The early diagnosis and treatment of cholangiocarcinoma may benefit from specific tumor markers to be used in clinical practice. To investigate whether the pGCsiRNA-vascular endothelial growth factor (VEGF) can affect the onset and progression of cholangiocarcinoma and its possible mechanism using the targeted therapy of nude mouse model of cholangiocarcinoma with attenuated Salmonella carrying the plasmid pGCsiRNA-VEGF. The nude mouse model of cholangiocarcinoma was established by tail vein injection of QBC939 cells and given attenuated Salmonella carrying the plasmid pGCsiRNA-VEGF. One month later, the tumor volume of nude mice was observed, and the tumor growth curve was plotted. The harvested tumors were weighed and detected for tissue structural changes and cell death status by hematoxylin-eosin staining. The protein and mRNA expressions of VEGF, matrix metalloproteinase 2 (MMP2), and MMP9 were detected by Western blotting and PCR, respectively. The tumor volume and weight of the pGCsiRNA-VEGF group were significantly smaller than those of the mock and the si-scramble groups (P < 0.05). The expressions of VEGF, MMP2, and MMP9 at the transcriptional and translational levels were inhibited by pGCsiRNA-VEGF. PGCsiRNA-VEGF promoted tissue apoptosis and destroyed the tissue structure. In vivo silencing of VEGF can affect cell survival and inhibit cell migration, invasion, and development, probably by enhancing apoptosis and inhibiting the expressions of MMP2 and MMP9.

The triple-negative breast cancer (TNBC) subtype, characterized by loss of HER2, estrogen, and progesterone receptors, displays aggressive phenotype and poor prognosis compared to other BC subtypes. Since the TNBC cells are devoid of receptors, endocrine therapy is an ineffective option for TNBC patients, necessitating canonical chemotherapy strategies to treat TNBC. It is crucial to use alternative and natural agents to support chemotherapy in TNBC. To clarify the molecular mechanism of the tumorigenic effects of gambogic acid (GA) on TNBC cells with different epithelial character since GA has a wide spectrum of anticancer activity for most cancer types. We determined the cytotoxic dose of GA incubation of TNBC cells (MDA-MB-231 and BT-20 cells) for 24 h. We performed the MTT test and toluidine blue (TB) staining protocol for TNBC cells. We analyzed E-cadherin, N-cadherin, Bax, and neuroserpin mRNAs in both cells by qPCR. We evaluated apoptosis using DAPI staining and assessed the ROS using the 2',7'-dichlorofluorescin diacetate (DCFH-DA) method. We determined the IC50 concentrations of GA in MDA-MB-231 and BT-20 cells to be 315.8 nM and 441.8 nM, respectively. TB staining showed that BT-20 cells survive at excessive cytotoxic doses of GA, while most of the MDA-MB-231 cells were killed. Also, we found that BT-20 cells are more resistant to GA-induced apoptosis and oxidative stress than the MDA-MB-231 cells. qPCR results showed that GA upregulated neuroserpin, an oxidative stress-relieving factor in the BT-20 cells, but not in the MDA-MB-231 cells. The elevated level of neuroserpin could be a predictive marker to determine the development of resistance to chemotherapeutic agents.

The AO Foundation/Orthopaedic Trauma Association (AO/OTA) introduced a new trochanteric fracture classification in January 2018, concerning the lateral wall integrity. It suggested the intramedullary nail fixation in patients with an incompetent lateral wall fracture. To determine the reliability of lateral wall-thickness measurement and the fracture parameters associated with lateral wall integrity. This retrospective study evaluated patients with an intertrochanteric fracture who had had surgery in King Chulalongkorn Memorial Hospital between January 2014 and January 2019. The lateral wall was measured by anteroposterior plain radiography by four raters, two times each. The demographic data and fracture parameters were assessed and compared with respect to lateral wall integrity. In a total of 236 femurs and 232 patients having the 2018 AO/OTA-specified 31A1 and 31A2 intertrochanteric fractures, the lateral wall-thickness measurement showed excellent inter-rater reliability at 0.944 (0.927-0.957) and good-to-excellent intra-rater reliability ranging from 0.835 to 0.972. The parameters associated with lateral wall incompetence as per the multivariate logistic regression analysis were fracture angle (odds ratio [OR] = 0.95), distal greater trochanter involvement (OR = 9.47), and fragments at the intertrochanter area (OR = 4.49) and at the lesser trochanter (OR = 2.6). Some of the parameters related to trochanteric fractures are associated with lateral wall incompetence. Lateral wall-thickness measurement is a reproducible method, which has been suggested for use by the AO/OTA 2018 classification. It is easy to use and can help select the appropriate treatment for intertrochanteric fracture patients.

Dietary protein restriction has been considered to be a nutritional-related strategy to reduce risk for end-stage kidney disease among patients with non-dialysis-dependent chronic kidney disease (CKD). However, there is insufficient evidence to recommend a particular type of protein to slow down the CKD progression. Recently, various plant-based diets could demonstrate some additional benefits such as a blood pressure-lowering effect, a reduction of metabolic acidosis as well as hyperphosphatemia, and gut-derived uremic toxins. Furthermore, the former concerns about the risk of undernutrition and hyperkalemia observed with plant-based diets may be inconsistent in real clinical practice. In this review, we summarize the current evidence of the proposed pleiotropic effects of plant-based diets and their associations with clinical outcomes among pre-dialysis CKD patients.

Postoperative pain management is an important aspect of anesthesia care and multimodal analgesic techniques are generally recommended. To compare the effect of spinal anesthesia + transversus abdominis plane (TAP) block application on postoperative analgesia quality and patient satisfaction with spinal anesthesia + intrathecal morphine (ITM) application. A total of 70 patients were randomly separated into 2 groups as spinal anesthesia + TAP block (TAP block group, n = 34) and spinal anesthesia + ITM group (ITM group, n = 36). The groups were compared in respect of age, body mass index values, and visual analog scale (VAS) values at 0 h, 2 h, 6 h, 12 h, and 18 h, and patient satisfaction was scored by Quality Improvement in Postoperative Pain Management at 24 h. The mean age of the patients was 32.52 ± 6.50 years in the TAP block group and 30.11 ± 5.62 years in the ITM group, with no statistically significant difference determined. There was no statistically significant difference in terms of VAS values at 0 h, 2 h, 6 h, 12 h, and 18 h. When the factors affecting postoperative patient satisfaction were evaluated, feeling fatigue after the surgery (r = -0.811, P = 0.001) and postoperative complications such as nausea, vomiting, and itching (r = -0.831, P = 0.001) were found to have a negative effect on patient satisfaction. Due to low complication rates, TAP block is an effective application for postoperative analgesia management in varicocele operations that increases patient satisfaction postoperatively.

Targeting autophagy at gene level may be promising in multiple myeloma (MM) treatment depending on chromosomal abnormality (ABN) status. We aimed to investigate the role of ABN on survival of MM patients and to identify prognosis related autophagy-related genes (ARGs) for patients with or without ABN. Gene intensity values of 222 ARG for 548 MM patients were obtained from the Affymetrix Human Genome U133 Plus 2.0 Array (GPL570) platform containing 54,675 probes (GSE24080). A dataset containing data from 1576 MM patients with 1q21 amplification (GSE4204, GSE4452, GSE4581, and GSE2658) was used for validation. Survival analysis of the patients was analyzed using univariate and multivariate Cox regression method with the help of R3.53 programming language and Kaplan-Meier graphics were created. The Gene Ontology enRIchmentanaLysis and visuaLizAtion (GOrilla) tool was used to define the related biological processes and pathways. The overall survival (OS) and event-free survival (EFS) in all MM patients were strongly influenced by ABN. In the group of patients with ABN, 41 ARGs were found to be important in prognosis, whereas in the group of patients without ABN, 13 ARGs were found to be important in prognosis. CDKN1A, FKBP1B, FOXO3, and NCKAP1 ARGs were commonly significant in both groups and found to be survival triggering. The classification of MM patients according to the absence or presence of ABN is important in the determination of survival status. Detection of survival related ARGs in patients with chromosomal anomalies may be a new therapeutic target in treatment.

Venomous arthropods have substances in their venom with antiproliferative potential for neoplastic cells. To identify a polypeptide from Myrmeleon bore (antlion) with antiproliferative activity against neoplastic cells, and to elucidate the molecular mechanism of the activity. We used gel filtration and ion exchange chromatography to purify a polypeptide with antiproliferative activity against MG-63 human osteosarcoma cells from a proteinaceous extract of antlion. The polypeptide was sequenced and the stability of its antiproliferative activity was tested under a range of conditions in vitro. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the antiproliferative activity of the polypeptide against the MG-63 osteosarcoma cells and MC3T3-E1 mouse calvarial osteoblasts, which were used as a non-neoplastic control. We used western blotting to compare the levels of expression of heat shock transcription factor 1 (HSF1), heat shock protein 90 (HSP90), cyclin-dependent kinase 4 (CDK4), and protein kinase B alpha (ATK1) in MG-63 osteosarcoma cells and their mouse homologs in MC3T3-E1 osteoblasts after their treatment with the antlion antiproliferative polypeptide (ALAPP). The 85-amino-acid ALAPP has a 56% sequence identity with the human heat shock factor binding protein 1 (HSBP1). The antiproliferative activity of the polypeptide is relatively insensitive to temperature, pH, and metal ions. ALAPP has a strong concentration-dependent antiproliferative activity against MG-63 osteosarcoma cells compared with its effect on MC3T3-E1 osteoblasts. ALAPP significantly upregulates the expression of HSF1 in MC3T3-EL osteoblasts, but not in MG-63 osteosarcoma. ALAPP significantly downregulated the expression of HSP90, CDK4, and AKT1 expression in MG-63 osteosarcoma, but not in the osteoblasts. ALAPP has significant antiproliferative activity against MG-63 osteosarcoma cells, but not nonneoplastic MC3T3-E1 osteoblasts. We speculate that non-neoplastic cells may evade the antiproliferative effect of ALAPP by upregulating HSF1 to maintain their HSP90, CDK4, and AKT1 expression at a relatively constant level.

Chronic pancreatitis is the most common etiology of pancreaticopleural fistula (PPF) in children, and underlying genetic variations are now widely known, accounting for most chronic pediatric pancreatitis. We describe a case of previously undetected chronic pancreatitis and PPF with a SPINK1 variation in a 10-year-old Thai boy who presented with massive left pleural effusion. Magnetic resonance cholangiopancreatography (MRCP) revealed disruption of the pancreatic duct, which was communicating with a large pancreatic pseudocyst with mediastinal extension. The patient subsequently underwent endoscopic intervention with improved clinical symptoms. We also reviewed the imaging findings of 12 other reported cases of pediatric PPF. Massive pleural effusion due to PPF can be an atypical manifestation in children with chronic pancreatitis. MRCP is the preferable imaging study for PPF due to the production of highly detailed images of pancreatic duct disruptions and anatomy, and the imaging is helpful to guide for appropriate treatment. Tests for genetic variation are also recommended in a child with chronic pancreatitis.

Coronavirus disease 2019 (COVID-19) can affect the neurological as well as the respiratory system. Neurological manifestations may involve the central or peripheral nervous systems, or musculoskeletal system. Findings can range from mild presentations, such as headache and anosmia, to severe complications, such as stroke and seizure. To evaluate the neurological findings and to determine etiological risk factors for mortality in patients hospitalized for COVID-19. Medical records of patients with COVID-19 who were hospitalized and sought neurological consultation between March 2020 and March 2021 at a reference pandemic hospital in Turkey were reviewed retrospectively in a cross-sectional study design. We included data from 150 (94 male) patients. Their mean age ± standard deviation was 68.56 ± 16.02 (range 21-97) years. The patients were categorized into 2 groups according to any acute neurological event or progression of neurological disease. Ischemic cerebrovascular events, seizures, and encephalopathy were the most common acute neurological events, while deterioration in consciousness, epileptic seizures, and Parkinson disease were observed in those with progression of neurological disease. Abnormal neurological findings were found at a mean of 7.8 ± 9.7 days following COVID-19 diagnosis and 50 (a third of) patients died. A logistic regression model found that advanced age, increased Modified Charlson Comorbidity Index (MCCI) score, and prolonged duration of hospitalization were factors significantly associated with increased mortality; however, sex and day of abnormal neurological findings after COVID-19 diagnosis were not. Common conditions accompanying neurological events were hypertension, coronary artery disease-heart failure, and diabetes mellitus. COVID-19 may present with neurological symptoms in our Turkish patients and comorbidities are often present.

Tuberculosis is caused by Mycobacterium tuberculosis. Tuberculosis of the central nervous system is common and manifestations include meningeal and intraparenchymal diseases. However, intraventricular tuberculous abscess is a rare manifestation of intracranial tuberculous infection. We present a case of an immunocompromised female patient with high-grade fever and signs of meningism. The computed tomography and magnetic resonance imaging (MRI) of the brain showed hydrocephalus with rim-enhancing lesion in the right lateral ventricle. The MRI demonstrated a hypointense signal on T1-weighted imaging, hyperintense signal on T2-weighted imaging, and mild restricted diffusion in diffusion-weighted imaging. She underwent emergency external ventricular drainage and frank pus was drained. Diagnosis of tuberculosis was made via polymerase chain reaction analysis and culture. Understanding the intracranial manifestation of neurotuberculosis is imperative to arrive at the diagnosis correctly and ensure prompt treatment.