OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals’ phase 0 clinical trials （hereinafter referred to as “phase 0 clinical trials”） and advancing the development of innovative drug by medical institutions. METHODS Initiated by the First Affiliated Hospital of Jinan University， a panel of experts consisting of pharmacy， clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape， and discuss the necessary conditions， procedures， and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies， regulations and expert consensus. Finally， an agreement was reached to formulate this consensus. RESULTS & CONCLUSIONS Currently， most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials. In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions， this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials （2020 edition）， providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research. Additionally， in consideration of some constraints imposed by current relevant regulations， this consensus also proposes strategic recommendations， such as encouraging medical institutions to form a consortium， leading to the establishment of dedicated bases or industrial parks， holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.

Objective To study the protective effect of Wedelolactone(WEL)against inflammatory injury in human umbilical vein endothelial cells(HUVECs)and its molecular mechanism by inducing PI3K/Akt/mTOR.Methods The model of atherosclerosis(AS)oxidative stress injury in HUVECs was induced with 200 μmol·L-1 of hydrogen peroxide for 24 h.The experimental groups were as follows:normal control group,DMSO(dimethyl sulfoxide)group,H2O2 group,and WEL group.MTT was used to measure the cell survival rate of each group;flow cytometry was used to assess intracellular ROS levels;fluorescence microscopy was used to detect the expression of p62 protein;immunoblotting assay was used to determine the protein expression levels for apoptosis-related proteins associated with PI3K/Akt/mTOR signaling pathway and autophagy-related proteins.Results Compared with the H2 O2 group,the HUVEC cell survival rate was significantly inhibited in the WEL group(P＜0.05).ROS production was significantly lower,and the protein expressions of SOD1 and p62 were significantly increased in the WEL group as compared to the hydrogen peroxide group.The protein expression of p-mTOR,p-Akt,and p-PI3K was significantly decreased in hydrogen peroxide(P＜0.01);In the WEL experiment,p-mTOR,p-Akt,and p-PI3K were increased significantly in the post-injury HUVECs(P＜0.01).Conclusion Wedelolactone inhibits HUVECs'autophagy by suppressing H2O2-induced inflammatory damage in HUVECs,which may be related to the fact that WEL promotes the phosphorylation of PI3K,Akt,and mTOR proteins,inhibits autophagy and thus resists oxidative stress damage in HUVECs cells.

Objective:To analyze the application value of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9 and CA242 in screening colorectal cancer with a meta-analysis.Methods:A literature search was conducted in the databases of Pubmed, Embase, Cochrane, CNKI, Wanfang and VIP to identify studies on applying CEA, CA19-9 and CA242 for detection of colorectal cancer from the establishment of the databases to October 2023. The Quality Evaluation Tool of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of the literature. Stata17.0 statistical software was used for meta-analysis. Deeks funnel plot was used to analyze publication bias.Results:A total of 34 articles of case-control studies met the criteria. Meta-analysis revealed that the diagnostic accuracy and sensitivity of CEA, CA19-9 and CA242 were all low, the area under the curve (AUC) of summary receiver operating characteristic curve was 0.62, 0.63 and 0.73, the sensitivity was 0.42, 0.27 and 0.36, respectively. The combined detection of CEA+CA19-9+CA242 significantly improved the pooled diagnostic accuracy (AUC: 0.92(95% CI: 0.89-0.94) and sensitivity: 0.75(95% CI: 0.65-0.83)), the specificity was mildly reduced (dropped from above 0.95 to 0.90(95% CI 0.87-0.93)). The Deek′s test indicated no publication bias. Conclusions:Combined detection of CEA+CA19-9+CA242 can significantly improve the diagnostic accuracy and sensitivity in screening colorectal cancer with a compromised specificity. However, due to the lack of data, whether it can meet the demand for opportunistic screening in the physical examination population needs to be confirmed.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the feasibility of active surveillance for low-risk papillary thyroid microcarcinoma.Methods:This is a cross-sectional study. From 2013 to 2017, 61 patients with pathologically confirmed papillary thyroid microcarcinoma were followed-up dynamically. The growth of nodules, newly-developed nodules and lymph node metastasis were recorded and were set as the criteria for disease progression. And the disease progression was the outcome event of survival analysis. The patients were divided into two groups based on the median age at diagnosis. Univariate analysis of factors influencing disease progression in different age groups was performed using Cox proportional hazards regression. The differences in disease progression between different age groups were compared using the Kaplan-Meier method and the log-rank test.Results:Of the 61 patients, there were 9 males and 52 females. The median age of disease onset was 43 years (ranged 23-74 years). The median follow-up time was 2 years (ranged 2-7 years), and 22 (36.1%) patients with tumor diameter increased by ≥3 mm, including 5 males and 17 females. A total of 22 cases (36.1%) showed an increase in tumor diameter of ≥3 mm, including 5 males and 17 females. Thirteen cases (21.3%) developed new malignancies, including 2 males and 11 females. Three cases (5%) had lymph node metastasis, all of which were females. In total, 24 cases (39.3%) showed disease progression, including 5 males and 19 females. Disease progression was more frequent in the <43 years age group compared to the ≥43 years age group.Conclusions:For patients with low-risk papillary thyroid microcarcinoma, strict adherence to the indications for active surveillance and consideration of patient preferences make active surveillance a feasible tumor management approach.

Ebola virus (EBOV) is an enveloped negative-sense RNA virus and a member of the filovirus family. Nucleoprotein (NP) expression alone leads to the formation of inclusion bodies (IBs), which are critical for viral RNA synthesis. The matrix protein, VP40, not only plays a critical role in virus assembly/budding, but also can regulate transcription and replication of the viral genome. However, the molecular mechanism by which VP40 regulates viral RNA synthesis and virion assembly/budding is unknown. Here, we show that within IBs the N-terminus of NP recruits VP40 and is required for VLP-containing NP release. Furthermore, we find four point mutations (L692A, P697A, P698A and W699A) within the C-terminal hydrophobic core of NP result in a stronger VP40-NP interaction within IBs, sequestering VP40 within IBs, reducing VP40-VLP egress, abolishing the incorporation of NC-like structures into VP40-VLP, and inhibiting viral RNA synthesis, suggesting that the interaction of N-terminus of NP with VP40 induces a conformational change in the C-terminus of NP. Consequently, the C-terminal hydrophobic core of NP is exposed and binds VP40, thereby inhibiting RNA synthesis and initiating virion assembly/budding.
Ebolavirus/physiology* ; HEK293 Cells ; HeLa Cells ; Humans ; Nucleocapsid Proteins/metabolism* ; RNA, Viral/metabolism* ; Viral Matrix Proteins/metabolism* ; Virion/metabolism* ; Virus Assembly

Objective:To study the correlation between hearing loss and cognitive decline in community-dwelling older adults and to analyze the influencing factors.Methods:Using Pure-tone audiometry, the Hearing Handicap Inventory for the Elderly (HHIE), Mini-Mental State Examination (MMSE), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder, a survey was conducted with 492 community-dwelling older adults aged 60 years and above in Beijing. Age, gender, education level, hearing loss, levels of anxiety and depression, and other factors were used as independent variables, and the MMSE scores were used as dependent variables. Analysis of variance and multiple linear regression were performed.Results:Among the 492 subjects, based on the better ears, 418 (85.0%) had hearing loss and 160 (32.5%) had disabled hearing loss. Factors such as age (β=-0.33, P<0.01), gender (β=0.09, P=0.04), education level (β=0.31, P<0.01), hearing loss (β=-0.11, P=0.02) and marital status (β=0.56, P=0.02) were significantly related to cognitive decline. Gender (β=-0.17, P<0.01) and hearing loss (β=0.08, P=0.02) correlated with anxiety indicators; gender (β=-0.84, P=0.02) and hearing loss (β=0.04, P=0.01) also correlated with depression indicators. Conclusion:Results indicated a correlation between hearing loss and cognitive decline, and between hearing loss and anxiety and depression among community-dwelling older adults in Beijing.

Objective:To investigate the prevalence and risk factors of hypertensive retinopathy (HRP) in a non-diabetic population over 30 years old during routine health examinations.Methods:This was a cross-sectional study of a non-diabetic population over 30 years of age. The study was conducted during routine health examinations at the Tongren Hospital, Beijing, from January to December 2020. Fundus photographs were taken, and data including medical history, height, weight, and blood pressure were collected. Routine laboratory examinations were performed. The study population was divided into hypertension, transient hypertension, and non-hypertension groups. The prevalence of HRP was compared among the three groups. OR and 95% CI of HRP risk factors was estimated by binary logistic regression, adjusted for age and gender. Results:The prevalence of HRP was 4.3% in the non-diabetic population over 30 years old. Adjusted for age, gender, and systolic blood pressure, the prevalence of HRP in hypertension and transient hypertension groups, was both higher than in the non-hypertension group [ OR(95% CI) of 3.11(2.25-4.30) and 1.72(1.21-2.45), respectively]. The proportion of grade 1-2 HRP was higher (76.2%). There was no significant difference in the prevalence of grade 3 HRP among the three groups. Adjusted for age and gender, systolic blood pressure and creatinine clearance rate were independent risk factors for HRP in the hypertension group [ OR(95% CI): 1.22(1.01-1.48) and 1.66(1.12-2.46)] and transient hypertension group [ OR(95% CI): 1.48(1.10-2.06) and 1.95(1.03-3.46)]. SBP and DBP were independent risk factors for HRP in the non-hypertension group [ OR(95% CI): 1.68(1.07-2.63) and 1.61(1.06-2.44)]. Conclusions:There was a high prevalence of HRP among the non-diabetic population over the age of 30 and there was still relatively high risk of grade 3 HRP among the normotensive population.

Objective:To investigate the prevalence and characteristics of adult hearing loss.Methods:From March 2018 to November 2019, 8, 439 adult physical examinees were screened for hearing (i.e., 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz pure tone air conduction audiometry), while some were examined for hearing diagnosis (i.e., 250 Hz, 500 Hz, 1, 000 Hz, 2, 000 Hz, 4 000 Hz, and 8 000 Hz pure tone bone air conduction audiometry). Prevalence, location, frequency and type of hearing loss in different age and gender groups were analyzed using SPSS 25.0.Results:The prevalence of hearing loss was 32.2%, which increased with age. The prevalence in males was higher than that of females (40.1% vs. 21.6%). The rate of single frequency damage was higher in male than in female, while the rate of multiple frequency damage was higher in women than in men ( P<0.001). The high frequency (4 000 Hz) damage rate in male was higher than that of females, while the low-middle frequency (500-2 000 Hz) damage rate in females was higher than that of males ( P<0.001). Sensorineural hearing loss accounted for 90.8%, while conductive hearing loss was 3.9%, mixed hearing loss was 5.0%, and others were 0.3%. Conductive hearing loss was mainly concentrated in the younger age group. Conclusion:Physical examination population has a relatively high prevalence of hearing loss. The characteristics of hearing loss differed with age and gender.

Objective: To explore the effect of axial flap of adjacent artery perforator with vascular pedicle in repairing scar deformity of face and neck in patients. Methods: From January 2010 to June 2018, 38 patients with cicatricial deformity of face and neck after deep burn were admitted to author′s unit, including 22 males and 16 females, aged 5-56 years. The time of admission was 7 months to 19 years after burn injury. The size of wounds ranged from 7.0 cm×4.0 cm to 20.0 cm×10.0 cm after scar tissue was released. Nineteen patients were treated by upper thoracic internal artery perforator flap with size ranged from 7.0 cm×5.0 cm to 18.0 cm×8.5 cm. Among them, 16 cases were preexpanded with expanders at thorax whose rated capacity ranged from 300 to 500 mL and times of water injection of 1.8 to 3.1, and 3 cases were directly used. Twelve patients were treated by transverse carotid artery perforator flap with size ranging from 7.0 cm×4.5 cm to 11.0 cm×8.5 cm, of which 8 patients were preexpanded and 4 cases were directly used. The rated capacity of expander placed at the supraclavicular region ranged from 200 to 350 mL with times of water injection from 1.5 to 2.0. Seven patients were treated by preexpanded superficial temporal frontal branch artery perforator flap with size of 5.5 cm×3.8 cm to 8.0 cm×5.0 cm. The rated capacity of expanders placed at forehead was 150 to 300 mL with times of water injection of 1.5 to 2.0. Donor sites were directly sutured or reversely repaired by pedicled skin tube plasty. After operation, operation times and treatment time were recorded. The survival condition and complications of flaps and follow-up were observed. Results: The patients each received 1 to 4 operation (s) with treatment time of 5 to 11 months. All flaps survived after operation. Among them, three flaps with perforating branches of internal thoracic artery had slight blood circulation disturbance at the distal end and were healed after conservative dressing change, etc. Pigment changes were observed at the distal end of thoracic internal artery perforator flaps in two patients in the later stage and was resected and repaired in the second stage. The patients were followed up for 5 to 18 months. The appearance and function of operation area were good with high satisfaction of patient. Conclusions The axial flap of adjacent artery perforator with vascular pedicle for repairing scar deformity of face and neck used directly or preexpanded can solve the problem of lack of normal skin around scar deformity without vascular anastomosis during the operation and with better appearance and function after operation. The donor site often can be directly sutured, but many operations often need to be completed for finishing whole treatment.