Protein Phosphatase 2a Inhibits Gastric Cancer Cell Glycolysis by Reducing MYC Signaling.

Aerobic glycolysis, also known as the Warburg effect, has emerged as a hallmark of cancer and is associated with tumor progression and unfavorable clinical outcomes in cancer patients. PP2A is a highly conserved eukaryotic serine/threonine protein phosphatase that functions as a tumor suppressor in a variety of human cancers. However, the relationship between PP2A and the Warburg effect in gastric cancer has yet to be fully understood. In this study, the expression profile of two endogenous inhibitors of PP2A, SET and CIP2A, in gastric cancer, were analyzed by real-time quantitative polymerase chain reaction. Loss-of-function and gain-of-function studies were performed to investigate the roles of PP2A in gastric cancer cell proliferation and glycolysis. Cell biological, molecular, and biochemical approaches were employed to uncover the underlying mechanisms. The results showed that SET and CIP2A were overexpressed in gastric cancer and associated with a decreased PP2A activity. Pharmacological activation of PP2A with FTY-720 and DT-061 in two gastric cancer cell lines significantly reduced gastric cancer cell proliferation and glycolytic ability. Importantly, inhibition of PP2A activity by genetic silencing of PPP2R5A resulted in a growth advantage, which can be largely compromised by the addition of the glycolysis inhibitor 2-Deoxy-D-glucose, suggesting a glycolysis-dependent effect of PP2A in gastric cancer. Mechanistically, the well-known transcription factor and glycolysis regulator c-Myc was discovered as the functional mediator of PP2A in regulating cell glycolysis. Ectopic expression of a phosphorylation-mutant c-Myc resistant to PP2A (MycT58A) restored the inhibitory effect of FTY-720 and DT-061 on lactate production and glucose uptake. Furthermore, there was a close association between SET and CIP2A expression and c-Myc gene signatures in gastric cancer samples. Collectively, this study provides strong evidence of the involvement of PP2A in the Warburg effect and indicates that it could be a novel antitumor strategy to target tumor metabolism in gastric cancer.

Analgesic effect of epidural anesthesia via the intervertebral foramen approach in percutaneous transforaminal endoscopic discectomy: a retrospective study.

BACKGROUND: Satisfactory intraoperative analgesia is critical for percutaneous transforaminal endoscopic discectomy (PTED). Local anesthesia (LA) and epidural anesthesia (EA) are recommended for PTED. LA alone does not achieve satisfactory pain management during PTED and other analgesics or sedatives are usually needed. Traditional EA, which involves implanting an epidural catheter through the midline or paramedian, has disadvantages such as difficulty in catheterization and increased preoperative preparation time. Rather than performing conventional EA, we injected local anesthetics through the intervertebral foramen during the puncture process, which we termed lumbar transforaminal EA (LTEA), and observed its feasibility and safety. This study aimed to conduct a comprehensive comparison of differences in analgesia between LA and LTEA in patients with PTED. METHODS: We performed a retrospective analysis of patients who underwent PTED between January 2018 and January 2021. Patients were divided into LA and LTEA groups. Data obtained from the electronic medical records included primary outcomes (visual analog scale [VAS] scores and anesthesia satisfaction rate) and secondary outcomes, including vital signs such as heart rate (HR), mean arterial pressure (MAP), total dosage of fentanyl, operation time, X-ray exposure time, Oswestry Disability Index (ODI) scores, and complications. RESULTS: In total, 160 patients (80 in each group) were analyzed in this study. The VAS scores for lumbar and leg pain were significantly lower in the LTEA group than in the LA group (P < 0.0001). The anesthesia satisfaction rate was 90.0% in the LTEA group and 72.5% in the LA group (P < 0.005). MAP and HR values in the LTEA group were significantly lower than those in the LA group (P < 0.05). The total dose of fentanyl in the LTEA group was significantly lower than that in the LA group (P < 0.05). As for ODI values, the average operation time, X-ray exposure time, and incidence of complications were not significantly different between the two groups (P > 0.05). CONCLUSIONS: LTEA simplifies the process of EA and can achieve a good analgesic effect intraoperatively without increasing the preoperative preparation time; thus, it may be adopted as an alternative mode of anesthesia during PTED surgery.

High-voltage long-duration pulsed radiofrequency attenuates neuropathic pain in CCI rats by inhibiting Cav2.2 in spinal dorsal horn and dorsal root ganglion.

Inclinicalpractice, high-voltage, long-duration pulsed radiofrequency (HL-PRF) is effective for several types of intractable neuropathic pain (NP), but the mechanisms have not been well explored. Cav2.2 channels could increase neuronal excitability and neurotransmission accompanying NP. This study investigated the relationship of the efficacy of HL-PRF on NP with the levels of Cav2.2 in the spinal dorsal horn (SDH) and dorsal root ganglions (DRGs) of chronic constriction injury (CCI) in rats. Sham HL-PRF, GVIA (a specific Cav2.2 channel blocker), HL-PRF, or GVIA + HL-PRF was applied to CCI rats. The results showed: compared with the sham group, the PWT and PWL of CCI rats decreased significantly (P < 0.05), and Cav2.2 expression was elevated significantly in the SDH and DRGs (P < 0.05). Compared with the CCI group, both HL-PRF and ω-conotoxin GVIA treatment reversed the increased PWT and PWL (P < 0.05) and downregulated the overexpression of Cav2.2 in the SDH and DRGs (P < 0.05). Furthermore, PWT, PWL, and the expression of Cav2.2 in the SDH and DRGs were not significantly different among the 3 treatment groups. HL-PRF on L5 DRG reversed the hyperalgesia behavior of NP and reduced the levels of Cav2.2 in the ipsilateral SDH and DRGs in CCI rats. Moreover, the underlying mechanism may be related to the downregulation of CaV2.2 protein levels in both SDH and DRG.

Splanchnic nerve neurolysis via the transdiscal approach under fluoroscopic guidance: a retrospective study.

Background: Neurolytic celiac plexus block (NCPB) is a typical treatment for severe epigastric cancer pain, but the therapeutic effect is often affected by the variation of local anatomical structures induced by the tumor. Greater and lesser splanchnic nerve neurolysis (SNN) had similar effects to the NCPB, and was recently performed with a paravertebral approach under the image guidance, or with the transdiscal approach under the guidance of computed tomography. This study observed the feasibility and safety of SNN via a transdiscal approach under fluoroscopic guidance. Methods: The follow-up records of 34 patients with epigastric cancer pain who underwent the splanchnic nerve block via the T11-12 transdiscal approach under fluoroscopic guidance were investigated retrospectively. The numerical rating scale (NRS), the patient satisfaction scale (PSS) and quality of life (QOL) of the patient, the dose of morphine consumed, and the occurrence and severity of adverse events were recorded preoperatively and 1 day, 1 week, 1 month, and 2 months after surgery. Results: Compared with the preoperative scores, the NRS scores and daily morphine consumption decreased and the QOL and PSS scores increased at each postoperative time point (P < 0.001). No patients experienced serious complications. Conclusions: SNN via the transdiscal approach under flouroscopic guidance was an effective, safe, and easy operation for epigastric cancer pain, with fewer complications.

Graphene acoustic transducers based on electromagnetic interactions.

Graphene acoustic transducers have high sensitivity in receiving mode. However, they are used in transmitting mode with low radiation performance. A graphene acoustic transducer with high sensitivity and radiation performance is proposed in this study. The transducer is composed of graphene diaphragm, an insulating layer embedded in a copper planar coil, and a bottom layer plated with copper. The proposed capacitive transducer is driven by electrostatic and electromagnetic excitation. The sensitivity and radiation performance of the transducer are analyzed by transceiver theory and simulation models. The results demonstrate that the proposed capacitive transducer has excellent acoustic performance with sensitivity of -42 dB and the sound pressure level of 106 dB at 4 kHz with a 20-turn coil that is more than doubled compared without a copper coil. In addition, the radiation performance of the transducer is discussed by the coil parameters including coil turns and coil current, which can provide a theoretical basis for further experiments.

Disruption of CTLA-4 expression on peripheral blood CD8 + T cell enhances anti-tumor efficacy in bladder cancer.

Activation of programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on T cells leads to T cell exhaustion and ultimately facilitates tumor progression. Recent success of using immune cell checkpoint inhibitors offers a great promise to treat various cancers, including bladder cancer. However, the expression pattern and therapeutic value of PD-1 and CTLA-4 in peripheral blood T cells remain largely unexplored. In this study, we presume that disruption of the potential dysregulated checkpoint molecules in peripheral blood T cells may improve the anti-tumor efficacy of cytotoxic T cells in bladder cancer. We showed that both PD-1 and CTLA-4 expression were specifically elevated on CD8 + T cells but not CD4 + T cells in peripheral blood of patients with bladder cancer compared with that in healthy donors. Notably, CTLA-4 expression was significantly higher in muscle-invasive bladder cancer (MIBC) and correlated with tumor size. By blocking CTLA-4 with anti-CTLA-4 antibody and CRISPR-Cas9-mediated CTLA-4 disruption, we revealed that CTLA-4-disrupted CTLs had enhanced cellular immune response and superior cytotoxicity to the CD80/CD86-positive bladder cancer cells in vitro. Moreover, the CTLA-4-disrupted CTLs exhibited a pronounced anti-tumor effect in vivo as demonstrated by prophylactic assay and therapeutic assay in the subcutaneous xenograft model. Collectively, our findings confirm improved therapeutic efficacy of CTLA-4-disrupted CTLs and provides the potential strategy for targeting immune checkpoints to enhance the promising immunotherapy.

Propofol decreases etomidate-related myoclonus in gastroscopy.

OBJECTIVE: Myoclonus, a common complication during intravenous induction with etomidate, is bothersome to both anesthesiologists and patients. This study explored the preventive effect of pretreatment with propofol on etomidate-related myoclonus. METHODS: This was a prospective, double-blind, clinical, randomized controlled study. Totally, 363 patients who were scheduled for a short-duration, painless gastrointestinal endoscopy were divided into 5 groups. Four groups received 0 mg/kg (E group), 0.25 mg/kg (LPE group), 0.50 mg/kg (MPE group), or 0.75 mg/kg (HPE group) propofol pretreatment before etomidate anesthesia. Another group only received 1 to 2 mg/kg of propofol (P group) as anesthesia. The incidence and severity of myoclonus, patient circulation and respiratory status, and intraoperative and postoperative complications were recorded. RESULTS: The incidence of myoclonus in the LPE group (26.8%), MPE group (16.4%), HPE group (14.9%), and P group (0) was lower than the E group (48.6%, P < .05). The incidence of grade 1, 2, and 3 of myoclonus in the LPE group, MPE group, HPE group, and P group was significantly lower than the E group, and that in the P group was lower than the LPE group (P < .05). The incidence of hypoxemia in the P group was higher than the E group, and the incidence of adverse events in the HPE group and P group was lower than the E group (P < .05). DISCUSSION: Pretreatment with propofol was feasible for preventing etomidate-related myoclonus. Furthermore, as propofol dosage increased, its effect on reducing the incidence and severity of myoclonic movements induced by etomidate increased.

Ultrasound-guided Versus Fluoroscopy-controlled Lumbar Transforaminal Epidural Injections: A Prospective Randomized Clinical Trial.

OBJECTIVES: Recently, most lumbar spine injections have been administered under ultrasound (US) guidance; however, there is no standard method for US-guided lumbar transforaminal epidural injection (TFEI). In this study, we evaluated the accuracy, effect on pain relief, and safety of US-guided lumbar TFEI. METHODS: A total of 80 patients with low back pain and radicular pain were enrolled. The patients were randomly assigned to either the fluoroscopy (FL) group or the US group. The FL-guided approaches were performed under standardized procedures using the C-arm, whereas the US-guided injections were performed with an US device with a linear probe, and were verified by FL. The needle tip reached the lateral side of the lamina in the axis view and the middle of the adjacent facet joints in the parasagittal view. Afterward, the needle was advanced slightly deeper until the loss-of-resistance test was positive. RESULTS: The success ratio of the US-guided interventions was 85%. The operation time in the US group (518±103 s) was shorter than the FL group (929±228 s) (P<0.05). In addition, the radiation dosage in the US group (2640±906 µGy m²) was lower than in the FL group (8992±2132 µGy m²). There was no significant difference in pain relief between the US and FL groups. No serious complication was observed in any of the patients in either group. DISCUSSION: Lumbar TFEI under US guidance was feasible, safe, and required less radiation to achieve the same benefit as the FL-guided interventions.

Association of the CTLA4 gene CT60/rs3087243 single-nucleotide polymorphisms with Graves' disease.

It has been widely reported that the CT60 single-nucleotide polymorphism (SNP), which is in the 3'-untranslated region of the cytotoxic T lymphocyte associated 4 (CTLA4) gene, is strongly correlated with certain immune-mediated diseases. The present case-control study aimed to investigate the genetic association between the CT60 SNP within the CTLA4 gene and Graves' disease (GD). A total of 288 patients with GD and 290 control subjects were recruited for the study. The CT60 SNP of the CTLA4 gene was detected by direct DNA sequencing. The results indicated that the frequencies of the GG genotype and G allele in the case group were evidently higher than that in the control group (P=4×10-6 and P=2.9×10-5, respectively). Furthermore, the G/G genotype of the CT60 SNP was associated with an increased risk for GD (odds ratio=2.223). In conclusion, these results suggested that the CT60 SNP is associated with susceptibility to GD. The frequency of the disease-susceptible G allele of CT60 was significantly associated with an increased risk of GD development.

Anatomical study on Meckel cave with endoscopic endonasal, endo-maxillary sinus, and endo-pterygoid process approaches.

OBJECTIVE: To study anatomical structures related to Meckel cave with endonasal endoscopic approach and to provide an anatomical basis for endoscopic surgery in Meckel cave. METHODS: Meckel cave of 5 adult skulls (10 sides) were fixed with 10% formalin. The anatomical structures of Meckel cave and the related zones adjacent to Meckel cave were observed and measured with endoscopic endonasal approach. RESULTS: Endoscopic endonasal, endo-maxillary sinus, and endo-pterygoid process approaches were successfully applied in observation of the anatomical structures of meckel cave and the rerated zones adjacent to Meckel cave and in measurement of distances between related anatomical structures for each case of samples. The relevant data were obtained. The distance between the front mouth of palatovaginal canal and vidian canal was 21.4±7 mm, the distance between opening of sphenoid sinus to the upper margin of the choana was 22.3±2.8 mm, the distance between the opening of vidian and foramen rotundum was 7.57±0.7 mm and the length of the pterygoid canal was 13.3±1.2 mm. Based on these data, the positions of the related important structures can be roughly located during surgical operation and various important structures in Meckel cave and its adjacent zones can be found out in a convenient and safe way. CONCLUSION: 1) It is feasible to use endonasal endoscopic approach to perform surgical operation in Meckel cave; 2) Use of endonasal endoscopic approach can protect and fully take the advantage of the vidian nerve to locate the position of foramina lacerum of the internal carotid artery during surgical operation; and 3) the observational and experimental data obtained with this approach can provide the rational basis for clinical operation procedures.

Unusual imaging appearance of a huge intracranial dermoid cyst located across the anterior and middle skull base.

Intracranial dermoid cysts are rare congenital neoplasms. Typical dermoid cysts are well-circumscribed fat-density masses with no associated contrast enhancement. We report a woman with a dermoid cyst across the anterior and middle skull base of unusual imaging appearance. This report highlights the challenge facing the diagnosis and management of intracranial dermoid cysts with unusual primary imaging findings.

Nonketotic hyperglycemia-related epileptic seizures.

Nonketotic hyperglycemia-related seizures (NKH) are rare. We report a case of NKH-related seizures in a patient following a traumatic brain injury.