Objective To investigate the relationship of compression area, time and weight as risky factors with local injury and systemic pathophysiological responses in rats so as to establish repeatable experimental model of crush syndrome. Methods A total of 144 male SD rats were divided into two groups, ie, mortality investigation group and biochemical indicator investigation group. Every group included the same 18 subgroups based on 18 kinds of combination with different levels of compression area (the right or both hind limbs), time (4, 6, 8 hours) and weight (2, 3, 4 kg). The circumference of the compressed hind limbs of all rats were measured and serum potassium (K+), serum creatine phosphokinase (CK), creatinine and carbamide were measured too before compression and three hours after decompression. Incidence of myoglobinuria of all rats was recorded. Muscles and kidneys were evaluated morphologically. Results The compressed hind limbs of all rats swelled significantly after three hours of reperfusion (P ＜ 0. 05). All serum K + , CK, CR and BUN were increased significantly with the increase and prolongation of the compression area, time and weight (P ＜ 0.05). Signs of direct cellular damage and ischemia-reperfusion injury were found in histology specimens of local compressed muscle.Hyperemia of glomeruli and renal tubule was found in the kidneys. Renal tubular necrosis and renal tubular cast were observed in group with compression weight ≥3 kg and compression duration ≥6 hours.Conclusions Increase and prolongation of the compression area, time and weight can aggravate the severity of crush injury. Compression area is more risky factor of severe crush injury. Both hind limbs ascompression area, compression weight ≥ 3 kg and compression duration ≥ 6 hours can be the effective experimental conditions for establishment of crush syndrome model in rats.

Objective To investigate the biofilm (BF)formation rule of nontypeable Haemophilus influenzae (NTHi)in vitro, and to observe the internal structure of BF by scanning electron microscope (SEM). Methods NTHi ATCC49247 was investigated in the present study,Pseudomonas aeruginosa (PA)PAO1 was cultured as positive control,at the same time blank control group was set up.The BF of the bacteria were cultured and then collected on day 1,2,3,4,5,6,and 7.The BF formation was detected by crystal violet staining and plate counting and the structure of BF formed by ATCC49247 was observed under SEM on day 3.Results The plate colony counting of biofilm BF by ATCC49247 and PAO1 raised during first 3 d, and then declined to (0.823 6±0.007 5)×107 cfu·mL-1 and (0.942 6±0.019 9)×107cfu·mL-1 respectively on day 7. The differences between two groups were statistically significant on day 3,4,5,and 6 (P<0.05).The differences between different time points in the same bacteria group were statistically significant (P<0.05).The densities of BF formed by ATCC49247 and PAO1 raised during the first 3 d.The absorbances on 570 nm wavelength (A570 )in two groups were 2.717 4±0.017 2 and 2.885 3±0.039 0 ,respectively;and then the A570 values in two groups declined to 0.151 7±0.074 5 and 1.196 9±1.108 5,respectively on day 7;the differences between bacteria groups and blank control were statistically significant (P<0.05 );the differences between two bacteria groups were statistically significant on day 3,4,5,and 6 (P<0.05);the differences between different time points in the same bacteria group were statistically significant (P<0.05).On day 3,the obvious BF formed by ATCC49247 were observed under SEM.Conclusion BF could be formed by NTHi in vitro;crystal violet staining,plate colony counting and SEM could be taken as conventional methods to detect BF.

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

We present a summary of important research in the field of urothelial carcinoma presented at the 2023 European Society for Medical Oncology (ESMO) conference. A total of 53 studies related to urothelial carcinoma were reported, including 6 late-breaking abstract, 7 oral presentations, and 40 poster presentations. Several new treatment options were reported in the non-muscle invasive bladder cancer (NMIBC) field, providing more choices for bacillus Calmette-Guerin (BCG) failing patients. For perioperative systemic treatment of muscle-invasive bladder cancer (MIBC), studies further explored various adaptation of neoadjuvant therapy strategies. For metastatic urothelial carcinoma (mUC), the data on CheckMate-901 and EV-302 studies provided thoughts on first-line treatment options. These studies provide important guidance for clinical practice in the field of urothelial carcinoma.

It has been found that the incidence of cardiovascular disease in patients with lower limb amputation is significantly higher than that in normal individuals, but the relationship between lower limb amputation and the episodes of cardiovascular disease has not been studied from the perspective of hemodynamics. In this paper, numerical simulation was used to study the effects of amputation on aortic hemodynamics by changing peripheral impedance and capacitance. The final results showed that after amputation, the aortic blood pressure increased, the time averaged wall shear stress of the infrarenal abdominal aorta decreased and the oscillatory shear index of the left and right sides was asymmetrically distributed, while the time averaged wall shear stress of the iliac artery decreased and the oscillatory shear index increased. The changes above were more significant with the increase of amputation level, which will result in a higher incidence of atherosclerosis and abdominal aortic aneurysm. These findings preliminarily revealed the influence of lower limb amputation on the occurrence of cardiovascular diseases, and provided theoretical guidance for the design of rehabilitation training and the optimization of cardiovascular diseases treatment.
Amputation ; Aorta, Abdominal/surgery* ; Aortic Aneurysm, Abdominal/surgery* ; Blood Flow Velocity/physiology* ; Hemodynamics/physiology* ; Humans ; Lower Extremity ; Models, Cardiovascular ; Stress, Mechanical

Lower limb amputation is a significant change in body structure. Loss of muscle, blood vessels, and blood leads to a redistribution of blood flow and changes in resistance at the end of blood vessels. In view of the significant increase in the prevalence of cardiovascular disease after lower limb amputation, the mechanism of which is still unclear, this study aims to establish an animal research model that can verify and explore the effects of amputation on cardiovascular system, and provide the experimental basis for subsequent animal experiments when exploring the effect of different amputation levels on the cardiovascular system. SPF New Zealand rabbits were divided into normal group ( n = 6) and amputation group ( n = 6). The amputation group was treated with above-knee amputation. The changes of low-density liptein cholesterol (LDL-C) and total cholesterol (TC) in serum of all the rabbits were monitored regularly after the surgery. The arterial pathological examination was conducted after the experimental rabbits were executed. The results showed that compared with the normal group, serum LDL-C content and TC content in the amputation group were significantly increased ( P<0.05); The blood vessels of the amputated rabbits had pathological changes such as degeneration and necrosis of smooth muscle cells in the middle membrane layer and rupture of elastic fibers. At the abdominal aorta and aortic arch, the elastic fiber area expression percentage (EFEP) of the experimental group was significantly lower than that of the normal group. The results suggest that the cardiovascular system of rabbits has the tendency of decreased arterial elasticity and lipid deposition in blood after amputation, indicating that the animal research model on the effect of amputation on the cardiovascular system has been successfully established, and can provide an experimental platform for further study on the mechanism of the effect of amputation on the cardiovascular system.
Rabbits ; Animals ; Cholesterol, LDL ; Disease Models, Animal ; Amputation, Surgical ; Myocytes, Smooth Muscle ; Arteries

Objective To analyze the rebleeding rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) after endoscopic treatment of esophagogastric variceal bleeding and then assessed the risk factors of the rebleeding in the patients. Methods This study retrospectively recruited 169 hepatitis B-associated HCC patients complicated with PVTT and esophagogastric variceal bleeding treated by endoscopy in Department of Gastroenterology, Beijing Ditan Hospital from September 2008 to December 2016. Among them, 47 patients had PVTT Ⅱ, 67 patients had PVTT Ⅲ, and 55 patients had PVTT Ⅳ. Their clinicopathological and follow-up data were retrieved from the medical records and statistically analyzed. Continuous data were compared among groups using ANOVA or Kruskal-Wallis H test. Categorial data were compared among groups using Chi-square test or corrected Fisher test. The Kaplan-Meier curves and Log-rank test were performed to analyze the rebleeding rate and cumulative survival rates after treatment. The univariate multivariate Cox regression analyses were used to identify the risk factors affecting the rebleeding of patients. Results Compared with PVTT Ⅱ and Ⅲ, PVTT Ⅳ patients had a higher serum level of the direct bilirubin ( Z =6.153, P =0.046). The endoscopy treatment successfully blocked esophagogastric variceal bleeding in all patients. There was no significant difference in the rebleeding rates within six months and a year after the treatment (all P > 0.05). It was also no statistically significant difference in cumulative survival rates in six months and l-, 2-, and 3-year after the treatment in PVTT Ⅱ, Ⅲ, and Ⅳ patients (all P > 0.05). Cox multivariate regression analysis showed that hepatic encephalopathy ( HR =3.643, 95% CI : 2.099-6.325, P < 0.001), γ-glutamyltransferase ( HR =1.002, 95% CI : 1.000-1.005, P =0.029), AFP ( HR =1.000, 95% CI : 1.000-1.000, P =0.002) and numbers of tumor lesions ( HR =1.647, 95% CI : 1.011-2.684, P =0.045) were all independent risk factors for 1-year rebleeding in these PVTT patients with esophagogastric variceal bleeding after endoscopic treatment. Conclusion Endoscopic hemostasis is a feasible treatment option for HCC patients with PVTT and esophagogastric variceal bleeding. However, there was no significant difference in the rebleeding and cumulative survival rates in these patients. Furthermore, hepatic encephalopathy, γ-glutamyltransferase, AFP and numbers of tumor lesions were all independent risk factors for 1-year rebleeding in these patients.