The investigator-initiated trials （IIT）， as a widely existing form of clinical research both domestically and internationally， have attracted the attention of governments around the world due to the potential legal risks and issues they may cause， and the trend of legal supervision has gradually strengthened. The legal regulation of IIT in China is still in its early stages， with numerous legal issues that need to be clarified and sorted out. Based on the domestic and international legal reviews of IIT， this paper systematically sorted out the current situation of legal supervision of IIT in China and examined the existing issues， including weak legislative rules， incomplete regulatory systems， imperfect protection rules for research participants and informed consent systems， inadequate regulation of conflicts of interest management， and lax legal supervision of ethical review. Furthermore， this paper proposed suggestions for legal regulation of IIT from three perspectives， including strengthening legislation and emphasizing regulation， improving the mechanism for protecting research participants’ rights and interests， and balancing the legalization of IIT and the scientific development of clinical research， with a view to providing references for legal regulatory paths of IIT in China.

Acute leukemia is a common hematological malignancy.Conventional chemotherapy,targe-ted drug therapy,hematopoietic stem cell transplantation and other treatment methods have made progress,but the mortality rate of patients after recurrence is still high.Adoptive cell therapy(ACT)has emerged as an effective therapeutic option for acute leukemia,particularly chimeric antigen receptor(CAR)T-cell therapy,which has demonstrated remarkable efficacy in treating B-cell acute lymphoblastic leukemia(B-ALL)and ma-lignant lymphoma.However,CAR-T cell therapy may induce cytokine release syndrome.Recent studies have highlighted the potent anti-leukemia effects of CAR-NK cell therapy.This review summarizeed the research progress of ACT employing various immune cells targeting different antigens in the treatment of acute leukemia.

Objective To investigate the differences in acute mountain sickness between individuals en-tering the plateau for the first time and those with multiple plateau experiences,and to examine the impact on psychological stress.Methods A total of 2 337 young plateau-acclimatized individuals from an acclimatization rotation area during November 2023 to January 2024 were selected as the study subjects.Those entering the plateau for the first time were classified into Group A(n=425),while those with previous plateau experience(at least one prior visit)were classified into Group B(n=1 912).Differences were analyzed between the two groups in terms of general characteristics,as well as acute mountain sickness(AMS)scores,Self-Rating De-pression Scale(SDS)scores,Symptom Checklist-90(SCL-90)scores,and various vital signs at the following time points:before entering the plateau(T0),on the 1st day(T1),4th day(T2),7th day(T3),and 10th day(T4)after entering the plateau.Results Group A was younger than Group B,with a statistically significant difference(P<0.05).At T1,T2,and T3,AMS scores in Group A were significantly higher than those in Group B(P<0.05).At T4,there was no statistically significant difference in AMS scores between the two groups(P>0.05).At T1,T2,and T3,blood oxygen saturation was lower and heart rate higher in Group A than in Group B,with statistically significant differences(P<0.05).After high-altitude acclimatization,no statistically significant differences in blood oxygen saturation or heart rate were observed between the groups at T4(P>0.05).At T1,there were no statistically significant differences in systolic or diastolic blood pres-sure between the groups(P>0.05).At T2,both systolic and diastolic blood pressure were higher in Group A than in Group B(P<0.05).At T3 and T4,after high-altitude acclimatization,systolic blood pressure de-creased in both groups but remained higher in Group A than in Group B(P<0.05).On the SDS scale,men-tal-emotional and somatic symptom scores were significantly higher in Group A than in Group B(P<0.001).On the SCL-90,all nine symptom factor scores were higher in Group A than in Group B(P<0.05).Conclusion Indi-viduals entering high-altitude areas for the first time experience more severe acute mountain sickness and more pronounced psychological stress.Therefore,enhanced monitoring,psychological counseling,and tailored pre-vention and treatment strategies should be implemented.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective:To evaluate the association between preoperative serum β 2-microglobulin (β 2MG) concentrations and postoperative delirium (POD) in elderly patients. Methods:The study selected patients who underwent knee or hip arthroplasty under spinal-epidural anesthesia on an elective basis at Qingdao Municipal Hospital from May 2021 to November 2022. The patients were divided into a POD group and a non-POD group based on the occurrence of POD. The study was conducted as part of the Perioperative Neurocognitive Impairment and Biomarkers Lifestyle Cohort, which was a nested case-control study. The study collected baseline data from two groups of patients and analyzed the differences between them. Logistic regression was used to identify the risk factors for POD. The stability of the regression model was tested using sensitivity analysis. The mediation model was used to examine whether cerebrospinal fluid (CSF) biomarkers mediated the relationship between β 2MG and POD. The receiver operating characteristic curve was drawn and the area under the curve was calculated to evaluate the accuracy of preoperative β 2MG concentrations and CSF biomarker concentration in predicting POD. Results:There were 57 cases in POD group and 449 cases in non-POD group. The results of logistic regression analysis showed that the increased β 2MG and CSF total tau protein (t-tau) concentrations were risk factors for POD, and the increased CSF β-amyloid 42 concentration was a protective factor for POD after adjustment for multiple confounders such as age, gender, education, Mini-Mental State Examination, history of hypertension and infusion volume ( P<0.05). The results of mediation analysis showed that the serum β 2MG′s effect on POD was partly mediated by t-tau (18.1%). The results of the receiver operating characteristic curve showed that the area under the curve of the β 2MG concentration combined with the CSF biomarker concentration was 0.742. Conclusions:Elevated preoperative serum β 2MG concentration is a risk factor for POD in elderly patients, and the relationship may be partly mediated by CSF t-tau.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective To analyze the expression and significance of BCAS3 and RFX3 proteins in mac-rophages from gout stone tissues.Methods Thirty gout stone excision specimens in this hospital from April 2019 to December 2022 were collected as the experimental group,and during the same period 25 specimens of synovial hyperplasia accompanied by foreign body giant cell reaction after joint replacement and 5 specimens of fat necrosis accompanied by macrophage hyperplasia served as the control group.The blood uric acid level of the control group was normal.Immunohistochemical staining was applied to conduct CD68,CD163,BCAS3 and RFX3 antibodies staining in all specimens.CD68 and CD163 were used to locate macrophages in tissues. The expression levels of BCAS3 and RFX3 in macrophages were detected.The expressions of the two antibod-ies and their correlation with age,sex and blood uric acid level were analyzed.The receiver operating character-istic (ROC) curve was used to evaluate the diagnostic value of the both on gout.Results The expression lev-els of BCAS3 and RFX3 in the experimental group were significantly higher than those in the control group (P<0.05).The BCAS3 and RFX3 protein expression levels in the control group had no statistical difference between the different sexes (P>0.05).The expression level of BCAS3 protein in the experimental group was positively correlated with the RFX3 protein expression (P<0.05);the uric acid level in the experimental group was positively correlated with the expression level of BCAS3 and RFX3 protein (P<0.05).The blood uric acid level in the control group had no correlation with BCAS3 and RFX3 protein (P>0.05).The age in the two groups had no correlation with the BCAS3 and RFX3 protein (P>0.05).The area under the curve (AUC),sensitivity and specificity of RFX3 were 0.935,96.55％ and 86.67％ respectively,which were higher than 0.742,70.00％ and 80.00％ of BCAS3.RFX3 had the higher diagnostic value for gout.Conclusion High expression of BCAS3 and RFX3 proteins in macrophages may participate in the pathogenesis of gout.There may be some synergistic promoting effect between the two.The diagnostic value of RFX3 for gout is higher than that of BCAS3.

Objective:To study the infection and epidemiological characteristics of soil borne nematode disease in Sihong County, Suqian City, and to provide scientific basis for further development of prevention and control measures.Methods:In 2022, according to geographic location, Sihong County was divided into east and west areas. Jieji Town, Shiji Township, and Linhuai Town were selected from the east area, and Tianganghu Township, Meihua Town from the west area. One administrative village was selected as a survey point in each township. Using cluster sampling method, 450 permanent residents aged 3 years old and older in the village were selected as the respondents for questionnaire survey and fecal sample collection. The infection status of hookworms, roundworms, whipworms and pinworms in fecal samples were examined, transparent tape anal swab method for detecting pinworm eggs in children, and influencing factors were analyzed.Results:A total of 2 264 survey subjects were included, 18 cases of soil borne nematodes were detected as positive, with an overall positive rate of 0.80%. Among them, 15 cases were positive for hookworms, 1 case was positive for whipworms, and 2 cases were positive for pinworms, with detection rates of 0.66%, 0.04%, and 0.09%, respectively. No ascaris lumbricoides were detected. Transparent tape anal swab method was used to examine 142 children, and the positivity rate of 1.41% (2/142). By township, the detection rate of soil borne nematodes was the highest in Jieji Town, at 2.41% (11/457); the others were Meihua Town, Tianganghu Township, Shiji Township, and Linhuai Town, with detection rates of 0.89% (4/451),0.66% (3/454), 0 (0/451) and 0 (0/451), respectively. There was a statistically significant difference between different townships (χ 2 = 19.21, P < 0.001). Among the 18 positive cases of soil borne nematode, 7 were males and 11 were females, with detection rates of 0.66% (7/1 063) and 0.92% (11/1 201), respectively, the difference was not statistically significant (χ 2 = 0.47, P = 0.491). The age distribution showed the highest detection rate in the 40 - < 60 age group, at 1.42% (9/634), with statistically significant differences between different age groups (χ 2 = 6.41, P = 0.033). The occupational distribution showed the highest detection rate in farmers, at 1.46% (9/617), with statistically significant differences between different professions (χ 2 = 8.00, P = 0.034). The differences in total soil borne nematode and hookworm detection rates were statistically significant among different methods of treating human and animal feces (χ 2 = 11.01, 9.02, P = 0.003, 0.011). Conclusions:The main species of soil borne nematode infections in Sihong County, Suqian City are hookworms, with fewer infections of whipworms and pinworms, and no roundworm infections observed. There are regional differences in detection rate. In the future, it is necessary to strengthen health education for key populations, enhance health knowledge publicity, and effectively intervene to change unhealthy production and lifestyle, further reducing the infection of soil borne nematodes in Suqian City.

Objective:The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations ( TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods:Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated.Results:(1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC . A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion:Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.