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 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 analyze changes in plasma amino acid profiles in adolescents and adults with atopic dermatitis (AD) by targeted metabolomics, to further analyze differences in plasma amino acid profiles between AD patients with elevated total IgE levels and those with normal total IgE levels, as well as between AD patients with and without allergic rhinitis, and to explore the pathogenesis of AD from the perspective of metabolic pathways.Methods:From December 2021 to June 2022, 40 AD patients aged > 12 years were collected as research subjects from the Department of Dermatology, the First Affiliated Hospital of Jinzhou Medical University, and 30 healthy checkup examinees served as a control group at the same time. Plasma samples were obtained from the subjects, and high-performance liquid chromatography-mass spectrometry was performed to detect levels of metabolites in the plasma samples. Principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were carried out to analyze data and screen out differential metabolites with the variable weight value (VIP) of the first principal component being > 1 in the OPLS-DA model and the P value being < 0.05 in the t test. Possible abnormal metabolic pathways were analyzed using MetaboAnalyst 5.0 software, and differential metabolic pathways were defined as those with an impact value of > 0.1 and a P value of < 0.05. Results:PCA and OPLS-DA model analysis showed that metabolites were well differentiated among the groups, and differential metabolites and metabolic pathways were screened out. Concretely speaking, 12 differential metabolites and 8 differential metabolic pathways were identified by comparing the AD group with the control group, among which differential metabolites included arginine (metabolic levels: 28.257 ± 11.517 μmol/L vs. 21.038 ± 8.500 μmol/L, VIP = 1.32, P = 0.001), ornithine (47.597 ± 18.158 μmol/L vs. 36.937 ± 5.813 μmol/L, VIP = 1.26, P < 0.001) and histidine (78.322 ± 14.971 μmol/L vs. 100.694 ± 32.419 μmol/L, VIP = 1.33, P < 0.001), and differential metabolic pathways included arginine biosynthesis (impact = 0.482, P < 0.001) and histidine metabolism (impact = 0.221, P < 0.001). Comparisons between the AD group with elevated IgE levels and those with normal IgE levels showed 5 differential metabolites and 3 differential metabolic pathways, among which differential metabolites included lysine (313.998 ± 61.252 μmol/L vs. 285.330 ± 58.388 μmol/L, VIP = 2.25, P < 0.001) and glycine (200.807 ± 53.320 μmol/L vs. 187.056 ± 50.941 μmol/L, VIP = 1.40, P = 0.014), and differential metabolic pathways included the glyoxylate and dicarboxylate metabolic pathway (impact = 0.105, P = 0.001) ; by comparing the AD group with and without allergic rhinitis, 6 differential metabolites and 3 differential metabolic pathways were identified, among which the arginine biosynthesis metabolic pathway was highlighted (impact = 0.116, P < 0.001) . Conclusion:The plasma amino acid metabolites in adolescents and adults with AD were different from those in healthy controls, and elevated plasma levels of arginine and ornithine and decreased plasma level of histidine may be involved in the pathogenesis of AD; increased plasma levels of lysine and glycine were associated with AD with elevated IgE levels; the arginine biosynthetic metabolic pathway was related to AD complicated by allergic rhinitis.

Click chemistry has been proven to be very useful in drug delivery. Due to the availability of a large number of click reactions with a various characteristics, selection of appropriate chemistry for a given application is often not a trivial task. This review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry experts. For this, the review gives an overview of available click reactions organized by application types. Further, the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain applications. For this, we highlight the need to analyze the relationship among reaction kinetics, concentration effects, and reaction time scales, knowing that lack of such analysis could easily lead to failures. Further, possible issues such as chemical stability with various click reagents are also discussed to aid experimental designs. Recent examples and extensive references are also provided to aid in-depth understanding of technical details. We hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.

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 observe the clinical features and therapeutic effect of 11p15/NUP98 rearrange-ments in acute leukemia. Methods A total of 598 newly diagnosed acute leukemia patients were detected by con-ventional cytogenetics analysis and fluorescence in situ hybridization(FISH)with the NUP98 double color probe, and the clinical data were analyzed retrospectively in the patients with 11p15/NUP98 abnormality. Results Six cases with 11p15/NUP98 rearrangement were found with a median age of 39 years old,one patient is male,the oth-ers are females. Three patients had acute monocytic leukemia(M5),one patient had acute monocytic leukemia (M2),one patient had acute monocytic leukemia(M4),and one patient had acute lymphoblastic leukemia. 11p15/NUP98 abnormality was detectable in all the patients. The median survival in all the patients was 9 months. Con-clusions Acute leukaemia with 11p15 abnormality frequently involves NUP98 gene and mainly occurrs in women. Patients with lower median age mainly developed in acute monocytic leukemia. The major clinical manifestations are anemia,low platelets and hyperleukocytosis. Acute leukemia with 11p15/NUP98 rearrangement is poorly re-sponsive to routine chemotherapies and to allogeneic hematopoietic stem cell transplantation,and thus has poor prognosis.

As a kind of intervention measures of traditional Chinese medicine, acupuncture-moxibustion is highly adopted on global clinical practice. Even though the global clinical trial registration system was established more than 10 years ago, the proportion of acupuncture-moxibustion clinical trial registration is still very low; and it is very problematic on the methodological quality and report quality in the published acupuncture-moxibustion clinical trials. In order to manage particularly the acupuncture-moxibustion clinical trials, China Academy of Chinese Medical Sciences, collaborated with China Association of Acupuncture and Moxibustion and World Federation of Acupuncture Societies, established the Acupuncture-Moxibustion Clinical Trail Registry (AMCTR). AMCTR is a secondary registry platform affiliated to the Chinese Clinical Trial Registry (ChiCTR) and WHO International Clinical Trials Registry Platform (ICTRP), specifically for the acceptance and management of clinical trials in the field of acupuncture and moxibustion. It is a nonprofit academic organization, located in China Academy of Chinese Medical Sciences.

Objective To discuss the clinical value of CT combined electronic level guided percutaneous transthoracic needle biopsy in diagnosis of small pulmonary nodules.Methods 44 cases of lung mini-nodule underwent CT combined electronic level guided percutaneous transthoracic needle biopsy.After operation the tissue was sent for pathologic examination.The nodules were divided into two groups,including Group A (diameter 0.5-1.0 cm,N=10) and Group B (diameter 1.1-2.0 cm,N=34),according to the different sizes of diameter.The excision of postoperative pathological and diagnosis result of clinical diagnosis and treatment of more than 12 months follow up were taken as the final result.The sensitivity,specificity,veracity and complications were compared and analyzed using paired x2 test,taking P＜0.05 as significant difference.Results (1)The arrival rate of target puncture were 100 ％ in 44 cases,with the sensitivity rate of 90.9％,specificity rate of 100 ％,veracity rate of 88.6 ％,positive predictive value of 97.5 ％,and negative predictive value of 100 ％.The sensitivity,specificity and veracity of Group A were 77.8％,100％ and 70.0％ respectively.And the sensitivity,specificity and veracity of Group B were 94.1％,100％ and 94.1％ respectively.The sensitivity,veracity of Group A was higher than Group B (P＜0.05),while there was no difference in specificity.(2)Complication:the incidence rate of pneumothorax,pulmonary bleeding symptoms and hemothorax were 9.1％,11.4％,2.3％,respectively.The incidence rate of total complication was 22.7％,and all be cured after the treatment.The lesions with emphysema around is a risk factor for pneumothorax and pulmonary bleeding symptoms (x2 =11.2,10.2,P＜0.05).However,the position,size and deepness was not correlated with the complications mentioned above (P ＞0.05).Conclusion CT combined electronic level guided percutaneous transthoracic needle biopsy is a safe,effective and accurate diagnostic method for lung mini-nodule lesion.