was analyzed, and the combination drugs were classified. The potential clinical drug-drug interactions of nirmatrelvir/ritonavir were analyzed through micromedex drug interaction database and the severity was graded. RESULTS A total of 48 patients using nirmatrelvir/ritonavir tablets were collected, with a median age of 6.71 years old(87 d-17.75 years old). The usage departments were mainly in the departments of hematology, ICU, infectious disease, and general internal medicine, and the main underlying disease being tumors. The median fever-reducing time after medication was 3 d. Many drugs were combined during medication period. A total of 15 potential drug-drug interaction drugs of nirmatrelvir/ritonavir tablets were collected, and potential drug interaction with antifungals should be considered. CONCLUSION The department with more usage of nirmatrelvir/ritonavir tablets in children is hematology, and the main underlying disease is tumors. When nirmatrelvir/ritonavir tablets are used in combination with potential drug-drug interaction drugs, attention should be paid to monitoring the efficacy and adverse reactions.

Posttranslational modifications(PTMs)of proteins,particularly acetylation,phosphory-lation,and ubiquitination,play critical roles in the host innate immune response.PTMs'dynamic changes and the crosstalk among them are complicated.To build a comprehensive dynamic net-work of inflammation-related proteins,we integrated data from the whole-cell proteome(WCP),acetylome,phosphoproteome,and ubiquitinome of human and mouse macrophages.Our datasets of acetylation,phosphorylation,and ubiquitination sites helped identify PTM crosstalk within and across proteins involved in the inflammatory response.Stimulation of macrophages by lipopolysac-charide(LPS)resulted in both degradative and non-degradative ubiquitination.Moreover,this study contributes to the interpretation of the roles of known inflammatory molecules and the dis-covery of novel inflammatory proteins.

AIM: To analyze the adverse events (AE) of tocilizumab by using the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports related to tocilizumab were extracted from the FAERS database. Disproportionality analysis of reporting odds ratio (ROR) and Medicines and Healthcare Products Regulatory Agency (MHRA) methods were performed for safety signal detection. RESULTS: A total of 19 773 reports associated with tocilizumab as the primary or secondary suspected drugs were extracted from the FAERS database between July 2014 to March 2019. AEs of drug ineffective, pain, drug intolerance, fatigue and rash were commonly reported. There were 13 642 serious AE reports, and 602 reports of death outcome. The proportion of serious and death outcome AEs of male patients was significantly higher than female, and these proportions were significantly higher in children and elderly compared with others. Respectively 602 and 490 of tocilizumab signals were detected by ROR method and MHRA method, including common AEs such as infection, drug hypersensitivity, leukopenia, and hepatic enzyme increased, and signals not indicated in label, for instance, pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, were also detected. CONCLUSION: The commonly reported AEs of tocilizumab include drug inefficiency, pain, drug intolerance, fatigue and rash. Pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, which not indicated in label, should be further assessed and be cautious in COVID-19 treatment.

Objective To explore the clinical effect of microgranular fat obtained by mechanical injection of autologous fat tissues in the treatment of lacrimal trough deformity.Methods Ten patients in this group were women,and the average age was 28 years.With tumescent technique,the thigh fat granules were aspirated;after the separation and purification using cell sorting screen,fat particles were obtained with uniform size and without fibrous tissue.Through mechanical pushing of the fat particles,the fat granules became chylomicron-like.The fat particles without fibrous tissue were injected into the superficial layer and deep layer of the orbicularis oculi muscle with depressed deformity.3-12 months after operation,the clinical efficacy was evaluated by doctors,patients and the third party.Results In 10 cases of lacrimal groove deformity,9 cases were transplanted once,and 1 case did twice.After 3 to 12 months follow-up the appearance of tear trough deformity was significantly improved,the texture of the ditch of eyelid and cheek skin was soft,and appeared young plump appearance.There were no complications,such as infection,hematoma,fat liquefaction,pigmentation and induration,and satisfactory results were obtained.Conclusions Ultrafine particles of fat are obtained using improved purification method in the treatment of lacrimal groove deformity,and the efficacy is satisfactory.

Objective To evaluate the role of microRNA-133b-Sp (miR-133b-Sp) in apoptosis hypoxia/reoxygenation (H/R) induced by in rat cardiomyocytes.Methods Rat myocardial cell line H9c2 was cultured in DMEM/F12 culture medium supplemented with 10％ fetal bovine serum.The cells were seeded in 96-well or 6-well plates and randomly divided into 4 groups (n=64 wells each):control group (group C);group H/R;miR-133b-5p mimic + H/R group (group M+H/R);miR-133b-Sp negative control + H/R group (group NC+H/R).The cells were exposed to 95％ N2-5％ CO2for 5 h at 37 ℃ followed by 1 h reoxygenation in DMEM/F12 culture medium supplemented with 10％ fetal bovine serum in all the groups except group C.The cells were cultured in normal culture atmosphere in group C.In M+H/R and NC+H/R groups,the cells were transfected with miR-133b-5p mimic (final concentration 30 nmol/L) and miR-133b-5p negative control (final concentration 30 nmol/L),respectively,for 24 h before H/R.Total RNA was extracted from cells to detect the expression of miR-133b-5p using quantitative real-time PCR.The cell viability (by CCK-8) and lactic dehydrogenase (LDH) activity in the culture medium were detected.Cell apoptosis was assessed by Annexin V/PI flow cytometry.Apoptotic rate was calculated.Result Compared with group C,the cell viability was significantly decreased,and the LDH activity and apoptotic rate were increased in H/R,M+H/R and NC+H/R groups,the expression of miR-133b-5p was down-regulated in H/R and NC+H/R groups,and the expression of miR-133b-Sp was up-regulated in group M+H/R.Compared with group H/R,the cell viability was significanttly increased,the LDH activity and apoptotic rate were decreased,and the expression of miR-133b-5p was up-regulated in group M+H/R,and no significant change was found in the parameters mentioned above in group NC+H/R.Conclusion H/R in rat cardiomyocytes can induce cell apoptosis possibility through down-regulating the expression of miR-133b-5p

Objective To evaluate the effect of morphine preconditioning on the expression of miR-133b-Sp and Fas in rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R).Methods Cardiomyocytes were isolated from healthy adult male Sprague-Dawley rats by using Langendorff perfusion.The cells were seeded into 24-well plates or 60 mm diameter dishes and randomly divided into 3 groups (n =24 each) using a random number table:control group (group C),group H/R,and morphine preconditioning group (group MPC).The cells in group C were cultured in normal culture atmosphere.In H/R and MPC groups,the cells were exposed to 95％ N2-5％ CO2 for 90 min followed by 120 min reoxygenation.In group MPC,the cells were cultured for 10 min in serum-free DMEM liquid culture medium containing morphine 1 μmol/L,and then were cultured for 30 min in morphine-free DMEM liquid culture medium before hypoxia.At 120 min of reoxygenation,the cells in 24-well plates were selected to detect the cell viability (by MTT),lactate dehydrogenase (LDH) activity in the culture medium,and cell apoptosis (by Hoechst 33234 staining).Apoptosis rate was calculated.Total RNA and protein were extracted from the cells in 60 mm dishes to detect the expression of miR-133b-5p and Fas mRNA (by quantitative real-time PCR) and Fas protein (by Western blot).Results Compared with C group,the cell viability was significantly decreased,LDH activity and apoptosis rate were increased,the expression of miR-133b-Sp was down-regulated,and the expression of Fas mRNA and protein was up-regulated in H/R group.Compared with H/R group,the cell viability was significantly increased,LDH activity and apoptosis rate were decreased,the expression of miR-133b-5p was up-regulatcd,and the expression of Fas mRNA and protein was down-regulated in MPC group.Conclusion The mechanism by which morphine preconditioning reduces H/R injury to rat cardiomyocytesis related to up-regulation of the expression of miR-133b-Sp and down-regulation of the expression of Fas.

Objective To Explore the therapy of elderly patients with hypoproliferative acute myeloid leukemia.Methods Twenty-six elderly patients with hypoproliferative acute myeloid leukemia had received induction of CAG regimen and 15 cases were treated intensive chemotherapy after complete remission,then if achieving complete remission had received subsequent intensive chemotherapy: stand or reduce AA, DA or HA regimen.Results In 26 cases patients who received CAG regimen,the complete remission rate, partial remis sionrat and the totle total effective rate were 53.85％ (14/26), 19.23％ (5/26) and 73.08％ (19/26), respectively.Accordance with response to CAG regimen and the therapy after complete remission, 26 patients were divided into 3 groups:intensive chemotherapy after complete remission(CR1), non-intensive chemotherapy after complete remission(CR2) and non-remission(NR, including partial remission patients).The median overall survival of CR1 ,CR2 and NR were 13.5 months, 8.2 months, and 4.5 months, respectively.There was higher median overall survival of CR1 group than CR2 and NR groups (P =0.041,0.001, respectively).There was higher OS of CR2 group than NR group (P =0.064).No serious bleeding events were found in chemotherapy.Conclusion CAG regimen was an effective and little adverse effect regimen for the treatment of elderly H-AML,and with well tolerance in patients.Advisable intensive chemotherapy can prolong the patient's survival time after complete remission.