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.

Depressive disorder is a common psychiatric condition clinically characterized by impaired cognitive function， which profoundly affects patients' daily living and social functioning. Despite extensive research on the mechanism underlying the interaction between ghrelin and depressive disorder， comprehensive reviews， summary， and systematic organization of these findings remain lacking. To address this gap， this study aims to conduct a systematic evaluation of the effects and mechanisms of ghrelin on cognitive function in patients with depressive disorder， thereby providing references for targeted clinical interventions. On October 20， 2024， literature exploring the role and mechanisms of ghrelin in improving cognitive function in depressive disorder was sourced from the CNKI， PubMed and Web of Science databases， covering the period from the inception of the database till October 20， 2024. Two researchers independently conducted literature screening and data extraction. Ultimately， 9 articles were included in this review. The findings suggest that ghrelin improves cognitive function in patients with depressive disorder through multiple mechanisms， including mitigating inflammatory responses， modulating oxidative stress， and activating the cyclic adenosine monophosphate response element binding protein-brain-derived neurotrophic factor （CREB-BDNF） signaling pathway.

Objective To study the mechanical response of tibial prostheses and the distal tibial cancellous bone after implantation of radial and axial functionally graded materials(FGM)into the ankle joint.Methods Three FGM were used:titanium alloy-bioactive glass composite FGM(FGM-Ⅰ),titanium(Ti)alloy-ideal bone elastic composite FGM(FGM-Ⅱ),and Ti alloy-hydroxylapatite composite FGM(FGM-Ⅲ).A three-dimensional finite element model of total ankle arthroplasty(TAA)was established,and the simulation software ABAQUS was used for secondary development based on Fortra.By changing the volume fraction,the mechanical properties of the FGM tibial prosthesis can be adjusted both axially and radially.The stress distributions of the tibial prosthesis and cancellous bone after FGM axial and radial tibial component implantation in the standing position were analyzed.Results Compared with Ti alloy tibial prosthesis,three kinds of FGM could effectively reduce the stress concentration on the tibial prosthesis,and the overall effect of FGM-Ⅲ tibial prosthesis was better than that of FGM-Ⅰ and FGM-Ⅱ tibial prosthesis;the radial distribution of FGM could effectively reduce the maximum von Mises stress of the prosthesis.For the tibial cancellous bone,the three types of FGM radial tibial prostheses and FGM-Ⅲ axial tibial prostheses could effectively increase the distal stress,thus,relieving the stress shielding on the cancellous bone;the FGM-Ⅲ radial tibial prosthesis was the most effective in improving the stress level of the cancellous bone.Conclusions FGM-Ⅲ radial ankle prosthesis can effectively reduce the stress concentration phenomenon and the stress shielding effect on the prosthesis to prolong its life,with potential application prospects.

In order to seek a patient friendly and low-cost intestinal examination method, a structurally simple pneumatic soft intestinal robot inspired by inchworms is designed and manufactured. The intestinal robot was consisted of two radially expanding cylindrical rubber film airbags for anchoring and one low density polyethylene film airbag for axial elongation, which achieved movement in the intestine by mimicking the crawling of inchworms. Theoretical derivation was conducted on the relationship between the internal air pressure of the anchored airbag and the free deformation size after expansion, and it pointed out that the uneven deformation of the airbag was a phenomenon of expansion instability caused by large deformation of the rubber material. The motion performance of the intestinal robot was validated in different sizes of hard tubes and ex vivo pig small intestine. The running speed in the ex vivo pig small intestine was 4.87 mm/s, with an anchoring force of 2.33 N when stationary, and could smoothly pass through a 90 ° bend. This work expects to provide patients with a new method of low pain and low-cost intestinal examination.
Animals ; Swine ; Robotics/instrumentation* ; Equipment Design ; Intestine, Small/physiology* ; Intestines/physiology* ; Humans

Objective    To establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis. Methods    RNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models. Results    The risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC. Conclusion 聽 聽The ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.

Objective: To analyze the disease burden and trend of attention deficit hyperactivity disorder (ADHD) in China from 1990 to 2019, so as to provide the basic theoretical basis for the health administrative departments to formulate policies. Methods: Using the 2019 Global Burden of Disease Database, the incidence, prevalence and disability adjusted life year (DALY) rates of ADHD were analyzed for both sex and different age groups, and the trends of ADHD were predicted. Results: In 2019, the incidence, prevalence and DALY rate of ADHD in China were 70.41/100 000, 1 546.15/100 000 and 18.87/100 000 respectively. Compared with 1990, the rates decreased by 27.30%, 25.35% and 55.80% respectively, and these rates of females were lower than those of males. In 2019, the incidence rate of ADHD was the highest in the age group 5-9 years old (837.76/100 000), while the highest prevalence and DALY rates were found in ages groups of 10-14 years old (5 740.47/100 000 and 70.49/100 000). The results of the Joinpoint regression model showed that the incidence, prevalence and DALY rate had a downward trend from 1990 to 2019. The AAPC was -1.35%, -1.16% and -1.16%, respectively, with a statistically significant difference ( P <0.05). The prediction results of grey prediction model GM (1,1) indicated that the incidence and prevalence rate of ADHD in China would decline from 2020 to 2030. Conclusion The burden of ADHD in China showed a decreasing trend from 1990 to 2019, indicating that the prevention and treatment effect of ADHD in children and adolescents of China was effective. China should take active preventive measures to reduce the burden of ADHD in children and adolescents.

OBJECTIVE: To analyze the expression of hydroxysteroid dehydrogenase like 2 (HSDL2) in rectal cancer tissues and the effect of changes in HSDL2 expression level on proliferation of rectal cancer cells. METHODS: Clinical data and tissue samples of 90 patients with rectal cancer admitted to our hospital from January 2020 to June 2022 were collected from the prospective clinical database and biological specimen database. The expression level of HSDL2 in rectal cancer and adjacent tissues was detected by immunohistochemistry, and based on the median level of HSDL2 expression, the patients were divided into high expression group (n=45) and low expression group (n=45) for analysis the correlation between HSDL2 expression level and the clinicopathological parameters. GO and KEGG enrichment analyses were performed to explore the role of HSDL2 in rectal cancer progression. The effects of changes in HSDL2 expression levels on rectal cancer cell proliferation, cell cycle and protein expressions were investigated in SW480 cells with lentivirus-mediated HSDL2 silencing or HSDL2 overexpression using CCK-8 assay, flow cytometry and Western blotting. RESULTS: The expressions of HSDL2 and Ki67 were significantly higher in rectal cancer tissues than in the adjacent tissues (P < 0.05). Spearman correlation analysis showed that the expression of HSDL2 protein was positively correlated with Ki67, CEA and CA19-9 expressions (P < 0.01). The rectal cancer patients with high HSDL2 expressions had significantly higher likelihood of having CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T3-4 stage, and N2-3 stage than those with a low HSDL2 expression (P < 0.05). GO and KEGG analysis showed that HSDL2 was mainly enriched in DNA replication and cell cycle. In SW480 cells, HSDL2 overexpression significantly promoted cell proliferation, increased cell percentage in S phase, and enhanced the expression levels of CDK6 and cyclinD1 (P < 0.05), and HSDL2 silencing produced the opposite effects (P < 0.05). CONCLUSION The high expression of HSDL2 in rectal cancer participates in malignant progression of the tumor by promoting the proliferation and cell cycle progress of the cancer cells.
Humans ; CA-19-9 Antigen ; Ki-67 Antigen/metabolism* ; Prospective Studies ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Rectal Neoplasms/genetics* ; Cell Cycle ; Gene Expression Regulation, Neoplastic ; Hydroxysteroid Dehydrogenases/metabolism*

Objective:To investigate the detecting method and clinical characteristics of anti-nodal/paranodal antibodies in chronic inflammatory demyelinating polyradiculopathy.Methods:Serum samples were collected from 212 patients with chronic inflammatory demyelinating polyradiculopathy who were admitted to Huashan Hospital of Fudan University or from other clinical centers from January 2018 to July 2021. Autoantibodies (anti-NF155, anti-NF186, anti-CNTN1) and IgG subtypes were detected with cell-based assay. According to the test results, patients were divided into anti-NF155 positive group, anti-NF186 positive group and anti-CNTN1 positive group, clinical characteristics of patients in each group, including limb weakness, superficial sensation and proprioception, tremor, cerebrospinal fluid protein level, brachial plexus magnetic resonance (MRI) were retrospectively analyzed and compared.Results:A total of 23 patients (10.8%,23/212) were positive for anti-NF155 antibody, 12 (5.7%,12/212) for anti-NF186 antibody, and 4 (1.9%,4/212) for anti-CNTN1 antibody. IgG 4 was the predominant subtype in anti-NF155 and anti-CNTN1 groups. In the anti-NF186 group, all cases were IgG positive and antibody subtypes could be detected in 4 cases (4/12). In anti-NF155 group, 23 patients (100%,23/23) had limb weakness and deep sensory disturbance, 19 patients (82.6%,19/23) had superficial sensory disturbance, 22 patients (95.7%,22/23) were symmetrically involved, 18 patients (78.3%,18/23) showed tremor, 19 patients (19/19) showed abnormal in brachial plexus MRI. In anti-NF186 group, 12 patients had limb weakness (12/12), 9 patients (9/12) and 6 patients (6/12) had superficial sensory disturbance and deep sensory disturbance respectively, 8 patients (8/12) were asymmetrically involved, and only 1 patient (1/12) showed tremor, 1 (1/7) showed abnormal brachial plexus MRI. In anti-CNTN1 group, 4 cases showed symmetrical limb weakness and sensory disturbance, 3 patients had tremor, and four patients showed brachial plexus MRI abnormality. There were statistically significant differences in onset age, proprioception, tremor and MRI abnormalities of brachial plexus among the 3 groups ( P<0.01). Conclusions:The clinical characteristics of CIDP patients with anti-NF155, anti-NF186 and anti-CNTN1 antibodies are different. Screening anti-nodal/paranodal antibodies is of great significance for accurate diagnosis and treatment of patients with peripheral neuropathy.

Localized peripheral neuropathy amyloidosis is a rare disease that mainly occurred in elder people who present with focal neurological symptoms. AL is the main type of amyloid protein. Biopsy is the golden standard for diagnosis. Mass spectrometry and immunohistochemical analysis help to confirm the type of amyloid protein. This paper retrospectively analyzes the clinical and imaging data, auxiliary examinations, histological, and immunohistochemical markers. The patient, a 34-year-old woman, presented with a right neck mass and weakness of the right arm. Brachial plexus magnetic resonance imaging (MRI) showed a tumor-like lesion in the nerve root at C5 and C6 and in upper trunk. Electrophysiological studies revealed damage in the upper trunk of the brachial plexus. Positive staining with Congo red was found in brachial plexus biopsy. Mass spectrometry showed that the type of amyloid protein was AHL(G-λ). The patient underwent nerve graft for treatment. Meanwhile, literature review revealed that the average onset age of localized spinal nerve amyloidosis was 62.4 years old.The radial nerve was the most susceptible, followed by the lumbosacral plexus. Fifty percent of the type of amyloid protein is AL.Until now, no consolidated treatment is available. Here, we summarize the clinical characteristics of localized peripheral neuropathy amyloidosis in order to raise the awareness of the disease.

Objective:To explore the relationship between the type of mutation and clinical features, prognosis, and clinical characteristics of chronic granulomatous disease (CGD) caused by compound heterozygous mutations in the NCF2 gene in children. Methods:The clinical data of 1 case of neonatal CGD caused by compound heterozygous mutations of NCF2 gene at Tianjin Children′s Hospital in August 2019 was analyzed, and domestic and international literatures were searched to summarize the clinical characteristics, gene mutation type and prognosis of CGD caused by NCF2 mutation. Results:The diagnosis of CGD was confirmed by the presence of compound heterozygous mutations c. 196_197insA (p.Arg66Glnfs23X) and c. 1180T>G (p.Tyr394Asp) in the NCF2 gene, accompanied with the clinical manifestations of fever, cough, multiple clumps and nodules in the chest CT at 25 days after birth, and the neutrophil respiratory burst test stimulation index(SI) 23.This new mutation was not reported in the Human Genetic Mutation Database.The child had a residual portion of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and was followed up until the age of 9 months with an antifungal drug without recurrent infection.A total of 101 cases of CGD patients with NCF2 gene mutation were reported in domestic and international databases.Totally, 33 cases had SI results, with 22 cases below 3, 11 cases above 3, and 8 cases of missense mutations. Conclusions:c. 196_197insA and c. 1180T>G are new mutations in NCF2 gene that can lead to CGD.CGD patients containing missense mutations in the NCF2 gene may have more residual NADPH oxidase activity.