OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Objective To investigate the relationship between serum microRNA(miRNA,miR)-9-5p,miR-21-5p and miR-206 and hemorrhagic transformation(HT)occurs and prognosis in patients with large ar-tery atherosclerotic cerebral infarction(ACI-LAA)after thrombolysis.Methods A total of 265 patients with ACI-LAA admitted to the hospital from April 2021 to November 2023 were selected as the research objects.According to whether HT occurred after intravenous thrombolysis,they were divided into non-HT group and HT group,and the expression levels of serum miR-9-5p,miR-21-5p and miR-206 were compared between the two groups.The general data of patients with ACI-LAA were collected.Univariate and multivariate Logistic regression analysis were used to analyze the influencing factors of HT occurs in patients with ACI-LAA after thrombolysis.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of serum miR-9-5p,miR-21-5p and miR-206 expression levels in predicting HT occurs after thrombolysis in patients with ACI-LAA.The patients with ACI-LAA were followed up for 90 d.According to the modified Rankin scale(mRS)score,the patients were divided into a good prognosis group and a poor prognosis group,and the expression levels of serum miR-9-5p,miR-21-5p and miR-206 were compared between the two groups.Univa-riate and multivariate Logistic regression analysis were used to analyze the influencing factors of poor progno-sis in patients with ACI-LAA.ROC curve was used to analyze the efficacy of serum miR-9-5p,miR-21-5p and miR-206 expression levels in predicting poor prognosis of patients with ACI-LAA.Results HT occurred in 74(27.92％)of 265 patients with ACI-LAA after thrombolysis.Compared with the non-HT group,the National Institutes of Health Stroke Scale(NIHSS)score atadmission,the proportion of hypertension,the proportion of infarct size ≥10 cm2,and the expression levels of serum miR-21-5p and miR-206 were significantly in-creased in the HT group(P＜0.05).However,the expression level of serum miR-9-5p was decreased(P＜0.05).Hypertension,high NIHSS score at admission,the proportion of infarct size ≥10 cm2,high expression of miR-21-5p and miR-206 were risk factors for HT occurs in patients with ACI-LAA after intravenous thrombolysis,and high expression of miR-9-5p was a protective factor(P＜0.05).The ROC curve showed that the area under the curve(AUC)and 95％CI of single and combined detection of serum miR-9-5p,miR-21-5p and miR-206 for predicting HT occurs were 0.796(0.726-0.866),0.779(0.711-0.846),0.784(0.714-0.854),0.891(0.839-0.943),respectively.Among 265 patients with ACI-LAA,83 patients(31.32％)had poor prognosis at 90 d of follow-up.Compared with the good prognosis group,the age,NIHSS score at admis-sion,the proportion of HT,the proportion of infarct size ≥10 cm2,and the expression levels of serum miR-21-5p and miR-206 were increased(P＜0.05),and the expression level of serum miR-9-5p was decreased(P＜0.05)in the poor prognosis group.Advanced age,high NIHSS score at admission,HT,infarct size ≥10 cm2,high expression of miR-21-5p,and high expression of miR-206 were risk factors for poor prognosis of ACI-LAA patients,and high expression of miR-9-5p was a protective factor(P＜0.05).The ROC curve showed that The AUC(95％CI)of single and combined detection of serum miR-9-5p,miR-21-5p and miR-206 for predicting poor prognosis were 0.754(0.691-0.818),0.779(0.719-0.838),0.792(0.815-0.919),0.931(0.902-0.960),respectively.Conclusion Low expression of serum miR-9-5p,high expression of miR-21-5p and high expression of miR-206 are associated with the HT occurs and poor prognosis in patients with ACI-LAA after thrombolysis,and the combined detection of the three indicators has a high predictive value for the HT occurs and poor prognosis.

Objective To investigate the perioperative management of antithrombotic drugs in patients undergoing non-cardiac surgery.Methods Patients on long-term antithrombotic drugs who underwent non-cardiac surgery in our hospital were included.Through interviews with patients and physicians,perioperative antithrombotic medication regimens were reviewed and compared with the"Multidisciplinary Expert Consensus on Perioperative Management of Antithrombotic Therapy"to evaluate compliance with consensus and analyze influencing factors.Results A total of 372 patients were included in the analysis.Among them,355 patients were on long-term antiplatelet therapy alone,and 17 were on long-term oral anticoagulantion.364(97.8％)discontinued antithrombotic medications prior to surgery.109 patients(29.3％)received low molecular weight heparin(LMWH)bridging therapy.Among the 355 patients on antiplatelet therapy,108(30.4％)had discontinuation durations consistent with the consensus recommendations,while 186(52.4％)discontinued medications for longer periods.Postoperatively,the average hospital stay for antiplatelet therapy patients was 6.64 days,with only 37(10.4％)resuming therapy during hospitalization.The average hospital stay for patients on anticoagulants was 9.94 days,with only 2(11.8％)resuming therapy during hospitalization.Regarding perioperative risk assessment,only 40(10.8％)of patients underwent additional internal medical evaluation for thromboembolic risk after medication discontinuation,with the remainder assessed soly by surgeons.Coronary heart disease was an independent risk factor associated with internal medical evaluation(OR 2.851,95％CI 1.160-7.011,P=0.022).For bleeding risk assessment,surgeons evaluations aligned with the consensus in 68.0％of cases,but surgeons tended to underestimate risk compared to the consensus.Conclusions In this single-center study,perioperative antithrombotic management showed low compliance with expert consensus,characterized by prolonged preoperative medication discontinuation,high rates of LMWH bridging,and low postoperative in-hospital resumption of therapy.A robust multidisciplinary collaboration system should be established to enhance comprehensive patient assessment.

Objective To estimate the prevalence of calcified nodule(CN)among patients with coronary artery disease(CAD)and identify the possible risk factors associated with an increased CN risk.Methods Databases include PubMed,Web of Science and Embase was conducted to identify studies reporting the prevalence and/or risk factors of CN.For this databases,the search was from inception to January 1,2024.Data analyses was performed using R statistical Software 4.2.2.Results A total of 46 studies involving 17 926 patients were included.Among them,13 studies with 4 187 patients reported both the prevalence and associated risk factors.The overall prevalence of CN was found to be 5.72％(95％CI 4.47％-7.31％),while in studies reporting both the prevalence and risk factors,the CN prevalence was slightly higher at 8.72％(95％CI 6.43％-11.71％).Hypertension(OR 1.75,95％CI 1.29-2.37),diabetes(OR 1.84,95％CI 1.46-2.33),chronic kidney disease(OR 2.50,95％CI 1.67-3.74),and hemodialysis(OR 7.77,95％CI 4.77-12.67)were associated with an elevated CN risk(all P＜0.001).Conversely,obesity(OR 0.39,95％CI 0.18-0.83)and history of smoking(OR 0.61,95％CI 0.47-0.80)were linked to a decreased CN risk(both P＜0.05).Conclusions The overall prevalence of CN is relatively low among patients with CAD.However,the prevalence of CN is influenced by a variety of clinical factors.Further research is warranted to elucidate the underlying mechanisms.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To investigate the relationship between screen time and content, and the mental health status of adolescents. The findings will inform the formulation of targeted intervention policies to enhance adolescent mental health.Methods:Between September and November 2023, 5 197 students from 64 junior high, senior high, and vocational schools across 13 districts in Wuhan were recruited, using the stratified whole-cluster random sampling to investigate their screen behavior and mental health status. Mental health status was measured using the Mental Health Inventory for Chinese Middle School Students (MMHI-60). A generalized additive model was used to explore the nonlinear association between screen time and mental health status. Additionally, a mixed-effects model was utilized to explore the dose-response associations between average daily total screen time, screen time for different content types, and adolescents' mental health status and the impact of the proportion of different screen contents on mental health outcomes.Results:The age of the participants was (14.40±1.48) years, with 56.07% being boys. The MMHI-60 score averaged 1.73±0.70. The M( Q1,Q3) for daily total screen time was 50.00 (0.00,128.57) minutes. The M( Q1,Q3) for screen time dedicated to gaming, studying, socializing, and watching videos were 0.00 (0.00, 20.00), 8.57 (1.64, 44.50), 4.28 (0.00, 30.00), and 0.00 (0.00, 25.71) minutes, respectively. A non-linear association was observed between average daily screen time and adolescent mental health problem score, 0-1 hour of daily screen time was beneficial for adolescent mental, compared to no screen time. However, screen time exceeding 1 hour was detrimental, with the negative impact increasing alongside screen time duration. When total daily screen time was held constant, the proportion of time spent on gaming ( β=0.14, 95% CI: 0.05-0.23, P=0.003) and video ( β=0.21, 95% CI: 0.09-0.28, P<0.001) was positively correlated with mental health problems, whereas the proportion of time spent on studying was negatively correlated with mental health problems ( β=-0.17, 95% CI: -0.24 - -0.11, P<0.001). Conclusions:Moderate screen time is advantageous for adolescent mental health. However, it is crucial to minimize the proportion of screen time dedicated to video and gaming activities to mitigate potential adverse effects.