Objective To explore the pain catastrophizing (PC) level of pain in patients with multiple fractures and its influencing factors. Methods A convenience sampling method was used to investigate 156 patients with multiple fractures in the orthopedic trauma department of the First Affiliated Hospital of Nanjing Medical University. The questionnaire included a general information survey, a Digital Pain Rating Scale, PC scale, Positive and Negative Emotion Scale, and Social Rating Scale. Results The average PC score of patients with multiple fractures was (23.22±12.05), with 27 patients (17.20%) reaching the PC level. The average score of the Digital Pain Rating Scale was (6.30±1.49), the score of the Positive Emotion Scale was (27.92±6.06), the score of the Negative Emotion Scale was (23.18±7.00), and the total score of the Social Rating Scale was (27.90±4.61). The results of multiple linear regression analysis showed that pain score, negative emotion level, and social support level had predictive effects in PC among patients with multiple fractures. Conclusion The incidence of PC among patients with multiple fractures is at a moderate to high level. Patients with high pain scores, high negative emotion scores, and low social support are more likely to develop PC.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro.Methods:The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons.Results:shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells ( P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) ( P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) ( P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group ( P > 0.05). Conclusions:SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

BACKGROUND: Lung cancer is the cancer with the highest mortality at home and abroad at present. The detection of lung nodules is a key step to reducing the mortality of lung cancer. Artificial intelligence-assisted diagnosis system presents as the state of the art in the area of nodule detection, differentiation between benign and malignant and diagnosis of invasive subtypes, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the effectiveness of artificial intelligence-assisted diagnosis system in predicting the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules. METHODS: Clinical data of 223 patients with early-stage lung adenocarcinoma appearing as pulmonary nodules admitted to the Lanzhou University Second Hospital from January 1st, 2016 to December 31th, 2021 were retrospectively analyzed, which were divided into invasive adenocarcinoma group (n=170) and non-invasive adenocarcinoma group (n=53), and the non-invasive adenocarcinoma group was subdivided into minimally invasive adenocarcinoma group (n=31) and preinvasive lesions group (n=22). The malignant probability and imaging characteristics of each group were compared to analyze their predictive ability for the invasive subtypes of early-stage lung adenocarcinoma. The concordance between qualitative diagnostic results of artificial intelligence-assisted diagnosis of the invasive subtypes of early-stage lung adenocarcinoma and postoperative pathology was then analyzed. RESULTS: In different invasive subtypes of early-stage lung adenocarcinoma, the mean CT value of pulmonary nodules (P<0.001), diameter (P<0.001), volume (P<0.001), malignant probability (P<0.001), pleural retraction sign (P<0.001), lobulation (P<0.001), spiculation (P<0.001) were significantly different. At the same time, it was also found that with the increased invasiveness of different invasive subtypes of early-stage lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. On the issue of binary classification, the sensitivity, specificity, and area under the curve (AUC) values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 81.76%, 92.45% and 0.871 respectively. On the issue of three classification, the accuracy, recall rate, F1 score, and AUC values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 83.86%, 85.03%, 76.46% and 0.879 respectively. CONCLUSIONS Artificial intelligence-assisted diagnosis system could predict the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules, and has a certain predictive value. With the optimization of algorithms and the improvement of data, it may provide guidance for individualized treatment of patients.
Adenocarcinoma/pathology* ; Adenocarcinoma of Lung/pathology* ; Artificial Intelligence ; Humans ; Lung Neoplasms/pathology* ; Multiple Pulmonary Nodules ; Neoplasm Invasiveness ; Retrospective Studies

Objective:To investigate the dynamic expression of protein tyrosine phosphatase SHP2 in liver tissue of rats with carbon tetrachloride (CCl 4)-induced liver fibrosis. Methods:Rat liver fibrosis model was established by intraperitoneal injection of CCl 4. Rat liver tissue histopathological changes were detected by HE and Masson-trichrome staining. Immunohistochemical staining, Western blot and real-time fluorescent quantitative PCR were used to detect SHP2 protein and mRNA expression in rat liver tissue. One-way analysis of variance was used for the comparison of means between multiple groups, and the LSD test was used for further inter-group comparison. Results:CCl 4-induced rat liver fibrosis model was successfully constructed, and with the extension of modeling time, the degree of liver fibrosis in rats were aggravated gradually. Immunohistochemical staining results showed that SHP2 was mainly expressed in the cytoplasm of rat liver tissues. With the aggravation of liver fibrosis, the number of cells with positive expression of SHP2 was aggravated gradually ( P < 0.05). Western blot and real-time fluorescent quantitative PCR results showed that the expressions of SHP2 protein and mRNA in rat fibrotic liver tissues at different times in week 2, 4, 6, and 8 were higher in modeling than control group ( P < 0.05), and was aggravated gradually with the liver fibrosis aggravation ( P < 0.05). Conclusion:The expression of SHP2 protein and mRNA in the liver tissue of rats with CCl 4-induced liver fibrosis increased gradually with the degree of liver fibrosis, and the degree of increase was consistent with the degree of liver fibrosis.

Objective To observe the clinical significance of serum pancreatic stone protein/regenerating protein (PSP/reg) in neonatal bacterial infectious diseases.Methods 92 cases of newborns with bacterial infection in our hospital from June 2016 to May 2017 were enrolled in the study.They were divided into severe infection group (36 cases) and mild infection group (56 cases) according to the severity of the infection.At the same period 58 newborns without infectious diseases in our hospital were also chosen as control group.The serum levels of PSP/reg,procalcitonin (PCT) and C-reactive protein (CRP) were quantitatively measured by enzyme-linked immunosorbent assay (ELISA).Results The serum levels of PSP/reg,PCT and CRP in severe infection group were significantly higher than those in mild infection group (P ＜0.01) and control group (P ＜ 0.01),while the levels of PSP/reg,PCT and CRP in mild infection group were significantly higher than those in control group (P ＜ 0.01).The levels of PSP/reg 3 day after treatment in both severe and mild infection group were significantly lower than those before treatment (P ＜0.01),while the level of PSP/reg in severe infection group was higher than that in another group.After treatment,the levels of PSP/reg,PCT and CRP in the two infection groups were significantly decreased (P ＜0.01),and there was no significant difference between the two groups after healing (P ＞ 0.05).Conclusions The level of PSP/reg is correlated with the severity of neonatal bacterial infectious disease.The change of serum PSP/reg level may be useful in the evaluation of therapy in neonatal bacterial infection.

Partial least square (PLS) combining with Raman spectroscopy was applied to develop predictive models for plasma paclitaxel concentration detection. In this experiment, 312 samples were scanned by Raman spectroscopy. High performance liquid chromatography (HPLC) was applied to determine the paclitaxel concentration in 312 rat plasma samples. Monte Carlo partial least square (MCPLS) method was successfully performed to identify the outliers and the numbers of calibration set. Based on the values of degree of approach ( ), moving window partial least square (MWPLS) was used to choose the suitable preprocessing method, optimum wavelength variables and the number of latent variables. The correlation coefficients between reference values and predictive values in both calibration set ( ) and validation set ( ) of optimum PLS model were 0.933 1 and 0.926 4, respectively. Furthermore, an independent verification test was performed on the prediction model. The results showed that the correlation error of the 20 validation samples was 9.36%±2.03%, which confirmed the well predictive ability of established PLS quantitative analysis model.

Objective To investigate the value of diffusion kurtosis imaging (DKI)quantitative parameters in evaluating patholog-ical grade of cervical squamous cell carcinoma (CSCC).Methods The DKI images of 45 patients with CSCC were analyzed retrospec-tively.According to the results of pathology,22 cases were divided into poorly differentiated group and 23 cases well-moderately dif-ferentiated group.The DKI parameters of two groups were measured by two observers,which included mean kurtosis (MK),axial kurtosis (Ka),radial kurtosis (Kr),fractional anisotropy of kurtosis (FAk),mean diffusivity (MD),axial diffusivity (Da),radial diffusivity (Dr)and fractional anisotropy (FA).The intra-class correlation coefficients (ICC)was used to test the consistency of the parameters measured results on two observers.The two independent samples t test was used to compare the parameters of two groups,and the ROC curve was used to evaluate the effectiveness of each parameter in order to evaluate the poorly differentiated CSCC and find the boundary values.Results The data consistency of two observers were good (ICC>0.75).The MK,Ka and Kr values on poorly differentiated CSCC were greater than that on well-moderately differentiated (P<0.05),the MD,Da and Dr values were less than that on well-moderately differentiated (P<0.05),the FAk and FA values had no difference (P>0.05).Thearea un-der curve (AUC)of MK,Ka,Kr,MD,Da and Dr values to diagnose poorly differentiated CSCC were 0.914,0.831,0.865,0.850, 0.778 and 0.865,respectively.The boundary values of diagnosing poorly differentiated CSCC were MK≥0.973,Ka≥1.075,Kr≥0.823, MD≤0.974μm2/ms,Da≤1.185μm2/ms and Dr≤0.762μm2/ms,respectively.Conclusion DKI can effectively predict the patho-logical grading of CSCC,which has a good clinical application prospects.

Objective To evaluate the value of ADC and FA of diffusion tensor imaging (DTI) in differentiating clear cell renal cell carcinoma (ccRCC) and transitional cell carcinoma (TCC) of kidney pelvis.Methods Thirty-eight histopathology proven ccRCC and TCC patients (29 cases of ccRCC and 9 cases of TCC) were retrospectively enrolled.All the patients were performed abdominal MR fat saturation T1WI,fat saturation T2WI,LAVA and DTI (b=0,600 s/mm2).MR images were reviewed and analyzed by two radiologists in a double-blind manner with the value of ADC and FA measured using the Functool on AW 4.4 workstation.The data of two observers were analyzed with intra-class correlation coefficients (ICC) to assess inter-observer consistency.The differences of ADC values and FA values between ccRCC and TCC were compared by independent t-test.The ROC curves were used to analyze and compare the diagnostic value of DTI in differentiating ccRCC and TCC.Results The inter-observer agreements were good (ICC＞0.75).The ADC value of ccRCC was statistically higher than that of TCC ([2.03 ± 0.49] × 10-3 mm2/s vs [1.57 ± 0.43] × 10-3 mm2/s,P =0.015).But the FA value of ccRCC was statistically lower than that of TCC ([0.24±0.10] vs [0.42±0.22],P=0.002).The area under the ROC curve of ADC was 0.761 (P＜0.05),and the sensitivity and specificity were 79.3％ and 77.8％.The ADC threshold for differentiating ccRCC from TCC was 1.59× 10-3 mm2/s.The area under the ROC of FA was 0.762 (P＜ 0.05),and the sensitivity and specificity were 66.7 ％ and 93.1％.The FA threshold for differentiating ccRCC from TCC was 0.326.Conclusion MR DTI can effectively discriminate ccRCC and TCC.FA values has good diagnostic specificity in differentiating between ccRCC and TCC.

Objective To explore the value of diffusion tensor imaging (DTI) in differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).Methods Fifty-two patients including 20 patients with ICC (ICC group) and 32 patients with HCC (HCC group) confirmed by histopathological examination were recruited in the study.All the patients were performed MR exams on a 1.5T scanner in a protocol containing the routine T1WI,T2WI,DWI and DTI.The values of ADC,fractional anisotropy (FA),diffusion coefficient (D) were blindly reviewed and analyzed by two experienced observers,and were compared between two groups.The ROC curve was used to evaluate the di agnostic efficiency.Results The border clear percentage of ICC group (9/20,45.00％) had no significant difference compared with that of HCC group (15/32,46.88％;x2 =0.02,P=0.90),the detection rate of bile duct expansion in ICC group (11/20,55.00％) was higher than that in HCC group (4/32,12.50％;x2=10.83,P=0.001).Theintraclasscor relation coefficient value of ADC,D and FA in the ICC group and HCC group were all more than 0.90.The mean FA of ICCgroup (0.45±0.16) were significantly higher than that of HCC group (0.30±0.13;P=0.001),while the mean ADC and D values in ICC and HCC groups had no significant difference (both P＞0.05).The area under the ROC curve of FA was 0.76.And when FA=0.31,there was a higher sensitivity (85.0％) in identifying ICC and HCC.Conclusion The FA of DTI shows a stronger capability than the ADC and D values in differentiating the ICC from HCC.