Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver injury of unknown etiology. The onset of this disease involves the activation and recruitment of diverse immune and non-immune cells, which in turn trigger hepatic damage. Immune checkpoint molecules (ICM) are expressed on the surface of multiple cell types. By regulating cellular functional states, they help limit the intensity and duration of immune responses, thereby preventing excessive inflammation and tissue damage, and maintaining immune homeostasis. In AIH, however, this natural "braking" mechanism is impaired, leading to aberrant activation of both immune and non-immune cells and the breakdown of immune homeostasis. Consequently, ICM are likely to play a critical role in the pathogenesis of AIH. A deeper understanding of the function of ICM in AIH not onlyadvances our insight into the disease mechanism, but also suggests that targeting these molecules may represent a promising therapeutic strategy for the treatment of AIH.

Objective:To investigate the brain iron status in the sensorimotor cortex of patients with chronic low back pain (CLBP) and its relationship with changes in resting-state functional connectivity (RS-FC).Methods:This was a cross-sectional study. Thirty-two patients with CLBP (CLBP group) who were treated at Wuxi People′s Hospital Affiliated to Nanjing Medical University from July 2023 to March 2024 and 30 age-and gender-matched healthy volunteers (control group) were prospectively included. All subjects underwent pain and neuropsychological assessments and head MRI examinations, including conventional sequences, quantitative susceptibility mapping (QSM), and blood oxygen level-dependent (BOLD) functional MRI. QSM values of the sensorimotor cortex and the left middle frontal gyrus, right inferior temporal gyrus, right olfactory cortex, and right posterior cingulate gyrus were extracted using the ANTs toolkit. The bilateral postcentral gyrus and posterior portion of the bilateral precentral gyrus in the sensorimotor cortex were selected as seed points using SPM software to extract the average time series of BOLD signals and evaluate the changes in RS-FC values with other brain regions. Two-sample t-tests were used to compare the differences in QSM values and RS-FC values between the two groups. Pearson correlation analysis was used to analyze the correlation between iron deposition in key brain regions and RS-FC values and clinical scale scores. Results:The QSM values in the posterior portion of the bilateral precentral gyrus and the left postcentral gyrus in the CLBP group were significantly higher than those in the control group ( t=2.17, P=0.009; t=4.44, P<0.001), and the QSM value in the left postcentral gyrus was positively correlated with pain-related scale scores ( P<0.05). Compared with the control group, the QSM values in the left orbital part of the middle frontal gyrus ( t=2.22, P=0.031) and the right inferior temporal gyrus ( t=2.98, P=0.004) were increased, while the QSM values in the right olfactory cortex ( t=2.54, P=0.014) and the right posterior cingulate gyrus ( t=2.70, P=0.009) were decreased in the CLBP group. Compared with the control group, the RS-FC values between the left postcentral gyrus, the posterior part of the bilateral precentral gyrus, and the left superior frontal gyrus were increased in the CLBP group ( P<0.001), the RS-FC value between the right postcentral gyrus and the right precuneus was increased ( P<0.001). The RS-FC of the bilateral motor cortex and the left dorsolateral superior frontal gyrus was positively correlated with the QSM values of the bilateral motor cortex ( r=0.444, P=0.015). Conclusion:Iron deposition in the sensorimotor cortex (posterior portion of the bilateral precentral gyrus and the left postcentral gyrus) is increased in CLBP patients and is correlated with abnormal functional connectivity within and between brain regions.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Objective:To investigate the brain iron status in the sensorimotor cortex of patients with chronic low back pain (CLBP) and its relationship with changes in resting-state functional connectivity (RS-FC).Methods:This was a cross-sectional study. Thirty-two patients with CLBP (CLBP group) who were treated at Wuxi People′s Hospital Affiliated to Nanjing Medical University from July 2023 to March 2024 and 30 age-and gender-matched healthy volunteers (control group) were prospectively included. All subjects underwent pain and neuropsychological assessments and head MRI examinations, including conventional sequences, quantitative susceptibility mapping (QSM), and blood oxygen level-dependent (BOLD) functional MRI. QSM values of the sensorimotor cortex and the left middle frontal gyrus, right inferior temporal gyrus, right olfactory cortex, and right posterior cingulate gyrus were extracted using the ANTs toolkit. The bilateral postcentral gyrus and posterior portion of the bilateral precentral gyrus in the sensorimotor cortex were selected as seed points using SPM software to extract the average time series of BOLD signals and evaluate the changes in RS-FC values with other brain regions. Two-sample t-tests were used to compare the differences in QSM values and RS-FC values between the two groups. Pearson correlation analysis was used to analyze the correlation between iron deposition in key brain regions and RS-FC values and clinical scale scores. Results:The QSM values in the posterior portion of the bilateral precentral gyrus and the left postcentral gyrus in the CLBP group were significantly higher than those in the control group ( t=2.17, P=0.009; t=4.44, P<0.001), and the QSM value in the left postcentral gyrus was positively correlated with pain-related scale scores ( P<0.05). Compared with the control group, the QSM values in the left orbital part of the middle frontal gyrus ( t=2.22, P=0.031) and the right inferior temporal gyrus ( t=2.98, P=0.004) were increased, while the QSM values in the right olfactory cortex ( t=2.54, P=0.014) and the right posterior cingulate gyrus ( t=2.70, P=0.009) were decreased in the CLBP group. Compared with the control group, the RS-FC values between the left postcentral gyrus, the posterior part of the bilateral precentral gyrus, and the left superior frontal gyrus were increased in the CLBP group ( P<0.001), the RS-FC value between the right postcentral gyrus and the right precuneus was increased ( P<0.001). The RS-FC of the bilateral motor cortex and the left dorsolateral superior frontal gyrus was positively correlated with the QSM values of the bilateral motor cortex ( r=0.444, P=0.015). Conclusion:Iron deposition in the sensorimotor cortex (posterior portion of the bilateral precentral gyrus and the left postcentral gyrus) is increased in CLBP patients and is correlated with abnormal functional connectivity within and between brain regions.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Objective To investigate the diagnosis value of contrast-enhanced ultrasound (CEUS) in the differentiation of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) of the liver with ≤3 cm of maximum diameter. Methods The image characteristics in 48 lesions of HCC with maximum diameter≤3 cm and 48 lesions of FNH with maximum diameter≤3 cm confirmed by pathology were retrospectively analyzed. The phase changes, enhancement patterns and enhancement characteristics of the lesions in the two groups were compared. Results All lesions in the two groups showed high-echo in the arterial phase. The contrast arrival time in HCC group and FNH group was 17(15, 19) s and 15(12, 18.75) s (P＝0.017); the peak time in the two groups was 21(17, 25) s and 22(19, 26) s (P＞0.05). The main enhancement patterns of HCC group and FNH group in arterial phase were homogeneous enhancement and centrifugal enhancement, respectively. All HCC lesions showed homogeneous enhancement, which was significantly higher than FNH (2.08%, P＜0.05); 97.91% of FHN lesions showed centrifugal enhancement, which was higher that of HCC lesions (0, P＜0.05). During the CEUS process, 87.5% of HCC lesions showed “rapid fill-in and rapid wash-out”, which was significantly higher than that of FNH lesions（8.33%，P＜0.05）; 91.67% of FNH lesions showed “rapid fill-in” and “synchronous/slow wash-out” which was significantly higher than that of HCC lesions （12.50%，P＜0.05）. Conclusion CEUS is helpful in the differential diagnosis of FNH and HCC with maximum diameter≤3 cm．

Objective To explore the effectiveness of high-definition diffusion weighted imaging(DWI)sequence combined with T1 WI-fat suppression(FS)dynamic contrast enhancement(DCE)sequence for preoperative T-stage of rectal cancer by using 3.0T MRI standardized scanning.Methods A retrospective analysis was conducted on MRI images of 57 patients with rectal cancer confirmed by pathology.Before surgery,the patients underwent 3.0T MRI standardized rectal cancer scan methods,including routine sequence,high-definition DWI sequence,and T1 WI-FS DCE sequence,etc.Then two experienced physicians evaluated the T-stage of preoperative rectal cancer through high-definition DWI(transverse and sagittal sections)and T1 WI-FS DCE sequences in the double-blind method.Using the postoperative pathological results of rectal cancer as the"gold standard",two sequences were combined to evaluate the accuracy,sensitivity,and specificity of rectal cancer T-stage.Results Among the 57 cases,there were 9 cases of upper rectal cancer,39 cases of middle rectal cancer,and 9 cases of lower rectal cancer.The accuracy rates of preoperative T-stage diagnosis for rectal cancer by two evaluator were both 85.7％(6/7)in T1 stage,88.2％(15/17)and 94.1％(16/17)in T2 stage,96.9％(31/32)and 93.8％(30/32)in T3 stage,and both 100.0％(1/1)in T4 stage.For evaluator 1,the sensitivity and specificity of the rectal cancer T-stage diagnosis were 96.1％and 83.3％,and for evaluator 2 were 94.1％and 83.3％,respectively.For rectal cancer MRI diagnosis,the accuracy rates and sensitivity were higher when combining the high-definition DWI sequence and T1 WI-FS DCE sequence,compared with a single high-definition DWI sequence or T1 WI-FS DCE sequence,and the difference was statistically significant.The average preoperative apparent diffusion coefficient(ADC)value of rectal cancer was compared between the corresponding postoperative pathological T1 to T4 stage groups,and the difference was statistically significant.Conclusion The combination of high-definition DWI sequence and T1 WI-FS DCE sequence improves the accuracy of rectal cancer T-stage,providing assistance for personalized clinical treatment.

Objective To explore the changes of resting-state degree centrality(DC)in elderly patients with chronic insomnia disorder(CID).Methods Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 26 untreated elderly patients with CID(CID group)and 45 healthy controls(HC)(HC group).Two-sample t-test was conducted to compare the intergroup differences in whole-brain DC values,and the correlation between DC values in different brain regions and clinical indicators were analyzed,and logistic regression analysis was performed to verify the diagnostic efficacy of changes in DC values for elderly CID.Results Compared with the HC group,the DC values of the right insula,left rolandic operculum,and opercular part of right inferior frontal gyrus in the elderly CID group decreased[P＜0.05,false discovery rate(FDR)corrected],while the DC values of the right middle frontal gyrus increased(P＜0.05,FDR corrected).And the DC values of the opercular part of right inferior frontal gyrus in the elderly CID group were positively correlated with sleep efficiency(r=0.504,P=0.009)and self-rating depression scale(SDS)(r=0.401,P=0.042),respectively.The sensitivity of DC value in the opercular part of right inferior frontal gyrus for diagnosing elderly CID was 0.822,the specificity was 0.615,and the accuracy was 0.701.Conclusion Elderly CID patients have abnormal DC values in the right insula,left rolandic operculum,opercular part of right inferior frontal gyrus and right middle frontal gyrus,which may provide imaging evidence for exploring the pathogenesis of CID and clinical diagnosis and treatment.

Objective:To explore the characteristics of gray matter volume (GMV) and structural covariant network (SCN) in patients with cerebral small vessel disease (CSVD) related cognitive impairment.Methods:This was a cross-sectional study. Ninety-eight patients with CSVD who attended Wuxi People′s Hospital of Nanjing Medical University between October 2021 and December 2022 were prospectively included. The patients were evaluated using the cognitive status assessment scale and were categorized into 57 cases in the CSVD with cognitive impairment group and 41 cases in the CSVD without cognitive impairment group according to the presence or absence of cognitive impairment. 3D-T 1WI structural image data were collected, and GMV differences between the two groups were compared by SPM 12 toolbox and CAT12 toolkit. At the same time, Pearson correlation analysis was also performed to analyze the GMV of differences between the 2 groups and cognitive status assessment scale scores. The BCT software package based on MATLAB platform was used to construct the GMV-related structural covariant network (SCN), and the graph theory method was utilized for SCN analysis to calculate the area under the curve (AUC) of the global and local parameters within the set sparsity range, and the permutation test was used to compare the differences in the AUC of the 2 groups. Results:In the CSVD with cognitive impairment group, GMV in bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala was significantly lower than that in the CSVD without cognitive impairment group (family wise error corrected P<0.05), and the GMV in these regions had correlation with cognitive status assessment scale ( P<0.05). At the global network level of the SCN, the area under the curve (AUC) of the characteristic path length was significantly higher in the CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.023), while the AUC of global efficiency was significantly lower in CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.005). At the local level, the nodal degree and nodal efficiency of the left putamen were significantly decreased in the CSVD with cognitive impairment group compared to the CSVD without cognitive impairment group (false discovery rate corrected P<0.05). Conclusions:GMV reduce in patients of CSVD with cognitive impairment in the bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala. In the structural covariance network, characteristic path length increase while global efficiency reduce, and node degree and nodal efficiency of the left putamen reduce.

Objective:To observe the expression of angiopoietin-like protein 4 (ANGPTL4) signaling pathway in adenine-induced chronic kidney disease (CKD) rat model, and to explore the role of this pathway in renal fibrosis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into control group (saline, intragastric administration, n=15) and CKD group (250 mg·kg -1·d -1 2.5% adenine, intragastric administration, n=21). At the end of the 1st, 2nd and 4th week, 5 rats were randomly selected from each group. Renal function and 24-hour urinary protein quantity were measured. HE and Masson staining were used to observe the pathological changes of kidneys. Immunohistochemistry and real-time PCR were used to detect renal protein and mRNA expressions of hypoxia-inducible factor-1α (HIF-1α), ANGPTL4, bone morphogenetic protein 7 (BMP7), Smad1, α-smooth muscle actin (α-SMA) and type Ⅰ collagen (Col-Ⅰ). Pearson correlation analysis was used to analyze the correlation between the different indicators. Results:(1) Compared with the control group, the expression levels of serum creatinine and blood urea nitrogen in CKD group were higher at each time point, and the expression levels of 24-hour urinary protein quantity were higher at the end of the 2nd and 4th week (all P < 0.05). (2) HE and Masson staining showed that there were obvious renal structural disorders and collagen fiber deposition at each time point in CKD group compared with the control group, which got worse with time. (3) The results of immunohistochemistry and real-time PCR showed that compared with the control group, the protein and mRNA expression levels of ANGPTL4, α-SMA and Col-Ⅰ were higher, while the protein and mRNA expression levels of BMP7 and Smad1 were lower at the end of the 1st, 2nd and 4th week, and the protein and mRNA expression levels of HIF-1α were higher at the end of 2nd and 4th week in CKD group (all P < 0.05). (4) Correlation analysis results showed that HIF-1α and ANGPTL4 mRNA expression were positively correlated with α-SMA mRNA ( r=0.919, P < 0.001; r=0.757, P < 0.001), and also positively correlated with Col-Ⅰ mRNA ( r=0.925, P < 0.001; r=0.777, P < 0.001). HIF-1α mRNA expression was positively correlated with ANGPTL4 mRNA ( r=0.766, P < 0.001). There were significant negative correlations between HIF-1α, ANGPTL4 mRNA and BMP7 mRNA ( r=-0.652, P < 0.001; r=-0.741, P < 0.001). Conclusions:ANGPTL4 signaling pathway may be activated in adenine-induced CKD rat model, and involved in the renal fibrosis process of CKD.