Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

Objective To explore the CT and MRI characteristic manifestations of nodular fasciitis(NF).Methods A retrospec-tive analysis was conducted on the imaging data of 27 cases pathologically confirmed NF,and their special CT and MRI signs were analyzed.Among them,21 cases underwent MRI examination,14 cases underwent CT examination,and another 8 cases underwent both CT and MRI examinations.Results Among the 27 cases of NF,16 cases were subcutaneous type,4 cases were intramuscular type,and 7 cases were intermuscular(fascial)type.Eleven cases were located in the head and neck,8 cases in the trunk,6 cases in the upper limbs,and 2 cases in the lower limbs.Fourteen cases underwent CT plain scan,and all lesions showed slightly low density,while 1 case showed mild enhancement on CT enhanced scan.On T1 WI,19 cases showed iso-or slightly hypointense signals,and 2 cases showed slightly hyperintense signals.On T2WI,16 cases showed inhomogeneous hyperintense signals and 5 cases showed homoge-neous hyperintense signals.Fifteen cases showed mixed hyperintense signals on diffusion weighted imaging(DWI).Among the 7 cases with MRI enhancement,5 cases showed significant inhomogeneous enhancement,and 2 cases showed rim enhancement."Fascial tail sign"was observed in 25 cases of NF;"double low signal sign"was seen in 16 cases of NF;"reverse target sign"was observed in 6 cases of NF lesions;peritumoral edema was seen in 9 cases;and small cystic degeneration and necrotic foci were found in 3 cases.Conclusion The imaging manifestations of NF have certain characteristics.When the tumor course is short and the tumor size is small and manifesta-tions such as"fascial tail sign""double low signal sign"and"reverse target sign"are present,the possibility of NF should be considered.

Objective:To analyze the X-ray imaging characteristics of calcaneus in adult patients with osteoarticular diseases and its impact on disease diagnosis.Methods:Totally 78 patients (156 ankle joints) with osteoarticular diseases admitted to the Affiliated Hospital of Jining Medical University from June 2019 to June 2022 were selected as research subjects, including 72 cases of osteoarthritis and 6 cases of Kashin-Beck disease. Another 50 volunteers who underwent health examination in this hospital during the same period were selected as control group, all of them underwent calcaneal X-ray examination. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of calcaneal X-ray parameters in predicting adult osteoarticular diseases.Results:Among 72 patients with osteoarthritis, 63 cases (87.50%) showed joint surface sclerosis in the calcaneal X-ray changes. Forty-seven cases (65.28%) had narrowing of the subtalar joint space; 14 cases showed disappearance of the subtalar joint space, accounting for 19.44%. Among the 6 patients with Kashin-Beck disease, the X-ray changes of the calcaneus showed joint surface sclerosis in 6 cases, narrowing of the subtalar joint space in 4 cases, and disappearance of the subtalar joint space in 2 cases. The length, height, Bohler angle, Gissane angle, and inclination angle of the calcaneus in patients with Kashin-Beck disease were all smaller than those in the osteoarthritis group and the control group, the height to length ratio of the calcaneus was higher than that in the osteoarthritis group and the control group, and the difference was statistically significant ( P < 0.05). The length, height, Bohler angle, Gissane angle, and inclination angle of the calcaneus in patients of the osteoarthritis group were all smaller than those in the control group, and the height to length ratio of the calcaneus was higher than that in control group, and the difference was statistically significant ( P < 0.05). ROC curve analysis showed that the sensitivity of Bohler angle, Gissane angle, and the height to length ratio of the calcaneus in predicting osteoarticular diseases (72 patients with osteoarthritis) were 92.5%, 87.6% and 80.4%, respectively, with specificity of 73.0%, 68.8% and 63.1%, respectively. Conclusion:The calcaneal X-ray manifestations of adult patients with osteoarticular diseases vary greatly, among which Bohler angle, Gissane angle, and height to length ratio of the calcaneus have certain accuracy in diagnosis of osteoarthritis.

Objective:To investigate the value of diffusion kurtosis imaging (DKI) combined with quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting axillary lymph node metastasis in breast cancer.Methods:A total of 150 cases of breast cancer confirmed by pathology in the Affiliated Hospital of Jining Medical University were retrospectively analyzed. 68 cases had axillary lymph node (ALN) metastasis and 82 cases had no ALN metastasis. All breast lesions were examined by DKI and DCE-MRI before operation. We analyzed clinical case data, routine MRI features, DKI, and DCE-MRI parameters between two groups, including diffusion kurtosis (MK), mean diffusion rate (MD), volume transfer constant (K trans), extravascular volume fraction (Ve), and rate constant (Kep); The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of quantitative parameters for ALN metastasis of breast cancer. Results:The proportion of lesions with blurred edges in the metastatic group was higher than that in the non ALN metastatic group ( P=0.032); The proportion of uneven and circular enhancement within the ALN metastasis group was relatively high ( P=0.018). The MD value of the ALN transfer group was lower than that of the group without ALN transfer ( P=0.021); The MK value, K trans value, and Kep value were higher than those in the group without ALN metastasis (all P<0.01). The K trans value of DCE-MRI model was the most effective in diagnosing ALN metastasis of breast cancer, and the area under the ROC curve (AUC) was 0.831; The AUC of DCE-MRI model was 0.833, which was higher than that of DKI model (AUC=0.733), and the difference was statistically significant ( Z=2.208; P=0.027). The AUC of DCE-MRI and DKI models were higher than that of conventional MRI models ( Z=3.184, P=0.002; Z=1.917, P=0.046). The sensitivity and accuracy of combined DKI and DCE-MRI models in the diagnosis of ALN metastasis in breast cancer were higher than those of single model. Conclusions:DKI and DCE-MRI models can be used to predict axillary lymph node metastasis in breast cancer. Among them, the K trans value of DCE-MRI model is the most effective in diagnosing axillary lymph node metastasis in breast cancer.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Objective:To explore the modification effect of physical activity on the genetic effects of type 2 diabetes mellitus (T2DM).Methods:The univariate moderation model was fitted to calculate the modifying effect of physical activity on the genetic effects of T2DM based on the data of 12 107 pairs of same gender twins aged 30 years and older enrolled by the Chinese National Twin Registry in 11 provinces/cities in China.Results:After adjusting for age and gender, the heritability of T2DM was 0.56 (0.31-0.84). Qualified physical activity could attenuate the genetic effects of T2DM. The heritability of T2DM in twin pairs with qualified physical activity was 0.46 (0.06-0.88), which was lower than that in twin pairs without qualified physical activity during the same model [0.68(0.36-0.94)].Conclusion:T2DM is a moderate genetic disease, physical activity can modify the genetic effects of T2DM.

Objective:To explore the gene-body mass index (BMI) interaction on coronary heart disease (CHD) in the Chinese adult twins.Methods:A total of 20 340 same-sex twin pairs registered in the Chinese National Twin Registry (CNTR) were enrolled in this study. Classical twin structure equation model was used to estimate the gene-BMI interaction on CHD.Results:After adjusting for age, we found that genetic variance of CHD differed as the function of BMI in male twins, which indicated the presence of a gene-BMI interaction on CHD ( P=0.008).The genetic moderating effect ( βa) was -0.14 (95% CI: -0.22--0.04), indicating that for each logarithmic transformation value of BMI increase, genetic path parameters would decrease by 0.14, which would result in the decrease of genetic variance of CHD. And the heritability of CHD was 0.77 (95% CI: 0.65-0.86) among the male twins with lower BMI (<24.0 kg/m 2), but 0.56 (95% CI: 0.33-0.74) among the male twins with high BMI (≥24.0 kg/m 2). However, there was no evidence suggesting that BMI could moderate genetic variants of CHD in female. Conclusion:We found a significant gene-BMI interaction on CHD in the Chinese male adult twins in China, and the heritability of CHD was higher among the twins whose BMI was <24.0 kg/m 2.

Objective:To quantitate the association between birth weight and phenotypes of physical indicators in adulthood, i.e. BMI and waist circumference (WC) and to what degree genetic or environmental factors affect birth weight-obesity association.Methods:A total of 6 623 gender matched twin pairs aged 25 to 79 years were recruited through the Chinese National Twin Registry. The twins reported their own birth weight, current height and weight, and WC using a self-administered questionnaire. BMI was calculated according to the self-reports of body height and weight. Within twin-pair design was used to quantitate the association between birth weight and phenotypes related to obesity while bivariate structural equation models were used to decompose the phenotype correlation.Results:After adjusted for multiple factors, twin-pair analyses within monozygotic (MZ) showed that, on average, a 1.0 kg increase in birth weight corresponded to an increase of 0.33 kg/m 2 in BMI and 0.95 cm in WC in adulthood ( P<0.001). Bivariate structural equation models showed significant positive unique environmental correlation between birth weight and the two obesity-related phenotypes. Conclusion:The study supported the role of twin-specific supply line factors on relationship between birth weight and physical indicators in adulthood.