OBJECTIVE To assess the scientific rigor， clarity and feasibility of the recommendations of the Guidelines for Evidence-based Use of Biological Agents for the Clinical Treatment of Osteoporosis （hereinafter referred to as the Guideline） through external review， in order to further revise and improve the Guideline recommendations. METHODS This study employed a cross-sectional survey research design， a convenience sampling method was adopted to select frontline medical workers in the field of osteoporosis （including clinical doctors， clinical pharmacists， and nurses） as well as patients or their family members. External review was conducted through a combination of closed-ended and open-ended electronic questionnaires to get feedback from them on the appreciation，clarity and feasibility of the 32 preliminary recommendations in the Guideline. RESULTS A total of 90 external review subjects from 15 hospitals were collected， including 45 clinical doctors， 15 clinical pharmacists， 15 nurses and 15 patients or their family members. The overall appreciation degree of recommendations was 99.38%， the overall clarity degree of recommendations was 98.92%， and the overall feasibility degree of recommendations was 99.65%. At the same time， 111 subjective suggestions were collected， which provided an important reference for the further improvement of the Guideline recommendations. Based on the above feedback， the Guideline steering committee and core expert group revised the wording of 12 draft recommendations without deletion， and finally determined 32 recommendations. CONCLUSIONS The external review provides an important basis for the final formation of the Guideline， further improves the scientific rigor， clarity and feasibility of the recommendations， and ensures the standardization， practicality and implementability of the Guideline.

OBJECTIVE To provide standardized guidance for the clinical application and management of biosimilars， and promote their widespread and rational use in clinical treatment. METHODS The design， planning， and drafting process as well as the full report of Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） followed the WHO Handbook for Guideline Development （2nd edition）， which fully considered the best current evidence from evidence-based medicine， multidisciplinary expert experience， and patient preferences and values. Grading of Recommendations Assessment， Development， and Evaluation （GRADE） approach was adopted to evaluate the quality of evidence and determine the strength of recommendations. RESULTS & CONCLUSIONS Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） presented 10 recommendations including 7 strong recommendations and 3 weak recommendations. The recommendations covered the entire process of clinical application and management of biosimilars. Medical institutions and relevant health regulatory departments can refer to this guideline for the scientific management of the extrapolation of unapproved indications of biosimilars. Healthcare providers can refer to this guideline for pre-treatment assessments， patient education， pre-treatment regimen before administration， and dosage regimen adjustments. Multidisciplinary medical teams can refer to this guideline to provide pharmacovigilance and patient management throughout the treatment process.

Objective To investigate the clinical features,treatment and prognosis of children with histiocytic necrotizing lymphadenitis(HNL).Methods The clinical data of 72 children with HNL diagnosed and treated in the Department of Infectious Diseases,Children's Hospital Affiliated to Shandong University from January 2019 to December 2023 were reviewed.The clinical symptoms,laboratory examination,imaging examination,pathological findings,treatment and follow-up were retrospectively analyzed.Results Among the 72 children,49 were males and 23 were females.The age was 3 to 15 years old,of which 55 cases(76.4％)ranged from 8 to 13 years.The duration of the first onset was 2-60 days,with an average of 15 days.All the children had fever and lymph node enlargement.Only abdominal lymph node lesions were present in 1 case,and cervical lymph nodes were involved in the rest.In the course of the disease,a few of the children had rash,joint swelling and pain and aseptic meningitis.One patient had coronary artery and jugular dilatation.In the acute stage of the disease,most children had decreased white blood cells and hemoglobin,increased erythrocyte sedimentation rate and lactate dehydrogenase.71 cases were treated with glucocorticoid,and 69 cases were treated for 8-12 weeks.The longest follow-up of the newly diagnosed cases has been nearly 5 years,except for one patient who developed cutaneous lupus,no case has recurred or progressed to other immune diseases.Conclusion Children HNL is more common in school-age children.The overall incidence is higher in boys than girls.Most children with HNL present with cervical lymph node enlargement,and very few patients only involve deep lymph nodes.It can also cause vascular lesions.Treatment with glucocorticoids for 2 to 3 months after diagnosis may reduce recurrence and prevent disease progression.

Objective:To investigate the predictive value of mucosal vascular pattern (MVP) under narrow-band imaging (NBI) enteroscopy in patients with ulcerative colitis (UC) in clinical remission for histological healing and clinical recurrence.Methods:A total of 142 patients with UC in clinical remission who visited the First Affiliated Hospital of Weifang Medical University from January 2018 to January 2021 were included in the study and underwent colonoscopy. The white light and NBI endoscopic images were collected and biopsies were obtained. The Mayo endoscopic score (MES) was calculated based on white light images, and MVP staging was evaluated based on mucosal vascular patterns under NBI. Nancy index (NI) was used to evaluate histological healing and patients were followed up for 1 year. The Spearman correlation coefficients of MES and MVP with histological healing and recurrence were calculated. The receiver operator characteristic (ROC) curve was plotted and the area under curve (AUC) was applied to evaluate the accuracy of white light and NBI endoscopy for predicting histological healing of UC in clinical remission.Results:According to the MVP criteria, 47 were defined as clear, 63 blurred, and 32 invisible. Spearman correlation analysis showed a significant correlation between MVP under NBI and histological healing ( r=0.549, P<0.001) and a moderate correlation between MES under white light and histological healing ( r=0.462, P<0.001). Spearman correlation analysis showed a moderate correlation between MVP under NBI and clinical recurrence ( r=0.451, P<0.001) and a moderate correlation between MES under white light and clinical recurrence ( r=0.352, P<0.001). AUC of NBI for diagnosing histological healing of UC in clinical remission was 0.809 (95% CI: 0.738-0.879), with a sensitivity of 84.6% (77/91) and specificity of 64.7% (33/51), superior to the white light endoscopy, of which AUC, sensitivity and specificity were 0.763 (95% CI: 0.678-0.848), 81.3% (74/91) and 66.7% (34/51). Conclusion:MVP staging under NBI could predict histological healing of UC patients in clinical remission and is superior to white light endoscopy.

Objective:To establish a performance validation method for mNGS applied in BALF samples.Method:Hela cells were used as a representative of host cells, and simulated BALF samples were prepared by adding different concentrations of Hela cells, seven species of isolated pathogens (including Streptococcus pneumonia, Hemophilus influenza, Klebsiella pneumonia, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Adenovirus), and interfering substances to sterile normal saline. Clinical BALF samples were collected simultaneously, and the results of mNGS were evaluated using traditional detection methods as a reference. The limit of detection (LOD), precision, anti-interference ability, stability, and accuracy of mNGS were determined. Results:In the simulated samples, the LOD of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Adenovirus were 150, 262, 102, 67, 96, 83 CFU/ml, and 439 copies/ml, respectively. The repeatability of the detection results for all pathogens of simulated positive BALF samples was 100%. The anti-interference test showed that the higher the concentration of human DNA, the fewer pathogen sequences detected by mNGS. Escherichia coli and Shigella sonnei were used to evaluate the ability of mNGS to distinguish closely related species. The results showed that the system could stably distinguish Escherichia coli and Shigella sonnei when the concentration of Shigella sonnei was 4, 000 CFU/ml. The stability test results showed that there was no significant change in the number of pathogen sequences detected whether after 1 to 3 freeze-thaw cycles or storage at 4 ℃, -20 ℃, or -80 ℃ for 36 h. Compared with traditional detection methods, the accuracy of 17 clinical samples was 82.4%(14/17). Continuous evaluation of clinical BALF samples simultaneously tested by mNGS and traditional methods at Tongji Hospital from October 25, 2021, to September 14, 2022, showed that the accuracy of mNGS compared to bacterial culture, fungal culture, mycobacterial culture, Mycobacterium tuberculosis culture, and conventional PCR techniques was 67.5%(472/699), 81.5%(570/699), 92.3%(335/363), 96.4%(350/363), and 86.8%(132/152), respectively. Compared with conventional PCR techniques, the accuracy of mNGS for detecting Pneumocystis jirovecii, Adenovirus, and Mycoplasma pneumoniae was 89.4%(84/94), 93.3%(56/60), and 87.1%(61/70), respectively. Conclusion:By preparing simulated BALF samples and using traditional detection methods as a reference, the performance characteristics of mNGS in detecting BALF samples can be preliminarily evaluated.

Objective:This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients.Methods:A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined.Results:The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] ( P<0.001). All mutations occurred in exon 2. MUC4 mutation ( OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups ( P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] ( P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group ( P=0.487) . Conclusion:MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.

Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment ， Development，and Evaluation （GRADE）approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ，this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ，involving evaluation prior to administration （liver and renal function ，pleural effusion and ascites ， comedication，genetic testing ），pre-treatment and routine dosing regimen （pretreatment of hydration and alkalization ，urine alkalization，routine dosing regimen ），therapeutic drug monitoring （necessity，method，timing，target concentration ），leucovorin rescue（rescue timing ，rescue regimen ，rescue dose optimization ），and management of toxicities （liver and kidney function monitoring，supportive treatment ，blood purification treatment ）. This article aims to summarize and interpret the recommendations of this guideline ，so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.

Objective:To understand the cognition and related factors on the use of HIV non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM).Methods:The snowballing method was applied to recruit research subjects who were ≥18 years old, had sex with men in the past three months, and were aware of nPEP in MSM groups in Beijing, Shenzhen, and Kunming from March 15 to April 14, 2019. Data on social demographics, behavioral characteristics, basic knowledge of nPEP, consultation, and using nPEP were collected through "i guardian Platform". The logistic regression model was used to analyze the related factors affecting the use of nPEP.Results:Among 1 809 investigated, 39.8% (720 persons) were aware of the basic knowledge of nPEP, 33.4% (605 persons) had consulted nPEP, and 15.0% (271 persons) had used nPEP. In addition, multivariate logistic regression analysis showed that factors as whether to have sex with men infected with HIV in the last three months ( OR=2.58, 95% CI: 1.64-4.07), the frequency of HIV testing in the past year ( OR=2.47, 95% CI: 1.28-5.11), nPEP knowledge awareness ( OR=0.70, 95% CI: 0.49-0.99), whether to consult nPEP ( OR=70.98, 95% CI: 40.51-136.83) were related to the use of nPEP. Conclusions:MSM still have poor cognition of nPEP. It is necessary to strengthen the publicity and education of nPEP in MSM and promote the use of nPEP after HIV exposure as soon as possible.

Objective: To investigate the prevalence of postoperative delirium(PD)and its risk factors in patients aged 80 and over with hip fracture treated with total hip arthroplasty(THA). Methods: Clinical history and perioperative data of patients aged 80 years and over with hip fractures who underwent THA in our hospital from Sep.2017 to Mar.2019 were analyzed.Patients were divided into delirium group and non-delirium group.The prevalence of postoperative delirium of THA and its risk factors were analyzed by multiple Logistic regression. Results: A total of 90 patients were eligible for inclusion for this study.Of them, 27 patients(30.0%)were diagnosed as PD and 63(70.0%)did not experience PD.Multivariate stepwise Logistic regression analysis showed that a history of stroke(OR=17.702, 95%CI: 1.514-207.034, P=0.022), preoperative lower serum albumin(OR=1.524, 95%CI: 1.132-2.051, P=0.005), Mini-Nutritional Assessment short-form score(MNA-SF)(OR=1.481, 95%CI: 1.045-2.099, P=0.027)were independent risk factors for PD. Conclusions The prevalence of postoperative delirium of THA is higher in patients aged 80 years and over with hip fractures.Prevention and correction of risk factors, such as malnutrition, may help prevent the postoperative delirium.

Objective Summarize and share the working practice of Investigator Research Ethics and Research Integrity Training conducted at Peking University Human Research Protection Program (PKU HRPP) ,to further explore continuing quality improvement of investigator ethical training at university level .Methods Conduct systematic review of the archiving files of PKU HRPP investigator training activities during 2012-2018 ,summarize feedback information from investigators to i-dentify possible experiences for sharing and space for improvement .Results There are some positive experiences for sharing a-bout the training mechanism and practices at PKU HRPP .Conclusions Based on the previous ethical training work and experi-ences at PKU HRPP ,possible proposals for continuing quality improvement may including :strengthening the requirements of ethical training of investigators ,encouraging and recognizing ethical training conducted by research teams ,emphasizing training Quality and the promotion of sharing and mutual recognition mechanisms for ethical training .