BACKGROUND:Nerve growth factor is a protein that induces nerve growth and regulates biological behaviors such as proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To investigate the promoting effect of nerve growth factor on chondrogenic differentiation of bone marrow mesenchymal stem cells. METHODS:Rabbit bone marrow mesenchymal stem cells were isolated and cultured,and nerve growth factor was transfected into bone marrow mesenchymal stem cells by lentiviral transfection.The effects of nerve growth factor on the proliferation,migration,hypertrophic differentiation,and chondrogenic differentiation of bone marrow mesenchymal stem cells were detected by CCK-8 assay,cell scratch assay,alizarin red staining,and western blot assay,using the transfected null-loaded virus as control.To further investigate the promoting effect of nerve growth factor on the chondrogenic differentiation of bone marrow mesenchymal stem cells,interleukin 1β was added in bone marrow mesenchymal stem cells transfected with empty virus and nerve growth factor for 14 days.The expression of proteins related to chondrogenic differentiation and hypertrophic differentiation was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that nerve growth factor had no significant effect on the proliferation of bone marrow mesenchymal stem cells.(2)Compared with the control group,overexpression of nerve growth factor enhanced the migration ability of the cells,and the expression of cartilage-associated proteins type II collagen and SOX9 was up-regulated(P<0.05),while the expression of hypertrophic-associated proteins type X collagen and Runx2 was down-regulated(P<0.05).(3)Compared with the empty virus+interleukin 1β group,the expression of cartilage-associated proteins type II collagen and Sox9 was up-regulated(P<0.05),and the expression of hypertrophy-associated proteins type X collagen and Runx2 was down-regulated after overexpression of nerve growth factor(P<0.05).(4)The results indicated that nerve growth factor could promote the chondrogenic differentiation of bone marrow mesenchymal stem cells.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

Objective To explore the relationship between serum soluble semaphorin 4D(sSema4D),CXC chemokine ligand 12(CXCL12)levels and left ventricular diastolic function in young and middle-aged patients with essential hypertension.Methods A total of 148 young and middle-aged patients with essential hyperten-sion admitted to a hospital from November 2020 to November 2022 were selected as the study subjects,and were grouped into left ventricular diastolic dysfunction group(n=41)and normal left ventricular diastolic function group(n=107)according to their left ventricular diastolic function.The serum levels of sSema4D and CXCL12 were detected by enzyme-linked immunosorbent assay.Pearson correlation analysis was applied to analyze the correlation between the serum levels of sSema4D and CXCL12 and the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular septal thickness(IVST),left ventricular end-diastolic posterior wall thickness(LVPWT),left ventricular ejection fraction(LVEF),E peak/A peak(E/A)and maximum velocity of tricuspid regurgitation(TRVmax).The predictive value of ser-um sSema4D and CXCL12 levels in left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension was analyzed by receiver operating characteristic(ROC)curve.Results There were significant differences in diastolic blood pressure and gender between the left ventricular diastolic dys-function group and the left ventricular diastolic function normal group(P＜0.05).Compared with the normal left ventricular diastolic function group,serum levels of sSema4D,CXCL12 in the left ventricular diastolic dys-function group were obviously increased,and the difference was statistically significant(P＜0.05).Compared with normal left ventricular diastolic function group,IVST and LVPWT in the left ventricular diastolic dys-function group were significantly increased,and E/A was significantly decreased,with statistical significance(P＜0.05).Pearson correlation analysis showed that serum sSema4D and CXCL12 levels were positively cor-related with LVEDD,IVST and LVPWT(P＜0.05),and negatively correlated with E/A(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of serum sSema4D and CXCL12 combined in pre-dicting left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension was 0.894(95％CI:0.833-0.939),which was significantly greater than that of sSema4D alone in predicting left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension(Z=3.142,P=0.002)and CXCL12 alone predicted the AUC of left ventricular diastolic dysfunction in young and middle-aged patients with essential hypertension(Z=3.268,P=0.001).Conclusion Serum sSema4D and CXCL12 levels are associated with left ventricular diastolic function in young and middle-aged patients with essential hypertension.

Objective To establish an auxiliary method for diagnosis of mild traumatic brain injury based on serum GFAP rapid detection test strips using immunochromatographic technology labeled with quantum dot microspheres.Methods The quantum dot microspheres were coupled with GFAP antibodies.The detection conditions were optimized to obtain the fluorescence probe in order to prepare the immunochromatographic test strips.An auxiliary diagnostic method was established after optimization of detection conditions.Finally,the auxiliary diagnostic effect of the test strips was evaluated using clinical samples.Results The serum concentration of GFAP could be detected by the optimized test strips within 13 mins with a detection limit of 0.15 ng/mL,and no more than 70μL of the serum sample was required.In addition,good reproducibility was achieved by different batches of test strips(CV=10.7%).The detection sensitivity and specificity of the strips to mild traumatic brain injury using 51 clinical samples were 95.24%and 96.67%respectively,indicating good effects of detection.Conclusion The developed test strips are user-friendly with reliable results,which can facilitate field rapid diagnosis of mild traumatic brain injury in complicated wartime environments.

Objective:To investigate the optimal monoenergetic level of virtual monoenergetic images (VMI) in transplanted renal artery on a dual-layer spectral detector CT.Methods:A retrospective study was performed on 16 renal transplant patients who underwent transplanted renal angiography on a dual-layer spectral detector CT in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to April 2021. Conventional 120 kVp polyenergetic images (PI) were reconstructed, and virtual monoenergetic images (VMIs) in range of 40-200 keV with interval of 10 keV were reconstructed, too. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of 120 kVp PI and VMIs were measured. Meanwhile, the subjective scores of the display of transplanted renal artery were performed on volume rendering images of 120 kVp PI and VMIs. Spearman correlation analysis was used to explore the correlation between energy levels and SNR or CNR. Rank sum tests were performed to compare the parameters of image quality between the VMI which had the highest SNR and CNR, and the other VMIs, or 120 kVp PI.Results:Among the VMIs, SNR or CNR was negatively correlated with energy levels ( r =-0.86 and -0.88, all P<0.001). The SNR [22.80(18.57, 34.16)] and CNR [35.38(25.97, 39.01)] of 40 keV VMI were the highest, and significantly higher than that of 120 kVp PI and 50-200 keV VMIs, all the differences were statistically significant (all P<0.05). The subjective scores of 40 keV VMI and 120 kVp PI were 5 (5, 5) and 4 (3, 5), respectively. The score of 40 keV VMI was significantly higher than that of 120 kVp PI ( Z=-2.60, P=0.009). There were no significant differences in subjective scores between 40 keV VMI and 50-70 keV VMIs ( Z=-1.00, -1.41, -1.73, P=0.317, 0.157, 0.083), but the subjective score of 40 keV VMI was higher than that of 80-200 keV VMIs and the differences were statistically significant (all P<0.05). Conclusions:As for the images of transplanted renal angiography on a dual-layer spectral detector CT, the image quality of 40 keV VMI was best, thus 40 keV was the optimal monoenergetic level.

Objective:To explore the clinical features, diagnosis and prognosis of renal transplant recipients with COVID-19.Methods:The clinical data were retrospectively analyzed for 2 kidney transplant recipients with COVID-19. Based upon clinical manifestations, blood routine, inflammatory factors, cell immunity, chest computed tomography(CT)and therapeutic efficacies, the diagnosis and treatment of COVID-19 in kidney transplant recipients(Interim Edition V)were compared to that of ordinary COVID-19 patients. Both recipients had an onset of low/moderate fever. There was no initial symptom of cough or fatigue. Blood routine indicated a normal count of leukocytes, a marked lymphocytopenia, elevated C-reactive protein(CRP)and slightly higher procalcitonin(PCT). Cellular immunity was extremely low and chest CT showed multiple patchy ground-glass opacities in both lungs.Results:After 1 week of onset, both patients had a marked disease progression. The pathogenesis and imaging changes were highly similar to those reported for ordinary COVID-19 patients. For preventing secondary infections, both received symptomatic supportive measures of antiviral agents, withdrawing immunosuppressants, tapering of hormone maintenance dose, intravenous drip of gamma globulin and respiratory supports. Currently the conditions of both patients obviously improved and renal function was stable. One case recovered and was discharged.Conclusions:The clinical manifestations of COVID-19 in renal transplant recipients are generally consistent with that of ordinary COVID-19 patients. Although there is no established treatment for COVID-19, withdrawing immunosuppressants, maintaining small and medium doses of hormones, actively restoring immunity and providing respiratory supports in a timely manner are effective.

Objective:To investigate the effects of short-term pulmonary rehabilitation on the exercise ability and life quality of men with acute exacerbations of chronic obstructive pulmonary disease (COPD).Methods:Thirty-eight male COPD patients with acute exacerbation were selected and randomly divided into a rehabilitation group ( n=20) and a control group ( n=18). Both groups were given routine health education and medication, while the rehabilitation group was additionally provided with a 7-day, three-stage rehabilitation intervention, including the respiratory training, resistance training using a resistance band and gradual low-intensity walking training, all under remote electrocardiographic monitoring. Before and after the intervention, both groups′ exercise ability was evaluated using the 30-second chair sitting test (30-STS) and a 30-second forearm load flexion test (30-ACT). Each subject′s quality of life and ability in the activities of daily living were evaluated by two qualified rehabilitation therapists. The subjects′ level of daily physical activity was assessed 2 months after discharge. Results:After the intervention the average 30-STS and 30-ACT results of the rehabilitation group had improved significantly. The 30-ACT results of the control group were also significantly improved. After the intervention the average 30-STS and 30-ACT results of the rehabilitation group were significantly better than the control group′s averages. The average CAT and MBI scores of both groups were significantly better after the intervention, with the rehabilitation group′s averages significantly better than those of the control group. Two months after discharge, the number of patients with at least moderate daily physical activity increased from 6 to 19 in the rehabilitation group and from 4 to in the control group, a significant difference between the two groups.Conclusion:The three-stage pulmonary rehabilitation program is helpful for improving the exercise ability and quality of life of COPD sufferers, and their ability in the activities of daily living. Their level of daily physical activity is higher 2 months after discharge.

Objective: To learn the interaction of serum direct bilirubin and blood lipids on the risk of carotid atherosclerosis and carotid plaque. Methods : The subjects were selected from Hangzhou Wuyunshan Sanatorium from March 2016 to December 2018. Demographic information,laboratory testing results and carotid intima-media thickness（IMT）were collected. The logistic regression model was employed for the association of direct bilirubin,blood lipids and their interaction with the risk of carotid atherosclerosis and carotid plaque. Results: Totally 8 308 subjects were recruited. Among them,616（7.41%） subjects had carotid atherosclerosis,and 2 409（29.00%）subjects had plaques. The results of multivariate and multinomial logistic regression analysis showed that high level of direct bilirubin was associated with decreased risks of carotid atherosclerosis（OR=0.701,95%CI：0.537-0.916）and carotid plaque（OR=0.647,95%CI：0.527-0.795）;high TC level（OR=1.335,95% CI：1.106-1.611）, high LDL-C level（OR=1.338,95%CI：1.098-1.629）and low HDL-C level（OR=1.431,95%CI：1.148-1.783）were associated with increased risks of carotid atherosclerosis;high TC level（OR=1.325,95% CI：1.151-1.525）and high LDL-C（OR=1.311,95%CI：1.130-1.520）were associated with increased risks of carotid plaque. There were interactions between direct bilirubin and TC or LDL-C on the risk of carotid plaque（P<0.05）. Compared with the subjects with high level of direct bilirubin and normal level of TC,the subjects with normal level of direct bilirubin and high level of TC had significantly higher risk of carotid plaque（OR=1.831,95%CI：1.438-2.333）;compared with the subjects with high level of direct bilirubin and normal level of LDL-C,the subjects with normal level of direct bilirubin and high level of LDL-C had significantly higher risk of carotid plaque（OR=1.814,95%CI：1.427-2.306）. Conclusion The interactions between direct bilirubin and TC or LDL-C increase the risk of carotid plaque. It is important to strengthen blood lipid control in the patients with normal level of direct bilirubin and hyperlipidemia.

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

Objective: To explore the clinical features, diagnosis and prognosis of renal transplant recipients with NCP. Method: The clinical data of 2 cases of kidney transplant recipients with NCP were retrospectively analyzed. Based onclinical manifestations, blood routine, inflammatory factors, cell immunity, chest CT andtherapeutic effects, the diagnosis and treatment of NCP in kidney transplant recipients (5th edition) were compared to that ofordinary NCP patients. Both recipients developed onset of low andmoderate fever, with no cough or fatigue at the initial stage. Blood routine indicated a normal range of leukocytes,buta significant decrease in lymphocyte counts, increased C-reactive protein (CRP) , and slightly higher procalcitonin (PCT) . The cellular immunity was extremely low, and the chest CT showed multiple patchy ground glass shadows in both lungs. Result: After 1 week of onset, both patients had significant disease progression. The pathogenesis and imaging changes were highly similar tothatreported in ordinary NCP patients.Two patients were givensymptomatic supportive treatment by antiviral agents, stop uses ofimmunosuppression agents, small amount of hormone maintenance, intravenous drip of gamma globulin andrespiratory support toavoid secondary infections. At present, the condition of both patients is obviously improved, and renal function is stable. One of them has recovered and was discharged. Conclusion The clinical manifestations of NCP in renal transplant recipients were generally consistent with that of ordinary NCP patients. Although there is no established method for the treatment of NCP, it is effective by stopping uses of immunosuppressive agents, maintaining small and medium doses of hormones, actively restoring immunity, and providing respiratory support in a timely manner.