GuiErBai: a potent inhibitor, exhibiting broadly antitumor effect against cervical cancer in vitro and in vivo.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

Target temperature management and therapeutic hypothermia in sever neuroprotection for traumatic brain injury: Clinic value and effect on oxidative stress.

This study is to explore the application of target temperature management and therapeutic hypothermia in the treatment of neuroprotection patients with severe traumatic brain injury and its effect on oxidative stress. From February 2019 to April 2021, 120 patients with severe traumatic brain injury cured were selected in our hospital. The patients were randomly divided into control and experimental groups. The control group accepted mild hypothermia therapy. The experimental group took targeted temperature management and mild hypothermia therapy. This study compared the prognosis, National Institute of Health Stroke Scale (NIHSS) score, oxidative stress level, brain function index and the incidence of complications in different groups. The prognosis of the experimental group was better (P < .05). After treatment, the NIHSS score lessened. The NIHSS score of the experimental group was lower at 3 and 6 weeks after treatment (P < .05). Following treatment, the level of superoxide dismutase-1 in the experimental group was higher and the level of malondialdehyde was lower (P < .05). After treatment, the brain function indexes of patients lessened. The experimental group's myelin basic protein, neuron specific enolase and glial fibrillary acidic protein indexes were lower (P < .05). The incidences of pendant pneumonia, atelectasis, venous thrombosis of extremities and ventricular arrhythmias in the experimental group were remarkably lower (P < .05). Targeted temperature management and mild hypothermia treatment can improve neurological function, maintain brain cell function, and reduce stress-reactions risk. The incidence of complications during hospitalization was reduced.

Circular RNA circ_0021001 regulates miR-148b-3p/GREM1 axis to modulate proliferation and apoptosis of vascular smooth muscle cells.

Intracranial aneurysm (IA) is an abnormal expression in the intracranial arteries, which is related to the growth and apoptosis of vascular smooth muscle cells (VSMCs). Circular RNA (circRNA) circ_0021001 (also named circARFIP2) has been identified to mediate the regulation of VSMCs proliferation. However, the molecular mechanism of circ_0021001 involved in VSMC dysfunction in IA is poorly defined. The expression levels of circ_0021001, microRNA-148b-3p (miR-148b-3p), and Gremlin 1 (GREM1) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, proliferation, cell cycle progression, and apoptosis were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Protein levels of proliferating cell nuclear antigen (PCNA), p21, B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), and GREM1 were examined by western blot assay. The binding relationship between miR-148b-3p and circ_0021001 or GREM1 was predicted by StarBase and then verified using a dual-luciferase reporter assay. The expression levels of circ_0021001 and GREM1 were increased, and that of miR-148b-3p was decreased in IA tissues and HUASMCs. Moreover, the downregulation of circ_0021001 could repress proliferation ability and induce apoptosis of HUASMCs. The mechanical analysis uncovered that circ_0021001 served as a sponge of miR-148b-3p to regulate GREM1 expression. Circ_0021001 silencing could suppress cell growth and induce apoptosis of HUASMCs partially through modulating the miR-148b-3p/GREM1, presented circ_0021001 as a promising therapeutic target for IA.

[Antagonistic effect of the Fengzhecao extract against human red blood cell hemolysis induced by wasp venom].

OBJECTIVE: To explore the antagonistic effect of Fengzhecao extract against human red blood cell (RBC) hemolysis induced by wasp venom. METHODS: Water extract method was used to extract dried Fengzhecao and vacuum-dried to obtain Fengzhecao extract. It was diluted into 1 g/L for next use. Wasp venom was collected from the wasp workers. A, B, O, AB type healthy blood donors' suspended RBC solution was obtain to make washed RBC solutions and adjust the RBCs count (4.0-80.0)×109/L (the number of RBC counted on the hemocytometer is 1-20 cells/small checker). According to treatment factors, they were divided into the normal saline controlled group (NS group; 200 µL RBC solution+20 µL normal saline), Fengzhecao extract group (FZC group; 200 µL RBC solution+10 µL Fengzhecao extract+10 µL normal saline), wasp venom group (FD group; 200 µL RBC solution+10 µL wasp venom+10 µL normal saline), and Fengzhecao extract+wasp venom group (FCD group; 200 µL RBC solution+10 µL Fengzhecao extract+10 µL wasp venom), with 10 blood samples per group of every blood type. The solutions were put into the glass test tube respectively, and then into 37 centigrade water bath thermostat. After 10 minutes, the blood cell counting plate was directly observed under the microscope and the RBCs was counted. Differences in RBC count was compared between the same treatment factors of different blood types and between different treatment factor groups of the same blood type. RESULTS: There was no statistically significant difference in RBC count between blood types under the same treatment factors. The RBC count (×109/L) of the type A, B, O, AB in the NS group were 5.567±1.368, 5.146±1.690, 4.577±0.774, 5.197±1.587 (F = 0.852, P = 0.475), the FZC group were 5.751±1.489, 5.268±1.418, 4.727±1.174, 5.298±1.229 (F = 0.987, P = 0.410), the FD group were 0.546±0.450, 0.804±0.428, 0.679±0.283, 0.846±0.453 (F = 1.089, P = 0.366), and the FCD group were 5.532±1.330, 5.051±1.596, 4.589±0.879, 5.140±1.492 (F = 0.820, P = 0.492), respectively. Comparison of RBC count between groups with different treatment factors of the same blood type was done. There was no significant difference between the FZC group and the NS group, indicating that the extract of Fengzhecao extract had no effect on hemolysis of RBC; in the FD group, it was significantly lower than the NS group (all P < 0.05), indicating that wasp venom had a significant hemolytic effect on RBC; but there was no statistically significant difference in RBC count between the FCD group and the NS group, indicating that the Fengzhecao extract antagonizes the hemolytic effect of wasp venom without affecting the RBC count; however, the RBC count in the FCD group was significantly higher than that in the FD group (all P < 0.05), further indicating that the Fengzhecao extract antagonizes the hemolytic effect of wasp venom. CONCLUSIONS: Wasp venom has a significant hemolytic effect which can be effectively antagonized by Fengzhecao extract and has nothing to do with the human ABO blood type.

Unruptured Epileptogenic Brain Arteriovenous Malformations.

AIM: To determine whether specific clinical and radiographic factors predispose arteriovenous malformations (AVMs) presenting with seizure and to predict the seizure risk for individual AVM patients. MATERIAL AND METHODS: Clinical features and cerebral angiograms of consecutive 45 unruptured AVM patients who were diagnosed in our center in a 2-year period were reviewed. Patient data (analysis cohort) was used to determine risk factors for seizure and to construct epileptogenic AVM groups. These risk groups were tested with the second half of the patient data (test cohort). RESULTS: Among 45 unruptured AVMs (47.9%), initial seizures occurred in 20 unruptured AVMs (44.4%). Two of these 20 patients had a bleed in 117 patient-years for an annual bleed rate of 1.7%. There was no significant difference in hemorrhagic risk between epileptogenic AVM and asymptomatic AVM (P=0.918). Multivariate analysis revealed 2 factors associated with seizure: frontal and temporal AVM locations (P < 0.001) and a compact AVM morphology (P=0.003). CONCLUSION: Analysis of a group of unruptured AVMs demonstrated that epileptogenic AVMs have an annual hemorrhage risk similar to that of the asymptomatic AVMs. Frontal and temporal AVM locations and a compact AVM morphology were significantly associated with epileptogenic AVMs.