OBJECTIVE To formulate the Expert Consensus on the Management of Radiopharmaceuticals in Medical Institutions （hereinafter referred to as “the Consensus”）， focusing on key aspects such as the procurement of radiopharmaceuticals， the management of self-made radiopharmaceutical preparations， standardized clinical application， and patient medication safety management， so as to provide a reference for improving the whole-process management of radiopharmaceuticals in medical institutions.METHODS The Consensus was initiated by the Chinese Society of Nuclear Medicine， the Clinical Pharmacy Professional Committee of the China Anti-Cancer Association， and the Committee of Integrative Oncology Pharmacy of the China Anti-Cancer Association. Organized by the consensus drafting group more than 90 experts from the fields of nuclear medicine， nuclear pharmacy， and pharmacy science across China were involved. The Consensus was developed through systematic review of relevant laws， regulations， policy documents， and existing experience in radiopharmaceutical management， followed by extensive discussion and deliberation to finalize the consensus. RESULTS &CONCLUSIONS The Consensus establishes 10 key points for whole-process management of radiopharmaceuticals in medical institutions， covering organizational management and personnel requirements， procurement， preparation， acceptance， storage， risk prevention and control during use， radiation protection， and waste disposal. The Consensus provides a reference for improving radiopharmaceutical management in medical institutions and for ensuring their efficacy and safety in clinical application.

Objective To study the role of photobiomodulation(PBM)in promoting the repair of spinal cord injury(SCI)by regulating microglial cells.Methods Forty-five C57BL/6J mice were randomly divided into the sham operation(Sham)group,surgery(SCI)group and the treatment(SCI+PBM)group,with 15 mice in each.After laminectomy of the T10 vertebral body in the three groups of mice,the SCI group and the SCI+PBM group were used to construct the model of spinal cord hemisection.The SCI+PBM group received immediate PBM treatment after spinal cord injury,while the other two groups did not.On the 1st,3rd,7th,14th,21st and 28th days(D1,D3,D7,D14,D21,D28)after the operation,the Basso Mouse Scale(BMS)was used to assess the recovery of the hind limb motor function of the mice.On the 28th day post operatively,immunofluorescence was used to detect the changes of neurons in the areas of injury in the three groups of mice.Quantitative real-time PCR and Western blotting experiments were used to detect the phenotypic changes of BV2 cells under the interventions of PBM with inflammatory stimulation.Western blotting experiments were conducted to detect the effects of PBM on the nuclear factor kappa-B(NF-κB)pathway.Results On the 28th day after the operation,the results of the mouse motor assessment showed that the BMS scores and related behaviors of the mice in the SCI+PBM group were better than those of the mice in the SCI group(P＜0.05),and the neurons in the SCI+PBM group far outnumbered those in the SCI group(P＜0.05).The results of quantitative real-time PCR and Western blotting experiments showed that on the 14th day after the operation,PBM promoted the activation of M2-type microglial cells in vivo but inhibited the activation of M1-type microglial cells.In vitro experiments confirmed that PBM could promote the polarization of BV2 cells towards M2-type microglial cells.In addition,PBM inhibited the activation of the NF-κB pathway in injured spinal cords and in activated BV2 cells.Conclusion PBM can promote the repair of spinal cord injury in SCI mice by promoting microglial cells through inhibiting the NF-κB pathway.

Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data,these models showcase remarkable efficacy across various tasks,including new drug design and drug target identification.The adaptability of pre-trained trans-former-based models renders them indispensable assets for driving data-centric advancements in drug discovery,chemistry,and biology,furnishing a robust framework that expedites innovation and dis-covery within these domains.Beyond their technical prowess,the success of transformer-based models in drug discovery,chemistry,and biology extends to their interdisciplinary potential,seamlessly combining biological,physical,chemical,and pharmacological insights to bridge gaps across diverse disciplines.This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields.In our review,we elucidate the myriad applications of transformers in drug discovery,as well as chemistry and biology,spanning from protein design and protein engineering,to molecular dynamics(MD),drug target iden-tification,transformer-enabled drug virtual screening(VS),drug lead optimization,drug addiction,small data set challenges,chemical and biological image analysis,chemical language understanding,and single cell data.Finally,we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

Objective:Objective The potential of a three- dimensional bioprinted cell-laden gelatin methactyloyl (GelMA)+ hyaluronic acid (HA) composite bioink in tissue engineering was assessed by evaluating cell viability, scaffold morphology, and cell compatibility.Methods:Rabbit chondrocytes were isolated and cultured. Composite hydrogels were prepared using GelMA and HA, and their applicability in tissue engineering was assessed by evaluating physicochemical properties, cytocompatibility, and printability. The swelling and mechanical properties of 100g/L GelMA inks as the control group, and 100g/L GelMA+ 20g/L HA inks as the experimental group were assessed following photocrosslinking of the cylindrical model. The printing resolution of the GelMA/HA mesh scaffold loaded with chondrocytes was evaluated based on appearance and expansion ratio. Cell viability was determined using cell live/dead test after 14 days, while cytocompatibility was observed through in vitro microscopy and multiple immunofluorescence staining after 7 days. GraphPad Prism 8.0 was utilized for data visualization and statistical analysis. Independent-samples t-test was employed to compare differences among groups. A P-value less than 0.05 was considered statistically significant. Results:The swelling ratio of GelMA group was 10.57±0.40, which exceeded that of the GelMA+ HA group (7.63±0.61, P<0.05). The compressive elastic modulus of GelMA+ HA group measured (77.53±4.30) kPa, significantly surpassing that of the GelMA group [(25.60±5.70) kPa, P<0.05]. The extension ratio of GelMA was 2.59±0.33, while the experimental group recorded 2.66±0.12, with no statistically significant difference between them ( P>0.05). There were no notable disparities in cell viability between the two groups; both exhibited viabilities greater than 85%. On the initial day of culture, both groups exhibited intact structures, regular pores, and a substantial number of spherical cells. After 14 days of culture, the GelMA scaffold structure appeared blurred with nearly vanished pores, while large live cells were visible. The GelMA+ HA scaffold structure was slightly more relaxed with relatively intact pores and a significant presence of live cells. Furthermore, multiple immunofluorescence staining after 7 days of culture revealed no notable disparity in cell count and collagen components between the two groups; however, cell morphology in the GelMA+ HA group displayed significant elongation and clustering. Conclusion:The GelMA+ HA hydrogel exhibits enhanced mechanical properties and reduced swelling ratio, rendering it suitable for the fabrication of complex structures. Additionally, it demonstrates excellent cell compatibility.

Objective To explore median effective dose(ED50)of 0.375％ropivacaine based on the cross sectional area(CSA)of supraclavicular brachial plexus block(SCBPB)with L-shaped baffle intervention.Methods Patients scheduled for upper limb surgery from September 2023 to May 2024 at Ningbo NO.6 Hospital were enrolled.Patients were randomly divided into two groups:L-shaped baffle compression group(group L)and non-compression group(group C).CSA of supraclavicular brachial plexus was measured by ultrasound,and 0.375％ropivacaine was administered based on the CSA.The ED50 was determined by using the Dixon up-and-down sequential method,with an initial dose of 0.4 ml/mm2 and an incremental difference of 0.04ml/mm2.If the block was effective within 30 minutes,the next patient received a lower dose;If ineffective,a higher dose was administered.The process continued until seven cross-over points(ineffective to effective)were observed.ED50 and its 95％CI were calculated by using the Probit method.Adverse reactions,such as phrenic nerve paralysis,nerve injury,dyspnea were recorded.Results The ED50 of 0.375％ropivacaine for SCBPB in group C was 0.254 ml/mm2(95％CI:0.228-0.278),while in group L,it was 0.239 ml/mm2(95％CI:0.215-0.262),with no statistically significant difference between two groups(P＞0.05).The incidence of phrenic nerve paralysis in group L was significantly lower than that in group C(14.29％vs.41.67％,P＜0.05).No significant nerve injuries,dyspnea,or local anesthetic toxicity were observed in either group.Conclusion The ED50 of 0.375％ropivacaine for SCBPB with L-shaped baffle compression,based on the CSA of the brachial plexus,was 0.239 ml/mm2(95％CI:0.215-0.262).L-shaped baffle compression significantly reduced the incidence of phrenic nerve paralysis without notable side effects.

Objective:To analyze the prevalence and risk factors of blindness and moderate to severe visual impairment among Han and Kazakh residents aged 50 years and older in Tacheng City, Xinjiang Uygur Autonomous Region.Methods:This study is a cross-sectional survey conducted using cluster random sampling from October 2015 to June 2018 in Emin County, Tacheng City, Xinjiang Uygur Autonomous Region. The study included individuals aged 50 years and older to survey blindness and moderate to severe visual impairment. Ophthalmological examinations combined with questionnaires were conducted to gather basic information. The data collected from the questionnaires included general demographic information and health conditions. The results of the eye examinations were used to diagnose a total of 12 risk factors including cataracts, glaucoma, pterygium, suspected glaucoma, glaucoma, and refractive errors. These risk factors were analyzed in relation to blindness and moderate to severe visual impairment. Univariate analysis was conducted first, followed by logistic regression to identify the significant factors.Results:A total of 2 114 patients were included in the final analysis, among which the prevalence of moderate to severe visual impairment was 18.54% (392/2 114), and the prevalence of blindness was 2.74% (58/2 114). Univariate analysis showed that blindness and moderate to severe visual impairment were associated with age ( χ2 = 32.97, P < 0.05), hypertension ( χ2 = 3.48, P < 0.05), age-related cataract ( χ2 = 17.43, P < 0.05), glaucoma ( χ2 = 3.90, P < 0.05), macular degeneration ( χ2 = 16.04, P < 0.05), diabetes ( χ2 = 3.09, P < 0.05), pterygium ( χ2 = 2.57, P < 0.05), and fundus arteriosclerosis ( χ2 = 2.31, P < 0.05). Multivariate logistic regression analysis indicated that moderate to severe visual impairment was correlated with age (50 to < 60 years: OR = 2.91, 95% CI: 0.44-13.45; 60 to < 70 years: OR = 3.52, 95% CI: 0.73-8.77; 70 to < 80 years: OR = 4.31, 95% CI: 0.85-8.96), ethnicity ( OR = 4.45, 95% CI: 0.56-5.95), sex ( OR = 0.47, 95% CI: 0.34-0.64), age-related cataract ( OR = 1.67, 95% CI: 1.05-2.65), glaucoma ( OR = 2.97, 95% CI: 1.67-5.30), and coronary heart disease ( OR = 2.56, P < 0.05). Blindness was correlated with age (70-79 years: OR = 1.54, 95% CI: 1.12-2.11), sex ( OR = 0.67, 95% CI: 0.34-0.64), glaucoma ( OR = 1.65, 95% CI: 0.42-6.49), diabetes ( OR = 2.05, 95% CI: 1.35-3.09), and coronary heart disease ( OR = 1.92, 95% CI: 1.07-3.43). Among these, age (70-79 years), glaucoma, diabetes, and coronary heart disease were identified as risk factors for blindness, while sex was observed as a protective factor against blindness in this region. Based on univariate and multivariate analyses as well as clinical practice, it was concluded that age (50 to < 60 years: OR = 4.42, 95% CI: 1.31-14.92; 60 to < 70 years: OR = 4.49, 95% CI: 1.70-11.84; 70 to < 80 years: OR = 3.19, 95% CI: 1.29-7.87), age-related cataract ( OR = 1.67, 95% CI: 1.05-2.65), and glaucoma ( OR = 2.97, 95% CI: 1.67-5.30) were identified as significant risk factors for moderate to severe visual impairment. Glaucoma ( OR = 1.65, 95% CI: 0.42-6.49) and diabetes ( OR = 2.05, 95% CI: 1.35-3.09) were identified as the main risk factors for blindness in this region (both P < 0.05). Conclusions:In Tacheng City, Xinjiang Uygur Autonomous Region, the prevalence rates of moderate to severe visual impairment and blindness among Han and Kazakh residents are relatively high. Age-related cataracts and glaucoma are the primary causes, while age and diabetes are the main risk factors.

Objective:To investigate the electron microscopic evaluation results of pre-transplant biopsies of deceased donor kidneys and the corresponding recovery of graft function in recipients after kidney transplantation.Methods:A retrospective analysis was conducted on the clinical data and donor kidney electron microscopy (EM) reports of 196 kidney transplant recipients who underwent pre-implantation kidney biopsies at Renmin Hospital of Wuhan University between October 2020 and June 2023. The ultrastructural pathological features assessed in the pre-transplant kidney biopsy included: the number of glomeruli, the presence of leukocytes and endothelial cells within the glomeruli, the arrangement of capillary loops, abnormalities in podocytes, mesangial cells, mesangial matrix and glomerular basement membrane (GBM), and multilayering of the peritubular capillary basement membrane. Referring to the Mayo Clinic/Renal Pathology Society Consensus Report on the pathological classification, diagnosis, and reporting of glomerulonephritis, the expert consensus on renal biopsy pathology reporting models, and the content of the 2019 Banff Transplant Pathology Meeting, a scoring system was established for ultrastructural pathology of donor kidneys. According to the scores, the recipients were divided into three groups: Group A (total score ≥ 8 points, 94 cases), Group B (total score between 6 and 8 points, 85 cases), and Group C (total score < 6 points, 17 cases). The serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria at postoperative day 1, day 7, month 1, month 3, month 6, and year 1 were compared among the three groups.Results:Among the 196 donor kidneys, EM examination before transplantation showed the following findings: 19 cases (9.7%) had prominent leukocyte infiltration within the glomeruli, 8 cases (4.1%) had mild leukocyte infiltration, and the remaining 169 cases (86.2%) showed no obvious increase in glomerular leukocytes. Glomerular capillary loop collapse or narrowing was seen in 19 cases (9.7%). Endothelial cell proliferation was observed in 32 cases (16.3%). Homogeneous thickening of the GBM (400-900 nm) was present in 82 cases (41.8%). Foot process effacement ranged from partial to diffuse. Podocyte vacuolar degeneration was seen in 62 cases (32.1%), and podocyte swelling in 10 cases (5.1%). Electron-dense deposits in the mesangial area were observed in 9 cases (4.6%). Mild tubular epithelial swelling was present in 6 cases (3.1%). Only 22 cases (11.2%) showed no multilayering of the peritubular capillary basement membrane, while 174 cases (88.8%) showed 2 to 5 layers of multilayering. All donor glomeruli showed irregular capillary loop arrangement, and the renal interstitium showed scattered inflammatory infiltration and varying degrees of collagen fiber deposition. Group C had significantly higher qualitative proteinuria levels at day 7 and month 1 post-transplantation compared with Groups A and B ( P=0.036, 0.004). There were no statistically significant differences in other renal function indicators among the groups (all P>0.05). Conclusions:Pre-transplant electron microscopy of donor kidneys helps in accurately assessing donor kidney quality and identifying subtle pre-existing pathological changes. It can serve as a reference tool for predicting post-transplant functional recovery. Mild ultrastructural abnormalities in donor kidneys have a relatively controllable impact on long-term graft outcomes.

Objective:To explore the effects and potential mechanisms of chemokine-like factor-like MARVEL transmembrane domain-containing Protein 3 (CMTM3) on the proliferation and migration of glioblastoma (GBM) cells.Methods:Using CMTM3 expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, we analyzed the differential expression of CMTM3 in GBM tissues and its impact on the prognosis of GBM patients. Immunohistochemical staining and protein content determination of CMTM3 was performed on GBM and adjacent non-cancerous tissue samples from 11 GBM patients who underwent surgical treatment at the Affiliated Hospital of Guizhou Medical University between November 3, 2022 and March 15, 2023. Additionally, the expression of CMTM3 was validated in GBM cell lines U87, U251, LN229, and the human astrocyte (NHA) cell line using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses. Stable cell lines with silenced and overexpressed CMTM3 (sh-CMTM3 group and OE-CMTM3 group) were constructed using U251 cells. The effect of CMTM3 expression on cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to examine the impact of CMTM3 expression on the cell cycle. Transwell assays were conducted to evaluate the influence of CMTM3 expression on cell migration. Bioinformatics analysis, Western blotting, NF-κB activation-nuclear translocation assays, and the NF-κB pathway inhibitor pyrrolidine dithiocarbamate ammonium (PDTC) were used to validate the effect of CMTM3 on the NF-κB pathway. Finally, a subcutaneous tumorigenesis assay in nude mice was performed to observe the impact of CMTM3 expression on the in vivo growth of U251 cells. Results:Bioinformatics analysis revealed that CMTM3 is highly expressed in GBM tissues. Patients with a high CMTM3 expression had lower overall survival (OS) and disease-free survival (DFS) rates compared with those with a low CMTM3 expression (with P values of 0.010 and 0.032, respectively). Among the 11 GBM pathological specimens, 10 samples exhibited higher CMTM3 protein expression levels in the cancerous tissue compared with the adjacent non-cancerous tissue. The average CMTM3 protein expression in these samples was 0.44±0.09, significantly higher than that in the adjacent non-cancerous tissues (0.12±0.02, P＜0.001). In one sample, the difference in CMTM3 protein expression between the cancerous and adjacent non-cancerous tissues was not statistically significant ( P=0.750).The RT-qPCR results showed that the mRNA expression level of CMTM3 in NHA cells was 1.0±0.1, whereas in GBM cells U87, LN229, and U251, the levels were 2.1±0.3, 3.4±0.5, and 3.7±0.8, respectively, all significantly higher than that in NHA cells (all P＜0.01). Western blot results demonstrated that the protein expression levels of CMTM3 in GBM cells U87, LN229, and U251 were 1.5±0.2, 1.8±0.2, and 1.9±0.1, respectively, also higher than that in NHA cells (0.7±0.2, all P＜0.01), with the highest level observed in U251 cells. The CCK-8 assay, Flow cytometry, and Transwell migration experiments indicated that cell viability was inhibited in the sh-CMTM3 group, with an increase in the proportion of cells in the G 0/G 1 phase ( P＜0.01) and a decrease in the S phase ( P＜0.01), and the number of migrated cells was 233.6±35.5, lower than that in the sh-NC group ( P＜0.001). Conversely, the OE-CMTM3 group showed enhanced cell viability, a reduction in the proportion of cells in the G 0/G 1 phase ( P＜0.01), and an increase in the S phase ( P＜0.01), and the number of migrated cells was 1212.0±20.8, higher than that in the OE-NC group ( P＜0.001). However, in the OE-CMTM3+PDTC group, cell viability, cell cycle distribution (G 1, S, and G 2 phases), and cell migration numbers showed no significant changes (all P＞0.05). Western blot analysis and NF-κB activation-nuclear translocation assay results indicated that in the sh-CMTM3 group, the p-p65/p65 ratio was 0.51±0.04 and the p-IκBα/IκBα ratio was 0.39±0.03, both lower than those in the sh-NC group (both P＜0.01). The cytoplasmic staining rate was (49.29±1.98)%, higher than that in the sh-NC group ( P＜0.01). In the OE-CMTM3 group, the p-p65/p65 ratio was 2.27±0.10 and the p-IκBα/IκBα ratio was 2.14±0.15, both higher than those in the OE-NC group (both P＜0.01). The cytoplasmic staining rate was (18.96±1.44)%, lower than that in the OE-NC group ( P＜0.01). In the OE-CMTM3+PDTC group, there were no significant differences in the p-p65/p65 ratio, p-IκBα/IκBα ratio, and cytoplasmic staining rate compared with the OE-NC group (all P＞0.05). The subcutaneous tumorigenesis assay in nude mice showed that the tumor volume in the sh-CMTM3 group was (408.9±96.2) mm3, smaller than that in the sh-NC group ( P=0.003). The tumor volume in the OE-CMTM3 group was (1 514.5±251.5) mm3, larger than that in the OE-NC group ( P=0.005). Conclusions:In GBM, CMTM3 is highly expressed and negatively correlated with both OS and DFS of patients. CMTM3 regulates the proliferation and migration abilities of U251 cells through the NF-κB signaling pathway.

In the 1950s and 1960s,Japan's implementation of policies prioritizing economic develop-ment caused a lack of effective supervision over the discharge of industrial wastewater and exhaust gases,which led to the occurrence of the"Four Major Pollution Diseases",including Minamata disease,causing serious social and public health problems.To more effectively address public nuisances and pro-vide compensation to victims,the Japanese government gradually established an environmental damage compensation system with administrative relief characteristics since the 1970s.Through long-term prac-tice and system optimization,this system has evolved into a mature institutional framework with a clear division of labor and efficient collaboration.This paper systematically reviews the development process of Japan's environmental damage compensation system and deeply analyzes its legal frame-work and supporting policies,aiming to provide useful references for the construction and improve-ment of China's environmental damage compensation system.Meanwhile,through the case analysis of Minamata disease,the paper explores the specific mechanisms and effects in the compensation practices,further revealing the system's operational characteristics and implications,and providing a reference ba-sis for the construction of China's environmental governance legal system.