Objective To establish the reference intervals for test indicators of thyroid function,namely thyroid stimulating hormone(TSH),free thyroxine(FT4),and free triiodothyronine(FT3),in the children aged 0 to 15 years old in Nanning,China.Methods A total of 1 289 healthy children aged 0 to 15 years old who attended the Guangxi International Zhuang Medicine Hospital Affiliated with Guangxi University of Chinese Medicine from October 2018 to August 2023 were selected.The concentrations in serum TSH,FT4,and FT3 were measured by chemiluminescent microparticle immunoassay(CMIA).According to the Clinical and Laboratory Standards Institute(CLSI)EP28-A3c guideline,the nonparametric percentile method was used to establish the reference intervals for TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area.Results The established reference intervals were as follows:TSH(male):0 to＜1 month:0.88-7.81 μIU/mL,1 month to 15 years:0.59-5.06 μIU/mL;TSH(female):0 to＜1 month:0.93-8.42μIU/mL,1 month to 15 years:0.60-4.30 μIU/mL.FT4(male):0 to＜1 month:0.99-1.92 pg/mL,1 month to 15 years:0.86-1.33 pg/mL;FT4(female):0 to＜1 month:1.05-2.06 pg/mL,1 month to 15 years:0.85-1.37 pg/mL;FT3:0 to＜1 month:2.16-4.24 pmol/L,1 month to＜11 years:2.75-4.49 pmol/L,11 to 15 years:2.45-4.34 pmol/L.Significant differences were observed among different gender and age groups for TSH,FT4,and FT3 levels(P＜0.05).Conclusion This study successfully established the refer-ence intervals of TSH,FT4,and FT3 in the children aged 0 to 15 years old in Nanning area,which were significantly different among various gender and age groups.

Background::In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors.Methods::A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities.Results::A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. Conclusions::The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Objective To establish a reference intervals(RIs)of serum squamous cell carcinoma antigen(SCC-Ag)in healthy population in Nanning region and provide clinical evidence to support diagnosis and prognosis of squamous cell carcinoma.Methods A total of 10 197 reference individuals who joined a routine physical examina-tion in the Health Management Center of Guangxi International Zhuang Medical Hospital from March 2019 to De-cember 2021 were collected.The level of serum SCC-Ag was detected by chemiluminescence microparticle immuno-assay.The Mann-Whitney U test was applied to compare the differences in serum SCC level between genders or ad-jacent age groups.The unilateral 95th percentile determined the upper limit of the RIs by the nonparametric method.Another 1 035 healthy subjects with the same conditions as the reference population were selected for refer-ence validation.Results The serum SCC-Ag level showed a skewed distribution(Z＝0.08,P＜0.05).The ser-um SCC-Ag level of males was considerably higher than that of females.There was significant difference in serum SCC-Ag level between males aged 18－30 and 31－40,51－60 and 61－90(P＜0.05).There was significant difference in serum SCC-Ag level between females aged 18－30 and 31－40,31－40 and 41－50,51－60 and 61－ 90(P＜0.05).The reference intervals of serum SCC-Ag was as follows:0－1.64 ng/mL for males and females aged 18－30 years;0－1.57 ng/mL and 0－1.70 ng/mL for males aged 31－60 years and 61－90 years,respec-tively;0－1.50 ng/mL,0－1.52 ng/mL and 0－1.42 ng/mL for females aged 31－40 years,41－60 years and 61－90 years,respectively.Conclusions The RIs of serum SCC-Ag in healthy population in the Nanning region are successfully established according to different genders and ages.

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Objective:To investigate the diagnostic value of integrated 18F-fluorodeoxyglucose (FDG) PET/MRI multimodal imaging in the grading of adult diffuse gliomas. Methods:A retrospective analysis was performed; 29 patients accepted cranial 18F-FDG PET/MRI multimodal imaging and diagnosed as having adult diffuse gliomas in our center from January 2020 to December 2021 were chosen; their clinical and image data were collected. These patients were divided into low-grade group (WHO grading II, n=13) and high-grade group (WHO grading III and IV, n=16) according to the pathological results confirmed by surgery or biopsy. T1WI, T2WI, DWI, arterial spin labeling (ASL), magnetic resonance spectroscopy (MRS) and PET were performed in these patients. Differences in T1WI and T2WI signs between the two groups were compared. Differences in maximum standard uptake value (SUV max), apparent diffusion coefficient (ADC), choline/ N-acetylaspartate (Cho/NAA), NAA/creatine (Cr), Cho/Cr, relative cerebral blood flow (rCBF) between the two groups were compared. The diagnostic efficacies of above parameters in differentiating high-grade from low-grade adult diffuse gliomas were determined by receiver-operating characteristic (ROC) curves. The predictive probabilities for differentiating high-grade from low-grade adult diffuse gliomas using combined parameters were obtained by binary Logistic regression analysis. Results:There were no statistical differences in T1WI and T2WI signs, proportion of adjacent parenchyma edema, proportion of crossing the midline into the contralateral side, proportion of mass effect, proportion of cystic degeneration/necrosis, or site of growth between low-grade and high-grade groups ( P>0.05). The values of SUV max, ADC, Cho/NAA, Cho/Cr and rCBF were statistically different between the two groups, and the order of diagnostic efficiency was SUV max>ADC>Cho/NAA>rCBF>Cho/Cr>NAA/Cr. SUV max had the highest diagnostic efficacy in differentiating high-grade from low-grade adult diffuse gliomas with an area under the curve (AUC) of 0.894, a sensitivity of 75% and a specificity of 100%; the diagnostic efficacy of combined parameters (mean AUC>0.9) was higher than that of single parameter, and the combined parameters of SUV max and Cho/NAA showed the highest diagnostic efficacy with an AUC of 0.933, a sensitivity of 81.3% and a specificity of 92.3%. Conclusion:The 18F-FDG PET/MRI multimodal imaging is helpful in the grading diagnosis of adult diffuse gliomas, and combination of PET and MRS may play a greater role.

Objective:To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm.Methods:A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results:The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively.Conclusions:LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.

Objective: To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype. Results: Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219. Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

Objective By analyzing the problems existed in the Investigator Initiated Trial (IIT),this article put forward the corresponding countermeasures and therefore provides reference for the standardization of clinical research project management.Methods Four types of problems identified in the supervision of hospital IIT projects are analyzed according to literature review,data analysis of clinical research project,comparative study and summary.Identified problems are existed in the following aspects:scientific research supervision function,research method guidelines,technical specification of the diagnosis and treatment,scientific research design and project approval review,research funds,medical ethics committee,construction of Biobank and Regulation Conflicts.Results This article put forward 6 countermeasures for improvement:establishing and perfect IIT project scientific research supervision entity,bring in the IIT project steering group to strengthen the scientific review;Strengthen risk management to ensure medical safety,carry out IIT training,establish IIT management database information system,build a comprehensive integrated development multi-point application model of hospital BioBank.Conclusions The establishment of the hospital's IIT scientific research supervision system,management mode and technical standard system is of great importance to standardize clinical research,ensure research quality and guide the clinical research work of the hospital effectively.

Objective To explore the significance of ADC value combined with MRI signs on identifying benign and malignant breast lump lesions with the type of TICⅡ.Methods 187 patients with breast lump lesions of TICⅡ,which were confirmed by surgical pathology,proceeded MRI.The ADC value,early-phase enhancement rate,length of lesions,lobulated appearance and spiculation, inverted nipple,thickening of the skin and the length of ipsilateral axillary lymph nodes were analyzed and recorded.T-tests was used to analyzed the measurement data,χ2test was used to analysis the attribute data.The ROC curves were used to evaluate the diagnostic efficiency of ADC value and MRI signs.Results The ADC value was (1.418±0.299)×10-3mm2/s and(0.860±0.142)× 10-3mm2/s (P<0.01)for breast benign and malignant lesions respectively,while the early-phase enhancement rate were (170.387± 74.580)% and (160.778±39.786)%(P=0.258)respectively.When ADC values were used for differential diagnosis of breast benign and malignant lesions with a threshold of 1.017×10-3mm2/s,the area under the sensitivity and specificity were 89.0% and 98.0% The sensitivity and specificity of lobulated appearance,spiculation,inverted nipple and thickening of the skin were 92.6% and 33.3%, 88.2% and 88.2%,20.5% and 94.1%,35.3% and 88.2%,respectively.When the 1.0 cm was used as the threshold of the length of ipsilateral axillary lymph,its sensitivity and specificity were 47.8% and 80.4%.The ROC curve of early-phase enhancement rate showed no diagnostic capability(P>0.05).Conclusion ADC value combined with MRI features are helpful to improve the sensitivity and specificity in breast lesions with the type of TICⅡ.

Objective To explore the value of MRI T2*quantification of visceral iron deposition in patients with β-thalassemia major. Methods A total of one hundred and two patients with β-thalassemia major were retrospectively analyzed. They underwent genetic testing and the cardiac and (or) abdominal MRI scanning. Among them, 47 patients underwent splenectomy operation, 95 patients underwent cardiac MRI scanning, 102 underwent abdominal MRI scanning for their livers, pancreases and kidneys, and 55 underwent splenic MRI scanning. The T2* values of the hearts, livers, pancreases and kidneys were measured, meanwhile the liver iron concentrations (LIC) were measured. The levels of serum ferritin (SF) patients were measured in 81 patients. The Spearman rank correlation was employed to analyze the relationship between SF, LIC, age and each organs T2* values. Independent sample t test (normal distribution) or the Mann- Whitney U test (non-normal distribution) were used to compare the hepatic, cardiac, renal and splenic T2* values differences between patients with splenectomy and those without. Results Serum ferritin were highly positively correlated with LIC, moderately correlatied with age, moderately negatively correlated with hepatic and pancreatic T2* values, with r values of 0.833, 0.537,-0.623 and -0.403, respectively (P<0.05). There was significantly negative correlation between hepatic T2*value and LIC (r=-0.925, P<0.01). There were moderately correlations between hepatic and splenic T2*values (r=0.634, P<0.01), hepatic and pancreatic T2*values (r=0.530, P<0.01). However, those T2*values of other organs had no correlation (P>0.05). The hepatic and pancreatic T2*values were reduced (P<0.05), the renal T2* value was increased (P<0.05) in the patients with splenectomy. The cardiac T2* value was not statistically different (P>0.05). Conclusions The patients with β-thalassemia major have prone to suffer from excessive iron deposition in the heart and abdominal organs. The technology of MRI quantification of T2*values could reflect the body iron overload.