Osteosarcoma neutrophil extracellular trap network-associated gene recurrence and metastasis model.

Osteosarcoma (OS) is the most common malignancy in children and adolescents and has a high probability of recurrence and metastasis. A growing number of studies have shown that neutrophil extracellular traps (NETs) are strongly associated with cancer metastasis, but in osteosarcoma, genes associated with NETs that promote osteosarcoma recurrence and metastasis remain to be explored. We systematically investigated the gene expression patterns of NETs in OS samples from the GEO database. NETs molecular typing was evaluated based on NETs expression profiles, and the association between NETs molecular subtypes and immune microenvironment and metastatic features were explored. Ultimately, we constructed a signature model and column line graph associated with metastasis prediction and screened possible potential drugs for metastatic osteosarcoma. We established two different molecular subtypes of NETs, which showed significant differences in metastatic status, metastasis time, tumor immune microenvironment, and biological effects. We also constructed a NETs-related gene metastasis signature(NRGMS) to assess the expression pattern of NETs in patients to predict metastatic recurrence in osteosarcoma patients. We screened for TOMM40 and FH associated with metastatic recurrence in osteosarcoma patients. Overall, this study constructs a predictive model for osteosarcoma metastasis of NETs-related genes, which is expected to provide new insights into the metastasis of osteosarcoma.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma: A case report.

BACKGROUND: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases. CASE SUMMARY: A 64-year-old patient presented with dysphagia, without obvious cause. A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results. After multi-disciplinary consultations, combination chemotherapy (a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14) and esophageal cancer radiotherapy were initiated. Based on the results of genetic testing, we switched to a regimen of leucovorin + fluorouracil + oxaliplatin and cetuximab regimen for 8 cycles. Subsequently, capecitabine and bevacizumab were administered until the most recent follow-up, at which the tumor remained stable. CONCLUSION: Successful cetuximab chemotherapy treatment provides a reference for the non-operative and homogeneous treatment of different pathological types of synchronous MCPs.

Ameliorative Role of Mitochondrial Therapy in Cognitive Function of Vascular Dementia Mice.

BACKGROUND: Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. OBJECTIVE: The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. METHODS: The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. RESULTS: The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. CONCLUSIONS: The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.

Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma: A case report.

BACKGROUND: Immune checkpoint inhibitors, including programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) have recently been approved to treat locally advanced and metastatic urothelial carcinoma (UC). However, some patients experience rapid tumor progression rather than any clinical benefit from anti-PD-L1/PD-1 therapy. CASE SUMMARY: A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo. The patient could not tolerate further chemotherapy. Next-generation sequencing was performed, and the results indicated that the tumor mutational burden was 6.4 mutations/Mb. The patient received the anti-PD-L1 agent toripalimab combined with albumin-bound paclitaxel. Compared with the baseline staging before immunotherapy, the patient had a treatment failure time of < 2 mo, an increase in tumor burden of > 50%, and a > 2-fold increase in progression, indicating hyperprogression. CONCLUSION: Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging. For older patients with advanced UC who have already exhausted multi-line chemotherapy options, immunotherapy should be used prudently if no effective biomarker is available. Further studies are required to clarify the causes and mechanisms of hyperprogression.

The relationship between cognitive impairment and superoxide dismutase activity in untreated first-episode patients with schizophrenia.

Objectives: Cognitive decline is an essential characteristic of schizophrenia and may be due to the disturbance between reactive oxygen species generation and antioxidant capacity. The study aimed to explore the association between cognitive deficits and antioxidant defence parameters in untreated first-episode patients with schizophrenia.Methods: We determined important antioxidant enzymes, total superoxide dismutase (SOD) and manganese SOD (MnSOD), and their relationship with cognitive impairment in 168 untreated patients with first-episode schizophrenia and 168 age- and sex-matched healthy controls. The evaluation of psychopathological symptoms of all patients was based on the Positive and Negative Syndrome Scale (PANSS). We measured cognitive function by the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) and activities of total SOD and MnSOD in all participants.Results: The results showed that untreated patients with first-episode schizophrenia had deficient cognitive functioning in four RBANS indices and total scores, except for the visuospatial/constructional index, as well as higher plasma total SOD activity compared with the control subjects. In addition, significant negative correlations were identified between MnSOD activity and attention index or RBANS total score in patients.Conclusions: Our results suggest that oxidative stress may be partly responsible for cognitive dysfunction in the early course of schizophrenia.

Strategy and Efficacy of Surgery for Congenital Cervicothoracic Scoliosis with or without Hemivertebra Osteotomy.

OBJECTIVE: Cervicothoracic scoliosis will cause severe deformities in the early stage, and its structure is complex and the surgical methods are varied. The purpose of this research is to explore the indication and analyze the corrective effect of the two different posterior approach surgical strategies, including correction with fusion and hemivertebra osteotomy, for congenital cervicothoracic scoliosis deformities in children and adolescents. METHODS: This was a retrospective study of 21 patients with cervicothoracic scoliosis who received surgical treatment from January 2010 to June 2020, including nine cases of posterior hemivertebra osteotomy and fusion surgery and 12 cases of posterior correction and fusion alone. The Cobb angle, T1 tilt angle, clavicular angle, neck tilt angle, radiographic shoulder height, sagittal vertical axis, coronal balance distance, and local kyphosis angle were measured preoperatively, postoperatively, and at the last follow-up. Posterior approach hemivertebra resection or correction with fusion surgery was adopted based on the different individual characteristics of deformity such as main curve Cobb angle, growth potential, and flexibility. Patients were divided into two groups (osteotomy group and nonosteotomy group) according to whether a hemivertebra osteotomy was performed, and the corrective results in the two groups were compared. Paired-sample t tests or independent-sample t tests were used. RESULTS: The median follow-up after surgery of the 21 patients was 36 months (range, 18-72 months). The Cobb angle was corrected from 45.81° ± 14.23° preoperatively to 10.48° ± 5.56° postoperatively (correction rate, 77.78% ± 8.93%). The T1 tilt angle decreased from 15.26° ± 7.08° preoperatively to 3.33° ± 2.14° postoperatively (correction rate,73.42% ± 21.86%). The radiographic shoulder height was corrected from 1.13 ± 0.74 cm preoperatively to 0.52 ± 0.42 cm postoperatively (correction rate, 39.51% ± 35.65%). The clavicular angle improved from 2.52° ± 1.55° preoperatively to 1.16° ± 0.96° postoperatively (correction rate, 47.18% ± 35.84%). No significant differences were found at the last follow-up (p > 0.05). The Cobb angle of the main curve, T1 tilt angle, clavicular angle, cervical tilt angle, and shoulder height difference were similar in the two groups (p > 0.05). CONCLUSIONS: Posterior approach hemivertebra resection or correction with fusion surgery can be used in the treatment of congenital cervicothoracic scoliosis with satisfactory results, and the surgeon can make an individualized surgical plan according to individual characteristics of deformity.

Association of depressive symptoms with cognitive impairment in patients with never-treated first-episode schizophrenia: Analysis of the Depression in Schizophrenia in China (DISC) study.

OBJECTIVE: Depressive symptoms and cognitive dysfunction are common in patients with schizophrenia and depressive disorder. This study aimed at exploring whether and how depressive symptoms were correlated with neuro-cognitive impairment in patients with never-treated first-episode (NTFE) schizophrenia. METHODS: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to 79 patients and 80 healthy controls to assess neuropsychological function. For all patients, the 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, and the Positive and Negative Syndrome Scale (PANSS) was utilized to assess psychopathological symptoms. RESULTS: Thirty-nine patients (49.37%) met the criteria for comorbid depressive symptoms. The RBANS total and the four index scores in the patients were significantly lower than those in the healthy controls. Further, compared with patients without depressive symptoms, patients with depressive symptoms scored lower in attention index, but higher in PANSS general psychopathology and total scores. The HAMD-17 total score was significantly correlated with attention, PANSS total, and PANSS general psychopathology scores. Moreover, multiple regression analysis identified education and HAMD-17 score as the contributors to attention. CONCLUSION: Our results suggest that the rate of depressive symptoms in NTFE schizophrenia is high, which is correlated with neuro-cognitive impairment, especially attention and psychopathology.

Mortality trends of liver cancer among patients with type 2 diabetes at the global and national level.

BACKGROUND: Primary liver cancer (PLC) is a commonly diagnosed malignancy, especially in developing countries. Diabetes is one of the well-determined risk factors for PLC. We aimed to describe the temporal trends of PLC mortality among diabetic patients. METHODS: We retrieved the PLC mortality data among diabetic patients from the Global Burden of Disease (GBD) study 2017 online database. Estimated average percentage change (EAPC) was used to quantify the PLC age-standardized mortality rate (ASMR) trends, by sex and country, between 1990 and 2017. RESULTS: Globally, the number of PLC related deaths increased from 3732.1 in 1990 to 9506.4 in 2017, with the ASMR increased from 0.09/100,000 to 0.12/100,000 (EAPC = 0.98, 95% CI 0.82, 1.14) among diabetic patients. Both the ASMR of PLC and its temporal trend were highly heterogeneous across the world. Between 1990 and 2017, a total of 135, 19, and 41 countries or territories experienced a significant increase, remained stable, and experienced a significant decrease in PLC ASMR, respectively. The greatest increase was mainly detected in developed countries, such as the USA, the UK, and Australia. By contrast, the most pronounced decrease was majorly found in developing regions. CONCLUSIONS: In diabetic patients, the PLC mortality was significantly increased at the global level and in approximately 70% of countries or territories over the last three decades. The increasing trend indicated that diabetes is an increasingly important risk factor for PLC and suggested that more tailored prevention strategies are needed for each country.