Spalt-like transcription factor 4 (SALL4), as a proto-oncogene, is expressed in various tumors and correlates with poor prognosis of patients. Entinostat, a histone deacetylase (HDAC) inhibitor, has emerged as a potentially promising anti-cancer drug. This study aims to explore the biological role and underlying mechanism of SALL4 targeting by entinostat in gastric cancer.Online databases were used to exam the link between SALL4 and prognosis. We tested the biological roles of SALL4 in gastric cancer cells. Cell viability and growth were analyzed using the Cell Counting Kit-8 (CCK-8) assay and clone formation assay. Cell migration was assessed using the wound healing assay. The effects of entinostat on gastric cancer cell lines were measured by the CCK-8 assay, clone formation assay, wound healing assay and transwell assay. Epithelial-mesenchymal transition (EMT) signaling pathways were detected by western blot.SALL4 expression was upregulated in gastric cancer tissues and positively correlated with tumor stage and prognosis of patients by TCGA dataset analysis. Knockdown of SALL4 by siRNA inhibited the proliferation and migration of gastric cancer cells. In contrast, SALL4 overexpression by stably transfecting a SALL4-expressing plasmid promoted the proliferation and invasiveness of gastric cancer cells in vitro through alteration of EMT-related genes. In addition, entinostat, a HDAC inhibitor targeting SALL4, could suppress the proliferation, migration, and invasion of gastric cancer cells via regulating expression of EMT-associated proteins.SALL4 may be a new therapeutic target for the treatment of gastric cancer, and entinostat is a potential novel agent for the treatment of gastric cancer partially by targeting SALL4. 

Targeting SALL4 by Entinostat Inhibits the Malignant Phenotype of Gastric Cancer Cells by Reducing EMT Signaling

We previously identified a unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus. This study aims to understand its gene architecture and preliminarily suggest its functions. The results showed that there were about 19,666 genes in this nucleus, of which 913 were distinct from the dorsal raphe nucleus (non-CSF contacting). The top 40 highly-expressed genes are mainly related to energy metabolism, protein synthesis, transport, secretion, and hydrolysis. The main neurotransmitter is 5-HT. The receptors of 5-HT and GABA are abundant. The channels for Cl-, Na+, K+, and Ca2+ are routinely expressed. The signaling molecules associated with the CaMK, JAK, and MAPK pathways were identified accurately. In particular, the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed. The relationship between the main genes of the nucleus and life activities is preliminarily verified. 

/pdf/genetic-architecture-and-functional-implications-of-the-csf-2125iq2a.pdf

Genetic Architecture and Functional Implications of the CSF-Contacting Nucleus

Peripheral giant cell granuloma (PGCG) is a non-neoplastic, tumour-like reactive lesion that exclusively involves the gingiva and/or the alveolar crest. The surgical approach with a scalpel has been the golden standard of treatment for PGCG, but the scientific literature reports a high rate of lesion recurrence. Hence, this unique case report aimed to evaluate the efficacy of λ 10,600 nm high-level laser therapy (HLLT) in eradicating persistent, aggressive, and recurrent PGCG that failed to respond to standard surgical treatment. A fit and healthy thirty-four-year-old Caucasian male presented with a two-month history of recurrent episodes of an oral mucosal lesion involving the buccal and lingual interdental papillae between the lower right second premolar (LR5) and lower right first molar (LR6), which was surgically excised with a scalpel three times previously. A λ 10,600 nm-induced HLLT was chosen as a treatment modality at a lower peak power of 1.62 W, measured with a power metre, emitted in gated emission mode (50% duty cycle), whereby the average output power reaching the target tissue was 0.81 W. The spot size was 0.8 mm. Ninety seconds was the total treatment duration, and the total energy density was 7934.78 J/cm2. Patient self-reporting outcomes revealed minimal to no post-operative complications. Initial healing was observed on the 4th day of the post-laser treatment, and a complete healing occurred at two-weeks post-operatively. The histological analysis revealed PGCG. This unique case report study demonstrated the efficacy of λ 10,600 nm-induced HLLT and its superiority to eradicate persistent aggressive PGCG over the standard surgical approach with minimal to no post-operative complications, accelerating wound healing beyond the physiological healing time associated with no evidence of PGCG recurrence at the six-month follow-up timepoint. Based on the significant findings of this unique study and the results of our previous clinical studies, we can confirm the validity and effectiveness of our standardised λ 10,600 nm laser dosimetry-induced HLLT and treatment protocol in achieving optimal outcomes. Randomised controlled clinical trials with large data comparing λ 10,600 nm with our dosimetry protocol to the standard surgical treatment modality at long follow-up timepoints are warranted.

10,600 nm High Level-Laser Therapy Dosimetry in Management of Unresponsive Persistent Peripheral Giant Cell Granuloma to Standard Surgical Approach: A Case Report with 6-Month Follow-Up.

pdf/introductory-chapter-understanding-postoperative-pain-1we99bw1t8.pdf

Introductory Chapter: Understanding Postoperative Pain

To evaluate the effect of lateral versus supine positioning on incidence of hypoxaemia in sedated patients and to provide evidence based recommendations for respiratory strategies. Prospective, multicentre, randomised controlled trial. 14 tertiary hospitals in China, July to November 2024. 2159 adults (≥18 years) who underwent sedation. Sedated patients were randomly assigned (1:1) to receive either lateral positioning or conventional supine positioning, stratified by study centres. The primary outcome was incidence of hypoxaemia (peripheral oxygen saturation (SpO2) ≤90%) within the first 10 minutes after positioning. Secondary outcomes included airway rescue interventions, incidence of severe hypoxaemia (SpO2 ≤85%), lowest oxygen saturation recorded, length of stay in the post-anaesthesia care unit, and safety measures (eg, bradycardia, tachycardia, hypotension, new onset arrhythmia). Analyses were performed on an intention-to-treat basis. Of 2159 patients randomised, 2143 were included in the primary analysis. The mean age of the patients was 53.1 years, mean body mass index was 23.9, and 53.7% (1150/2143) were women. The incidence of hypoxaemia was significantly lower in the lateral group compared with supine group (5.4% (58/1073) v 15.0% (161/1070); adjusted risk ratio 0.36, 95% confidence interval (CI) 0.27 to 0.49; P<0.001). Compared with patients in the supine group, patients in the lateral group required fewer airway rescue interventions (6.3% (68/1073) v 13.8% (148/1070); adjusted risk ratio 0.46, 0.34 to 0.61; P<0.001), had a lower incidence of severe hypoxaemia (0.7% (8/1073) v 4.8% (51/1070); adjusted risk ratio 0.16, 0.07 to 0.33; P<0.001), and had a higher mean lowest SpO2 level (96.9% v 95.7%, absolute adjusted mean difference 1.20%, 95% CI 0.87% to 1.54%; P<0.001). Additionally, length of stay in the post-anaesthesia care unit was shorter in the lateral group (38.2 v 40.5 minutes; absolute adjusted mean difference -2.22 minutes; 95% CI -3.63 to -0.80; P=0.002). Safety outcomes were comparable between the groups, but tachycardia was less frequent in the lateral group. Placing sedated adults in the lateral position significantly reduces the incidence and severity of hypoxaemia and decreases the need for airway rescue interventions without compromising safety. Given its simplicity and low cost, lateral positioning could offer advantages in remote or resource constrained clinical settings. Further replication studies targeting patients with advanced age and high body mass index are needed to improve the generalisability of the findings. ClinicalTrials.gov NCT06459167. 

Effect of lateral versus supine positioning on hypoxaemia in sedated adults: multicentre randomised controlled trial

Background Measuring pain on digital devices using classic unidimensional pain scales such as the visual analog scale (VAS), numerical rating scale (NRS), and faces pain scale (FPS) has been proven to be reliable and valid. Emoji are pictographs designed in colorful form following the Unicode standard. It could be more beneficial to use emoji as faces of FPS on digital devices because emoji can easily fit on most devices and emoji are open-source so no approval would be needed before use. With a concise and user-friendly design, the emoji faces pain scale (Emoji-FPS) might be more generalizable to a wider population and more preferred by digital device users. Objective This study was designed to develop an Emoji-FPS as well as to evaluate its reliability, validity, and preference on mobile devices in adult patients who underwent surgery. Methods A modified Delphi technique with 2 rounds of web-based surveys was applied to obtain panelists’ consensus on the sequence of emoji that can best represent 6 levels of pain. The initial candidate sequences of emoji for the Delphi process were constructed referring to 2 well-validated FPSs (Wong-Baker FACES pain rating scale [Wong-Baker FACES] and faces pain scale-revised [FPS-R]). Then, a prospective cohort of patients scheduled to receive perianal surgery was recruited and asked to complete a web-based questionnaire on a mobile device at 5 time points (before surgery [T1], wake up after surgery [T2], 4 hours after surgery [T3], the second day after surgery [T4], and 15 minutes after T4 [T5]). The 4 well-validated pain scales (NRS, VAS, Wong-Baker FACES, and FPS-R) were used as reference scales. Results After 2 rounds of surveys on 40 Delphi panelists, an Emoji-FPS was finally determined to represent 6 pain levels (0, 2, 4, 6, 8, and 10) from “no hurt” to “hurts worst.” For validation, 300 patients were recruited and 299 were analyzed, the mean age of whom was 38.5 (SD 10.5) years, and 106 (35.5%) were women. For concurrent validity, the Emoji-FPS was highly correlated with 4 reference scales with Spearman correlation coefficient ρ ranging from 0.91 to 0.95. Excellent agreements were observed between 4 versions of Emoji-FPS (iOS, Android, Microsoft, and OpenMoji), with weighted κ coefficients ranging from 0.96 to 0.97. For discriminant validity, patients’ mean preoperative Emoji-FPS score (T1) was significantly higher than their postoperative Emoji-FPS score (T4) with a difference of 1.4 (95% CI 1.3-1.6; P<.001). For test-retest reliability, Emoji-FPS scores measured at T4 and T5 were highly correlated with a ρ of 0.91. The Emoji-FPS was mostly preferred, followed by the Wong-Baker FACES, FPS-R, NRS, and VAS. Conclusions The Emoji-FPS is reliable and valid compared with traditional pain scales in adult surgery patients.

Development of the Emoji Faces Pain Scale and Its Validation on Mobile Devices in Adult Surgery Patients: Longitudinal Observational Study

Objective The objective of this study is to explore the effects of microRNA-33a-5p (miR-33a-5p)-ras-related protein Rap-2a (RAP2A) on biological functions of gastric cancer (GC) and to find the potential functional mechanism. Methods We measured the miR-33a-5p expression in 30 GC tissues and cellular level and 30 adjacent normal tissues as control. Besides, the expression of miR-33a-5p was checked at cell level as well. To screen the possible targets of miR-33a-5p, prediction software was used and gene RAP2A attracted our attention. Through a series of experiments including real-time polymerase chain reaction (qRT-PCR), luciferase assay, and western blotting (WB), we verified RAP2A as a potential target of miR-33a-5p. The impacts of miR-33a-5p and RAP2A on biological functions of GC cell lines (BGC-823 and MGC-803) were analyzed by subsequent experiments. Cell invasion was tested by invasion assays. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. Cell clone was measured by clone formation assays. Finally, the expression of RAP2A protein was analyzed by WB assay. Results We found miR-33a-5p was expressed lowly in GC tissues and cells. Overexpression of miR-33a-5p in BGC-823 and MGC-803 cells greatly inhibited the cell invasion and colony number. Furthermore, compared to sh-control (shControl), RAP2A knockdown (sh-RAP2A/shRAP2A) raised the sensitivity of GC cells to 5-FU significantly, characterized as reducing cell apoptosis. Conclusions The expression of miR-33a-5p was lower in GC cell lines and tissues obviously, indicating that miR-33a-5p served as the antitumor gene in GC. The expression of RAP2A regulated negatively the sensitivity of GC cells to 5-FU. According to our in vitro experiments, miR-33a-5p/RAP2A was likely to become a new therapeutic target for GC.

/pdf/mir-33a-5p-targets-rap2a-to-mediate-the-sensitivity-of-3ag1h0w3.pdf

miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU

Safety of prone emergence from general endotracheal anesthesia in patients undergoing ERCP: a randomized controlled trial.

Activation of P2X4 receptors in midbrain cerebrospinal fluid-contacting nucleus leads to mechanical hyperalgesia in chronic constriction injury rats.

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Development of the Emoji Faces Pain Scale and Its Validation on Mobile Devices in Adult Surgery Patients: Longitudinal Observational Study

miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU

Safety of prone emergence from general endotracheal anesthesia in patients undergoing ERCP: a randomized controlled trial.

Activation of P2X4 receptors in midbrain cerebrospinal fluid-contacting nucleus leads to mechanical hyperalgesia in chronic constriction injury rats.