This case report describes a 68-year-old male patient diagnosed with primary hepatocellular carcinoma (HCC). After receiving Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT), the tumor significantly reduced in size, and tumor markers alpha fetoprotein (AFP) and abnormal prothrombin (PIVKA-Ⅱ) decreased. Postoperative pathological results showed minimal residual tumor cells, indicating that ⁹⁰Y-SIRT has good efficacy and safety in downstaging and conversion of HCC, thereby facilitating subsequent surgical resection.

BACKGROUND:Early exercise treatment is the main prevention way for traumatic joint contracture and is also a research focus.Swimming may be a potential intervention for joint contracture due to the special physical properties of water. OBJECTIVE:To explore the effects of swimming on the development of joint contracture in a rat model and study its mechanisms. METHODS:Twenty-four Sprague-Dawley rats were randomly divided into a blank control group(n=8)and a joint contracture group(n=16).After the surgical operation of knee joint contracture rat models,the joint contracture group was randomly subdivided into a surgical control group(n=8)and a swimming treatment group(n=8).Swimming started in the swimming treatment group in the second week after surgery and lasted for a total of 5 weeks.At the 6th week after surgery,the body mass,knee joint range of motion,and quadriceps diameter were tested,and the diameter/body mass index was calculated.Hematoxylin-eosin staining was performed to detect the pathological changes in the knee joint capsule and quadriceps muscle,and Masson staining was used to observe fibrotic changes in the knee joint capsule.Furthermore,the protein expression of transforming growth factor β1 and type I collagen in the knee joint capsule was quantified by immunohistochemical assay and western blot was performed to detect the protein expression of MuRF1 in the quadriceps femoris. RESULTS AND CONCLUSION:Compared with the blank control group,the knee range of motion decreased in the surgical control and swimming treatment groups(P<0.01),and knee extension deficit and arthrogenic extension deficit were significantly increased(P<0.01),the diameter of the quadriceps muscle was decreased(P<0.01),the joint capsule showed significant fibrosis,the quadriceps muscle was atrophied,and the diameter/body mass index was decreased(P<0.01).Compared with the surgical control group,the swimming treatment group showed a significant increase in knee joint range of motion and quadriceps diameter(P<0.01),and significant improvement in joint capsule fibrosis and quadriceps atrophy.Compared with the blank control group,collagen fiber content and expression of transforming growth factor β1 and type I collagen were increased in the joint capsule of rats in both the surgical control group and the swimming treatment group(P<0.01).Compared with the surgical control group,collagen fiber content and expression of transforming growth factor β1 and type I collagen protein in the joint capsule were decreased in the swimming treatment group.Compared with the blank control group,the expression of MuRF1 protein in the quadriceps muscle of rats in the surgical control group and the swimming treatment group was increased(P<0.05).Compared with the surgical control group,the expression of MuRF1 protein in the quadriceps muscle of rats in the swimming treatment group was decreased(P<0.05).To conclude,early swimming intervention reduces transforming growth factor β1 and type I collagen expression in the joint capsule of traumatic joint contracture rats,decreases MuRF1 expression in the quadriceps muscle,and increases joint range of motion and quadriceps diameter,thereby inhibiting the development of joint contracture.

ObjectiveTo clearly identify the difference between rescue injuries and agonal injuries and to avoid duplicate identifications and misidentifications. MethodsBased on the forensic pathological data of 5 923 cases of death cause identification from 2013 to 2022 in Sun Yat-sen University Forensic Identification Center and Guangzhou Tianhe District Branch of Guangzhou Public Security Bureau， this study retrospectively studied the characteristics of rescue injuries and agonal injuries seen in cause of death identification and their influence on cause of death identification. ResultsAmong all the 5 923 cases， 640 cases were found to have rescue injuries or agonal injuries， and 624 cases received treatment， of which 609 cases were found to have rescue injuries （97.60%）， 44 cases were found to have agonal injuries， and 13 cases were found to have both types of injuries. Among the 640 cases， 441 were male and 199 were female. The age of death was discontinuously distributed from 0 to 95 years old. The leading cause of death was disease， followed by mechanical injury and asphyxia. The main manifestations of rescue injuries were rib and sternum fractures， soft tissue injuries in the prechest area or face， and pericardial rupture. The most common injuries in agonal stage were falling after unconsciousness， inhalation of foreign body in respiratory tract or multiple violent injuries. Among the 640 cases， 19 cases were repeatedly identified， including 15 cases of rescue injuries， 6 cases of agonal injuries， and 2 cases of both types of injuries. Compared with the cases where neither type of injuries was detected， the repeated identification rate of treatment injuries and agonal injuries was significantly increased （χ²=4.04， P=0.044； χ²=43.49， P<0.001）. Among the 640 cases， 11 cases （1.72%） were misidentified as the initial injuries in the first identification， and 13 cases had combined rescue injuries or agonal injuries that were involved in death. ConclusionsBy elucidating the epidemiological characteristics of the two types of injuries， this study proved that the two types of injuries were associated with higher rates of repeated identification and misidentification， which provided a reference for reducing repeated identification and misidentification and improving the accuracy of cause of death identification.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

Preclinical studies include pharmacology， toxicology， pharmacokinetics research of animal experiments and in vitro experiments， which are crucial steps in the pre-marketing drugs and medical products， and are essential for exploring the mechanisms of traditional Chinese Medicine （TCM） therapeutic mechanism and promoting clinical translation. Systematic reviews and meta-analyses of preclinical studies in the field of TCM can comprehensively integrate preclinical evidence， consolidate research findings， assess the quality and risk of bias of included studies， enhance the utilization of research results， reduce resource waste， and promote the iterative optimization of TCM research models and evaluation indicators. This article introduced the process and methodology of conducting systematic review and meta-analyses of preclinical studies in TCM from nine steps， defining the research question， forming a research team， writing and registering a study protocol， conducting a comprehensive search， screening literature， evaluating included studies， extracting data， synthesizing data （meta-analysis）， and reporting systematic reviews. It aims to provide methodological references for conducting systematic reviews and meta-analyses of preclinical studies in TCM and to promote the establishment and improvement of the evidence system in the field of TCM.

Objective To investigate and analyze clinical characteristics and related factors of elderly patients with type 2 diabetes mellitus (T2DM) and frailty. Methods A total of 310 elderly patients with T2DM admitted to the hospital from January 2023 to June 2024 were selected as the research subjects. Their general information and disease-related information was collected through questionnaires. The Fried Frailty Scale was used to evaluate frailty status, and the patients were divided into frailty group and non-frailty group based on the Fried Frailty Scale score. Factors related to T2DM with frailty in the elderly were analyzed. Results The incidence of frailty in this study was 31.61% (98/310), and those without frailty accounted for 68.39% (212/310). There were statistically significant differences between the two groups in terms of age, body mass index (BMI), Self-rating Depression Scale (SDS) score, number of chronic complications, glycosylated hemoglobin (HbA1c) level, hemoglobin level, Mini-Nutritional Assessment-Short Form (MNA-SF) score, and Charlson Comorbidity Index (CCI) score (P<0.05). Multivariate logistic regression analysis showed that age, HbA1c level, SDS score, MNA-SF score, and CCI score were risk factors for frailty in elderly patients with T2DM (P<0.05). Conclusion The incidence of frailty is relatively high in elderly patients with T2DM. It is influenced by factors such as age , SDS score , HbA1c level , MNA-SF score and CCI score, and deserves clinical attention.

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

Objective To explore the effects of growth hormone(GH)on the proliferation,cycle,inva-sion,and migration of colon cancer cells and its possible mechanism.Methods GH3 cells with growth hor-mone-type pituitary adenoma were cultured in vitro,and the secretion of growth hormone in the supernatant of GH3 cells was detected by ELISA.Colon cancer LoVo cells in logarithmic growth phase were randomly divid-ed into the control group and the experimental group.PBS was added to the control group,while high concen-trations of recombinant GH were added to the experimental group.The two groups of cells were cultured in vitro under the same conditions.CCK-8 method was used to detect the proliferation of the cells.Flow cytome-try was used to detect the cell cycle.Transwell assay was used to detect the effect of growth hormone on the invasion and migration of the cells.Western blot was used to detect the expressions levels of E-cadherin,N-cadherin,Vimentin,and Snail-1 proteins in the cells.Results The results of ELISA showed that GH3 cells could secrete a large amount of GH,and the concentration of GH in the supernatant was(1 208±9)ng/mL.GH promoted cell growth in a dose-dependent manner within a certain concentration range,and GH 200 ng/mL was the optimal intervention concentration for subsequent experiments.Compared with the control group,the cell cycle in the experimental group changed from G1 phase to S phase and G2 phase,the ratio of G1 phase cells decreased,and the ratio of S phase cells and G2 phase cells increased(P<0.05).Compared with the control group,the number of the cell invasion and migration increased in the experimental group(P<0.05),the expression levels of N-cadherin,Vimentin,and Snail-1 was up-regulated,while the expression level of E-cadherin was down-regulated(P<0.05).Conclusion High concentration of GH promotes the prolifera-tion,invasion and migration of colon cancer cells,and induces the transition of cell cycle from G1 to S and G2 phases.The mechanism may be related to the epithelial-mesenchymal transition(EMT)of colon cancer cells promoted by high concentration of GH.

Objective:To investigate the incidence of thyroid dysfunction in patients with chronic kidney disease and analyze the influencing factors.Methods:One hundred and ninety-eight patients with chronic kidney disease who were treated in Chronic Disease Management Department of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from Apr. 2021 to Apr. 2022 were selected, including 71 patients with abnormal thyroid function and 127 patients with normal thyroid function. The differences in TT3, FT3, TT4, FT4, and TSH between patients with abnormal thyroid function and those with normal thyroid function were analyzed. At the same time, the abnormal thyroid function of patients with different clinical characteristics and the influencing factors were analyzed. The intergroup differences were analyzed using t-test or χ2-test, and the influencing factors were analyzed using logistic regression analysis. Results:In one hundred and ninety-eight patients with chronic kidney disease, thyroid function abnormality occurred in 71 patients (35.86%), including two or more abnormal thyroid function indicators in 35 patients (49.30%). The total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4) and free thyroxine (FT4) in patients with abnormal thyroid function were (1.02 ± 0.29) nmol/mL, (3.03 ± 0.88) pmol/L, (77.93 ± 20.02) nmol/mL and (11.02 ± 1.95) pmol/L respectively, which was significantly lower in patients with normal thyroid function (1.32±0.25) nmol/mL, (4.20±0.92) pmol/L, (93.30±19.28) nmol/mL and (13.54±1.82) pmol/ ( P<0.05), while thyroid stimulating hormone (TSH) was (3.14 ± 0.96) mIU/L, which was significantly higher than that in patients with normal thyroid function (1.84±0.89) mIU/L ( P<0.05). The incidence of thyroid dysfunction in female patients was 50.59% (43/85), It was significantly higher than 24.78% (28/113) of male patients (P <0.05) ; The incidence of thyroid dysfunction in patients aged 60 years was 49.55% (55/111), It was significantly higher than 18.39% (16/87) of the patients aged <60 years ( P<0.05) ; The incidence of thyroid dysfunction in patients with 1-year duration of disease was 71.43% (30/42), It was significantly higher than 25.28% (41/156) of patients with a course of disease <1 year ( P<0.05) ; The incidence of thyroid dysfunction in patients with clinical stage G 4 to 5 was 50.62% (41/81), It was significantly higher than 25.64% (30/117) of patients in G1~3 stages ( P<0.05) ; The incidence of thyroid dysfunction in patients with diabetes was 74.36% (29/39), This was significantly higher than 26.42% (42/159) in patients without diabetes mellitus ( P<0.05). Logistic regression analysis showed that gender, age, course of disease and clinical stage were the influencing factors of thyroid dysfunction in patients with chronic kidney disease ( P<0.05) . Conclusion:A high proportion of patients with chronic kidney disease have abnormal thyroid function, which is affected by the patient's sex, age, course of disease and clinical stage,clinical attention should be paid to targeted intervention to prevent the incidence of thyroid dysfunction in chronic kidney disease population.

Objective:To measure the retinal structural and functional parameters of adult Macaca fascicularis, and explore the similarity of the retinal structural and functional parameters between non-human primates and normal human retinas.Methods:Six eyes of 3 5-year-old adult Macaca fascicularis were examined by in vivo detection including color fundus photography, retinal optical coherence tomography (OCT) and electroretinogram (ERG) to determine the thickness of the inner/outer retina at the fovea and 1 000/2 000 μm away from the nasal, temporal, superior and inferior regions of the fovea, the thickness of the retinal nerve fiber layer (RNFL), the area of optic disc, the area of optic cup, the area ratio of cup to disc and the biological parameters of flash ERG.Differences in the above parameters between left and right eyes were analyzed.The similarity of parameters between Macaca fascicularis and human was compared with reference to published literature.The use and care of animals complied with the Regulation on the Management of Experimental Animals.The study protocol was approved by the Institutional Animal Care and Use Committee of Hubei Topgene Biotechnology (NO.IACUC-2019-012). Results:The foveal thickness, optic disc area, cup-disc area ratio, and average RNFL thickness in normal adult Macaca fascicularis were (252.31±4.79)μm, (1.89±0.05)mm 2, 0.14±0.01, and (103.53±0.58)μm, respectively.The b-wave amplitude of dark-adapted 0.01 ERG was (66.75±7.29)μV.The a- and b-wave amplitudes of dark-adapted 3.0 ERG response were (57.15±15.01) and (122.10±25.51)μV, respectively.The a- and b-wave amplitudes, the amplitude of oscillation potentials, and the latency of dark-adapted 10.0 ERG response were (72.98±20.14)μV, (131.67±13.78)μV, (49.98±10.08)μV, and (30.02±5.76)ms, respectively.The a- and b-wave amplitudes of light-adapted 3.0 ERG were (9.16±2.75) and (40.43±5.57)μV, respectively.The latency and the amplitude of the light-adapted 30 Hz flicker was (26.61±1.19)ms and (24.72±5.10)μV, respectively.There was no significant difference in the parameters between left and right eyes (all at P>0.05). The retinal thickness in central fovea, mean RNFL thickness, waveform and amplitude of ERG of Macaca fascicularis were similar to normal human. Conclusions:The structure and function of the retina of adult Macaca fascicularis are similar to those of normal humans.As a laboratory animal for preclinical drug research, in vivo studies of Macaca fascicularis can refer to normal human retinal parameters.