Helical Hybrid Nanostructure Based on Chiral M13 Bacteriophage via Evaporation-Induced Three-Dimensional Process.

The use of naturally sourced organic materials with chirality, such as the M13 bacteriophage, holds intriguing implications, especially in the field of nanotechnology. The chirality properties of bacteriophages have been demonstrated through numerous studies, particularly in the analysis of liquid crystal phase transitions, developing specific applications. However, exploring the utilization of the M13 bacteriophage as a template for creating chiral nanostructures for optics and sensor applications comes with significant challenges. In this study, the chirality of the M13 bacteriophage was leveraged as a valuable tool for generating helical hybrid structures by combining it with nanoparticles through an evaporation-induced three-dimensional (3D) printing process. Utilizing on the self-assembly property of the M13 bacteriophage, metal nanoparticles were organized into a helical chain under the influence of the M13 bacteriophage at the meniscus interface. External parameters, including nanoparticle shape, the ratio between the bacteriophage and nanoparticles, and pulling speed, were demonstrated as crucial factors affecting the fabrication of helical nanostructures. This study aimed to explore the potential of chiral nanostructure fabrication by utilizing the chirality of the M13 bacteriophage and manipulating external parameters to control the properties of the resulting hybrid structures.

Temperature- and pH-induced dual-crosslinked methylcellulose/chitosan-gallol conjugate composite hydrogels with improved mechanical, tissue adhesive, and hemostatic properties.

Gauze or bandages are commonly used to effectively control bleeding during trauma and surgery. However, conventional treatment methods can sometimes lead to secondary damages. In recent years, there has been increased interest in developing adhesive hemostatic hydrogels as a safer alternative for achieving hemostasis. Methylcellulose (MC) is a well-known thermo-sensitive polymer with excellent biocompatibility that is capable of forming a hydrogel through physical crosslinking owing to its inherent thermo-reversible properties. However, the poor mechanical properties of the MC hydrogel comprising a single crosslinked network (SN) limit its application as a hemostatic material. To address this issue, we incorporated a chitosan-gallol (CS-GA) conjugate, which has the ability to form chemical crosslinks through self-crosslinking reactions under specific pH conditions, into the MC hydrogel to reinforce the MC hydrogel network. The resulting MC/CS-GA hydrogel with a dual-crosslinked network (DN), involving both physical and chemical crosslinks, exhibited synergistic effects of the two types of crosslinks. Thus, compared with those of the SN hydrogel, the composite DN hydrogel exhibited significantly enhanced mechanical strength and tissue adhesive properties. Moreover, the DN hydrogel presented excellent biological activity in vitro. Additionally, in rat hepatic hemorrhage models, the DN hydrogel exhibited high hemostatic efficiency, showcasing its multifunctional capabilities.

Pharmacologic inhibition of Il6st/gp130 improves dermatological inflammation and pruritus.

Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals. We hypothesized accordingly that pharmacological inhibition of Il6st can alter dermatitis pathology. Treatment with SC-144 and bazedoxifene, two representative small molecule Il6st inhibitors with different binding modes led to moderate but significant improvement of skin conditions in a 1-chloro-2,4-dinitrobenzene animal model. Part of cytokine expressions indicating the dermatological index were normalized particularly when treated with SC-144. Pruritic behaviors were blunted, also possibly giving limited contribution to disease improvement. In psoriatic skin and itch of an imiquimod animal model, those two treatments appeared to be relatively moderate. Collectively, pharmacological inhibition of Il6st seems to lessen pathological irritation. Inversely, this experimental attempt newly implies that Il6st participates in pathological mechanisms. In conclusion, we suggest Il6st as a novel target for improving dermatitis, and that agents with suitable efficacy and safety for its modulation are translatable.

A comparative analysis of canine pancreatic lipase tests for diagnosing pancreatitis in dogs.

IMPORTANCE: Early diagnosis of canine pancreatitis is challenging due to non-specific clinical signs. Currently, abdominal ultrasonography and measurement of canine pancreatic lipase (cPL) have been employed for the diagnosis of pancreatitis. OBJECTIVE: Many qualitative and quantitative commercial cPL tests have been developed and used in veterinary clinics. This study aimed to compare three different methodologies SNAP cPL, Spec cPL, and Vcheck cPL tests to assess the concordance of these assays. METHODS: Fifty serum samples were collected from 36 dogs with or without pancreatitis and subjected to SNAP cPL, Spec cPL, and Vcheck cPL tests. Agreement and correlation coefficients were calculated between the test results, and correlations were determined during the management of the patients. RESULTS: The results of the three cPL assays were strongly correlated in 47/50 serum samples (94%). Cohen's kappa analysis between the Spec cPL and Vcheck cPL showed near perfect agreement (κ = 0.960, p < 0.001), SNAP cPL and Vcheck cPL (κ = 0.920, p < 0.001), and Spec cPL and SNAP cPL (κ = 0.880, p < 0.001). The correlation coefficients (r) between data from Spec cPL and Vcheck cPL tests was calculated by Spearman's correlation test (r = 0.958, p < 0.001). Furthermore, the patterns of change in serum cPL concentrations determined using Spec cPL and Vcheck cPL were significantly consistent during the monitoring period in 11 patients. CONCLUSIONS AND RELEVANCE: Our data illustrated that Spec cPL and Vcheck cPL tests are compatible for clinical use in the diagnosis and monitoring of canine pancreatitis.

The therapeutic effects of vitamin D3 administration on the embryo implantation.

Various adjuvants have been tested clinically for patients with problems with embryo implantation during in vitro fertilization (IVF)-embryo transfer (ET). Vitamin D3, an essential modulator of various physiological processes, has received attention as an important adjuvant for successful pregnancy, as many studies have shown a strong association between vitamin D deficiency and implantation failure and fetal growth restriction. However, vitamin D has been widely utilized in different protocols, resulting in non-reproducible and debatable outcomes. In the present study, we demonstrated that cyclic intrauterine administration of vitamin D3 increased endometrial receptivity and angiogenesis, which could be attributed to increased recruitment of uterus-resident natural killer cells. In particular, cyclic treatment of vitamin D3 promoted stable attachment of the embryo onto endometrial cells in vitro, suggesting its merit during the early stage of embryo implantation to support the initial maternal-fetal interactions. Our findings suggest that women with repeated implantation failure may benefit from the use of vitamin D3 as a risk-free adjuvant prior to IVF-ET procedures to improve the uterine environment, and make it favorable for embryo implantation.

Trends in clinical outcomes of older hemodialysis patients: data from the 2023 Korean Renal Data System (KORDS).

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

Inpatient Hospice Care in Korea during the COVID-19 Pandemic: A Preliminary Study.

Purpose: This study examined the quality of life (QoL) and quality of care (QoC) in inpatient hospice settings in Korea before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Data were obtained from three institutions that participated in two prospective cohort studies. The primary outcomes measured were the QoL of patients with terminal cancer and their family caregivers (FCs), as well as the QoC as perceived by the FCs. Results: Multivariable regression analysis revealed that during the COVID-19 pandemic, both patients and FCs experienced better QoL than before the pandemic, and FCs reported a higher QoC. Conclusion: Health policymakers should consider our findings when planning for future pandemics.

Anti-Melanogenic Effects of Cnidium monnieri Extract via p38 Signaling-Mediated Proteasomal Degradation of Tyrosinase.

Cnidium monnieri fructus is widely used in traditional Oriental medicine for treating female genital disorders, male impotence, frigidity, and skin-related conditions in East Asia. However, the role of C. monnieri fructus extract (CMFE) in melanin synthesis is not well elucidated. This study aimed to investigate the anti-melanogenesis effect and mechanism of action of CMFE in α-MSH-stimulated B16F10 cells. Intracellular melanin content and tyrosinase activity were measured in α-MSH-stimulated B16F10 cells treated with various concentrations of CMFE (0.5-5 µg/mL). mRNA and protein levels of tyrosinase and MITF were evaluated using qRT-PCR and ting. CMFE's effect on the proteasomal degradation of tyrosinase was confirmed using a proteasomal degradation inhibitor, MG132. CMFE treatment activated p38, a protein associated with proteasomal degradation. Treatment with CMFE at up to 5 µg/mL showed no significant cytotoxicity. CMFE significantly reduced α-MSH-stimulated melanin production (43.29 ± 3.55% decrease, p < 0.05) and cellular tyrosinase activity (31.14 ± 3.15% decrease, p < 0.05). Although mRNA levels of MITF and tyrosinase increased, CMFE suppressed tyrosinase protein levels. The suppressive effect of CMFE on tyrosinase protein was blocked by MG132. CMFE inhibited melanogenesis by promoting the proteasome degradation of tyrosinase through p38 activation. These findings suggest that CMFE has the potential to be a natural whitening agent for inhibiting melanogenesis.

GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain.

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

Totally laparoscopic versus laparoscopy-assisted distal gastrectomy: the KLASS-07: a randomized controlled trial.

BACKGROUNDS: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG. METHODS: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT03393182). RESULTS: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year. CONCLUSIONS: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months.

JOURNAL/ijos/04.03/01279778-202408000-00031/figure1/v/2024-08-13T152924Z/r/image-jpeg.

The application of enhanced recovery after surgery protocol after distal gastrectomy for patients with gastric cancer: a prospective randomized clinical trial.

BACKGROUND: This study aimed to evaluate the clinical outcomes and efficacy of enhanced recovery after surgery (ERAS) protocol in patients undergoing distal gastrectomy for gastric cancer (GC). METHODS: Patients were randomly assigned to the ERAS group (EG) and the conventional care group (CG) by stratified randomization according to age and sex. The primary endpoint was adjusted postoperative hospital stay, calculated using discharge criteria developed to evaluate recovery. Nutritional data and quality of life (QoL) (European Organisation for Research and Treatment of Cancer [EORTC] C30 and STO22) during the perioperative period were also analyzed. RESULTS: We enrolled 198 eligible patients with GC for the study between June 2017 and January 2019. A total of 147 patients were finally enrolled in this study (full analysis set) and were assigned to EG (n = 71) and CG (n = 76). First flatus was faster significantly in EG (3.6 ± 1.5 vs 4.1 ± 1.2 days, P = .019). EG showed a faster start of the sips and soft diet than CG (1.3 ± 0.7 vs 3.1 ± 0.4 days, P < .001; 2.4 ± 0.9 vs 5.2 ± 0.7 days, P < .001) according to the protocol. The recorded hospital stay was not significantly different; however, adjusted hospital stay was significantly shorter in EG than in CG (6.5 ± 3.1 vs 7.8 ± 2.1 days, P = .005). There was no difference in morbidity, and no mortality occurred in both groups. EG did not show significant superiority in nutritional outcome and QoL improvement, except for pain scale in EORTC-STO22. CONCLUSION: The application of the ERAS protocol could reduce the adjusted hospital stay without an increase in postoperative complications. There was no significant difference in long-term nutritional outcome and QoL of the 2 groups.

Musculoskeletal Pain, Physical Activity, Muscle Mass, and Mortality in Older Adults: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in older adults, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyses were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived over a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pains. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pains. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Development of a method using QuEChERS and LC-MS/MS for analysis of per- and polyfluoroalkyl substances in rice matrix.

Detection of per- and polyfluoroalkyl substances (PFAS) in food is crucial for ensuring food safety. Therefore, we combined a quick, easy, cheap, rugged, and safe (QuEChERS) extraction method with liquid chromatography-triple-quadrupole mass spectrometry (LC-MS/MS) to detect 35 PFAS in rice. The solvents (water and acetonitrile) were adjusted to pH 2.4, a mixture of anhydrous MgSO4, NaCl, and NaOAc was used for extraction, and anhydrous MgSO4, a primary/secondary amine, and graphitized carbon black were applied for purification. The limits of detection and recovery were 0.005-0.100 ng·g-1 and 86.5 %-126.4 %, respectively. When this method was used to detect PFAS in packaged instant rice cooked in a microwave or boiled in water, the microwaved sample showed a lower PFAS content. However, both samples had PFAS contents within WHO guidelines and were safe for consumption. This method can be extended to detect PFAS levels in other foods exposed to packaging materials containing PFAS.

Clinical Outcome after Everolimus-Eluting Stent Implantation for Small Vessel Coronary Artery Disease: XIENCE Asia Small Vessel Study.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270). Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.

In Vitro Head-to-Head Comparison of Flow Reduction between Fibered and Non-Fibered Pushable Coils.

PURPOSE: To compare the embolization effects of a non-fibered pushable coil with a conventional fibered pushable coil in an in vitro bench-top experiment. MATERIALS AND METHODS: A simplified vascular phantom with 4 channels (1 for the non-fibered coil, 1 for the fibered coil, and 2 for continuous circuit flow) was used. A single coil of the longest length was inserted to evaluate the effect of single-coil embolization, and 3 consecutive coils were inserted to assess the effect of multiple-coil embolization. Post-embolization angiography was performed to obtain flow variables (time to peak [TTP], relative peak intensity [rPI], and angiographic flow reduction score [AFRS]) from time density curves. The packing densities of the two coil types were calculated, and the AFRS of each channel was determined by dividing the TTP by the rPI. RESULTS: When inserting a single coil, the conventional fibered coil demonstrated better flow reduction, as indicated by a higher AFRS (25.6 vs. 17.4, P=0.034). However, the non-fibered coil exhibited a significantly higher packing density (12.9 vs. 2.4, P=0.001). Similar trends were observed with multiple coils. CONCLUSION: The conventional fibered pushable coil showed better flow reduction efficiency, while the non-fibered pushable coil had a higher packing density, likely due to the flexibility of the coil loops. A better understanding of the distinct characteristics of different pushable coils can enhance the outcomes of various vascular embolization.

GPR161 structure uncovers the redundant role of sterol-regulated ciliary cAMP signaling in the Hedgehog pathway.

The orphan G protein-coupled receptor (GPCR) GPR161 plays a central role in development by suppressing Hedgehog signaling. The fundamental basis of how GPR161 is activated remains unclear. Here, we determined a cryogenic-electron microscopy structure of active human GPR161 bound to heterotrimeric Gs. This structure revealed an extracellular loop 2 that occupies the canonical GPCR orthosteric ligand pocket. Furthermore, a sterol that binds adjacent to transmembrane helices 6 and 7 stabilizes a GPR161 conformation required for Gs coupling. Mutations that prevent sterol binding to GPR161 suppress Gs-mediated signaling. These mutants retain the ability to suppress GLI2 transcription factor accumulation in primary cilia, a key function of ciliary GPR161. By contrast, a protein kinase A-binding site in the GPR161 C terminus is critical in suppressing GLI2 ciliary accumulation. Our work highlights how structural features of GPR161 interface with the Hedgehog pathway and sets a foundation to understand the role of GPR161 function in other signaling pathways.

Endometrial organoids: a reservoir of functional mitochondria for uterine repair.

Background: Asherman's syndrome (AS) is a dreadful gynecological disorder of the uterus characterized by intrauterine adhesion with severe fibrotic lesions, resulting in a damaged basalis layer with infertility. Despite extensive research on overcoming AS, evidence-based effective and reproducible treatments to improve the structural and functional morphology of the AS endometrium have not been established. Methods: Endometrial organoids generated from human or mouse endometrial tissues were transplanted into the uterine cavity of a murine model of AS to evaluate their transplantable feasibility to improve the AS uterine environment. The successful engraftment of organoid was confirmed by detection of human mitochondria and cytosol (for human endometrial organoid) or enhanced green fluorescent protein signals (for mouse endometrial organoid) in the recipient endometrium. The therapeutic effects mediated by organoid transplantation were examined by the measurements of fibrotic lesions, endometrial receptivity and angiogenesis, and fertility assessment by recording the number of implantation sites and weighing the fetuses and placenta. To explore the cellular and molecular mechanisms underlying the recovery of AS endometrium, we evaluated the status of mitochondrial movement and biogenetics in organoid transplanted endometrium. Results: Successfully engrafted endometrial organoids with similar morphological and molecular features to the parental tissues dramatically repaired the AS-induced damaged endometrium, significantly reducing fibrotic lesions and increasing fertility outcomes in mice. Moreover, dysfunctional mitochondria in damaged tissues, which we propose might be a key cellular feature of the AS endometrium, was fully recovered by functional mitochondria transferred from engrafted endometrial organoids. Endometrial organoid-originating mitochondria restored excessive collagen accumulation in fibrotic lesions and shifted uterine metabolic environment to levels observed in the normal endometrium. Conclusions: Our findings suggest that endometrial organoid-originating mitochondria might be key players to mediate uterine repair resulting in fertility enhancement by recovering abrogated metabolic circumstance of the endometrium with AS. Further studies addressing the clinical applicability of endometrial organoids may aid in identifying new therapeutic strategies for infertility in patients with AS.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed. We investigated the intestinal microbiome of GC patients and attempted to reverse the immunosuppression of the immune and cancer cells of GC patients through the modulation of microbiome metabolites. We evaluated the levels of programmed death-ligand 1 (PD-L1) and interleukin (IL)-10 in the peripheral blood immunocytes of GC patients. Cancer tissues were obtained from patients who underwent surgical resection of GC, and stained sections of cancer tissues were visualized via confocal microscopy. The intestinal microbiome was analyzed using stool samples of healthy individuals and GC patients. Patient-derived avatar model was developed by injecting peripheral blood mononuclear cells (PBMCs) from advanced GC (AGC) patients into NSG mice, followed by injection of AGS cells. PD-L1 and IL-10 had higher expression levels in immune cells of GC patients than in those of healthy controls. The levels of immunosuppressive factors were increased in the immune and tumor cells of tumor tissues of GC patients. The abundances of Faecalibacterium and Bifidobacterium in the intestinal flora were lower in GC patients than in healthy individuals. Butyrate, a representative microbiome metabolite, suppressed the expression levels of PD-L1 and IL-10 in immune cells. In addition, the PBMCs of AGC patients showed increased levels of immunosuppressive factors in the avatar mouse model. Butyrate inhibited tumor growth in mice. Restoration of the intestinal microbiome and its metabolic functions inhibit tumor growth and reverse the immunosuppression due to increased PD-L1 and IL-10 levels in PBMCs and tumor cells of GC patients.

Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen's hernia: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.