Objective:This study aimed to explore the spectrum of adverse events associated with hydroxyprogesterone and provide a comprehensive understanding of the drug's safety profile based on the Food and Drug Administration's Adverse Event Reporting System database. Methods:Adverse events associated with hydroxyprogesterone were extracted from the Food and Drug Administration's Adverse Event Reporting System database, covering the period from the first quarter of 2004 to the second quarter of 2025. Disproportionality analysis methods were used to detect potential safety signals related to hydroxyprogesterone. We further analyzed the demographic characteristics of the population and the onset time of adverse events. Results:A total of 40,450 adverse event reports related to hydroxyprogesterone were included, corresponding to 197 significant preferred terms categorized into 21 system organ classes per Medical Dictionary for Regulatory Activities criteria. In addition to commonly observed adverse events, several clinically relevant adverse events not previously documented were identified, including fetal distress syndrome, abnormal fetal heart rate deceleration, neonatal jaundice, neonatal respiratory distress, and low birth weight infant. The median time to the onset of hydroxyprogesterone-induced adverse events was 20 days (interquartile range: 0-72 d), with 57.8% of adverse events occurring within the initial 30 days following hydroxyprogesterone administration. Conclusions:In this study, we identified both clinically observed adverse events and potential safety signals associated with hydroxyprogesterone. These results provide valuable evidence to support clinical monitoring, safety risk identification, and the development of subsequent safety investigations.

The aim of this study was to evaluate hepatobiliary disorders adverse events associated with pembrolizumab by using the Food and Drug Administration Adverse Event Reporting System (FAERS).We collected FAERS data from the first quarter of 2009 to the third quarter of 2024 and used reporting odds ratio (ROR) to detect pembrolizumab-associated hepatobiliary adverse events (AEs). A signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and≥5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale.A total of 20,225,379 AEs were reported in the FAERS database, of which 45,774 AEs listed pembrolizumab as the 'primary suspected' drug. Pembrolizumab treatment was significantly associated with hepatobiliary disorders. Among these AEs, 101 signals were detected at the preferred term (PT) levels, and 56 of them were identified as significant signals by using disproportionality analyses. The median time-to-onset (TTO) was 63 days. Notably, most hepatobiliary AEs occurred within three months after pembrolizumab therapy.Based on pharmacovigilance data from FAERS, different hepatobiliary AEs should be closely monitored and managed according to the indications for which pembrolizumab is used.

Lycium barbarum polysaccharides (LBP) have shown renal protection effects. However, research on other active components of L. barbarum extract (ELB) for the therapy of chronic kidney disease (CKD) is limited. This study aims to investigate the renoprotective effects and molecular mechanisms of ELB in CKD. ELB was extracted from L. barbarum fruits using 85% ethanol reflux, followed by vacuum concentration and sequential extraction to remove polysaccharides. Chemical components and target genes were identified using TCMSP and UniProt databases, followed by pharmacology network construction and GO/KEGG pathway analysis. A 5/6 nephrectomy model in Sprague-Dawley rats was used to study the renoprotective effects of ELB, with H&E staining and biochemical analyses. Western blot analysis assessed IL-6 and VEGF expression in renal tissues. Chemical analysis of ELB identified 188 components, with 45 meeting screening criteria, and 34 linked to 94 target genes. The intersection with CKD-related genes yielded 39 overlapping genes, with quercetin having the most targets. GO/KEGG pathway analyses highlighted significant biological processes and pathways. A PPI network identified IL-6, VEGFA, CASP3, EGFR, ESR1, and PPARG as hub genes. In a 5/6 nephrectomy rat model, ELB treatment significantly reduced renal damage, serum BUN and SCr levels, as well as IL-6 and VEGF expression in renal tissues, validating its renoprotective effects and supporting bioinformatics predictions. This work identified the intricate components and pharmacological actions of ELB, which is devoid of LBP. The findings preliminarily confirm the potential of ELB as a novel therapeutic agent for preventing and managing CKD.

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel-group, open-label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty-two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long-term safety profile and efficacy have not been specifically studied in this population.

In recent years, repeated incidents of composite insulator deterioration leading to breakages have posed serious threats to the safety of power systems in China. This study examines a 500kV decay-like composite insulator collected from a field operation, evaluating its outer sheath and core rod degradation status through visual inspection. Infrared and ultraviolet imaging devices were employed to measure the infrared temperature rise and the distribution of ultraviolet discharge under standard operating voltage. The findings indicate that the temperature rise features captured via infrared imaging and the ultraviolet discharge characteristics effectively reflect the deteriorated state of decay-like composite insulators. It was observed that measured temperature rise values decrease with increasing test distance. Additionally, infrared thermography more accurately depicts the internal defects of composite insulators compared to ultraviolet imaging, with reduced interference from surrounding irrelevant discharges.

Abnormal aggregation and fibrillogenesis of amyloid-β protein (Aβ) can cause Alzheimerʼs disease (AD). Thus, the discovery of effective drugs that inhibit Aβ fibrillogenesis in the brain is crucial for the treatment of AD. Luteoloside, as one of the polyphenolic compounds, is found to have a certain therapeutic effect on nervous system diseases. However, it remains unknown whether luteoloside is a potential drug for treating AD by modulating Aβ aggregation pathway. In this study, we performed diverse biophysical and biochemical methods to explore the inhibition of luteoloside on Aβ1–42 which is linked to AD. The results demonstrated that luteoloside efficiently prevented amyloid oligomerization and cross-β-sheet formation, reduced the rate of amyloid growth and the length of amyloid fibrils in a dose-dependent manner. Moreover, luteoloside was able to influence aggregation and conformation of Aβ1–42 during different fiber-forming phases, and it could disintegrate already preformed fibrils of Aβ1–42 and convert them into nontoxic aggregates. Furthermore, luteoloside protected cells from amyloid-induced cytotoxicity and hemolysis, and attenuated the level of reactive oxygen species (ROS). The molecular docking study showed that luteoloside interacted with Aβ1–42 mainly via Conventional Hydrogen Bond, Carbon Hydrogen Bond, Pi-Pi T-shaped, Pi-Alkyl and Pi-Anion, thereby possibly preventing it from forming the aggregates. These observations indicate that luteoloside, a natural anti-oxidant molecule, may be applicable as an effective inhibitor of Aβ, and promote further exploration of the therapeutic strategy against AD.

The existing long-distance transmission line perception mainly focuses on the measurement and analysis of electrical parameters. When the line is subject to wind vibration, icing or galloping, the changes of electrical parameters are not obvious and difficult to capture, resulting in poor performance of long-distance transmission line fault state perception. In this regard, the long-distance transmission line condition sensing based on distributed optical fiber sensing technology is studied. This method designs corresponding sensing methods for four working conditions: using the back Brillouin scattering sensor and phase sensitive Rayleigh scattering sensor in the optical fiber sensing technology to form a multi parameter distributed optical fiber sensing device, which is used to sense the surface temperature, vibration, strain and other data of the long-distance transmission line; By analyzing the linear relationship between fiber Brillouin frequency shift and Brillouin power and fiber strain and temperature, the sensing results of icing thickness of long-distance transmission lines are obtained; By calculating the amplitude and phase information of the detection signal, the sensing results of long-distance transmission line vibration are obtained; By calculating the time difference of polarization mutation signal at both ends of long-distance transmission line, combined with the propagation speed of optical signal and the length of long-distance transmission line, the perception result of lightning fault location of long-distance transmission line can be obtained. The experimental results show that this method can more accurately collect the real-time operation data of long-distance transmission lines, and can effectively perceive the galloping, wind vibration and lightning fault location of long-distance transmission lines.

This paper investigates the deterioration of, and the abnormal temperature rise in, the GFRP core rod material of compact V-string composite insulators subjected to prolonged alternating flexural loading under wind-induced stresses. The axial stress on the GFRP (Glass Fiber Reinforced Plastic) core rod, resulting from transverse wind loads, is a focal point of examination. By establishing a stress model and damage model, the paper simulates and computes the evolution of damage in the outer arc material of composite insulator core rods subjected to alternating flexural loads. Additionally, a multi-factor coupled aging platform is set up, integrating humidity, heat, and mechanical stress, to simulate the crazing deterioration process of composite insulators under alternating flexural loads. Experimental results reveal that during 400,000 alternating load cycles, the core rod underwent stages of surface damage, damage increasing, fatigue embrittlement, matrix hydrolysis, and fiber fracture. Simultaneously, the silicone rubber sheath on the outer side of the composite insulator's bending arc develops cracks over aging time, creating pathways for moisture ingress into the interface and core rod. The dielectric constant and dielectric loss factor of the aging region of the core rod increase to varying degrees compared to the non-aging part. Moreover, the degree of abnormal heating of the samples intensifies with the duration of aging experiments. These findings underscore the significance of understanding the aging and decay-like fracture process of compact line V-string composite insulators. They provide crucial insights for future research aimed at enhancing the material properties of composite insulator core rods.

Colorectal cancer (CRC) is one of the most common types of malignant cancers worldwide. Although molecularly targeted therapies have significantly improved treatment outcomes, most of these target inhibitors are resistant. Novel inhibitors as potential anticancer drug candidates are still needed to be discovered. Therefore, in the present study, we synthesized a novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative (compound 4) using fragment- and structure-based techniques and then investigated the anticancer effect and underlying mechanism of anti-CRC. The results revealed that compound 4 significantly inhibited HCT116 cell proliferation with IC50 values of 8.04 ± 0.94 µmol L–1 after 48 h and 5.52 ± 0.42 µmol L–1 after 72 h, respectively. Compound 4 also inhibited colony formation, migration, and invasion of HCT116 cells in a dose-dependent manner, as well as inducing cell apoptosis and arresting the cell cycle in the G2/M phase. In addition, compound 4 was able to inhibit the activation of the MEK/ERK signaling in HCT116 cells. And compound 4 yielded the same effects as the MEK inhibitor U0126 on cell apoptosis and MEK/ERK-related proteins. These findings suggested that compound 4 inhi bited cell proliferation and growth, and induced cell apoptosis, indicating its use as a novel and potent anticancer agent against CRC via the MEK/ERK signaling pathway.

In order to study the application of Internet of things energy system in complex fault risk dynamic assessment of transmission line. Firstly, the concept of power grid dynamic risk assessment is introduced, and the process of power grid dynamic risk assessment system based on Internet of things is designed. Then, it puts forward how to use the ubiquitous Internet of things multisource data to solve the key problems such as dynamic perception of fault probability, dynamic selection of fault set, dynamic generation of post fault state, and dynamic risk assessment of operation process. Finally, taking the maximum operation mode of a provincial power grid in summer 2013 as an example, this paper selects key 500 kV transmission lines for risk assessment, and the actual power grid example shows that. The power grid comprehensive risk assessment system considering the fault characteristics of transmission lines can effectively predict the fault probability of transmission lines; distinguish the two risks of high loss, low probability, and low loss and high probability; and provide guidance for operators. It is practical and effective.

Monoclonal antibody (mAb) drugs belong to protein drugs, which are characterized by high relative molecular weight, strong polarity, and limited transmembrane. Their pharmacokinetics have certain particularity and complexity, and problems such as large individual differences in therapeutic effects, diverse biological effects, and loss of therapeutic response exist in clinical application. The blood concentration of mAb drugs is affected by many factors including the number of receptors at the target site, the level of anti-drug antibody, and the interaction between drugs. Early monitoring is helpful to timely adjust the dose of mAb drugs, improve the efficacy, and avoid or reduce the occurrence of adverse reactions. Clinical monitoring should be actively carried out to improve the level of rational use of mAb drugs and the ability of early warning of adverse reactions, so as to reduce the drug-induced injury in patients.

SHR0302, as a novel Janus kinase (JAK) inhibitor 1, is used for treatment of rheumatoid arthritis (RA) in human for the first time. A novel and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for determining the concentration of SHR0302 in human plasma. A precipitation deproteinization method was used for the plasma pretreatment with methanol. Detection was carried on an Agilent 1260 UPLC coupled with Triple Quad 4000 mass spectrometer operated in positive MRM mode, and the analysts were separated on a Synergi Polar-RP C18 (50×2.0 mm, 4μm, Phenomenex) analytical column with gradient elution of 0.1% formic acid, and 2 mmol/L ammonium acetate in water and 0.1% formic acid and 2 mmol/L ammonium acetate in methanol, The selected ion transitions were m/z 415.2→258.2 and m/z 398.2→258.2 for SHR0302 and SHR143181 (IS), respectively. A full validation, including selectivity, linearity, carry-over, precision, accuracy, recovery, matrix effect, dilution integrity and stability, was carried out in human plasma. It was successfully applied to a pharmacokinetic study in Chinese healthy subjects after oral administration of SHR0302 tablet.

目的:研究脯氨酸恒格列净片(SHR3824)在健康受试者以及轻、中、重度肝功能不全患者中的药动学(PK)特征,为临床给药方案的制定提供参考.方法:采用多中心、开放、平行、单剂量实验设计,筛选32例受试者,包括肝功能正常的健康受试者和轻、中、重度肝功能不全受试者各8例,空腹口服脯氨酸恒格列净片20 mg后,于给药前和给药后不同时间点采集静脉血,高效液相色谱-串联质谱(LC-MS/MS)法测定受试者血浆中恒格列净浓度,Phoenix WinNonLin 7.0软件统计药动学参数.结果:SHR3824单次给药后,健康受试者,轻度、中度及重度肝功能不全组的Cmax分别为(324±58.3),(400±83.9),(419±97.8)和(453±71.8)ng·ml-1,t1/2分别为(9.70±1.86),(11.5±3.05),(11.6±1.95)和(12.9±2.28)h,AUC0-t分别为(2130±350),(2920±717),(4200±738)和(4290±921)ng·h·ml-1,AUC0-"分别为(2160±349),(2960±729),(4260±748)和(4440±1020)ng·h·ml-1,Vd分别为(132±26.6),(116±28.4),(80.6±18.2),(86.6±19.1)L,CL分别为(9.54±1.90),(7.20±2.07),(4.86±1.04),(4.75±1.03)L·h-1.肝功能不全组血浆中恒格列净片的平均暴露水平(Cmax、AUC0-t和AUC0-")均显著高于肝功能正常组,差异有统计学意义(P<0.05).结论:脯氨酸恒格列净片的药动学会受肝功能水平的影响,应根据肝功能调整用药剂量,保证用药安全.

In order to study the dynamic assessment system of composite fault risk of transmission line based on blockchain energy and in order to study the transmission line compound fault risk dynamic assessment system based on blockchain, firstly, according to the coupling relationship between power grid and natural disasters, the information resources such as data collected by power grid intelligent devices and natural meteorology are excavated, and the overall architecture of power grid disaster early warning and decision-making system supported by blockchain is built. Then, from the perspective of risk, combined with analytic hierarchy process, an index system for reasonable evaluation of distribution network fault benchmark risk is established. Quantitative assessment and risk classification shall be carried out for the failure probability, failure impact consequence, and comprehensive failure risk, so as to facilitate the adoption of risk response measures. Finally, taking several 220 kV lines in the northwest and central part of a city as examples, the icing prediction analysis verifies the feasibility and effectiveness of the proposed power grid disaster early warning decision system based on blockchain to predict the icing thickness. The experimental results show that taking the icing disaster as an example, the MPC method is used to modify the icing thickness prediction model, improve the accuracy of the icing prediction model, and verify the feasibility and effectiveness of the prediction and early warning system based on blockchain.

Context Effective treatment of ischaemic stroke is required to combat its high prevalence and incidence. Although the combination of Astragalus membranaeus (Fisch.) Bge. (Fabaceae) and Carthamus tinctorius L. (Asteraceae) is used in traditional Chinese medicine for the treatment of stroke, its underlying mechanism remains unclear. Objective The objective of this study is to elucidate the mechanism underlying Huangqi-Honghua (HQ-HH) for the treatment of ischaemic stroke by gut microbiota analysis and metabonomics. Materials and methods Sprague-Dawley rats were randomly assigned to the sham, model, HQ-HH, and Naoxintong (NXT) groups. The middle cerebral artery occlusion-reperfusion model was established after 7 days of intragastric administration in the HQ-HH (4.5 g/kg, qd) and NXT (1.0 g/kg, qd) groups. The neurological examination, infarct volume, gut microbiota, bile acids, and inflammation markers were assessed after 72 h of reperfusion. Results Compared with the model group, HQ-HH significantly reduced the neurological deficit scores of the model rats (2.0 +/- 0.2 vs. 3.16 +/- 0.56), and reduced the cerebral infarct volume (27.83 +/- 3.95 vs. 45.17 +/- 2.75), and reduced the rate of necrotic neurons (26.35 +/- 4.37 vs. 53.50 +/- 9.61). HQ-HH regulating gut microbiota, activating the bile acid receptor FXR, maintaining the homeostasis of bile acid, reducing Th17 cells and increasing Treg cells in the rat brain, reducing the inflammatory response, and improving cerebral ischaemia-reperfusion injury. Conclusions These data indicate that HQ-HH combination can improve ischaemic stroke by regulating the gut microbiota to affect bile acid metabolism, providing experimental evidence for the wide application of HQ-HH in clinical practice of ischaemic stroke.

目的 通过比较艾瑞昔布及代谢产物在肝功能不全和健康受试者的药代动力学特征,为制订艾瑞昔布在肝功能不全患者的临床给药方案提供参考.方法 采用1:1平行开放对照试验设计,入选肝功能Child-Pugh B级的受试者10例,设为A组;然后根据A组受试者的年龄、性别、体重特征匹配相应的健康受试者作为平行对照的B组.2组受试者于试验第1天早餐后30 min单次口服艾瑞昔布片0.1 g,并于给药后0～96 h采集血样和分段尿样.用高效液相色谱-串联质谱(LC-MS/MS)法测定受试者血浆和尿样中艾瑞昔布(M0)及代谢物M1(羟基代谢物)和M2(羧基代谢物)的浓度.结果 单次口服艾瑞昔布0.1 g后,原型药物和其代谢物在肝功能不全组的达峰时间均晚于健康受试者.中度肝功能不全受试者血浆中艾瑞昔布原型M0的Cmax和AUC0-∞分别为健康受试者的5.56倍和10.8倍,代谢物M1的Cmax和AUC0-∞分别为健康受试者的1.74倍和3.21倍,M2的Cmax和AUC0-∞分别为健康受试者的66.6％和1.35倍.然而,艾瑞昔布尿液中代谢物累积排泄率和肾清除率差异不大.安全性评价显示2组受试者单次给药总体耐受性良好,均无SAE发生.结论 对于轻、中度肝功能不全患者,艾瑞昔布的给药方案可不作调整;而对于肝功能不全同时伴有肾功能减退患者,建议调整给药方案,其剂量的调整幅度需根据患者肾功能减退的程度而定;不推荐重度肝功能不全患者使用艾瑞昔布片.

Abstracts Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Objective:To explore the application value of radioisotope tracer technology in clinical research of biological drugs.Methods:The pharmacokinetic properties of mepuzumab in healthy volunteers were evaluated by measuring the radioactive concentrations of iodine in blood and urine samples of 3 healthy volunteers at different time points within 14 days after intravenous infusion of 131I-labeled international class I new drug mepuzumab (Trial 1). Positron emission computed tomography (PET/CT) was performed on 6 healthy volunteers after intravenous injection of 68Ga-labeled nucleic acid aptamer Sgc8, and the standard uptake values of 68Ga-Sgc8 in different organs were measured to evaluate its biodistribution in healthy humans (Trial 2). Nine patients with suspected neuroendocrine tumors underwent single photon emission and X-ray computed tomography (SPECT/CT) 4 hours after intravenous injection of 99mTc-labeled octreotide to determine the radioactive uptake level in the regions of interest; the affinity and targeting of 99mTc-labeled octreotide to somatostatin receptor subtype 2 (SSTR2) were evaluated in combination with the immunohistochemical staining results of SSTR2 in patients′ biopsy tissues (Trial 3). Results:The 3 healthy volunteers included in Trial 1 were male, aged 28, 45, and 25 years respectively; the injection doses of 131I-labeled mepuzumab were 21.0, 25.9, and 17.6 mg, and the injection doses of radioactivity were 364, 420, and 304 MBq, respectively. Among the 6 healthy volunteers included in Trial 2, 3 were male and 3 were female, with an age of (46±11) years, ranging from 35 to 63 years. The dose of radioactivity injected was (80±7) MBq, ranging from 69 to 87 MBq. Among the 9 patients included in Trial 3, 5 were male and 4 were female, with an age of (54±10) years, ranging from 39 to 69 years. The dose of radioactivity injected was (777±74) MBq, ranging from 740 to 925 MBq. After intravenous infusion of 131I-labeled mepuzumab, the blood radioactivity concentration reached the peak 1.5 hours later. 131I-labeled mepuzumab mainly bound to blood cells, and its whole-blood clearance half-life was 420 hours. The urine radioactivity concentration reached the peak 16-24 hours after administration and then gradually decreased after 24 hours of administration. After intravenous injection of 68Ga-labeled Sgc8, the organs with strong to weak radioactive signals were bladder, kidney, heart, uterus, liver, spleen, gallbladder, large intestine and lung. Within 3 hours after drug administration, the clearance rate was fastest in heart, followed by uterus, kidney, and liver; the clearance rate was slower in spleen and gallbladder and were slowest in large intestine and lung. All of the 9 patients had abnormal radioactivity accumulation 4 hours after intravenous injection of 99mTc-labeled octreotide and the immunohistochemical staining results of biopsy tissues showed strong positive expression of SSTR2, indicating that 99mTc-labeled octreotide had good affinity and targeting to SSTR2. The safety evaluation showed that in Trail 1, one subject developed iodine-related hyperthyroidism one month after intravenously infusion of 131I-labeled mepuzumab, which returned to normal after 8 months of continuous monitoring without intervention. No adverse reactions occurred in other subjects. Conclusions:Radioisotope tracer technology can noninvasively, dynamically, and visually evaluate the pharmacokinetics, biological distribution, and targeting of biological drugs in human body. It has good safety and great application value in the clinical evaluation of biological drugs.

With the key mechanism of disease occurrence being revealed and rapid development of modern biopharmaceutical technology, more and more biological innovative drugs have been approved for marketing. With more clinical application of innovative biological drugs in recent years, more adverse reactions were reported. Therefore, it is of great significance and urgent in clinic to construct the supervision standard and system for the safe use of biological innovative drugs. At present, the main problems hindering the clinical safety supervision of biological innovative drugs are as follows. Firstly, the mechanism of adverse drug reactions is unclear and there is a lack of specific detection indicators to predict them. Secondly, the study on the relationship of "exposure-clinical efficacy-toxic and side effects" of drugs in vivo is still insufficient, so it is difficult to support the establishment of the rule of "quantity and toxicity" for safe drug use. Thirdly, there is a lack of clinical research evidence in line with the physiological and pathological characteristics of Chinese people, and the ideal randomized controlled trials results of clinical research on new drugs are not enough to support its safe drug use in the real world. Therefore, it is necessary to strengthen the supervision awareness of the clinical safe use, accelerate the process of clinical monitoring research on biological innovative drugs, reveal more scientific evidence of clinical safe use, so as to help the construction of the supervision standards and system for the safe use of biological innovative drugs.

目的 研究松果菊苷防晒乳膏剂的制备工艺,并对其质量进行评价.方法 通过正交试验对松果菊苷防晒乳膏剂基质处方进行优化,优选出最佳处方;通过紫外扫描法建立质量评价标准.结果 优选出松果菊苷防晒乳膏剂的最佳处方为松果菊苷5％、硬脂酸10％、单硬脂酸甘油酯5％、液状石蜡5％、白凡士林10％、三乙醇胺4％、氮酮3％、尼泊金乙酯0.1％.按照该处方制备的乳膏剂在最大吸收波长334 nm处的吸光度值相对稳定.结论 松果菊苷防晒乳膏剂的制备工艺简单,所得制剂性质稳定,质量可控,测定方法简便、快捷、准确,为后期进一步研究和应用奠定了基础.