Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

Objective To develop the Evidence-Based Health Care Related Competence Assessment Scale for Health Professionals(hereinafter referred to as the Scale),and to test its validity and reliability.Methods Based on the JBI evidence-based health care model as the theoretical framework,the initial items of the Scale were formed by reviewing the literature.Through the discussion of the research group,two rounds of Delphi expert consultation and pre-inspection,the items of the Scale were optimized.The convenience sam-pling method was adopted to extract 928 health professionals as the research subjects.The Scale conducted the validity and reliability testing.Results The Scale included the four dimensions of evidence generation,evi-dence synthesis,evidence transfer and evidence implementation,including 47 entries in total.The cumulative variance contribution rate was 59.08%.The confirmatory factor analysis results indicated that the model had good fitness.The convergent validity of all dimensions reached the standard,and the distinguishing validity was good.Finally,the Cronbach's α coefficient of the Scale was 0.971,and the split-half reliability was 0.928.Conclusion The developed Scale possesses good reliability and validity,which can be used to evaluate the competence of health professionals carrying the evidence-based healthcare related link works.

Objective:To explore the application efficacy of the continuous oral care program led by dental nurses in adolescent patients with fixed orthodontics and to provide a reference for continuous care to enhance the oral health level of patients.Methods:A randomized controlled trial was carried out in the Orthodontic Department of Shanghai Stomatological Hospital from June to December 2022. A total of 132 adolescent patients with fixed orthodontics were selected through the convenience sampling method and divided into the experimental group and the control group by the random number table method, with 66 patients in each group. The experimental group was provided with the continuous oral care program led by dental specialist nurses, while the control group received routine care. The intervention lasted for 12 months. The Oral Health Impact Scale, the Oral Health Self-Management Ability Questionnaire, and the plaque index were utilized to assess the intervention effect before and after the intervention.Results:A total of 65 participants in the experimental group completed the study, with an age of (14.41 ± 1.60) years, comprising 32 males and 33 females. In the control group, 64 participants completed the study, with an age of (14.15 ± 1.69) years, including 28 males and 36 females. Prior to intervention, there were no statistically significant differences in scores for oral health self-management ability, Oral Health Impact Profile-14, or total plaque index between the experimental and control groups (all P>0.05). Following intervention, the score for oral health self-management ability in the experimental group was (77.42 ± 11.70) points, significantly higher than (70.47 ± 17.49) points of the control group ( t = 2.65, P<0.05). Additionally, the score on the Oral Health Impact Profile-14 for the experimental group was (16.40 ± 3.45) points and their total plaque index was measured at 1.68 ± 0.55 both significantly lower than those recorded in the control group at (18.16 ± 3.79) points and a total plaque index of 1.92 ± 0.47 respectively ( t = - 2.75, - 2.55, both P<0.05). Conclusions:The implementation of the continuous oral care program led by dental specialist nurses is conducive to improving the oral health self-management ability of adolescent patients with fixed orthodontics, reducing dental plaque, improving oral cleanliness, and improving the oral health-related quality of life of patients.

Objective:To explore the application efficacy of the continuous oral care program led by dental nurses in adolescent patients with fixed orthodontics and to provide a reference for continuous care to enhance the oral health level of patients.Methods:A randomized controlled trial was carried out in the Orthodontic Department of Shanghai Stomatological Hospital from June to December 2022. A total of 132 adolescent patients with fixed orthodontics were selected through the convenience sampling method and divided into the experimental group and the control group by the random number table method, with 66 patients in each group. The experimental group was provided with the continuous oral care program led by dental specialist nurses, while the control group received routine care. The intervention lasted for 12 months. The Oral Health Impact Scale, the Oral Health Self-Management Ability Questionnaire, and the plaque index were utilized to assess the intervention effect before and after the intervention.Results:A total of 65 participants in the experimental group completed the study, with an age of (14.41 ± 1.60) years, comprising 32 males and 33 females. In the control group, 64 participants completed the study, with an age of (14.15 ± 1.69) years, including 28 males and 36 females. Prior to intervention, there were no statistically significant differences in scores for oral health self-management ability, Oral Health Impact Profile-14, or total plaque index between the experimental and control groups (all P>0.05). Following intervention, the score for oral health self-management ability in the experimental group was (77.42 ± 11.70) points, significantly higher than (70.47 ± 17.49) points of the control group ( t = 2.65, P<0.05). Additionally, the score on the Oral Health Impact Profile-14 for the experimental group was (16.40 ± 3.45) points and their total plaque index was measured at 1.68 ± 0.55 both significantly lower than those recorded in the control group at (18.16 ± 3.79) points and a total plaque index of 1.92 ± 0.47 respectively ( t = - 2.75, - 2.55, both P<0.05). Conclusions:The implementation of the continuous oral care program led by dental specialist nurses is conducive to improving the oral health self-management ability of adolescent patients with fixed orthodontics, reducing dental plaque, improving oral cleanliness, and improving the oral health-related quality of life of patients.

Objective:To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. Methods:Two children with 17β hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children′s Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools.Results:The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5: 1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c. 347G>A (p.R116Q) variant and a c. 274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c. 547G>A (p.G183R) and a c. 331G>C (p.A111P). Among these, the c. 274G>A (p.A92T) and c. 331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+ PM2_supporting) and likely pathogenic (PM3+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c. 274G>A (p.A92T) variant and the ACAT1: c. 331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To study the teaching effect of traditional teaching combined with virtual simulation teaching in pharmaceutical content analysis using high performance liquid chromatography (HPLC).Methods:The students in two parallel classes of grade 2016 were divided into experimental group (44 students) and control group (38 students). Taking the content analysis and its related analytical methodology of Metronidazole by HPLC as an example, the experimental group adopted the traditional offline teaching combines with virtual simulation teaching, and the control group adopted the traditional offline teaching. The teaching effects of the two groups were compared. SPSS 22.0 was used to conduct independent-samples t-test. Results:According to the mid-term test results, the experimental group was superior to the control group in practical operation assessment [(17.98±6.75) vs. (14.03±5.92)], and the difference was statistically significant ( P < 0.05). But there were no differences between the two groups in the scores of theory, discussion report and presentation. There was no significant difference in the final exam scores between the two groups. Conclusion:The ability of practical training and the teaching effect can be improved by the teaching method of traditional offline teaching combined with virtual simulation. Through the training of this project, students have mastered the operation of HPLC, the content determination of pharmaceutical preparations, the verification of analytical methods, data processing, and the writing of analytical reports, and have certain practical analysis ability.

Objective To analyze the risk factors and pathogen drug resistance of senile stroke-associated pneumonia (SAP), and to provide references for early clinical intervention. Methods A total of 859 elderly patients with cerebral stroke admitted to our hospital from June 2018 to June 2020 were selected and divided into the study group (SAP, n=375) and the control group (no SAP, n=484) according to the occurrence of stroke associated pneumonia. Clinical data of age, gender, and other complications of the two groups were analyzed. The sputum culture and drug sensitivity test of senile SAP patients were analyzed. Results A total of 313 pathogens were detected in 375 SAP patients, including 211 strains of gram-negative bacteria (67.41%), mainly consisting of 92 Acinetobacter baumannii (29.39%), 54 Pseudomonas aeruginosa (17.25%), and 42 Klebsiella pneumoniae (13.42%), and 73 strains (23.32%) of gram-positive bacteria, mainly 62 strains of Staphylococcus aureus (19.81%). In addition, there were 29 strains of fungi (9.27%). Pseudomonas aeruginosa was highly sensitive to piperacillin/tazobactam and ceftazidime. Acinetobacter baumannii and Klebsiella pneumoniae were highly sensitive to imipenem, meropenem, and cefoperazone sodium and sulbactam sodium. Staphylococcus aureus and Enterococcus were highly sensitive to teicolanin, linezolid and vancomycin. The proportion of patients aged ≥80 years old, mechanical ventilation, bed rest and use of prophylactic antibiotics in the experimental group was significantly higher than that in the control group (P<0.05). Logistic regression analysis showed that age ≥80 years, mechanical ventilation, hypoproteinemia and use of prophylactic antibiotics were independent risk factors for SAP (P<0.05). Conclusion The main pathogens of stroke-associated pneumonia in the elderly are Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter baumannii. It is necessary to rationally choose antibiotics according to the results of drug sensitivity. The risk factors are patients' age ≥ 80 years old, mechanical ventilation, and bed rest. Clinicians should attach great importance to the prevention of stroke-related pneumonia in the elderly.