Metformin alleviates bevacizumab-induced vascular endothelial injury in mice through growth differentiation factor 15 upregulation.

Objectives: Bevacizumab is a commonly used anticancer drug in clinical practice, but it often leads to adverse reactions such as vascular endothelial damage, hypertension, arterial and venous thrombosis, and bleeding. This study investigated the protective effects of metformin against bevacizumab-induced vascular injury in a mouse model and examined the possible involvement of GDF15/PI3K/AKT/FOXO/PPARγ signaling in the effects. Materials and Methods: C57 male mice were purchased. To investigate metformin, the mice were assigned to the saline, bevacizumab (15 mg every 3 days), metformin (1200 mg/day), and bevacizumab+metformin groups. To investigate GDF15, the mice were assigned to the siNC+bevacizumab, siNC+bevacizumab+metformin, siGDF15+bevacizumab, and siGDF15+bevacizumab+metformin groups. Histological staining was used to evaluate vascular injury. Flow cytometry was used to evaluate apoptosis. ELISA was used to measure plasma endothelial injury markers and proinflammatory cytokines. qRT-PCR and western blot were used to determine the expression of GDF15 and PI3K/AKT/FOXO/PPARγ in aortic tissues. Results: Metformin alleviated bevacizumab-induced abdominal aortic injury, endothelial cell apoptosis, and systemic inflammation in mice (all P<0.05). Metformin up-regulated GDF15 expression and PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P<0.05). siGDF15 abolished the vascular protective and anti-inflammatory effects of metformin (all P<0.05). siGDF15 suppressed PI3K/AKT/FOXO/PPARγ signaling in the abdominal aorta of mice treated with bevacizumab (all P<0.05). Conclusion: Metformin attenuates bevacizumab-induced vascular endothelial injury, apoptosis, and systemic inflammation by activating GDF15/PI3K/AKT/FOXO/PPARγ signaling.

Effectiveness of Noninvasive Positive Pressure Ventilation Combined with Enteral Nutrition in the Treatment of Patients with Combined Respiratory Failure after Lung Cancer Surgery and Its Effect on Blood Gas Indexes.

Purpose: To investigate the effect of noninvasive positive pressure ventilation (NIPPV) combined with enteral nutrition support in the treatment of patients with combined respiratory failure after lung cancer surgery and its effect on blood gas indexes. Methods: A total of 82 patients with combined respiratory failure after lung cancer surgery who were treated in our hospital from March 2016∼September 2021 were selected as the research subjects, and according to the random number table method, they were equally divided into the parenteral nutrition group (n = 41) with NIPPV + parenteral nutrition support treatment and the enteral nutrition group (n = 41) with NIPPV + enteral nutrition support treatment. The curative effects of two groups after treatment were compared, and the pulmonary function indexes (maximum expiratory pressure (PEmax), maximum midexpiratory flow rate (MMF), and maximum ventilation volume (MVV)), blood gas indexes (blood oxygen partial pressure (PaO2) and partial pressure of carbon dioxide (PaCO2)), oxygen metabolism indicators [mixed venous oxygen tension (PvO2) and central venous oxygen saturation (ScvO2)], nutritional status indicators (hemoglobin (HGB), serum albumin (ALB), and total protein (TP)), and nutritional score before and after treatment in two groups were detected, and the 6-month follow-up of the two groups was recorded. Results: After treatment, the total effective rate of the enteral nutrition group 95.12% (39/41) was higher than that of the parenteral nutrition group 80.49% (33/41) (P < 0.05). At 3, 12, 24, and 48 hours after the operation, the levels of PEmax, MMF, and MVV in two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group at the same time point (P < 0.05). At 3, 12, 24, and 48 hours after the operation, the PaO2 levels in two groups were higher than those before treatment, and the PaCO2 levels were lower than those before treatment. The PaO2 levels in the enteral nutrition group were higher than those in the parenteral nutrition group at the same time point, and the PaCO2 levels were lower than those in the parenteral nutrition group at the same time point (P < 0.05). At 3, 12, 24, and 48 hours after the operation, the levels of PvO2 and ScvO2 in two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group at the same time point (P < 0.05). After treatment, the levels of HGB, ALB, and TP in two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group (P < 0.05). After treatment, the nutritional scores of the two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group (P < 0.05). At 6-month postoperative follow-up, the incidence of death in the enteral nutrition group 2.44% (1/41) was lower than that of the parenteral nutrition group 17.07% (7/41) (P < 0.05). Conclusions: The efficacy of NIPPV combined with enteral nutrition support in treating patients with combined respiratory failure after lung cancer surgery is remarkable. It can improve patients' pulmonary function and blood gas index, correct patients' hypoxia status and the patients' nutritional level was significantly improved, which helped to reduce the mortality rate and improve the prognosis.

Incidence and Related Factors for Low-Extremity Deep Vein Thrombosis in Breast Cancer Patients Who Underwent Surgical Resection: What Do We Know and What Should We Care.

Malignancy, surgical resection, and neoadjuvant and/or adjuvant chemotherapy increase the low-extremity deep vein thrombosis (LDVT) risk in patients with breast cancer, bringing in great physical burdens, disabilities, and worse survivals. However, LDVT in surgical breast cancer patients is scarcely reported. Therefore, this study aimed to evaluate the incidence and related factors for LDVT in these patients. Patients with breast cancer who underwent surgical resection were included. LDVT was examined on the day of discharge and 1 month after the discharge. A total of 491 eligible patients were included, among which 11 (2.2%) patients occurred LDVT. Besides, higher age, history of diabetes mellitus, advanced T and tumor node metastasis (TNM) stages, higher platelet count, and shorter activated partial thromboplastin time (APTT) were correlated with increased LDVT incidence (all p < 0.05). Additionally, higher age [p = 0.004, odds ratio (OR) (95% CI): 1.082 (1.023-1.144)], history of diabetes mellitus [p = 0.003, OR (95% CI): 10.426 (2.219-48.986)], and a higher platelet count [p = 0.008, OR (95% CI): 1.017 (1.004-1.029)] were independent factors for increased LDVT incidence, while higher APTT [p = 0.004, OR (95% CI): 0.636 (0.467-0.866)] was an independent factor for decreased LDVT incidence. Lastly, the risk prediction model involving age, history of diabetes mellitus, platelet count, and APTT showed a good ability to predict LDVT occurrence (area under curve: 0.919, 95% CI: 0.869-0.968). In conclusion, the LDVT incidence is 2.2%, and its independent factors consist of age, history of diabetes mellitus, platelet count, and APTT in patients with breast cancer who underwent surgical resection, which provides evidence for the prevention and surveillance of LDVT in surgical breast cancer.

[Three dimensional reconstruction and measurement of the proximal femur in adult developmental dysplasia of the hip].

OBJECTIVE: To investigate characteristics and the differences of the anatomical parameters of the proximal femur of the developmental dysplasia of the hip (DDH). METHODS: A total of 38 patients(47 hips) diagnosed as DDH with CT scan data and the pelvis radiograph from January 2012 to December 2014 in China-Japan Union Hospital of Jilin University were retrospectively analyzed. All the hips were divided into 3 groups according to Crowe classification method. Thirty normal hips were selected as controls who admitted at the same time. CT data of the patients were imported into Mimics 17.0. The three-dimensional models of the proximal femur were then reconstructed, and the following parameters were measured: neck-shaft angle, neck length, offset, height of the centre of femoral head, height of the isthmus, height of greater trochanter, the medullary canal diameter of isthmus (Di), the medullary canal diameter 10 mm above the apex of the lesser trochanter (DT+ 10), the medullary canal diameter 20 mm below the apex of the lesser trochanter (DT-20), and then DT+ 10/Di, DT-20/Di and DT+ 10/DT-20 were calculated.Variance discrepancy analysis was used to compare the difference among the four groups, and LSD method was used to compare the difference between either two groups. RESULTS: The parameters of neck-shaft angle of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (131.8°±7.1°), (131.7°±6.5°), (122.8°±11.4°) and (131.8°±5.9°), respectively; the parameters of neck-shaft angle of DDH with Crowe IV was smaller than that of DDH with Crowe I, Crowe II-III and control group (all P<0.05). The parameters of the neck length of DDH with Crowe IV ((44.6±6.6) mm) was smaller than that of DDH with Crowe I ((48.6±6.7) mm), Crowe II-III ((50.4±4.7) mm) (all P<0.05). There is no statistic difference in the offset among the groups (F=2.392, P>0.05). The parameters of the height of greater trochanter of DDH with Crowe IV ((12.1±6.1) mm) was bigger than that of DDH with Crowe I ((8.9±7.2) mm), Crowe II-III ((7.5±3.3) mm) and control group ((6.1±3.9) mm) (all P<0.05). The parameters of the height of the centre of femoral head of DDH with Crowe I, Crowe II-III, Crowe IV were (39.6±6.5) mm, (39.1±4.2) mm, (38.8±8.6) mm, which were smaller than that of the control group ((46.5±6.2) mm) (all P<0.05). The parameters of Di of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (9.9±2.2) mm, (8.3±1.8) mm, (8.7±1.7) mm and (10.1±1.4) mm; the parameters of Di of DDH with Crowe II-III and Crowe IV were smaller than that of the control group (all P<0.05). The parameters of DT+ 10 ((17.2±5.3) mm) and DT-20 ((12.2±3.0) mm) of DDH with Crowe IV were smaller than that of DDH with Crowe I ((25.2±3.4) mm, (17.1±2.3) mm) and Crowe II-III ((21.9±4.2) mm, (16.3±3.2) mm) (all P<0.05). The parameter of the height of the isthmus of DDH with Crowe IV ((94.1±19.7) mm) was smaller than that of DDH with Crowe I ((106.2±13.8) mm), Crowe II-III ((108.8±10.5) mm) and control group ((116.5±10.6) mm), respectively (P=0.010, 0.008, 0.000). The parameters of DT+ 10/Di (2.0±0.4) and DT-20/Di (1.4±0.2) of DDH with Crowe IV were smaller than that of DDH with Crowe I (2.6±0.5, 1.8±0.3), Crowe II-III (2.7±0.60, 1.9±0.3) (all P<0.05). CONCLUSIONS: Comparing to DDH with Crowe I-III and control group, DDH with Crowe IV has a dramatic change in the intramedullary and extramedullary parameters. The isthmus and the great trochanter are higher and there is apparent narrowing of the medullary canal around the level of the lesser trochanter.

A novel CHD7 mutation in a Chinese patient with CHARGE syndrome.

In Genetics Out-patient Department of Shanghai Children's Medical Center, we consulted a 3-year-old boy with multiple anomaly syndrome (congenital heart disease, cryptorchidism, congenital deafness, mental retardation, exophthalmos, laryngeal cartilage dysplasia and high arched palate). We ruled out the possibility of multiple deformities caused by genomic imbalances. The patient was then clinically considered to have CHARGE syndrome, an autosomal dominant multi-system disorder involving defects in multiple organs, and CHD7 is the only known gene associated with the syndrome. Sequencing analysis of CHD7 of the proband identified a de novo heterogeneous mutation (c.2916_2917del, p.Gln972HisfsX22), a two-nucleotide deletion causing reading frame shift and resulting in a truncated CHD7 protein. Computational structure analysis suggests that the truncated protein only contains the chromodomains of CHD7, but lacks the SWI2/SNF2-like ATPase/helicase domain and the DNA binding domain, which are indispensable for the proper function of the protein, especially on chromatin remodeling. The patient then received follow up treatment in different clinical departments in a long period. To our best knowledge, this is the first CHARGE syndrome in Chinese patients diagnosed by gene analysis. In summary, the clinical symptoms and the description of treatment in the present case, combined with genetic test and functional prediction of CHD7, are helpful for further understanding and genetic counseling of the CHARGE syndrome.