OBJECTIVES: Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression. METHODS: Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‍‒‍12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression. RESULTS: Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania. CONCLUSIONS This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans ; Bipolar Disorder/drug therapy* ; Vortioxetine/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Valproic Acid/administration & dosage* ; Lurasidone Hydrochloride/administration & dosage* ; Prospective Studies ; Treatment Outcome ; Pilot Projects ; Drug Therapy, Combination ; Sulfides/therapeutic use* ; Antidepressive Agents/therapeutic use*

Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Objective To study the intervention effect of nursing staff's participation in antimicrobial stewardship(AMS)on the rational use of antimicrobial agents,and explore its role in constructing a scientific healthcare-associa-ted infection(HAI)control management.Methods The data on perioperative prophylactic use of antimicrobial agents,surgical-related HAI control,and pathogen detection before therapeutic use of antimicrobial agents among hospitalized patients in a hospital from January 2016 to December 2024 were collected.Relevant evaluation indica-tors before and after nursing staff participating in AMS were compared.2016-2018,2019-2021,and 2022-2024 were stages before intervention,during intervention,and after intervention,respectively.Results After nursing staff participated in AMS,the use rate of prophylactic antimicrobial agents 0.5-1 hour before surgery and discon-tinuation rate of antimicrobial agents within 24 hours after class Ⅰ incision surgery increased from 64.54％and 81.41％before intervention to 75.31％and 84.56％after intervention,respectively.Incidences of surgical-related HAI and surgical site infection in patients decreased from 3.11％and 0.96％before intervention to 1.37％and 0.17％after intervention,respectively.Pathogen detection rates before restricted-and special-grade antimicrobial agents treatment increased from 50.80％and 68.70％before intervention to 55.19％and 80.53％after interven-tion,respectively.Proportion of blood specimen from which coagulase-negative Staphylococcus was detected de-creased from 29.30％before intervention to 21.26％after intervention.Proportion of respiratory specimen from which Haemophilus influenzae was detected increased from 2.00％to 3.98％.Differences were all statistically sig-nificant(all P＜0.05).Conclusion As important members of the AMS team,nursing staff can effectively reduce irrational antimicrobial use,optimize medication timing and duration,and have a positive effect on ensuring patient safety through participating in the use and management of antimicrobial agents in hospitalized patients.

Objective:To investigate the effect of intravitreal injection of 7, 8-dihydroxyflavone (DHF) on N-methyl-D-aspartate (NMDA)-induced apoptosis of retinal ganglion cells (RGCs).Methods:A total of 138 male Sprague-Dawley rats aged 6-8 weeks were randomly divided into normal control group (30 rats), model control group (36 rats), DHF treatment group (36 rats), and brain-derived neurotrophic factor (BDNF) control group (36 rats) using the random number table method, which received intravitreal injections of 5 μl 0.1 mmol/L phosphate buffered saline, 10 mmol/L NMDA, 10 mmol/L NMDA+ 100 mmol/L DHF, and 10 mmol/L NMDA+ 100 mmol/L BDNF, according to the group.The right eye was taken as the experimental eye.At 12 hours, 1 day, 3 days, 7 days, 14 days, and 28 days after modeling, RGCs were observed and counted by immunofluorescence staining.The apoptosis rate of peripapillary cells was assessed by TUNEL staining.At 12 hours, 3 days, 14 days, and 28 days after treatment, the expression of caspase-3, B-cell lymphoma-2 (bcl-2), bcl-2 associated X protein (bax), and tyrosine kinase receptor B (TrkB) were detected by real-time quantitative fluorescence PCR.The use and feeding of experimental animals in this study followed the Regulations on the Management of Laboratory Animals issued by the Ministry of Science and Technology.This research protocol was reviewed and approved by the Medical Ethics Committee of Southwest Jiaotong University (No.SWJTU-2303-NSFC[066]).Results:The RGCs count and the apoptosis rates in the normal control group, DHF treatment group, and BDNF control group were significantly higher than those in the model control group at each time point after treatment (all P<0.05).There was no significant difference in the apoptosis rate of peripapillary cells between the DHF treatment group and the BDNF control group at different time points after treatment (all P>0.05).Compared with the model control group, the TrkB mRNA expressions were significantly increased in the DHF treatment group at 12 hours, 3 days, and 14 days after treatment and in the BDNF control group at 3, 14, and 28 days after treatment (all P<0.05).At 12 hours and 3 days after treatment, the expression of caspase-3 mRNA was significantly decreased in the DHF treatment group and BDNF control group compared with the model control group (all P<0.05).At 12 hours after treatment, the relative expressions of bax and bcl-2 mRNA were significantly higher in the DHF treatment group than in the normal control group (both P<0.05).Compared with normal control group, the relative expression of bax mRNA at 14 days after treatment and the relative expression of bcl-2 mRNA in the BDNF control group were significantly increased at 12 hours and 3 days (all P<0.05). Conclusions:Intravitreal injection of DHF effectively alleviates NMDA-induced RGCs damage in the rat model.Its neuroprotective mechanism may be achieved by promoting TrkB expression and inhibiting related apoptotic factors.

Objective To study the intervention effect of nursing staff's participation in antimicrobial stewardship(AMS)on the rational use of antimicrobial agents,and explore its role in constructing a scientific healthcare-associa-ted infection(HAI)control management.Methods The data on perioperative prophylactic use of antimicrobial agents,surgical-related HAI control,and pathogen detection before therapeutic use of antimicrobial agents among hospitalized patients in a hospital from January 2016 to December 2024 were collected.Relevant evaluation indica-tors before and after nursing staff participating in AMS were compared.2016-2018,2019-2021,and 2022-2024 were stages before intervention,during intervention,and after intervention,respectively.Results After nursing staff participated in AMS,the use rate of prophylactic antimicrobial agents 0.5-1 hour before surgery and discon-tinuation rate of antimicrobial agents within 24 hours after class Ⅰ incision surgery increased from 64.54％and 81.41％before intervention to 75.31％and 84.56％after intervention,respectively.Incidences of surgical-related HAI and surgical site infection in patients decreased from 3.11％and 0.96％before intervention to 1.37％and 0.17％after intervention,respectively.Pathogen detection rates before restricted-and special-grade antimicrobial agents treatment increased from 50.80％and 68.70％before intervention to 55.19％and 80.53％after interven-tion,respectively.Proportion of blood specimen from which coagulase-negative Staphylococcus was detected de-creased from 29.30％before intervention to 21.26％after intervention.Proportion of respiratory specimen from which Haemophilus influenzae was detected increased from 2.00％to 3.98％.Differences were all statistically sig-nificant(all P＜0.05).Conclusion As important members of the AMS team,nursing staff can effectively reduce irrational antimicrobial use,optimize medication timing and duration,and have a positive effect on ensuring patient safety through participating in the use and management of antimicrobial agents in hospitalized patients.

Objective:To study the level of regulatory T cell(Treg)in peripheral blood of diffuse large B-cell lymphoma(DLBCL)patients at initial diagnosis,and its value in the evaluation of efficacy and prognosis.Methods:A total of 72 newly diagnosed DLBCL patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 2018 to February 2022 were selected as research objects,and 17 healthy volunteers were taken as the control group.The level of CD4+CD25+CD127lowTreg in peripheral blood of patients was detected by flow cytometry,and a comparative analysis was conducted in conjunction with the clinical characteristics of patients.Results:The percentage of Treg in peripheral blood before treatment was correlated with Ann Arbor stage,IPI score,ECOG score and hemoglobin(HB).The levels of Treg in peripheral blood at initial diagnosis were significantly lower than that of healthy con-trols(3.85±0.22 vs 5.15±0.31,P=0.007).DLBCL patients were divided into high Treg group and low Treg group according to the me-dian percentage of CD4+CD25+CD127lowTreg in peripheral blood to CD4+T cells at initial diagnosis,the total effective rate of high Treg group was significantly higher than that of low Treg group(P=0.035).ECOG score(P=0.040)and low level of Treg before treatment(P=0.014)were independent risk factors for progression-free survival(PFS)in DLBCL patients.Having B symptom(P=0.028),ECOG score≥2(P=0.041)and low level of Treg before treatment(P=0.036)were independent risk factors for OS.PFS(P=0.020)and OS(P=0.036)in low Treg group were significantly lower than those in high Treg group.Conclusion:The low percentage of CD4+CD25+CD127lowTreg in peripheral blood of newly diagnosed DLBCL patients indicates a poor prognosis.

Objective:To study the level of regulatory T cell(Treg)in peripheral blood of diffuse large B-cell lymphoma(DLBCL)patients at initial diagnosis,and its value in the evaluation of efficacy and prognosis.Methods:A total of 72 newly diagnosed DLBCL patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 2018 to February 2022 were selected as research objects,and 17 healthy volunteers were taken as the control group.The level of CD4+CD25+CD127lowTreg in peripheral blood of patients was detected by flow cytometry,and a comparative analysis was conducted in conjunction with the clinical characteristics of patients.Results:The percentage of Treg in peripheral blood before treatment was correlated with Ann Arbor stage,IPI score,ECOG score and hemoglobin(HB).The levels of Treg in peripheral blood at initial diagnosis were significantly lower than that of healthy con-trols(3.85±0.22 vs 5.15±0.31,P=0.007).DLBCL patients were divided into high Treg group and low Treg group according to the me-dian percentage of CD4+CD25+CD127lowTreg in peripheral blood to CD4+T cells at initial diagnosis,the total effective rate of high Treg group was significantly higher than that of low Treg group(P=0.035).ECOG score(P=0.040)and low level of Treg before treatment(P=0.014)were independent risk factors for progression-free survival(PFS)in DLBCL patients.Having B symptom(P=0.028),ECOG score≥2(P=0.041)and low level of Treg before treatment(P=0.036)were independent risk factors for OS.PFS(P=0.020)and OS(P=0.036)in low Treg group were significantly lower than those in high Treg group.Conclusion:The low percentage of CD4+CD25+CD127lowTreg in peripheral blood of newly diagnosed DLBCL patients indicates a poor prognosis.

Objective:To investigate the effect of intravitreal injection of 7, 8-dihydroxyflavone (DHF) on N-methyl-D-aspartate (NMDA)-induced apoptosis of retinal ganglion cells (RGCs).Methods:A total of 138 male Sprague-Dawley rats aged 6-8 weeks were randomly divided into normal control group (30 rats), model control group (36 rats), DHF treatment group (36 rats), and brain-derived neurotrophic factor (BDNF) control group (36 rats) using the random number table method, which received intravitreal injections of 5 μl 0.1 mmol/L phosphate buffered saline, 10 mmol/L NMDA, 10 mmol/L NMDA+ 100 mmol/L DHF, and 10 mmol/L NMDA+ 100 mmol/L BDNF, according to the group.The right eye was taken as the experimental eye.At 12 hours, 1 day, 3 days, 7 days, 14 days, and 28 days after modeling, RGCs were observed and counted by immunofluorescence staining.The apoptosis rate of peripapillary cells was assessed by TUNEL staining.At 12 hours, 3 days, 14 days, and 28 days after treatment, the expression of caspase-3, B-cell lymphoma-2 (bcl-2), bcl-2 associated X protein (bax), and tyrosine kinase receptor B (TrkB) were detected by real-time quantitative fluorescence PCR.The use and feeding of experimental animals in this study followed the Regulations on the Management of Laboratory Animals issued by the Ministry of Science and Technology.This research protocol was reviewed and approved by the Medical Ethics Committee of Southwest Jiaotong University (No.SWJTU-2303-NSFC[066]).Results:The RGCs count and the apoptosis rates in the normal control group, DHF treatment group, and BDNF control group were significantly higher than those in the model control group at each time point after treatment (all P<0.05).There was no significant difference in the apoptosis rate of peripapillary cells between the DHF treatment group and the BDNF control group at different time points after treatment (all P>0.05).Compared with the model control group, the TrkB mRNA expressions were significantly increased in the DHF treatment group at 12 hours, 3 days, and 14 days after treatment and in the BDNF control group at 3, 14, and 28 days after treatment (all P<0.05).At 12 hours and 3 days after treatment, the expression of caspase-3 mRNA was significantly decreased in the DHF treatment group and BDNF control group compared with the model control group (all P<0.05).At 12 hours after treatment, the relative expressions of bax and bcl-2 mRNA were significantly higher in the DHF treatment group than in the normal control group (both P<0.05).Compared with normal control group, the relative expression of bax mRNA at 14 days after treatment and the relative expression of bcl-2 mRNA in the BDNF control group were significantly increased at 12 hours and 3 days (all P<0.05). Conclusions:Intravitreal injection of DHF effectively alleviates NMDA-induced RGCs damage in the rat model.Its neuroprotective mechanism may be achieved by promoting TrkB expression and inhibiting related apoptotic factors.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.