Neuronal repair after spinal cord injury by in vivo astrocyte reprogramming mediated by the overexpression of NeuroD1 and Neurogenin-2.

BACKGROUND: As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. METHODS: A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-ß (TGF-ß) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). RESULTS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p < 0.0001). Immunofluorescence staining identified astrocytes with neuroblasts and immature neurons cell properties at the site of injury while neuronal marker-specific staining revealed an increased number of mature astrocytes at the injury site. Behavioral assessments showed that the intervention did not improve The BMS (Basso mouse scale) score (p = 0.0726) and gait (p > 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p < 0.0001) and a significant improvement in glial scar proliferation. Electrophysiological assessments revealed a significant improvement in spinal nerve conduction (p < 0.0001) while immunostaining revealed that the levels of TGF-ß protein at the site of injury in the intervention group were lower than control group (p = 0.0034); in addition, P70 s6 and PP2A related to the TGF-ß pathway showed ascending trend (p = 0.0036, p = 0.0152 respectively). CONCLUSIONS: The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord after spinal cord injury can reprogram astrocytes into neurons and significantly enhance cell regeneration at the injury site. The reprogramming of astrocytes can lead to tissue repair, thus improving the reduced threshold and increasing voluntary movements. This strategy can also improve the integrity of the blood-spinal cord barrier and enhance nerve conduction function. However, the simple reprogramming of astrocytes cannot lead to significant improvements in the striding function of the lower limbs.

Effects of 6-methoxybenzoxazolinone (6-MBOA) on animals: state of knowledge and open questions.

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-ß-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry.

Structural basis of TRPV1 inhibition by SAF312 and cholesterol.

Transient Receptor Potential Vanilloid 1 (TRPV1) plays a central role in pain sensation and is thus an attractive pharmacological drug target. SAF312 is a potent, selective, and non-competitive antagonist of TRPV1 and shows promising potential in treating ocular surface pain. However, the precise mechanism by which SAF312 inhibits TRPV1 remains poorly understood. Here, we present the cryo-EM structure of human TRPV1 in complex with SAF312, elucidating the structural foundation of its antagonistic effects on TRPV1. SAF312 binds to the vanilloid binding pocket, preventing conformational changes in S4 and S5 helices, which are essential for channel gating. Unexpectedly, a putative cholesterol was found to contribute to SAF312's inhibition. Complemented by mutagenesis experiments and molecular dynamics simulations, our research offers substantial mechanistic insights into the regulation of TRPV1 by SAF312, highlighting the interplay between the antagonist and cholesterol in modulating TRPV1 function. This work not only expands our understanding of TRPV1 inhibition by SAF312 but also lays the groundwork for further developments in the design and optimization of TRPV1-related therapies.

Exploring microbial and moist-heat effects on Pu-erh tea volatiles and understanding the methoxybenzene formation mechanism using molecular sensory science.

Piling fermentation (PF) is crucial for Pu-erh tea aroma, yet its microbial and moist-heat impact on aroma quality is poorly understood. Solid-phase microextraction, solvent-assisted flavor evaporation, and gas chromatography-mass spectrometry were used to detected and analyses the samples of sun-green green tea, sterile PF and spontaneous PF. Microbiological action promotes the formation of stale aromas. Moist-heat action promotes the formation of plum-fragrance and sweet aroma. 20 microbial markers and 28 moist-heat markers were screened from 184 volatile components. Combining odor activity values and gas chromatography-olfactometry, 22 aroma-active compounds were screened (1,2,3-trimethoxybenzene, linalool, 1,2,4-trimethoxybenzene …), and analyzed during PF processing. Aroma omission and addition experiments verified its importance. Gallic acid addition experiments successfully verified that microorganisms are the main contributors to the synthesis of methoxybenzenes. Finally, Blastobotrys, Rasamsonia, and Thermomyces showed positive correlation with the synthesis of 1-ethyl-4-methoxybenzene, 1,2,4-trimethoxybenzene, 1,2,3-trimethoxybenzene, and 1,2-dimethoxybenzene. The formation mechanism of Pu-erh tea's aroma was clarified. Exploring microbial and moist-heat effects on Pu-erh tea volatiles and understanding the methoxybenzene formation mechanism using molecular sensory science.

Effects of enzyme-induced carbonate precipitation technique on multiple heavy metals immobilization and unconfined compressive strength improvement of contaminated sand.

Enzyme-induced carbonate precipitation (EICP) has been studied in remediation of heavy metal contaminated water or soil in recent years. This paper aims to investigate the immobilization mechanism of Zn2+, Ni2+, and Cr(VI) in contaminated sand, as well as strength enhancement of sand specimens by using EICP method with crude sword bean urease extracts. A series of liquid batch tests and artificially contaminated sand remediation experiments were conducted to explore the heavy metal immobilization efficacy and mechanisms. Results showed that the urea hydrolysis completion efficiency decreased as the Ca2+ concentration increased and the heavy metal immobilization percentage increased with the concentration of Ca2+ and treatment cycles in contaminated sand. After four treatment cycles with 0.5 mol/L Ca2+ added, the immobilization percentage of Zn2+, Ni2+, and Cr(VI) were 99.99 %, 86.38 %, and 75.18 %, respectively. The microscale analysis results presented that carbonate precipitates and metallic oxide such as CaCO3, ZnCO3, NiCO3, Zn(OH)2, and CrO(OH) were generated in liquid batch tests and sand remediation experiments. The SEM-EDS and FTIR results also showed that organic molecules and CaCO3 may adsorb or complex heavy metal ions. Thus, the immobilization mechanism of EICP method with crude sword bean urease can be considered as biomineralization, as well as adsorption and complexation by organic matter and calcium carbonate. The unconfined compressive strength of EICP-treated contaminated sand specimens demonstrated a positive correlation with the increased generation of carbonate precipitates, being up to 306 kPa after four treatment cycles with shear failure mode. Crude sword bean urease with 0.5 mol/L Ca2+ added is recommended to immobilize multiple heavy metal ions and enhance soil strength.

A novel glycoglycerolipid from Holotrichia diomphalia Bates: Structure characteristics and protective effect against DNA damage.

A lipidated polysaccharide, HDPS-2II, was isolated from the dried larva of Holotrichia diomphalia, which is used in traditional Chinese medicine. The molecular weight of HDPS-2II was 5.9 kDa, which contained a polysaccharide backbone of →4)-ß-Manp-(1 â†’ 4,6)-ß-Manp-(1 â†’ [6)-α-Glcp-(1]n â†’ 6)-α-Glcp→ with the side chain α-Glcp-(6 â†’ 1)-α-Glcp-(6 â†’ linked to the C-4 of ß-1,4,6-Manp and four types of lipid chains including 4-(4-methyl-2-(methylamino)pentanamido)pentanoic acid, 5-(3-(tert-butyl)phenoxy)hexan-2-ol, N-(3-methyl-5-oxopentan-2-yl)palmitamide, and N-(5-amino-3-methyl-5-oxopentan-2-yl)stearamide. The lipid chains were linked to C-1 of terminal α-1,6-Glcp in carbohydrate chain through diacyl-glycerol. HDPS-2II exhibited DNA protective effects and antioxidative activity on H2O2- or adriamycin (ADM)-induced Chinese hamster lung cells. Furthermore, HDPS-2II significantly ameliorated chromosome aberrations and the accumulation of reactive oxygen species (ROS), reduced γ-H2AX signaling and the expressions of NADPH oxidase (NOX)2, NOX4, P22phox, and P47phox in ADM-induced cardiomyocytes. Mechanistically, HDPS-2II suppressed ADM-induced up-regulation of NOX2 and NOX4 in cardiomyocytes, but not in NOX2 or NOX4 knocked-down cardiomyocytes, indicating that HDPS-2II could relieve intracellular DNA damage by regulating NOX2/NOX4 signaling. These findings demonstrate that HDPS-2II is a new potential DNA protective agent.

Structural Pharmacology of TRPV4 Antagonists.

The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo-electron microscopy (cryo-EM) structures of human TRPV4 are presented in-complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage-sensing-like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small-molecule antagonists, which may facilitate future drug discovery targeting TRPV4.

Inhibition of phospholipase D promotes neurological function recovery and reduces neuroinflammation after spinal cord injury in mice.

Introduction: Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation is one of the main pathophysiological features of secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), a critical lipid-signaling molecule, is known to be involved in various physiological processes, including the regulation of inflammation. Despite this knowledge, the specific role of PLD in SCI remains unclear. Methods: In this study, we constructed mouse models of SCI and administered PLD inhibitor (FIPI) treatment to investigate the efficacy of PLD. Additionally, transcriptome sequencing and protein microarray analysis of spinal cord tissues were conducted to further elucidate its mechanism of action. Results: The results showed that PLD expression increased after SCI, and inhibition of PLD significantly improved the locomotor ability, reduced glial scarring, and decreased the damage of spinal cord tissues in mice with SCI. Transcriptome sequencing analysis showed that inhibition of PLD altered gene expression in inflammation regulation. Subsequently, the protein microarray analysis of spinal cord tissues revealed variations in numerous inflammatory factors. Biosignature analysis pointed to an association with immunity, thus confirming the results obtained from transcriptome sequencing. Discussion: Collectively, these observations furnish compelling evidence supporting the anti-inflammatory effect of FIPI in the context of SCI, while also offering important insights into the PLD function which may be a potential therapeutic target for SCI.

The role of foam cells in spinal cord injury: challenges and opportunities for intervention.

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

Enzymatic Degradation of Deoxynivalenol with the Engineered Detoxification Enzyme Fhb7.

In the era of global climate change, the increasingly severe Fusarium head blight (FHB) and deoxynivalenol (DON) contamination have caused economic losses and brought food and feed safety concerns. Recently, an FHB resistance gene Fhb7 coding a glutathione-S transferase (GST) to degrade DON by opening the critical toxic epoxide moiety was identified and opened a new window for wheat breeding and DON detoxification. However, the poor stability of Fhb7 and the elusiveness of the catalytic mechanism hinder its practical application. Herein, we report the first structure of Fhb7 at 2.41 Å and reveal a unique catalytic mechanism of epoxide opening transformation in GST family proteins. Furthermore, variants V29P and M10 showed that 5.5-fold and 266.7-fold longer half-life time than wild-type, respectively, were identified. These variants offer broad substrate scope, and the engineered biosafe Bacillus subtilis overexpressing the variants shows excellent DON degradation performance, exhibiting potential at bacterium engineering to achieve DON detoxification in the feed and biomedicine industry. This work provides a profound mechanistic insight into the enzymatic activities of Fhb7 and paves the way for further utilizing Fhb7-related enzymes in crop breeding and DON detoxification by synthetic biology.

Nicotinamide Riboside Regulates Chemotaxis to Decrease Inflammation and Ameliorate Functional Recovery Following Spinal Cord Injury in Mice.

Changes in intracellular nicotinamide adenine dinucleotide (NAD+) levels have been observed in various disease states. A decrease in NAD+ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD+. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6-8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD+ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1ß, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.

Metagenomic analysis of the microbial communities and associated network of nitrogen metabolism genes in the Ryukyu limestone aquifer.

While microbial biogeochemical activities such as those involving denitrification and sulfate reduction have been considered to play important roles in material cycling in various aquatic ecosystems, our current understanding of the microbial community in groundwater ecosystems is remarkably insufficient. To assess the groundwater in the Ryukyu limestone aquifer of Okinawa Island, which is located in the southernmost region of Japan, we performed metagenomic analysis on the microbial communities at the three sites and screened for functional genes associated with nitrogen metabolism. 16S rRNA amplicon analysis showed that bacteria accounted for 94-98% of the microbial communities, which included archaea at all three sites. The bacterial communities associated with nitrogen metabolism shifted by month at each site, indicating that this metabolism was accomplished by the bacterial community as a whole. Interestingly, site 3 contained much higher levels of the denitrification genes such as narG and napA than the other two sites. This site was thought to have undergone denitrification that was driven by high quantities of dissolved organic carbon (DOC). In contrast, site 2 was characterized by a high nitrate-nitrogen (NO3-N) content and a low amount of DOC, and this site yielded a moderate amount of denitrification genes. Site 1 showed markedly low amounts of all nitrogen metabolism genes. Overall, nitrogen metabolism in the Ryukyu limestone aquifer was found to change based on environmental factors.

Periodic injection of liquefied kitchen and food waste in municipal solid waste: Effects on leachate and gas generation.

With continuous advancements in the zero-waste strategy in China, transportation of fresh municipal solid waste to landfills has ceased in most first-tier cities. Consequently, the production of landfill gas has sharply declined because the supply of organic matter has decreased, rendering power generation facilities idle. However, by incorporating liquefied kitchen and food waste (LKFW), sustainable methane production can be achieved while consuming organic wastewater. In this study, LKFW and water (as a control group) were periodically injected into high and low organic wastes, respectively. The biochemical characteristics of the resulting gas and leachate were analyzed. LKFW used in this research generated 19.5-37.6 L of methane per liter in the post-methane production phase, highlighting the effectiveness of LKFW injection in enhancing the methane-producing capacity of the system. The release of H2S was prominent during both the rapid and post-methane production phases, whereas that of NH3 was prominent in the post-methane production phase. As injection continued, the concentrations of chemical oxygen demand, 5-d biological oxygen demand, total organic carbon, ammonia nitrogen, total nitrogen, and oil in the output leachate decreased and eventually reached levels comparable to those in the water injection cases. After nine rounds of injections, the biologically degradable matter of the two LKFW-injected wastes decreased by 8.2 % and 15.1 %, respectively. This study sheds light on determining the organic load, controlling odor, and assessing the biochemical characteristics of leachate during LKFW injection.

Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III.

Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9αH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.

The Crosstalk Between Immune Cells After Intracerebral Hemorrhage.

The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood-brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve.

Mechanism of denitrification in subsurface-dammed Ryukyu limestone aquifer, southern Okinawa Island, Japan.

Denitrification crucially regulates the attenuation of groundwater nitrate and is unlikely to occur in a fast-flowing aquifer such as the Ryukyu limestone aquifer in southern Okinawa Island, Japan. However, evidences of denitrification have been observed in several wells within this region. This study analyzed environmental isotopes (δ15NNO3 and ẟ18ONO3) to derive the rationale for denitrification at this site. Additionally, the presence of two subsurface dams in the study area may influence the processes involved in nitrate attenuation. Herein, we analyzed 150 groundwater samples collected spatially and seasonally to characterize the variations in the groundwater chemistry and stable isotopes during denitrification. The values of δ15NNO3 and δ18ONO3 displayed a progressive trend up to +59.7 ‰ and + 21 ‰, respectively, whereas the concentrations of NO3--N decreased to 0.1 mg L-1. In several wells, the enrichment factors of δ15NNO3 ranged from -6.6 to -2.1, indicating rapid denitrification, and the δ15NNO3 to δ18ONO3 ratios varied from 1.3:1 to 2:1, confirming the occurrence of denitrification. Denitrification intensively proceeds under conditions of depleted dissolved oxygen concentrations (<2 mg L-1), sluggish groundwater flow with longer residence times, high concentrations of dissolved organic carbon (>1.2 mg L-1), and low groundwater levels during the dry season with precipitation rates of <100 mm per month (Jun-Sep). SF6 analysis indicated the exclusive occurrence of denitrification in specific wells with groundwater residence times exceeding 30 years. These wells are located in close proximity to the major NE-SW fault system in the Komesu area, where the hydraulic gradient was below 0.005. Detailed geological and lithological investigations based on borehole data revealed that subsurface dams did not cause denitrification while the major NE-SW fault system uplifted the impermeable basement rock of the Shimajiri Group, creating a lithological gap at an equivalent depth that ultimately formed a sluggish groundwater area, promoting denitrification.

Application of` the variable angle traction method by using clip with dental in super minimally invasive non full thickness resection of early gastric cancer / 中国医师进修杂志

Objective:Assisted traction technology is effective in increasing the rate of super minimally invasive surgery (SMIS) in patients with early gastric cancer (EGC), and shortening the operator′s learning curve. We adopt the variable angle traction technique of tissue clamp dental floss as a traction technique in this research.Methods:Patients with early gastric cancer who were treated with SMIS - non full layer resection of EGC were enrolled in the First Medical Center of Chinese PLA General Hospital from January 2022 to June 2023. This research was carried out by experts at the same level. It was divided into two groups: traction and non-traction. Submucosal detachment time (SDT), submucosal detachment rate (SDS), lamina propria exposure, muscularis propria defect (MPD), bleeding during operation, block resection, surgical resection, hand operation expenses, and surgical instruments were recorded.Results:Nine patients adopted variable angle traction, and 9 patients did not. The overall resection rate and curative resection rate of both groups were 100%. The mean SDT time was 28.00 (21.00, 34.00) min in traction group and 56.00 (40.00, 85.00) min in non traction group. And it had statistical significance ( P = 0.005). The SDS was (0.58 ± 0.21) cm 2/min in traction group and (0.23 ± 0.10) cm 2/min in non-traction group. And it had statistical significance ( P<0.05). Exposure of intrinsic muscle layer (IML): 8 cases in the traction group and 6 cases in the non-traction group. Intraoperative IML injury: in the traction group, 8 cases were MPD-0 and 1 case was MPD-Ft; in the non-traction group, 4 cases were MPD-0, 1 case was MPD-Pt, and 4 cases were MPD-Ft. There was no statistical difference between the two groups in terms of intraoperative bleeding, hospitalization expenses, surgical expenses, and the total hospitalization time. There were no serious adverse reactions or outcomes. Conclusions:The variable angle traction method accelerates SDT and SDS for SMIS-non full layer resection of EGC. It has the advantages of the sufficient separation of IML and mucosal layer, the deeper dissection depth, the low injury of IML, low intraoperative bleeding, and no additional medical costs. Therefore, this method can become an auxiliary treatment technology for SMIS.

Study on the cognition, learning habit and learning effect of Clinical Epidemiology among different types of postgraduates / 中华医学教育探索杂志

Objective:To investigate the cognition and learning habits of different types of postgraduates and evaluate learning effect and its potential risk factors on clinical epidemiology in a medical college, so as to provide relevant data for improving the teaching method and learning effect of clinical research methods for postgraduates.Methods:A cross-sectional study design was conducted to enroll all the postgraduates of Grade 2020 in a military medical school. A self-filled questionnaire was adopted to collect data. The discrepancy of cognition and learning habits between different types of postgraduates was evaluated by univariate analysis. Discussion was conducted to clarify the potential risk factors of learning effect. t tests or Mann-Whitney U tests were conducted to test the differences between groups for continuous variables. Chi-squared tests or McNemar tests were applied to evaluate the difference between groups for categorical variables. Results:A total of 652 postgraduate students were enrolled for analysis, including 409 master students (62.7) and 243 doctoral students (37.3). The proportion of doctoral students who have heard of clinical epidemiology ( χ2=19.99, P<0.001), who have learned clinical epidemiology ( χ2=9.20, P=0.002), who are interested in ( χ2=11.41, P=0.001) and think the course is important ( χ2=10.71, P=0.001), who previewed before class( χ2=11.21, P=0.001), reviewed after class ( χ2=3.29, P=0.001) and actively discuss in class ( χ2=11.64, P=0.001) is significantly higher than that of master students, the difference was statistically significance. The average score of all the postgraduates was (5.50±1.62) points before teaching and (7.47±1.90) points after teaching, the difference was statistically significant ( t=-23.49, P<0.001). After teaching, the grades of full-time students improved more than that of part-time graduate students, there was statistical significance in the master group ( t=4.41, P<0.001), while not in the doctor group ( t=0.94, P=0.351). Conclusions:The mastery of key points on clinical epidemiology have significantly improved after teaching among the postgraduates of different types. Different teaching methods and processes should be adopted to the variety of postgraduates according to their knowledge foundations and shortcomings. Besides, standardizing their learning habits are of certain significance to improve the learning effect.

Dickkopf-related protein 1 as a biomarker of local immune status and worse prognosis of Oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. OBJECTIVE: To examine the role and effect of DKK1 in OSCC. METHODS: The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. RESULTS: The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4+ T cells were associated with improved 5-year survival rates. CONCLUSION: DKK1 is a prognostic biomarker for patients with OSCC.

Letter to the editor: Aggressive variant prostate cancer: An exemplary case study and comprehensive literature survey.

This article enthusiastically explores the study of highly aggressive variant prostate cancer (AVPC), acknowledging its relatively rare yet highly menacing presence within the realm of prostate cancer. The paper delves into the pathological characteristics of AVPC, diagnostic and therapeutic challenges, and the potential applications of precision medicine and molecular imaging in the future.