FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival.

JOURNAL/nrgr/04.03/01300535-202507000-00031/figure1/v/2024-09-09T124005Z/r/image-tiff FK506 (Tacrolimus) is a systemic immunosuppressant approved by the U.S. Food and Drug Administration. FK506 has been shown to promote peripheral nerve regeneration, however, its precise mechanism of action and its pathways remain unclear. In this study, we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve, increased the numbers of motor and sensory neurons, reduced inflammatory responses, markedly improved the conduction function of the injured nerve, and promoted motor function recovery. These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Enhancing the performance of a lithium-sulfur battery with spatially confined mesoporous nanoreactors in sulfurized polyacrylonitrile cathodes.

Sulfurized polyacrylonitrile (SPAN), which is recognized as a promising cathode material for lithium-sulfur batteries (Li-SBs), effectively mitigates the shuttle effect resulting from polysulfide dissolution. However, conventional SPAN cathodes typically exhibit sulfur loadings below 40 wt%. While encapsulation of sulfur within pores via a solid electrolyte interface addresses the low sulfur loading issue, the suboptimal kinetics of the solid-solid reactions hinder effective utilization of sulfur within the pores. In this work, Me-SeSPAN/SeS fibrous membranes were successfully synthesized through electrospinning and molten salt-assisted pyrolysis of ZIF-8, which resulted in the formation of spatially confined interconnected mesoporous nanoreactors. These nanoreactors function as supplementary storage spaces, loading and constraining the size of internal active material clusters. The fibrous membranes facilitate Li+ movement through pore spaces and promote adsorption of the discharge product Li2S on the pore walls via the spatial confinement effect. Based on density functional theory (DFT) calculations, this process guarantees a supply of electrons and Li+ to the active material, thereby enabling continuous electron transfer during redox reactions. The optimized Me-SeSPAN/SeS electrode, featuring a sulfur and selenium loading of 70 wt%, demonstrates exceptional cycling stability in both coin and pouch cells. This study presents an effective strategy for enhancing the kinetics of active materials encapsulated in SPAN cathodes.

Pleiotropically activation of azaphilone biosynthesis by overexpressing a pathway-specific transcription factor in marine-derived Aspergillus terreus RA2905.

The genome sequencing of Aspergillus terreus reveals that the vast number of predicted biosynthetic gene clusters have not reflected by the metabolic profile observed under conventional culture conditions. In this study, a silent azaphilone biosynthetic gene cluster was activated by overexpressing a pathway-specific transcription factor gene2642 in marine-derived fungus A. terreus RA2905. Consequently, twenty azaphilone compounds were identified from the OE2642 mutant, including 11 new azaphilones and their precursors, azasperones C-J (1-5, 7-9) and preazasperones A-C (15-17). The structures of those new compounds were unambiguously determined on the basis of NMR and HRESIMS spectra analysis, and the absolute configurations were established depending on ECD calculations. Compounds 1 and 2 were the rarely reported naturally occurring azaphilones with 2-N coupled phenyl-derivative. The bioactivity assay revealed that compounds 18-20 exhibited significant anti-inflammatory activity. Based on the occurrence of diverse intermediates and the putative gene functions, a plausible biosynthetic pathway of these compounds was proposed. The above results demonstrated that overexpression of the pathway-specific transcription factor presents a promising approach for enriching fungal secondary metabolites and accelerating the targeted discovery of novel biosynthetic products.

Immune-enhancing effect of fermented soybean food, Cheonggukjang on cyclophosphamide-treated immunosuppressed rat.

Cheonggukjang (CGJ) is a traditional food, made by the fermentation of beans, and it has different recipes for different regions in Korea. However, it has anti-inflammatory, anti-cancer, and anti-obesity effects, and is known to affect changes in the intestinal microbiota. In this study, we investigated the immune-enhancing effects of four type CGJs (one commercial and three transitional CGJs). In the cyclophosphamide (CP)-treated immunosuppressed rat, oral administration of CGJs for 4 weeks was used to investigate weight of body and immune organ, change of microbiota, blood and serum parameters, inflammation pathways (MAPKs and NFκB) and histology of spleen. It showed an immunity-enhancing effect through increase Bacteroidetes in gut, the recovery of complete blood count, levels of cytokines and IgG, activation of inflammatory pathways, and histology of spleen. In conclusion, these results show that the intake of a commercial brand CGJ, and traditional CGJs can maintain or promote the body's immunity.

Structural characterization of polysaccharides from Panax ginseng C. A. Meyer root and their triggered potential immunoregulatory and radioprotective activities.

With people's increasing awareness of healthy diet, the diverse health-promoting functions of ginseng have been widely recognized. As one of the key functional components, ginseng polysaccharides have attracted increasing research interest. Here, three purified polysaccharide fractions, GPS-1a, GPS-1b, and GPS-2, were obtained from the root extract of Panax ginseng C. A. Meyer. Structurally, GPS-1a and GPS-1b were both linked in a â†’ 6)-α-D-Glcp-(1 â†’ pattern but composed of glucose and galactose in molar ratios of 9.76:0.24 and 9.81:0.19. In contrast, GPS-2 was composed of glucose, galactose, arabinose, rhamnose, and galacturonic acid in a molar ratio of 1.82:1.94:0.79:0.52:4.93. The main backbone consisted of →4)-α-D-GalpA-(1→, →4)-α-D-GalpA-6OMe-(1→, →3, 4)-α-D-GalpA-(1→, →3)-α-L-Rhap-(1 â†’ linages, and its branches are composed of →5)-α-L-Araf-(1→, →4)-ß-D-Galp-(1→, →2)-ß-D-Glcp-(1→, α-D-GalAp-(1→. Benefitting from this structural variance, GPS-2 exhibited the most significant immunoregulatory and radioprotective efficacies. Specifically, GPS-2 promoted TLR2, NF-κB, and TRAF6 protein expression levels, thereby significantly improving macrophage phagocytosis, splenic lymphocyte proliferation, and stimulation of NO, IL-1ß, IL-6, and TNF-α secretion, which activated RAW264.7 and splenic lymphocytes. The following radioprotection activity tests unveiled that GPS-2 increased the organ index, number of peripheral blood cells, cellularity of splenocytes, and bone marrow cell numbers in irradiated mice. This investigation revealed the contribution of polysaccharide structure characteristics to the bioactive expression and elucidated the potential utilization of GPS-2 as a radioprotective agent or immunomodulator.

A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet.

BACKGROUND: Cinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified. PURPOSE: Our study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary. METHODS: The toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS. RESULTS: Cin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12­hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae_NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed. CONCLUSION: As a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines.

An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.

Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1+ memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation.

Polystyrene nanoparticles regulate microbial stress response and cold adaptation in mainstream anammox process at low temperature.

Nanoplastic pollution has become one of the most pressing environmental issues, and its bioaccumulation in aquatic environment also causes a great difficulty in treatment. Therefore, this work investigated the microbial dynamics of mainstream anaerobic ammonia oxidizing (anammox) process to treat the wastewater containing typical nanoplastics, as well as the fate and regulation mechanism of polystyrene nanoparticles (PS-NPs) with different concentrations. The results showed that 0.1-0.5 mg L-1 of PS-NPs had no significant effect on the nitrogen removal efficiency (NRE). When the concentration of PS-NPs increased from 0.5 mg L-1 to 2 mg L-1, the NRE of R1 with PS-NPs decreased from 94.9 ± 2.3 % to 77.0 ± 1.6 %, while the control reactor R0 maintained a stable NRE. Notably, the relative abundance of Ca. Kuenenia decreased from 17.4 % to 14.8 %, and that of Ca. Brocadia slightly decreased from 5.9 % to 5.0 % in R1. In addition, PS-NPs induced oxidative stress in anammox consortia, leading to the significant increase in reactive oxygen species (ROS) and lactate dehydrogenase (LDH) as well as cell membrane damage. PS-NPs also downregulated the content of heme c and further inhibited anammox activity. Based on the molecular docking simulation and western blotting, cold shock proteins (CSPs) could bind to PS-NPs and reduce the performance of anammox processes at low temperatures.

A novel prognostic scoring system for AML patients undergoing allogeneic hematopoietic stem cell transplantation with real world validation.

OBJECTIVES: This study aims to develop a robust predictive model for survival in AML patients undergoing allo-HSCT. METHODS: It was performed a retrospective analysis of 336 AML patients who underwent allo-HSCT at Peking University First Hospital between September 2003 and March 2023. Univariable and multivariable Cox regression analyses were conducted to determine hazard ratios (HR) for overall survival. A predictive model was developed based on multivariable analysis results. Internal validation was carried out through bootstrap resampling, and the model's performance was assessed using the Concordance Index (C-index), Receiver Operating Characteristics (ROC) curve, calibration plots, and Decision Curve Analysis (DCA). RESULTS: Our prognostic model, which includes age, disease stage, donor/recipient gender, mononuclear cell counts, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), effectively stratified patients into low-risk and high-risk groups. The two groups showed significant differences in overall survival (P<0.0001), disease-free survival (P<0.0001), non-relapse mortality (NRM) (P<0.0001), and relapse rates (P=0.08). The model achieved a C-index of 0.71. Calibration plots and DCA confirmed strong alignment between predicted and observed outcomes. Subgroup analysis revealed that overall survival was significantly lower in the high-risk group compared to the low-risk group in both measurable residual disease (MRD) negative and MRD positive subgroups (P=0.015 for both). CONCLUSION: The developed prognostic model, which integrates comprehensive disease and patient characteristics, enhances risk stratification for AML patients undergoing allo-HSCT. This model effectively stratifies risk in both MRD-negative and MRD-positive subgroups and may facilitate more informed MRD-based treatment decisions.

The spatiotemporal analysis of SARS-CoV-2 transmission in China since the termination of the dynamic zero-COVID policy.

China's dynamic zero-COVID policy has effectively curbed the spread of SARS-CoV-2, while inadvertently creating immunity gaps within its population. Subsequent surges in COVID-19 cases linked to various SARS-CoV-2 lineages post-policy termination necessitate a thorough investigation into the epidemiological landscape. This study addresses this issue by analyzing a comprehensive dataset of 39,456 high-quality genomes collected nationwide over an 11-month period since policy termination. Through lineage assignment, phylogenetic analysis, pandemic pattern comparison, phylodynamic reconstruction, and recombination detection, we found that China's post-epidemic period could be divided into three stages, along with dynamic changes in dominant lineages. Geographical clustering of similar lineages implies the importance of cross-border cooperation among neighboring regions. Compared to the USA, UK, and Japan, China exhibits unique trajectories of lineage epidemics, characterized by initial lagging followed by subsequent advancement, indicating the potential influence of diverse prevention and control policies on lineage epidemic patterns. Hong Kong, Shanghai, and Hubei emerge as pivotal nodes in the nationwide spread, marking a shift in the transmission center from east to central regions of China. Although China hasn't experienced significant variant emergence, the detection and validation of the novel recombination event, XCN lineage, underscore the ongoing virus evolution. Overall, this study systematically analyzes the spatiotemporal transmission of SARS-CoV-2 virus in China since the termination of the dynamic zero-COVID policy, offering valuable insights for regional surveillance and evidence-based public health policymaking.

Sulforaphane regulates cell proliferation and induces apoptotic cell death mediated by ROS-cell cycle arrest in pancreatic cancer cells.

Background: Pancreatic cancer (PC), sometimes referred to as pancreatic ductal adenocarcinoma (PDAC), is a major cause of global mortality from cancer. Pancreatic cancer is a very aggressive and devastating kind of cancer, characterized by limited options for therapy and low possibilities of survival. Sulforaphane (SFN), a naturally occurring sulfur-containing compound, is believed to possess anti-inflammatory, anti-obesity, and anti-cancer characteristics. Objective: However, efficient preventative and treatment measures are essential and SFN has been studied for its ability to suppress pancreatic cancer cell proliferation and induce apoptosis. Methods: Here, SFN induced cytotoxicity and apoptosis in PDAC cell lines such as MIA PaCa-2 and PANC-1 cells, as evaluated by cytotoxicity, colony formation, western blot analysis, fluorescence-activated cell sorting (FACS), reactive oxygen species (ROS) detection, caspase-3 activity assay, immunofluorescence assay, and mitochondrial membrane potential assay. Results: In MIA PaCa-2 and PANC-1 cells, SFN inhibited cell survival and proliferation in a dose-dependent manner. The activation of caspase zymogens results in cleaved PARP and cleaved caspase-3, which is associated with an accumulation in the sub G1 phase. Furthermore, SFN increased ROS level and γH2A.X expression while decreasing mitochondrial membrane potential (ΔΨm). Notably, the ROS scavenger N-Acetyl-L-cysteine (NAC) was shown to reverse SFN-induced cytotoxicity and ROS level. Subsequently, SFN-induced cell cycle arrest and apoptosis induction as a Trojan horse to eliminate pancreatic cancer cells via ROS-mediated pathways were used to inhibit pancreatic cancer cells. Conclusion: Collectively, our data demonstrates that SFN-induced cell death follows the apoptosis pathway, making it a viable target for therapeutic interventions against pancreatic cancer.

Prognostic factors in children and adolescents with differentiated thyroid cancer treated with total thyroidectomy and radioiodine therapy: a retrospective two-center study from China.

Purpose: This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT). Materials and methods: All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients' disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients' ultimate disease outcomes. Results: A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg ≥20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion: In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Dynamic changes in the gut microbiota composition during adalimumab therapy in patients with ulcerative colitis: implications for treatment response prediction and therapeutic targets.

BACKGROUND: While significant research exists on gut microbiota changes after anti-tumor necrosis factor-alpha (anti TNF-α) therapy for ulcerative colitis, little is known about the longitudinal changes related to the effects of anti TNF-α. This study aimed to investigate the dynamics of gut microbiome changes during anti TNF-α (adalimumab) therapy in patients with ulcerative colitis (UC). RESULTS: The microbiota composition was affected by the disease severity and extent in patients with UC. Regardless of clinical remission status at each time point, patients with UC exhibited microbial community distinctions from healthy controls. Distinct amplicon sequence variants (ASVs) differences were identified throughout the course of Adalimumab (ADA) treatment at each time point. A notable reduction in gut microbiome dissimilarity was observed only in remitters. Remitters demonstrated a decrease in the relative abundances of Burkholderia-Caballeronia-Paraburkholderia and Staphylococcus as the treatment progressed. Additionally, there was an observed increase in the relative abundances of Bifidobacterium and Dorea. Given the distribution of the 48 ASVs with high or low relative abundances in the pre-treatment samples according to clinical remission at week 8, a clinical remission at week 8 with a sensitivity and specificity of 72.4% and 84.3%, respectively, was predicted on the receiver operating characteristic curve (area under the curve, 0.851). CONCLUSIONS: The gut microbiota undergoes diverse changes according to the treatment response during ADA treatment. These changes provide insights into predicting treatment responses to ADA and offer new therapeutic targets for UC.

Impact of Diabetes on COVID-19 Susceptibility: A Nationwide Propensity Score Matching Study.

Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P<0.001). Logistic regression analysis indicated that diabetes significantly increased the risk of COVID-19 test positivity (odds ratio, 1.307; 95% confidence interval, 1.144 to 1.493; P<0.001). Patients with diabetes exhibited heightened COVID-19 infection rates compared to individuals without diabetes, and diabetes increased the susceptibility to COVID-19, reinforcing the need for heightened preventive measures, particularly considering the poor clinical outcomes in this group.

Acculturation, Enculturation, Culture-Specific Emotional Distress, and Parenting Among Korean Immigrant Mothers.

This study examined how Korean immigrant mothers' cultural orientations (i.e., acculturation and enculturation) were related to their mental health, specifically depression and the culturally specific syndrome of Hwa-byung (HB), and had direct and indirect relations to their parenting practices (i.e., authoritative, authoritarian, acceptance, rejection). In a sample of 412 Korean immigrant mothers (99.5% foreign-born; Mage = 45.31), a path analysis was conducted by using the maximum-likelihood and bootstrapping methods. Results revealed that mothers' cultural orientations were indirectly related to parenting practices via depression and HB. Specifically, mothers' acculturation and enculturation had positive indirect relationships to authoritative parenting and acceptance versus a negative relationship to rejection, via their links to depression. Mothers' acculturation had a negative relationship to rejection via its link to HB, while enculturation was not related to HB. Additionally, cultural orientations were directly associated with parenting. Overall, the current findings highlighted that HB holds a unique role in parenting after controlling for the effects of depression, which suggests the importance of assessing culture specific syndrome, above and beyond depression, to have a better understanding of Korean immigrant mothers' mental health and its relation to parenting. Implications for research and practice are discussed.

Effect of home-based tongue-strengthening exercise using a portable tool on oropharyngeal muscles in older adults with sarcopenic dysphagia: A randomised controlled study.

BACKGROUND: Tongue-strengthening exercises may be used at home to strengthen swallowing-related oropharyngeal muscles in community-dwelling older adults with sarcopenic dysphagia; however, evidence of their effectiveness remains unclear. OBJECTIVE: This study aimed to investigate the effects of a home-based tongue-strengthening exercise (hTSE) using portable tool on swallowing-related oropharyngeal muscles in community-dwelling older adults with sarcopenic dysphagia. METHODS: Forth community-dwelling older adults with sarcopenic dysphagia were enrolled in the study. The participants were randomly assigned to the experimental and control groups. 1-Repetition Maximum (1-RM) of tongue muscle was measured in the experimental group using the Iowa Oral Performance Instrument, and hTSE was performed using a portable tool with an intensity corresponding to approximately 70%-80% of the range based on the 1-RM value (90 times/day, 5 days/week, for 8 weeks). The control group did not perform any tongue exercises. The primary outcome measures were tongue strength and thickness. The secondary outcome measure was suprahyoid muscle strength (digastric and mylohyoid muscles). RESULTS: The experimental group showed significantly greater increases in suprahyoid muscle (mylohyoid and digastric) thickness (p = .01 and .011, d = 1.0 and .55), as well as tongue strength and thickness (p < .001 and .029, d = 2.2 and .6) than the control group. CONCLUSION: This study confirmed that hTSE using a portable tool is effective in increasing swallowing-related oropharyngeal muscle activity in older adults with sarcopenic dysphagia. Therefore, hTSE is recommended as an inexpensive, safe, and easy-to-use therapy for sarcopenic dysphagia in older adults.

Efficacy and safety of variceal embolization for primary prophylaxis in cirrhosis patients with challenges in standard treatments: preliminary results.

Objectives: Nonselective beta blockers (NSBBs) or endoscopic therapies are currently recommended by guidelines for preventing the first variceal bleed in patients with high-risk varices. However, there is a lack of detailed treatment strategies for patients who are intolerant to both NSBBs and endoscopic approaches. Our study aimed to assess the efficacy and safety of variceal embolization as a primary prophylaxis method in cirrhosis patients who are not suitable candidates for NSBBs or endoscopic treatments. Methods: The study included 43 cirrhotic patients with high-risk varices who were candidates for primary prophylaxis against variceal bleeding. These patients underwent variceal embolization at the Xijing Hospital between January 2020 and June 2022. The primary endpoint was the occurrence of bleeding from varices, and the secondary endpoints were the recurrence of varices and the emergence of complications. Results: The procedure of variceal embolization had a success rate of 93.0% (40 out of 43 patients). Over a 2-year follow-up period, the rate of variceal bleeding was 11.6% (5 out of 43 patients), the recurrence rate of varices was 14.0% (6 out of 43 patients), and the rate of severe complications was limited to 2.3% (1 out of 43 patients). Conclusion: Variceal embolization is a viable primary prophylactic intervention for cirrhotic patients who are at risk of variceal bleeding when standard treatments, such as NSBBs or endoscopic therapies, are difficult to perform.

Tumor mutation burden and FAT3 mutation influence long-term survival in surgically resected small cell lung cancer.

Background: Small cell lung cancer (SCLC) is highly malignant and has a higher risk of recurrence even in patients who undergo early surgery. However, a subgroup of patients survived for many years. So far, the factors that determine the long-term survivorship remain largely unknown. To determine the genetic characteristics of long-term survival (LTS) after surgery in SCLC, we performed comprehensive comparative genomic profiling and tumor mutation burden (TMB) analysis of resected tumor tissues from patients with LTS and short-term survival (STS) after surgery. Methods: The present study screened 11 patients from 52 patients with SCLC who underwent surgery at Zhejiang Cancer Hospital from April 2008 to December 2017. A total of six LTS patients (≥4 years) with stage IIB or IIIA SCLC and five STS patients (<2 years) with stage IA or IB SCLC were included in the study. The STS patients were used as a control. All the patients underwent resection without neoadjuvant therapy. We assessed the genomic profiles of the resected tumor tissues and calculated the TMB using next-generation sequencing. We then analyzed and compared the molecular characteristics between the LTS and STS groups. Results: Our data indicated that tumor tissues from patients with LTS harbor a high TMB. The median TMB for LTS patients was high (approximately 16.4 mutations/Mb), while that for STS patients was low (approximately 8.5 mutations/Mb). The median TMB of patients with LTS and STS showed a trend of significant difference (P=0.08). Gene alterations characterized the survival differences between the two groups. The FAT3 mutation was only found in the LTS group, and the P value determined by Fisher's exact test was 0.06. Conclusions: A high non-synonymous TMB and the FAT3 mutation could potentially influence LTS after SCLC resection. This study provides valuable information about the molecular differences between LTS and STS patients. Studies with larger sample sizes need to be conducted to confirm our findings in the future.